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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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

Gene therapy is the most effective treatment option for diseases, but its effectiveness is affected by the choice and design of gene carriers. The genes themselves have to pass through multiple barriers in order to enter the cell and therefore require additional vectors to carry them inside the cell. In gene therapy, peptides have unique properties and potential as gene carriers, which can effectively deliver genes into specific cells or tissues, protect genes from degradation, improve gene transfection efficiency, and enhance gene targeting and biological responsiveness. This paper reviews the research progress of peptides and their derivatives in the field of gene delivery recently, describes the obstacles encountered by foreign materials to enter the interior of the cell, and introduces the following classes of functional peptides that can carry materials into the interior of the cell, and assist in transmembrane translocation of carriers, thus breaking through endosomal traps to enable successful entry of genetic materials into the nucleus of the cell. The paper also discusses the combined application of peptide vectors with other vectors to enhance its transfection ability, explores current challenges encountered by peptide vectors, and looks forward to future developments in the field. [Display omitted] [ABSTRACT FROM AUTHOR]

Phage display enables to screen probes such as peptide, antibody and nanobody with high specificity and affinity to the target, providing excellent probes for various analytical or biosensing platforms. Furthermore, by employing techniques like as genetic engineering and chemical modification, it is possible to conveniently functionalize these ligands for analytical chemistry with selectivity and sensitivity. This review initially presents the fundamental aspects of phage biology that are commonly employed in phage display vectors, elaborates the construction process of phage display peptide library and phage display antibody library, and evaluates different biopanning strategies. Then from the viewpoint of analytes, this paper summarizes phage display based biosensing or bioanalysis of a wide range of target molecules. This paper presents knowledge insights and research foundations for the identification of additional phage display probes and their subsequent application in biosensing or bioanalysis with excellent performance. • An overview of phage-display to screen peptide, antibody and nanobody. • Phage display derived probes in biosensing are summarized. • Challenges and perspectives in phage display and biosensing application envisioned. [ABSTRACT FROM AUTHOR]

[Display omitted] • Hydrolysed peptide fragments instead of the whole cardiac troponin I for surface imprinted. • Good Raman signal peaks obtained by staining the peptides with Coomassie Brilliant Blue G-250. • MMIPs could be stored for more than half a year without affecting its adsorption properties. • The materials open wide possibilities for efficient, specific and economic detection of cardiac troponin I. This paper proposes a selective strategy for quantitative detecting cardiac troponin I (cTnI) in clinical serum samples by using Raman spectroscopy combined with magnetic molecularly imprinted polymers (MMIPs). The signature peptide was selected as a template for molecular imprinting due to its chemical stability and small molecular mass. MMIPs were synthetized with the signature peptide as template and methylacrylic acid as monomer in presence of vinyl-modified magnetic particles. MMIPs with high magnetic character and adsorption properties were able to be stained by Coomassie Brilliant Blue G-250 after the target template was specifically captured, which showing a characteristic absorption peak at Raman shift 1610 cm−1. The Raman signal intensity at 1610 cm−1 showed a linear relationship in the 0.01 to 100 ng·mL−1 concentration range. The recovery of cTnI in serum were 92.7–111.2 % with relative standard deviation in the range of 2.51 % to 8.52 %. This paper has important practical application for preliminary rapid detection of cTnI in clinical serum samples. [ABSTRACT FROM AUTHOR]

Peptide/protein quantitation using mass spectrometry (MS) is advantageous due to its high sensitivity. Traditional absolute peptide quantitation methods rely on making calibration curves using peptide standards or isotope-labelled peptide standards, which are expensive and take time to synthesize. A method which can eliminate the need for using standards would be beneficial. Recently, we developed coulometric mass spectrometry (CMS) which can be used to quantify peptides that are oxidizable (e.g., those containing tyrosine or tryptophan), without using peptide standard. The method is based on electrochemical oxidation of peptides followed by MS measurement of the oxidation yield. However, it cannot be directly used to quantify peptides without oxidizable residues. To extend this method for quantifying peptides/proteins in general, in this study, we adopted a derivatization strategy, in which a target peptide is first tagged with an electroactive reagent such as monocarboxymethylene blue NHS ester (MCMB-NHS ester), followed with quantitation by CMS. To illustrate the power of this method, we have analyzed peptides MG and RPPGFSPFR. The quantification error was less than 5%. Using RPPGFSPFR as an example, the quantitation sensitivity of the technique was found to be 0.25 pmol. Furthermore, we also used the strategy to quantify proteins cytochrome C and β-casein with an error of 2–26 %. [Display omitted] • Coulometric mass spectrometry (CMS) in combination with derivatization strategy can be used for absolute quantitation of peptides and proteins in general. • Our quantitation method reported in this paper does not require the use of standards or isotope-labelled standards. • Our quantitation method reported in this paper is applicable to peptides that are not electrochemically active. • The derivatization of peptide with methylene blue electrochemical tag allows the oxidation of peptides at a very low potential (0.2 V vs. Ag/AgCl), thus providing the method selectivity. [ABSTRACT FROM AUTHOR]

• Structure and properties of β-casein mutants in dairy products were summarized. • Impact of A1/A2 β-casein on gastrointestinal health in vivo studies was analyzed. • The detection method of β-casomorhin7 and A1/A2 β-casein was summarized. • Limitations and future directions in this promising field were presented. β-casein is the second most abundant form of casein in milk. Changes in amino acid sequence at specific positions in the primary structure of β-casein in milk will produce gene mutations that affect the physicochemical properties of dairy products and the hydrolysis site of digestive enzymes. The screening method of β-casein allele frequency detection in dairy products also has attracted the extensive attention of scientists and farmers. The A1 and A2 β-casein is the two usual mutation types, distinguished by histidine and proline at position 67 in the peptide chain. This paper summarizes the effects of A1 and A2 β-casein on the physicochemical properties of dairy products and evaluates the effects on human health, and the genotyping methods were also concluded. Impressively, this review presents possible future opportunities and challenges for the promising field of A2 β-casein, providing a valuable reference for the development of the functional dairy market. [ABSTRACT FROM AUTHOR]

An Erratum to this paper has been published: https://doi.org/10.1134/S0026261724030019 [ABSTRACT FROM AUTHOR]

Plants live in a highly dynamic environment and require to rapidly respond to a plethora of environmental stimuli, so that to maintain their optimal growth and development. A small plant peptide, rapid alkalization factor (RALF), can rapidly increase the pH value of the extracellular matrix in plant cells. RALFs always function with its corresponding receptors. Mechanistically, effective amount of RALF is induced and released at the critical period of plant growth and development or under different external environmental factors. Recent studies also highlighted the role of RALF peptides as important regulators in plant intercellular communications, as well as their operation in signal perception and as ligands for different receptor kinases on the surface of the plasma membrane, to integrate various environmental cues. In this context, understanding the fine-print of above processes may be essential to solve the problems of crop adaptation to various harsh environments under current climate trends scenarios, by genetic means. This paper summarizes the current knowledge about the structure and diversity of RALF peptides and their roles in plant development and response to stresses, highlighting unanswered questions and problems to be solved. • Rapid alkalinization factor (RALF) peptides modulate pH of the extracellular matrix in plant cells. • RALFs play key role in plant growth and development. • RALFs are important regulators in plant intercellular communications, integrating various environmental cues. • Important role of RALFs as component of abiotic stress tolerance mechanisms has emerged. [ABSTRACT FROM AUTHOR]

Brain-derived neurotrophic factor (BDNF) is a neurotrophic protein that promotes neuronal survival, increases neurotransmitter synthesis, and has potential therapeutic effects in neurodegenerative and psychiatric diseases, but its drug development has been limited by the fact that recombinant proteins of BDNF are unstable and do not penetrate the blood-brain barrier (BBB). In this study, we fused a TAT membrane-penetrating peptide with BDNF to express a recombinant protein (TBDNF), which was then PEG-modified to P-TBDNF. Protein characterization showed that P-TBDNF significantly improved the stability of the recombinant protein and possessed the ability to penetrate the BBB, and in cellular experiments, P-TBDNF prevented MPTP-induced nerve cell oxidative stress damage, apoptosis and inflammatory response, and its mechanism of action was closely related to the activation of tyrosine kinase B (TrkB) receptor and inhibition of microglia activation. In animal experiments, P-TBDNF improved motor and cognitive deficits in MPTP mice and inhibited pathological changes in Parkinson's disease (PD). In conclusion, this paper is expected to reveal the mechanism of action of P-TBDNF in inhibiting neurotoxicity, provide a new way for treating PD, and lay the foundation for the future development of recombinant P-TBDNF. • P-TBDNF exhibited significant stability and the ability to penetrate the BBB. • P-TBDNF could prevent MPTP-induced oxidative stress, apoptosis, and inflammatory reactions in neuronal cells. • Its mechanism of action was closely related to the activation of tyrosine kinase B (TrkB) receptor and inhibition of microglia activation. • P-TBDNF improved motor and cognitive deficits in MPTP mice and inhibited pathological changes in Parkinson's disease (PD). [ABSTRACT FROM AUTHOR]

Biological nanopore refers to a type of pore-forming membrane proteins, providing a unique platform for single molecule detection of DNA, RNA, peptide, etc. The direct detection of small molecules, especially of food chemical contaminants by biological nanopore, remains challenging due to their fast translocation dynamics, trace amount, and the interference from the complex food matrix. The effective recognition and signal conversion methods need to be developed. Herein, we employ an aptamer-triggered hybridization chain reaction (AtHCR) strategy for the detection of a mycotoxin, aflatoxin B1 (AFB1) by an α -hemolysin nanopore. In the absence of AFB1, the formed dsDNA polymers in HCR show a low frequency of long-time blockage signals. The presence of AFB1 can inhibit the hybridization chain reaction through the interaction between AFB1 and its aptamer, so the remaining hairpins can easily block the nanopore and induce frequent long-time blockage signals. The results show that the event frequency of long-blockage has a linear relationship with the AFB1 concentration in the range of 6.6 × 10−1–6.6 × 102 pmol/L. The recognition and amplification effect of AtHCR allows nanopore to detect AFB1 at a detection limit of 0.54 pmol/L. Furthermore, the developed AtHCR strategy can help biological nanopore to detect AFB1 in corn sample with satisfactory accuracy. The recognition and amplification effect achieved by coupling AtHCR to biological nanopore offers an enzyme-free single-molecule technology for the rapid detection of food chemical contaminants. • The paper incorporates aptamer and hybridization chain reaction into the biological nanopore sensing. • The recognition and amplification effect of AtHCR strategy allows nanopore to detect AFB1 sensitively. • The AtHCR strategy in nanopore offers an enzyme-free single-molecule technology for the rapid detection of food chemical contaminants. [ABSTRACT FROM AUTHOR]

Aquatic foods, also known as blue foods, contain a wide range of unique bioactive substances. Among these substances, aquatic foods-derived bioactive peptides exhibit diverse structures and activities, including blood pressure reduction, antibacterial effects, uric acid level reduction, and antioxidant effects. As a result, these peptides show considerable potential for application in functional foods. Existing reviews on aquatic foods-derived bioactive peptides have focused primarily on their functional activities and preparation methods, while neglecting the latest trends in rapid discovery and large-scale production of peptides. Therefore, in addition to summarizing the most recent preparation methods of aquatic foods-derived bioactive peptides, this paper also examines the structure-activity relationships and strategies for large-scale production of active peptides. The use of bioinformatics techniques, such as docking and data mining, can significantly expedite the process of discovering and purifying of aquatic foods-derived bioactive peptides. Furthermore, the precise design and optimization of peptides based on their structure-activity relationships can effectively enhance their activity. Heterologous biosynthesis via the modification of host and target peptides holds promise for enabling large-scale production of these peptides. These methods represent the future direction of research on aquatic foods-derived bioactive peptides. • Bioinformatics accelerates the discovery of aquatic foods derived-active peptides. • Active peptide can be rationally designed based on structure-activity relationship. • Heterologous biosynthesis could facilitate the large-scale preparation of peptides. [ABSTRACT FROM AUTHOR]

[Display omitted] • A 9 K is cytostatic in human cancer cells causing mitochondrial depolarization. • A novel in vivo Zebrafish toxicity assay shows that A 9 K is safe at low doses. • A 9 K delivers nucleic acids to 2D cancer cell cultures and penetrates 3D cancer spheroids. • The uptake of FITC-labelled A 9 K is driven by an active endocytic mechanism. Designed peptides are promising biomaterials for biomedical applications. The amphiphilic cationic antimicrobial peptide (AMP), A 9 K, can self-assemble into nano-rod structures and has shown cancer cell selectivity and could therefore be a promising candidate for therapeutic delivery into cancer cells. In this paper, we investigate the selectivity of A 9 K for cancer cell models, examining its effect on two human cancer cell lines, A431 and HCT-116. Little or no activity was observed on the control, human dermal fibroblasts (HDFs). In the cancer cell lines the peptide inhibited cellular growth through changes in mitochondrial morphology and membrane potential while remaining harmless towards HDFs. In addition, the peptide can bind to and protect nucleic acids while transporting them into both 2D cultures and 3D spheroids of cancer cells. A 9 K showed high efficiency in delivering siRNA molecules into the centre of the spheroids. A 9 K was also explored in vivo , using a zebrafish (Danio rerio) development toxicity assay, showing that the peptide is safe at low doses. Finally, a high-content imaging screen, using RNA interference (RNAi) targeted towards cellular uptake, in HCT-116 cells was carried out. Our findings suggest that active cellular uptake is involved in peptide internalisation, mediated through clathrin-mediated endocytosis. These new discoveries make A 9 K attractive for future developments in clinical and biotechnological applications. [ABSTRACT FROM AUTHOR]

Due to the putative role of butyrylcholinesterase (BChE) in regulation of acetylcholine levels and functions in the late stages of the Alzheimer's disease (AD), the potential of selective inhibitors (BChEIs) has been envisaged as an alternative to administration of acetylcholinesterase inhibitors (AChEIs). Starting from our recent findings, herein the synthesis and in vitro evaluation of cholinesterase (ChE) inhibition of a novel series of some twenty 3,4,5,6-tetrahydroazepino[4,3- b ]indol-1(2 H)-one derivatives, bearing at the indole nitrogen diverse alkyl-bridged 4-arylalkylpiperazin-1-yl chains, are reported. The length of the spacers, as well as the type of arylalkyl group affected the enzyme inhibition potency and BChE/AChE selectivity. Two compounds, namely 14c (IC 50 = 163 nM) and 14d (IC 50 = 65 nM), bearing at the nitrogen atom in position 6 a n -pentyl- or n -heptyl-bridged 4-phenethylpiperazin-1-yl chains, respectively, proved to be highly potent mixed-type inhibitors of both equine and human BChE isoforms, showing more than two order magnitude of selectivity over AChE. The study of binding kinetics through surface plasmon resonance (SPR) highlighted differences in their BChE residence times (8 and 47 s for 14c and 14d , respectively). Moreover, 14c and 14d proved to hit other mechanisms known to trigger neurodegeneration underlying AD and other CNS disorders. Unlike 14c, compound 14d proved also capable of inhibiting by more than 60% the in vitro self-induced aggregation of neurotoxic amyloid-β (Aβ) peptide at 100 μM concentration. On the other hand, 14c was slightly better than 14d in counteracting, at 1 and 10 μM concentration, glutamate excitotoxicity, due to over-excitation of NMDA receptors, and hydrogen peroxide-induced oxidative stress assessed in neuroblastoma cell line SH-SY5Y. This paper is dedicated to Prof. Marcello Ferappi, former dean of the Faculty of Pharmacy of the University of Bari, in the occasion of his 90th birthday. [Display omitted] • New 4-arylalkylpiperazin-1-yl derivatives of azepino[4,3- b ]indol-1(2 H)-one were synthesized as neuroprotective agents. • Compound 14d proved to be a potent BChE-selective inhibitor (IC 50 = 65 nM). • Structure-activity relationships revealed key molecular features for BChE inhibitory potency and selectivity. • Biophysical assays characterized the kinetic parameters of interaction with BChE. • Compounds 14c and 14d showed additional protective effects against NMDA, and H 2 O 2 -induced cell damage (SH-SY5Y cells). [ABSTRACT FROM AUTHOR]

As a potential natural active substance, natural biologically active peptides (NBAPs) are recently attracting increasing attention. The traditional proteolysis methods of obtaining effective NBAPs are considerably vexing, especially since multiple proteases can be used, which blocks the exploration of available NBAPs. Although the development of virtual digesting brings some degree of convenience, the activity of the obtained peptides remains unclear, which would still not allow efficient access to the NBAPs. It is necessary to develop an efficient and accurate strategy for acquiring NBAPs. A new in silico scheme named SSA-LSTM-VD, which combines a sparrow search algorithm-long short-term memory (SSA-LSTM) deep learning and virtually digested, was presented to optimize the proteolysis acquisition of NBAPs. Therein, SSA-LSTM reached the highest Efficiency value reached 98.00 % compared to traditional machine learning algorithms, and basic LSTM algorithm. SSA-LSTM was trained to predict the activity of peptides in the proteins virtually digested results, obtain the percentage of target active peptide, and select the appropriate protease for the actual experiment. As an application, SSA-LSTM was employed to predict the percentage of neuroprotective peptides in the virtual digested result of walnut protein, and trypsin was ultimately found to possess the highest value (85.29 %). The walnut protein was digested by trypsin (WPTrH) and the peptide sequence obtained was analyzed closely matches the theoretical neuroprotective peptide. More importantly, the neuroprotective effects of WPTrH had been demonstrated in nerve damage mouse models. The proposed SSA-LSTM-VD in this paper makes the acquisition of NBAPs efficient and accurate. The approach combines deep learning and virtually digested skillfully. Utilizing the SSA-LSTM-VD based strategy holds promise for discovering and developing peptides with neuroprotective properties or other desired biological activities. [Display omitted] • Machine learning and virtual digestion were combined for the first time to enzymatic acquisition of naturally active peptides. • The SSA-LSTM machine learning model exhibited high accuracy performance in identifying neuroprotective peptides. • The neuroprotective efficacy of walnut protein hydrolysate obtained by SSA-LSTM-VD was verified by the mice model. [ABSTRACT FROM AUTHOR]

Electromembrane extraction (EME) involves the process of mass transfer of charged analytes from an aqueous sample through an organic liquid membrane into an aqueous acceptor medium under the influence of an electrical field. Successful solvation of the analyte within the liquid membrane is of paramount importance and involves molecular interactions with the liquid membrane. In this comprehensive investigation, parallel EME was examined using a training set of 13 model peptides employing deep eutectic solvents as the liquid membrane. These deep eutectic solvents were formulated by mixing specific monoterpenes (thymol, menthol, camphor) with medium-chain fatty acids (1-octanoic acid and 1-decanoic acid). From an array of different liquid membrane compositions explored, it was revealed that the combination of camphor and 1-decanoic acid (in a 1:1 w/w ratio) with 2% di (2-ethylhexyl) phosphate (DEHP) delivered the most efficient extraction system. The solvation of the model peptides within this liquid membrane predominantly relied on ionic interactions between protonated basic functionalities and DEHP, along with hydrogen bond interactions between the deprotonated acid functionalities (hydrogen bond acceptor) and 1-decanoic acid (hydrogen bond donor). Selectivity was modulated by the pH of the sample and acceptor solutions, with a direct correlation to the polarity and net charge of the model peptides. The ionization of 1-decanoic acid in the interfacial region between the sample and liquid membrane emerged as an important factor influencing the selectivity. Although parallel EME of peptides has been reported previously, the current liquid membrane provides an extraction system with sufficient stability for the first time. Selective extraction of peptides through EME holds substantial promise within the realm of next-generation environmentally-friendly sample preparation methodologies. The findings presented in this paper contribute significantly to our fundamental understanding of these processes, and may serve as an important reference for the development of future methods in this field. [Display omitted] • Camphor and 1-decanoic acid containing 2% di (2-ethylhexyl) phosphate (DEHP) was used as liquid membrane for electromembrane extraction of peptides. • With this liquid membrane, the current across the liquid membrane was low and the system was highly stable during extraction from human plasma. • Recoveries exceeding 40% was obtained for nine of 13 model peptides included in our training set of analytes. [ABSTRACT FROM AUTHOR]

This paper reports the development of a highly sensitive and selective electrochemical peptide-based biosensor for the detection of the inflammatory disease biomarker, interleukin-1beta (IL-1β). To this end, flower-like Au–Ag@MoS 2 -rGO nanocomposites were used as the signal amplification platform to achieve a label-free biosensor with a high sensitivity and selectivity. First, a high-affinity peptide for IL-1β was identified through biopanning with M13 random peptide libraries, and was newly designed by incorporating cysteine at the C-terminus. An IL-1β specific binding peptide was used as the bio-receptor, and the interaction between the IL-1β binding peptide and IL-1β was confirmed via enzyme-linked immunosorbent assay and various physicochemical and electrochemical analyses. Under optimal conditions, the biosensor achieved an ultrasensitive and specific IL-1β detection in a wide linear concentration range of 0–250 ng/mL with a picomolar-level detection limit (∼2.4 pM), low binding constant (∼0.62 pM), and a low coefficient of variation (<1.65 %). The biosensor was successfully utilized for IL-1β determination in the serum of Crohn's disease patients with a good correlation coefficient. In addition, the detection performance was comparable to that of commercially available IL-1β ELISA kit. This indicates that the electrochemical peptide-based biosensor may offer a potentially valuable platform for the clinical diagnosis of various inflammatory disease biomarkers. [Display omitted] • A novel affinity peptide-tethered Au–Ag–MoS 2 -rGO nanocomposite electrode for the detection of IL-1β. • The peptide-tethered Au–Ag–MoS 2 -rGO nanocomposite electrode exhibited good conductivity and improved electrochemical activity. • The proposed biosensor has a good linear range with a picomolar detection limit and low coefficient variation. • The detection ability of the developed sensor is comparable to that of a commercial IL-1β ELISA kit. [ABSTRACT FROM AUTHOR]

Peptide Science publishes peer‐reviewed papers covering all aspects of peptide synthesis, materials, structure and bioactivity. The journal includes both experimental and theoretical studies and serves the interdisciplinary biochemical, biomaterials, biophysical and biomedical research communities. [ABSTRACT FROM AUTHOR]

Nutritional calcium is necessary for constituting human tissues and maintaining normal physiological functions. Calcium deficiency is easy to cause many nutritional deficiency diseases. Calcium-chelating peptide is a kind of peptide that can improve the bioavailability of calcium. Blue foods are rich in high-quality proteins and considered to be optimal resources for functional peptides preparation. This paper summarized the research status of calcium-chelating peptides and peptide-calcium complexes derived from blue food proteins, including sources, preparation, structural properties, characterization, and mechanisms of improving calcium bioavailability. The molecular weights of calcium-chelating peptides identified from blue food proteins are between 200 and 2000 Da, which rich in Glu, Asp, Gly, Pro, Leu and Val. The carbonyl/carboxy oxygen, amino nitrogen, and phosphate groups are the chelating sites for calcium. Calcium chelation caused structural and morphological variation in peptides. Peptide-calcium complexes not only improve cellular calcium absorption via multiple cellular pathways, promote the differentiation of osteoblast precursor cells, but also enhance bone status in rats via increasing serum calcium levels, improving bone parameters, and modulating intestinal flora. This review will provide valuable insights into utilization of calcium-chelating peptides and peptide-calcium complexes obtained from blue food proteins as dietary calcium supplements. • Comprehensive review of calcium-chelating peptides and peptide-calcium complexes derived from blue food proteins. • Calcium-chelating peptides have characteristic amino acids, special molecular weights, and specific spatial structures. • Calcium chelation cause structural and morphological variation in peptides. • Peptide-calcium complexes can enhance the bioavailability of calcium in cellular and animal models. • Peptide-calcium complexes can promote the differentiation of osteoblast precursor cells into osteoblasts. [ABSTRACT FROM AUTHOR]

In this paper, we use FTIR spectroscopy to characterize the hydration water of ectoine, its interactions with two peptides–diglycine and NAGMA, and the properties of water molecules in the hydration spheres of both peptides changed by the presence of the osmolyte. We found that the interaction of ectoine with the peptide hydration shells had no effect on its own hydration sphere. However, the enhanced hydration layer of the osmolyte influences the hydration shells of both peptides and does so in a different way for both peptides: (1) the interfacial interaction of the NAGMA peptide and ectoine hydration spheres strengthened the hydration shell of this peptide; (2) the inclusion of water molecules from the ectoine hydration sphere into the diglycine hydration sphere had only a marginally enhancing effect. Since ectoine is being used in more and more biopharmaceutical products and cosmetics, knowledge of the properties of its hydration shell and its effect on the hydration shell of other molecules is extremely relevant to understanding its protective mechanism. [Display omitted] • The hydration sphere of ectoine is very stable. • Ectoine strengthens the water hydrogen bonds in the hydration shells of peptides. • The mechanism underlying shell enhancement is based on the specific peptide type. [ABSTRACT FROM AUTHOR]

[Display omitted] • This paper constitutes a step forward in ultrasonic extraction of biomolecules from clays rich sample and meteorites. • It presents a fast and efficient ultrasonic extraction compared to highly energy and time-consuming hot water extraction. • The proof of concept has been made extracting amino acids and nucleobases from meteorites. The study of organic molecules in meteorite and return samples allows for the understanding of the chemistry that undergoes in our Solar System. The present work aims at studying ultrasound assisted extraction technique as effective extraction method for these molecules in extraterrestrial samples and analogs. Optimal conditions were selected from the investigation of ultrasonic frequency, irradiation duration and solvent effects on amino acids, nucleobases and dipeptides extraction yields from a model clay-rich mineral matrix. Optimal ultrasound-assisted extraction parameters were frequency of 20 kHz within 20 min irradiation time and methanol/water solvent ratio of 1. We then validated this protocol on Mukundpura and Tarda meteorite fragments and compared it to the reference extraction protocol used in astrobiology and based on 24 h extraction time at 100 °C in water We obtained similar quantitative results without any racemization with both methodologies. [ABSTRACT FROM AUTHOR]

The development of new drug delivery systems for targeted chemotherapy release in cancer cells represents a very promising tool. In this contest, protein-based nanocages have considerable potential as drug delivery devices. Notably, ferritin has emerged as an excellent candidate due to its unique architecture, surface properties and high biocompatibility. A promising strategy might then involve ferritin cargos for specifical release of AntiMicrobial Peptides endowed with anticancer activity to cancer cells. In this paper, we encapsulated the TRIL analogue of Temporin-L peptide within a ferritin nanocage and evaluated the cargo biological properties. The results demonstrated a reduced haemolytic activity of the peptide and a selective cytotoxicity activity on cancer cells likely mediated by oxidative stress while having no effects on non-tumoral cells. The combination of the properties of ferritin with TRIL, might open up the way to the development of novel peptide delivery systems for future pharmaceutical applications. • Ferritin nanocages have emerged as an excellent and promising protein-based delivery system. • The antimicrobial peptide TRIL was encapsulated in ferritin nanocage. • The new nanocage reduced haemolytic activity of the peptide and shown a selective cytotoxicity activity on cancer cells. [ABSTRACT FROM AUTHOR]

• The increase in CAT activity was associated with Zn-induced structural changes. • Zinc exposure induces changes in CAT skeleton and enzyme activity. • Zinc interacts with amino acid residues near the binding site mainly through electrostatic forces. As a common metal, Zinc was widely used in the in the galvanising industry. However, the overuse had contributed to the environmental overexposure of zinc, which had caused a number of health issues in environmental organisms. Catalase (CAT) plays a critical part in regulating oxidative stress in the body of humans. Interactions between Zn(II) and CAT were examined in this paper using a variety of spectroscopic techniques, molecular docking, isothermal titration calorimetry (ITC) and enzyme activity assay. According to the results, Zn(II) can interact with CAT fluorophore residues like Trp and Tyr and demonstrate fluorescence sensitization to these amino acids. Direct contact between CAT and Zn(II) led to the disruption of protein backbone structure and peptide chain tightening. When exposed to Zn(II), the secondary structure of CAT was altered, including the decreased α -helix of CAT, increased β -sheet content, and the increased grain size of the zinc-CAT complex. Measurement of thermodynamic parameters of the binding reaction by ITC showed that the force between Zn(II) and CAT was electrostatic force. In addition, the binding site of Zn(II) is close to the active center of CAT which boosted enzyme activity. In conclusion, our research demonstrates that Zinc has an impact on both the structure and function of CAT. [ABSTRACT FROM AUTHOR]

Proteases have been proposed as potential biomarkers for several pathological conditions including cancers, multiple sclerosis and cardiovascular diseases, due to their ability to break down the components of extracellular matrix and basement membrane. The development of protease biosensors opened up the possibility to investigate the proteolytic activity of dysregulated proteases with higher efficiency over the traditional detection assays due to their quick detection capability, high sensitivity and selectivity, simple instrumentation and cost-effective fabrication processes. In contrast to the recently published review papers that primarily focused on one specific class of proteases or one specific detection method, this review article presents different optical and electrochemical detection methods that can be used to design biosensors for all major protease families. The benefits and drawbacks of various transducer techniques integrated into protease biosensing platforms are analyzed and compared. The main focus is on activity-based biosensors that use peptides as biorecognition elements. The effects of nanomaterials on biosensor performance are also discussed. This review should help readers to select the biosensor that best fits their needs, and contribute to the further development of this research field. Protease biosensors may allow better comprehension of protease overexperession and potentially enable novel devices for point-of-care testing. [ABSTRACT FROM AUTHOR]

• Dimethyl carbonate is used as organic modifier in preparative chromatography. • Dimethyl carbonate and acetonitrile lead to comparable purity values. • Solvent consumption is considerably reduced with dimethyl carbonate. Preparative liquid chromatography in reversed phase conditions (RPLC) is the most common approach adopted in the downstream processing for the purification of therapeutic peptides at industrial level. Due to the strict requirements on the quality imposed by the Regulatory Agencies, routinary methods based on the use of aqueous buffers and acetonitrile (ACN) as organic modifier are commonly used, where ACN is practically the only available choice for the purification of peptide derivatives. However, ACN is known to suffers of many shortcomings, such as drastic shortage in the market, high costs and, most importantly, it shows unwanted toxicity for human health and environment, which led it among the less environmentally friendly ones. For this reason, the selection of a suitable alternative becomes crucial for the sustainable downstream processing of peptides and biopharmaceuticals in general. In this paper, a promising green solvent, namely dimethyl carbonate (DMC) has been used for the separation of a peptide not only in linear conditions but also for its purification through non-linear overloaded chromatography. The performance of the process has been compared to that achievable with the common method where ACN is used as organic modifier and to that obtained with two additional solvents (namely ethanol and isopropanol), already used as greener alternatives to ACN. This proof-of-concept study showed that, thanks to its higher elution strength, DMC can be considered a green alternative to ACN, since it allows to reduce method duration while reaching good purities and recoveries. Indeed, at a target purity fixed to 98.5 %, DMC led to the best productivity with respect to all the other solvents tested, confirming its suitability as a sustainable alternative to ACN for the purification of complex biopharmaceutical products. [ABSTRACT FROM AUTHOR]

Peptide Science publishes peer‐reviewed papers covering all aspects of peptide synthesis, materials, structure and bioactivity. The journal includes both experimental and theoretical studies and serves the interdisciplinary biochemical, biomaterials, biophysical and biomedical research communities. [ABSTRACT FROM AUTHOR]

In recent years, food-derived peptides have gained much attention for their potential health benefits. Some short and medium-sized peptides released from food proteins after their enzymatic hydrolysis may exhibit hypocholesterolemic activity. Hypocholesterolemic peptides act either by targeting exogenous cholesterol in the gastrointestinal (GI) tract or by modulating endogenous cholesterol levels via cholesterol metabolism pathways in the liver after being absorbed. This paper provides a comprehensive review of current pieces of evidence regarding the production, transepithelial transport, and cellular mechanisms underlying the hypocholesterolemic activities of food-derived peptides. The molecular mechanisms of hypocholesterolemic peptides involve bile acid binding, inhibition of cholesterol micellar solubility, statin-like effects through the modulation of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCoAR), as well as the targeting of interactions between proprotein convertase subtilisin/kexin type 9 (PCSK9) and low-density lipoprotein receptor (LDLR), sterol regulatory element-binding protein 2 (SREBP-2), and hepatocyte nuclear factor 1α (HNF-1α) pathways. Furthermore, some peptides exhibit multiple biological activities, such as anti-inflammatory and antioxidant activities, besides cholesterol-lowering properties, thereby safeguarding cellular components against high levels of cholesterol-induced damage. However, since only a few studies have evaluated the in vivo effects of hypocholesterolemic peptides, further studies carried out in animal models or human are necessary to exploit these ingredients in the prevention and management of hypercholesterolemia. • Some peptides exert their activity through the modulation of HMGCoAR. • Some peptides inhibit the interactions between PCSK9 and LDL receptor. • They may be used in the prevention of hypercholesterolemia. [ABSTRACT FROM AUTHOR]