Class Of Biomolecules Research Articles

Poly(lactide)-Based Materials Modified with Biomolecules: A Review.

Poly(lactic acid) (PLA) is characterized by unique features, e.g., it is environmentally friendly, biocompatible, has good thermomechanical properties, and is readily available and biodegradable. Due to the increasing pollution of the environment, PLA is a promising alternative that can potentially replace petroleum-derived polymers. Different biodegradable polymers have numerous biomedical applications and are used as packaging materials. Because the pure form of PLA is delicate, brittle, and is characterized by a slow degradation rate and a low thermal resistance and crystallization rate, these disadvantages limit the range of applications of this polymer. However, the properties of PLA can be improved by chemical or physical modification, e.g., with biomolecules. The subject of this review is the modification of PLA properties with three classes of biomolecules: polysaccharides, proteins, and nucleic acids. A quite extensive description of the most promising strategies leading to improvement of the bioactivity of PLA, through modification with these biomolecules, is presented in this review. Thus, this article deals mainly with a presentation of the major developments and research results concerning PLA-based materials modified with different biomolecules (described in the world literature during the last decades), with a focus on such methods as blending, copolymerization, or composites fabrication. The biomedical and unique biological applications of PLA-based materials, especially modified with polysaccharides and proteins, are reviewed, taking into account the growing interest and great practical potential of these new biodegradable biomaterials.

Detection Strategies for Sialic Acid and Sialoglycoconjugates.

Glycoconjugates are a vast class of biomolecules implicated in biological processes important for human health and disease. The structural complexity of glycoconjugates remains a challenge to deciphering their precise biological roles and for their development as biomarkers and therapeutics. Human glycoconjugates on the outside of the cell are modified with sialic (neuraminic) acid residues at their termini. The enzymes that install sialic acids are sialyltransferases (SiaTs), a family of 20 different isoenzymes. The removal and degradation of sialic acids is mediated by neuraminidase (NEU; sialidase) enzymes, of which there are four isoenzymes. In this review, we discuss chemical and biochemical approaches for the detection and analysis of sialoglycoconjugate (SGC) structures and their enzymatic products. The most common methods include affinity probes and synthetic substrates. Fluorogenic and radiolabelled substrates are also important tools for many applications, including screening for enzyme inhibitors. Strategies that give insight into the native substrate-specificity of enzymes that regulate SGCs (SiaT & NEU) are necessary to improve our understanding of the role of sialic acid metabolism in health and disease.

Molecular Characterization of Adhesives (Glue Lining Pastes) Used in Restoration.

The molecular characterization of samples from works of art can provide valuable insights into the composition of ancient restoration materials and their conservation state. Here, we present a novel analytical protocol for the molecular characterization of a specific adhesive used in historical painting restoration, known as "glue lining pastes." Due to the high molecular complexity of these adhesives, we propose a multistep extraction protocol to recover and fractionate from a single microsample the three main classes of biomolecules contained in glue pastes (lipids, polysaccharides, and proteins). High-performance separation coupled with high-resolution mass spectrometry (MS) techniques were applied to the isolated fractions to identify specific components. The proposed method was optimized using test specimens of various traditional glue pastes applied to canvases and successfully applied to a historical glue paste sample from the 17th-century painting "La fuga in Egitto," part of the Pagliara collection at the University Suor Orsola Benincasa (Naples, Italy). The data collected in this work provide insights into the specific recipe used for adhesive preparation, supporting artistic and historical interpretations and contributing to a broader understanding of old restoration practices. Data are available via ProteomeXchange with the identifier PXD051480.

Ultrasound-Assisted Solid-Phase Affibody Synthesis Using ZEGFR:1907 as an Example-Superior to the Conventional Protocol?

Affibody molecules represent a class of highly specific binders of particular interest for the development of highly affine target-specific radiopharmaceuticals. Their chemical synthesis is, however, intricate due to their considerable length of 58 amino acids; thus, approaches to optimize their preparation are constantly being sought. As ultrasound assistance has recently been shown to increase the efficiency of amino acid conjugation during solid-phase peptide synthesis (SPPS), the influence of ultrasonication on the outcome of the SPPS-based preparation of the EGFR-specific affibody ZEGFR:1907 was compared to a common protocol relying on mechanical shaking. After the identification of a suitable solid support for the study, the execution of the systematic comparison of both approaches showed that conventional and ultrasound-assisted syntheses yielded equivalent results with analogous composition of the raw products. Further, both approaches produced the affibody in good isolated yields of >20% when applying the same optimal reagent excesses and coupling times for the conjugation of each amino acid. This indicates that, under optimal reaction conditions, the choice of solid support used has a much stronger influence on the outcome of the preparation of ZEGFR:1907 than the application of ultrasound, which did not further improve the synthesis results. Therefore, for the chemical synthesis of affibodies, great attention should be paid to the choice of a suitable solid support, enabling this highly interesting class of biomolecules to be obtained in good yields and to bring them more into the focus of radiopharmaceutical research.

Correlative Imaging for Comprehensive Molecular Mapping of Individual Cell Types in Biological Tissues.

Mass spectrometry imaging (MSI) is a powerful technique for label-free spatial mapping of multiple classes of biomolecules in tissue sections. However, differences in desorption and ionization efficiency of different classes of molecules make it challenging to simultaneously map biomolecules at each omics layer in the same tissue sample. Herein, we present a correlative imaging method using nanospray desorption electrospray ionization (nano-DESI) MSI, which enables the spatial mapping of lipids, metabolites, peptides, and proteins with cellular-level spatial resolution in a single tissue section. We demonstrate the molecular profiling of specific cell types and identify truncated peptides in mouse pancreatic tissue. Distinct chemical gradients of peptides and lipids extending from endocrine cells to exocrine cells indicate their different roles in endocrine-exocrine crosstalk and intracellular signaling. The results underscore the power of the developed imaging approach for spatial multi-omics analysis that provides deep insights into cellular diversity and the intricate molecular interactions that occur within heterogenous biological tissues.

Allenamides as a Powerful Tool to Incorporate Diversity: Thia-Michael Lipidation of Semisynthetic Peptides and Access to β-Keto Amides.

Lipopeptides are an important class of biomolecules for drug development. Compared with conventional acylation, a chemoselective lipidation strategy offers a more efficient strategy for late-stage structural derivatisation of a peptide scaffold. It provides access to chemically diverse compounds possessing intriguing and non-native moieties. Utilising an allenamide, we report the first semisynthesis of antimicrobial lipopeptides leveraging a highly efficient thia-Michael addition of chemically diverse lipophilic thiols. Using chemoenzymatically prepared polymyxin B nonapeptide (PMBN) as a model scaffold, an optimised allenamide-mediated thia-Michael addition effected rapid and near quantitative lipidation, affording vinyl sulfide-linked lipopeptide derivatives. Harnessing the utility of this new methodology, 22 lipophilic thiols of unprecedented chemical diversity were introduced to the PMBN framework. These included alkyl thiols, substituted aromatic thiols, heterocyclic thiols and those bearing additional functional groups (e.g., amines), ultimately yielding analogues with potent Gram-negative antimicrobial activity and substantially attenuated nephrotoxicity. Furthermore, we report facile routes to transform the allenamide into a β-keto amide on unprotected peptides, offering a powerful "jack-of-all-trades" synthetic intermediate to enable further peptide modification.

Allenamides as a Powerful Tool to Incorporate Diversity: Thia‐Michael Lipidation of Semisynthetic Peptides and Access to β‐Keto Amides

AbstractLipopeptides are an important class of biomolecules for drug development. Compared with conventional acylation, a chemoselective lipidation strategy offers a more efficient strategy for late‐stage structural derivatisation of a peptide scaffold. It provides access to chemically diverse compounds possessing intriguing and non‐native moieties. Utilising an allenamide, we report the first semisynthesis of antimicrobial lipopeptides leveraging a highly efficient thia‐Michael addition of chemically diverse lipophilic thiols. Using chemoenzymatically prepared polymyxin B nonapeptide (PMBN) as a model scaffold, an optimised allenamide‐mediated thia‐Michael addition effected rapid and near quantitative lipidation, affording vinyl sulfide‐linked lipopeptide derivatives. Harnessing the utility of this new methodology, 22 lipophilic thiols of unprecedented chemical diversity were introduced to the PMBN framework. These included alkyl thiols, substituted aromatic thiols, heterocyclic thiols and those bearing additional functional groups (e.g., amines), ultimately yielding analogues with potent Gram‐negative antimicrobial activity and substantially attenuated nephrotoxicity. Furthermore, we report facile routes to transform the allenamide into a β‐keto amide on unprotected peptides, offering a powerful “jack‐of‐all‐trades” synthetic intermediate to enable further peptide modification.

Anchorless Bacterial Moonlighting Metabolic Enzymes Modulate the Immune System and Contribute to Pathogenesis.

Moonlighting proteins (MPs), characterized by their ability to perform multiple physiologically unrelated functions without alterations to their primary structures, represent a fascinating class of biomolecules with significant implications for host-pathogen interactions. This Review highlights the emerging importance of metabolic moonlighting proteins (MetMPs) in bacterial pathogenesis, focusing on their non-canonical secretion and unconventional surface anchoring mechanisms. Despite lacking typical signal peptides and anchoring motifs, MetMPs such as acetaldehyde alcohol dehydrogenase (AdhE) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) are secreted and localized to the bacterial surface under stress conditions, facilitating host colonization and immune evasion. The secretion of MetMPs, often observed during conditions such as resource scarcity or infection, suggests a complex regulation akin to the overexpression of heat shock proteins in response to environmental stresses. This Review proposes two potential pathways for MetMP secretion: membrane damage-induced permeability and co-transportation with traditionally secreted proteins, highlighting a remarkable bacterial adaptability. Biophysically, surface anchoring of MetMPs is driven by electrostatic interactions, bypassing the need for conventional anchoring sequences. This mechanism is exemplified by the interaction between the bifunctional enzyme AdhE (known as Listeria adhesion protein, LAP) and the internalin B (InlB) in Listeria monocytogenes, which is mediated by charged residues facilitating adhesion to host tissues. Furthermore, MetMPs play critical roles in iron homeostasis, immune modulation, and evasion, underscoring their multifaceted roles in bacterial pathogenicity. The intricate dynamics of MetMP secretion and anchoring underline the need for further research to unravel the molecular mechanisms underpinning these processes, offering potential new targets for therapeutic intervention against bacterial infections.

MotifQuest: An Automated Pipeline for Motif Database Creation to Improve Peptidomics Database Searching Programs.

Endogenous peptides are an abundant and versatile class of biomolecules with vital roles pertinent to the functionality of the nervous, endocrine, and immune systems and others. Mass spectrometry stands as a premier technique for identifying endogenous peptides, yet the field still faces challenges due to the lack of optimized computational resources for reliable raw mass spectra analysis and interpretation. Current database searching programs can exhibit discrepancies due to the unique properties of endogenous peptides, which typically require specialized search considerations. Herein, we present a high throughput, novel scoring algorithm for the extraction and ranking of conserved amino acid sequence motifs within any endogenous peptide database. Motifs are conserved patterns across organisms, representing sequence moieties crucial for biological functions, including maintenance of homeostasis. MotifQuest, our novel motif database generation algorithm, is designed to work in partnership with EndoGenius, a program optimized for database searching of endogenous peptides and that is powered by a motif database to capitalize on biological context to produce identifications. MotifQuest aims to quickly develop motif databases without any prior knowledge, a laborious task not possible with traditional sequence alignment resources. In this work we illustrate the utility of MotifQuest to expand EndoGenius' identification utility to other endogenous peptides by showcasing its ability to identify antimicrobial peptides. Additionally, we discuss the potential utility of MotifQuest to parse out motifs from a FASTA database file that can be further validated as new peptide drug candidates.

Glucosinolates and Their Hydrolytic Products-A Love Story of Environmental, Biological and Chemical Conditions.

Glucosinolates play important role in providing defense to plants and helps them in coping against various biotic as well as abiotic stress. Many living beings including humans, animals, and even some herbivores have adapted themselves to use this defense mechanism for their own use. More than 120 glucosinolates are distributed within a large number of plants. Many factors are known to influence the GSL composition in a plant. Among these, cofactors, myrosinase isozymes, heavy metals and the environmental conditions such as light, CO2 and temperature are important in the regulation. These factors ensure that different glucosinolate composition could be produced by the plants, thus impacting the defense mechanism. The objective of the current review is to highlight the importance of factors responsible for affecting glucosinolate composition and concentration. The review has been compiled using accessible literature from Pubmed, Scopus, and Google scholar. Efforts have been made to restrict the literature to the last 5 years (2018-2023), with some exceptions. The current critical review acts as a resource for all the researchers working on this essential compound. It provides information on the factors that may influence the glucosinolate production. It also gives them an opportunity to modify the glucosinolate composition of a plant using the given information. Glucosinolates have long been an ignored class of biomolecule. The plethora of biological activities of the compounds can be useful. Though there are some harmful components such as goitrin and progoitrin, these can be easily removed by modulating some of the factors highlighted in the review. The current review has touched base on almost all the factors that have the ability to modify glucosinolate composition and concentration. The mechanistic action of these factors have also been discussed using the current available literature.

Machine Learning-Enhanced Quantum Chemistry-Assisted Refinement of the Active Site Structure of Metalloproteins.

Understanding the fine structural details of inhibitor binding at the active site of metalloenzymes can have a profound impact on the rational drug design targeted to this broad class of biomolecules. Structural techniques such as NMR, cryo-EM, and X-ray crystallography can provide bond lengths and angles, but the uncertainties in these measurements can be as large as the range of values that have been observed for these quantities in all the published structures. This uncertainty is far too large to allow for reliable calculations at the quantum chemical (QC) levels for developing precise structure-activity relationships or for improving the energetic considerations in protein-inhibitor studies. Therefore, the need arises to rely upon computational methods to refine the active site structures well beyond the resolution obtained with routine application of structural methods. In a recent paper, we have shown that it is possible to refine the active site of cobalt(II)-substituted MMP12, a metalloprotein that is a relevant drug target, by matching to the experimental pseudocontact shifts (PCS) those calculated using multireference ab initio QC methods. The computational cost of this methodology becomes a significant bottleneck when the starting structure is not sufficiently close to the final one, which is often the case with biomolecular structures. To tackle this problem, we have developed an approach based on a neural network (NN) and a support vector regression (SVR) and applied it to the refinement of the active site structure of oxalate-inhibited human carbonic anhydrase 2 (hCAII), another prototypical metalloprotein target. The refined structure gives a remarkably good agreement between the QC-calculated and the experimental PCS. This study not only contributes to the knowledge of CAII but also demonstrates the utility of combining machine learning (ML) algorithms with QC calculations, offering a promising avenue for investigating other drug targets and complex biological systems in general.

Optical Nanosensor Passivation Enables Highly Sensitive Detection of the Inflammatory Cytokine Interleukin-6.

Interleukin-6 (IL-6) is known to play a critical role in the progression of inflammatory diseases such as cardiovascular disease, cancer, sepsis, viral infection, neurological disease, and autoimmune diseases. Emerging diagnostic and prognostic tools, such as optical nanosensors, experience challenges in translation to the clinic in part due to protein corona formation, dampening their selectivity and sensitivity. To address this problem, we explored the rational screening of several classes of biomolecules to be employed as agents in noncovalent surface passivation as a strategy to screen interference from nonspecific proteins. Findings from this screening were applied to the detection of IL-6 by a fluorescent-antibody-conjugated single-walled carbon nanotube (SWCNT)-based nanosensor. The IL-6 nanosensor exhibited highly sensitive and specific detection after passivation with a polymer, poly-l-lysine, as demonstrated by IL-6 detection in human serum within a clinically relevant range of 25 to 25,000 pg/mL, exhibiting a limit of detection over 3 orders of magnitude lower than prior antibody-conjugated SWCNT sensors. This work holds potential for the rapid and highly sensitive detection of IL-6 in clinical settings with future application to other cytokines or disease-specific biomarkers.

Biosurfactants as templates to inspire new environmental and health applications

Life exists at an interface. One of the key characteristics of biological cells is compartmentalization, which is facilitated by lipids that create a water-impenetrable barrier to control transport of materials across the hydrophilic-hydrophobic interface. Microbial systems utilize a rich diversity of surfactants beyond lipids to adapt to an environmental niche, modify the properties of an interface, facilitate solubilization of nutrients for metabolism and as antimicrobials. As such, they are a fascinating class of biomolecules to study in terms of how effectiveness in an application or niche environment depends on sequence, structure and chemical properties. Moreover, there is increasing appreciation of the negative health and environmental impacts petrochemical-based surfactants can have, such as soil erosion and toxicity to plants and aquatic life, as well as the carbon footprint and associated greenhouse gas emissions associated with petrochemical surfactant manufacturing. In this review, we discuss the properties of biosurfactants and applications, and highlight key glycolipid-, protein- and peptide-based surfactants described in literature as examples of biosurfactants with unique potential and applications. As society looks towards the transition to a circular bioeconomy, we are excited by the potential of synthetic biology to develop new materials such as biosurfactants to facilitate this important transition.

Lipid-Based Nanoparticle Functionalization with Coiled-Coil Peptides for In Vitro and In Vivo Drug Delivery.

For the delivery of drugs, different nanosized drug carriers (e.g., liposomes, lipid nanoparticles, and micelles) have been developed in order to treat diseases that afflict society. Frequently, these vehicles are formed by the self-assembly of small molecules to encapsulate the therapeutic cargo of interest. Over decades, nanoparticles have been optimized to make them more efficient and specific to fulfill tailor-made tasks, such as specific cell targeting or enhanced cellular uptake. In recent years, lipid-based nanoparticles in particular have taken center stage; however, off-targeting side effects and poor endosomal escape remain major challenges since therapies require high efficacy and acceptable toxicity.To overcome these issues, many different approaches have been explored to make drug delivery more specific, resulting in reduced side effects, to achieve an optimal therapeutic effect and a lower required dose. The fate of nanoparticles is largely dependent on size, shape, and surface charge. A common approach to designing drug carriers with targeting capability is surface modification. Different approaches to functionalize nanoparticles have been investigated since the attachment of targeting moieties plays a significant role in whether they can later interact with surface-exposed receptors of cells. To this end, various strategies have been used involving different classes of biomolecules, such as small molecules, nucleic acids, antibodies, aptamers, and peptides.Peptides in particular are often used since there are many receptors overexpressed in different specific cell types. Furthermore, peptides can be produced and modified at a low cost, enabling high therapeutic screening. Cell-penetrating peptides (CPPs) and cell-targeting peptides (CTPs) are frequently used for this purpose. Less studied in this context are fusogenic coiled-coil peptides. Lipid-based nanoparticles functionalized with these peptides are able to avoid the endolysosomal pathway; instead such particles can be taken up by membrane fusion, resulting in increased delivery of payload. Furthermore, they can be used for targeting cells/organs but are not directed at surface-exposed receptors. Instead, they recognize complementary peptide sequences, facilitating their uptake into cells.In this Account, we will discuss peptides as moieties for enhanced cytosolic delivery, targeted uptake, and how they can be attached to lipid-based nanoparticles to alter their properties. We will discuss the properties imparted to the particles by peptides, surface modification approaches, and recent examples showing the power of peptides for in vitro and in vivo drug delivery. The main focus will be on the functionalization of lipid-based nanoparticles by fusogenic coiled-coil peptides, highlighting the relevance of this concept for the development of future therapeutics.

Abstract 1860: The smallest antibody class: Cow ultralong CDR3 knobs as a new class of biomolecule for therapeutics and diagnostics

Abstract Engineered antibodies, including bispecifics and ADCs, are now a major drug class for oncology and other therapeutic areas. There are two fundamental antibody fragments: the Fv (heavy and light chain variable region fragments, derived from most species), and VHH (heavy chain ‘only’ V regions, derived from camelids and sharks). Cows produce antibodies with an unusually long VH CDR3 region, which can be up to seventy amino acids in length and is comprised of a β-ribbon “stalk” and disulfide-bonded “knob” minidomain which sits atop the stalk. The knob region is highly diverse and can bind cryptic epitopes with high affinity. We recently developed the technology to produce knob domains independently of the antibody, and at ~5 kDa are the smallest functional antibody fragment (https://doi.org/10.1073/pnas.2303455120). The high stability and small size could enable improved tissue penetration and development of novel therapeutics, including knob-drug conjugates or extremely small bispecific molecules. Citation Format: Vaughn Smider. The smallest antibody class: Cow ultralong CDR3 knobs as a new class of biomolecule for therapeutics and diagnostics [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1860.

Prolinyl Phosphoramidates of Nucleotides with Increased Reactivity

AbstractNucleoside monophosphates (NMPs) are the subunits of RNA. They are incorporated into growing complementary strands when sequences are copied in enzyme‐free reactions using organic leaving groups at the phosphates. Amino acids are rarely considered as leaving groups, but proline can act as a leaving group when N‐linked to NMPs, so that prolinyl NMPs hydrolyze in aqueous buffer at 37 °C, with half‐life times as short as 2.4 h, and they act as monomers in enzyme‐free primer extension. Still, their level of reactivity is insufficient for practical purposes, requiring months for some extensions. Herein we report the synthesis of eight substituted prolinyl AMPs together with seven related compounds and the results of a study of their reactivity. A δ‐carboxy prolinyl NMP was found to be converted with a half‐life time of just 11 min in magnesium‐free buffer, and a δ‐isopropyl prolinyl NMP was shown to react sevenfold faster than its prolinyl counterpart in enzyme‐free genetic copying of RNA. Our results indicate that both anchimeric and steric effects can be employed to increase the reactivity of aminoacidyl nucleotides, i.e. compounds that combine two fundamental classes of biomolecules in one functional entity.

Prolinyl Phosphoramidates of Nucleotides with Increased Reactivity.

Nucleoside monophosphates (NMPs) are the subunits of RNA. They are incorporated into growing complementary strands when sequences are copied in enzyme-free reactions using organic leaving groups at the phosphates. Amino acids are rarely considered as leaving groups, but proline can act as a leaving group when N-linked to NMPs, so that prolinyl NMPs hydrolyze in aqueous buffer at 37 °C, with half-life times as short as 2.4 h, and they act as monomers in enzyme-free primer extension. Still, their level of reactivity is insufficient for practical purposes, requiring months for some extensions. Herein we report the synthesis of eight substituted prolinyl AMPs together with seven related compounds and the results of a study of their reactivity. A δ-carboxy prolinyl NMP was found to be converted with a half-life time of just 11 min in magnesium-free buffer, and a δ-isopropyl prolinyl NMP was shown to react sevenfold faster than its prolinyl counterpart in enzyme-free genetic copying of RNA. Our results indicate that both anchimeric and steric effects can be employed to increase the reactivity of aminoacidyl nucleotides, i.e. compounds that combine two fundamental classes of biomolecules in one functional entity.

Fast insights into chitosan-cleaving enzymes by simultaneous analysis of polymers and oligomers through size exclusion chromatography

The thorough characterization of chitosan-cleaving enzymes is crucial to unveil structure–function relationships of this promising class of biomolecules for both, enzymatic fingerprinting analyses and to use the enzymes as biotechnological tools to produce tailor-made chitosans for diverse applications. Analyzing polymeric substrates as well as oligomeric products has been established as an effective way to understand the actions of enzymes, but it currently requires separate, rather laborious methods to obtain the full picture. Here, we present ultra high performance size exclusion chromatography coupled to refractive index and mass spectrometry detection (UHPSEC-RI-MS) as a straightforward method for the semi-quantitative analysis of chitosan oligomers of up to ten monomers in length. Additionally, the method allows to determine the average molecular weight of the remaining polymers and its distribution. By sampling live from an ongoing enzymatic reaction, UHPSEC-RI-MS offers the unique opportunity to analyze polymers and oligomers simultaneously—i.e., to monitor the molecular weight reduction of the polymeric substrate over the course of the digestion, while at the same time analyzing the emerging oligomeric products in a semi-quantitative manner. In this way, a single simple analysis yields detailed insights into an enzyme’s action on a given substrate.

Structurally Modified Polysaccharides: Physicochemical Properties, Biological Activities, Structure-Activity Relationship, and Applications.

Polysaccharides are an important class of biomolecules derived from several sources. However, the inherent structure of polysaccharides prevents them from exhibiting favorable physicochemical properties, which restricts their development in agriculture, industry, food, and biomedicine. This paper systematically summarizes the changes in the primary and advanced structures of modified polysaccharides, and focuses on the effects of various modification methods on the hydrophobicity, rheological properties, emulsifying properties, antioxidant activity, hypoglycemic, and hypolipidemic activities of polysaccharides. Then there is a list the applications of modified polysaccharides in treating heavy metal pollutants, purifying water resources, improving beverage stability and bread quality, and precisely delivering the drug. When summarized and reviewed, the information above can shed further light on the relationship between polysaccharide structure and function. Determining the structure-activity relationship provides a scientific basis for the direction of molecular modifications of polysaccharides.

Human myofiber-enriched aging-induced lncRNA FRAIL1 promotes loss of skeletal muscle function.

The loss of skeletal muscle mass during aging is a significant health concern linked to adverse outcomes in older individuals. Understanding the molecular basis of age-related muscle loss is crucial for developing strategies to combat this debilitating condition. Long noncoding RNAs (lncRNAs) are a largely uncharacterized class of biomolecules that have been implicated in cellular homeostasis and dysfunction across a many tissues and cell types. To identify lncRNAs that might contribute to skeletal muscle aging, we screened for lncRNAs whose expression was altered in vastus lateralis muscle from older compared to young adults. We identified FRAIL1 as an aging-induced lncRNA with high abundance in human skeletal muscle. In healthy young and older adults, skeletal muscle FRAIL1 was increased with age in conjunction with lower muscle function. Forced expression of FRAIL1 in mouse tibialis anterior muscle elicits a dose-dependent reduction in skeletal muscle fiber size that is independent of changes in muscle fiber type. Furthermore, this reduction in muscle size is dependent on an intact region of FRAIL1 that is highly conserved across non-human primates. Unbiased transcriptional and proteomic profiling of the effects of FRAIL1 expression in mouse skeletal muscle revealed widespread changes in mRNA and protein abundance that recapitulate age-related changes in pathways and processes that are known to be altered in aging skeletal muscle. Taken together, these findings shed light on the intricate molecular mechanisms underlying skeletal muscle aging and implicate FRAIL1 in age-related skeletal muscle phenotypes.