Search Results (4,279)

In human cells, the biogenesis of membrane proteins, which account for one quarter of polypeptides and sixty percent of human drug targets, is initiated at the membrane of the endoplasmic reticulum (ER). This process involves N-terminal signal peptides or transmembrane helices in the membrane protein precursors. Over one hundred proteins enable membrane-targeting and -insertion of the precursors as well as their folding and covalent modifications. Four targeting pathways to the Sec61 channel in the ER membrane with their effectors and three cooperating or independent membrane protein–insertases have been identified. We combined knock-down of individual components of these pathways and insertases in HeLa cells with label-free quantitative mass spectrometric analysis of the proteomes. Differential protein abundance analysis in comparison to control cells was employed to identify clients of components involved in the targeting or membrane insertion of precursors. Alternatively, knock-out cells or relevant patient fibroblasts were employed. The features of the client polypeptides were characterized to identify the client types of the different components and, ideally, their rules of engagement. In this review/article-hybrid, the focus is on global lessons from and limitations of the proteomic approach in answering the cell biological question, as well as on new aspects, such as N-terminal acetylation of membrane protein precursors. Full article

Antibodies, also called immunoglobulins, play a key role in the body’s immune response, binding to specific molecular targets. Of the five classes of antibodies, IgG has found the greatest clinical application. The article presents the mechanisms of antibody action, including interactions with FcR receptors on leukocytes, complement activation, and direct cytotoxic interactions, as well as the main methods of antibody production, which include hybridoma technology, phage display, and production using transgenic animals and their modifications, which allowed for the production of antibodies with reduced immunogenicity and increased their effectiveness and safety of use. It also characterizes various types of antibodies and presents the differences between them resulting from the structure and content of individual protein domains encoded by human genes and genes from other species. Antibodies are currently one of the most important groups of biological drugs used in the treatment of autoimmune, infectious, and neoplastic diseases. The properties of these large biomolecules and the achievements in the field of obtaining and modifying antibodies mean that they are currently the subject of many studies. New forms of antibodies, such as antibody–drug conjugates with highly potent cytotoxic agents, bispecific antibodies, and nanobodies, demonstrate an innovative approach to the treatment of cancer and autoimmune diseases. The dynamic development of the antibody market indicates its growing importance in modern pharmacy and medicine. Further research in this area may lead to the development of more effective and precise therapies, as well as to increase the safety of their use. Full article

This article provides a comprehensive review and explores the gaps in current knowledge of lysine metabolism in humans and its potential nutritional and therapeutic indications. The first part of this study examines lysine sources, requirements, transport through the plasma membrane, lysine catabolism, and its disorders. The central part is focused on post-translational modifications of lysine in proteins, primarily desmosine formation in elastin, hydroxylation in collagen, covalent bonds with glutamine, methylation, ubiquitination, sumoylation, neddylation, acylation, lactylation, carbamylation, and glycation. Special sections are devoted to using lysine as a substrate for homoarginine and carnitine synthesis and in nutrition and medicine. It is concluded that the identification and detailed knowledge of writers, readers, and erasers of specific post-translational modifications of lysine residues in proteins is needed for a better understanding of the role of lysine in epigenetic regulation. Further research is required to explore the influence of lysine availability on homoarginine formation and how the phenomenon of lysine–arginine antagonism can be used to influence immune and cardiovascular functions and cancer development. Of unique importance is the investigation of the use of lysine in osteoporosis therapy and in reducing the resorption of harmful substances in the kidneys, as well as the therapeutic potential of polylysine and lysine analogs. Full article

Long non-coding RNAs (lncRNAs) are essential regulatory molecules involved in various biological processes in mammals. However, their expression patterns across multiple porcine tissues have not been systematically characterized. We analyzed 607 RNA-seq datasets derived from 14 porcine tissues, including backfat, gallbladder, heart, ileum, jejunum, kidney, longissimus dorsi, liver, lung, skeletal muscle, ovary, pituitary, skeletal muscle, and spleen. Additionally, we examined 63 single-cell RNA-seq datasets from porcine primary oocytes at five developmental stages. For comparative analysis, we included 20 human and 17 mouse oocyte RNA-seq datasets. We identified 52,798 porcine lncRNAs, with tissue-specific expression patterns most prominent in oocytes and least in skeletal muscle. Among them, 2169 were classified as housekeeping and 14,469 as tissue-specific lncRNAs. Cross-species analysis revealed that a small subset of oocyte-expressed lncRNAs is conserved in humans and mice, associated with catalytic activity and circadian regulation. Additionally, 44 lncRNAs were differentially expressed during oocyte development, implicating them in neurogenesis, vesicle transport, and protein modification. Our findings not only contribute to the growing body of knowledge regarding lncRNAs in porcine biology but also pave the way for future research aimed at elucidating their functional roles in reproductive biology and other physiological processes. Full article

The anodic oxidation technique was used for surface modification, resulting in the creation of a titanium-based nanotube oxide layer on a coarse-grained and ultrafine-grained Ti-13Nb-13Zr alloy. The modified surface morphology was analyzed using scanning electron microscopy (SEM), atomic force microscopy (AFM), and X-ray diffraction (XRD). The electrochemical impedance spectroscopy (EIS) method was employed to evaluate the corrosion stability of the Ti-13Nb-13Zr alloy before and after anodic oxidation. Corrosion stability was determined by exposing the examined alloy to a solution that simulates environment in the human organism (Ringer’s solution). To examine the titanium-based nanotube oxide layer adhesion on the Ti-13Nb-13Zr alloy’s surface, a scratch test was performed. The hydrophilicity of the modified surface was measured using the contact angle between a drop of Ringer’s solution and the modified surface. The anodic oxidation led to the creation of a nanotube oxide layer on the surface of the Ti-13Nb-13Zr (wt.%) alloy. The impact of the ultrafine-grained structure on the homogeneity of the nanotube oxide layer obtained using anodic oxidation was observed. The ultrafine-grained structure contributed to the increased diameter of the nanotubes, while the combined effect of anodic oxidation and high-pressure torsion significantly increased the roughness of the Ti-13Nb-13Zr alloy’s surface, which is expected to enhance biomechanical compatibility by reducing cytotoxicity, providing a more adaptable modulus of elasticity for human body conditions and ensuring adequate corrosion resistance and hydrophilicity. In this study, it was established that the examined alloy had suitable corrosion resistance for utilization in medicine as a metallic implant in the human body. The scratch test showed acceptable adhesion from the titanium-based nanotube oxide layer created using anodic oxidation. Also, the determination of the surface contact angle showed that the surface after anodic oxidation was more hydrophilic than the surface before anodic oxidation. Full article

Antibiotics, valued for their remarkable efficacy, are widely employed across diverse domains. However, their rampant overuse has precipitated severe environmental and health crises, necessitating the development of efficient techniques for rapid and selective antibiotic detection. Electrochemical detection has emerged as a highly promising approach, offering unmatched advantages such as cost-effectiveness, speed, and reliability. The field has witnessed significant advancements through the innovation of advanced electrode modification materials. This review provides a comprehensive analysis of recent progress in the development and application of modified materials for antibiotic detection. Furthermore, the increasing need for real-time monitoring has spurred the development of wearable electrochemical sensors, which are revolutionizing applications in human health and food safety. Looking ahead, future research is poised to focus on synthesizing nanocomposites with superior electrochemical properties and advancing the miniaturization of sensors, promising transformative practical applications in antibiotic detection. Full article

The human gut microbiome is a metabolically active and ecologically dynamic consortium that profoundly influences host physiology, in part by modulating epigenetic mechanisms such as DNA and RNA methylation. These modifications regulate gene expression and phenotypic plasticity and are shaped by a combination of environmental factors, such as diet, stress, xenobiotics, and bioactive microbial metabolites. Despite growing evidence linking microbial signals to host epigenetic reprogramming, the underlying molecular pathways remain incompletely understood. This review highlights recent mechanistic discoveries and conceptual advances in understanding microbiome–host epigenome interactions. We discuss evolutionarily conserved pathways through which gut microbiota regulate host methylation patterns, including one-carbon metabolism, polyamine biosynthesis, short-chain fatty acid signaling, and extracellular vesicle-mediated communication. We also examine how host factors such as aging, diet, immune activity, and sociocultural context reciprocally influence microbial composition and function. Beyond basic mechanisms, we outline translational frontiers—including biomarker discovery, live biotherapeutic interventions, fecal microbiota transplantation, and adaptive clinical trial designs—that may enable microbiome-informed approaches to disease prevention and treatment. Advances in high-throughput methylation mapping, artificial intelligence, and single-cell multi-omics are accelerating our ability to model these complex interactions at high resolution. Finally, we emphasize the importance of rigorous standardization and ethical data governance through frameworks such as the FAIR and CARE principles. Deepening our understanding of how the gut microbiome modulates host epigenetic programs offers novel opportunities for precision health strategies and equitable clinical translation. Full article

Antibody–drug conjugates (ADCs) are a rapidly advancing class of targeted cancer therapeutics that couple the antigen specificity of monoclonal antibodies (mAbs) with the potent cytotoxicity of small-molecule drugs. In their core design, a tumor-targeting antibody is covalently linked to a cytotoxic payload via a chemical linker, enabling the selective delivery of highly potent agents to malignant cells while sparing normal tissues, thereby improving the therapeutic index. Humanized and fully human immunoglobulin G1(IgG1) antibodies are the most common ADC backbones due to their stability in systemic circulation, robust Fcγ receptor engagement for immune effector functions, and reduced immunogenicity. Antibody selection requires balancing tumor specificity, internalization rate, and binding affinity to avoid barriers to tissue penetration, such as the binding-site barrier effect, while emerging designs exploit tumor-specific antigen variants or unique post-translational modifications to further enhance selectivity. Advances in antibody engineering, linker chemistry, and payload innovation have reinforced the clinical success of ADCs, with more than a dozen agents FDA approved for hematologic malignancies and solid tumors and over 200 in active clinical trials. This review critically examines established and emerging conjugation strategies, including lysine- and cysteine-based chemistries, enzymatic tagging, glycan remodeling, non-canonical amino acid incorporation, and affinity peptide-mediated methods, and discusses how conjugation site, drug-to-antibody ratio (DAR) control, and linker stability influence pharmacokinetics, efficacy, and safety. Innovations in site-specific conjugation have improved ADC homogeneity, stability, and clinical predictability, though challenges in large-scale manufacturing and regulatory harmonization remain. Furthermore, novel ADC architectures such as bispecific ADCs, conditionally active (probody) ADCs, immune-stimulating ADCs, protein-degrader ADCs, and dual-payload designs are being developed to address tumor heterogeneity, drug resistance, and off-target toxicity. By integrating mechanistic insights, preclinical and clinical data, and recent technological advances, this work highlights current progress and future directions for next-generation ADCs aimed at achieving superior efficacy, safety, and patient outcomes, especially in treating refractory cancers. Full article

Pseudouridylation, the most abundant RNA modification, plays a critical role in modulating RNA structure, stability, and function. Among the family of pseudouridine synthases, Pseudouridine Synthase 7 (PUS7) has recently gained attention for its emerging roles in human health and disease. Originally characterized for its function in modifying tRNA and small non-coding RNAs, PUS7 is now recognized as a dynamic regulator of mRNA pseudouridylation, influencing gene expression at the post-transcriptional level. Aberrant expressions or activity of PUS7 have been linked to a variety of pathological conditions, including cancers such as colon cancer, glioblastoma, pancreatic cancer, and neuroblastoma, as well as potential roles in neurodevelopmental disorders and immune regulation. Through mechanisms involving translational reprogramming, stress adaptation, and epitranscriptomic remodeling, PUS7 contributes to disease progression and cellular plasticity. This review summarizes the current understanding of PUS7 biology, its functional relevance in the contexts of cancer progression, and the growing interest in targeting RNA-modifying enzymes for therapeutic intervention. Uncovering the full spectrum of PUS7-mediated pseudouridylation and its downstream effects holds promise for advancing our understanding of RNA-based regulation in human diseases, including gynecological disorders. Full article

With the rapid evolution of nanotechnology, magnetic iron oxide nanoparticles (MNPs)—primarily Fe₃O₄ and γ-Fe₂O₃—have gained prominence in biomedicine. Their extensive specific surface area, tunable surface functionalities, and intrinsic magnetic characteristics render them highly versatile for diverse clinical applications, including tumor visualization through Magnetic Resonance Imaging (MRI), radiolabeling, targeted radiotherapy, hyperthermia, gene transfer, drug delivery, Magnetic Particle Imaging (MPI), magnetic blood filtration and theranostic strategies. Nevertheless, ensuring the biocompatibility and non-toxicity of these nanostructures remains a fundamental prerequisite for their medical implementation. Hence, it is essential to continuously refine our understanding of MNP-related toxicity and pursue comprehensive research on this front. This article consolidates up-to-date insights into the evaluation of MNPs’ toxicological profiles, emphasizing the influence of physicochemical properties such as morphology, surface modifications, and electrostatic characteristics, along with operational factors like dosage and administration routes. Traditional toxicity testing strategies, including in vitro assays as first-line screening tools, together with standard ex vivo and in vivo models, are discussed. Special attention is given to the emerging role of New Approach Methodologies (NAMs), such as organoid formation, 3D bioprinting, in ovo chicken embryo assays, and image cytometry. These techniques offer ethical, human-relevant, and informative alternatives to animal testing, supporting more predictive and translationally relevant toxicity assessment of MNPs. Taken together, the integration of conventional assays with innovative NAMs, alongside careful consideration of physicochemical and operational factors, is essential to translate the laboratory promise of MNPs into safe and clinically effective nanomedicines. Full article

Oil spills and oily wastewater discharges have posed severe threats to the ecosystem and human health, yet efficient cleanup and recovery remain huge challenges. The absorption of crude oil is especially difficult due to its high viscosity. In this study, we propose a strategy for the fast and highly selective absorption of crude oil as well as other oils and organic solvents with variable viscosity by combining the desert beetle’s back-inspired gradient hydrophobicity with the photothermal effect to enhance the absorption rate. The oil-absorbent material was prepared through the alkylsilane-based gradient chemical modification of MXene-polyurethane sponges. The hydrophobic gradient across the composite sponge offers an extra driving force for the selective oil wetting in the sponge. Owing to the synergistic effect between gradient wettability and photothermal heating, a faster absorption rate, in addition to the high separation rate, was achieved for a variety of oils, including thick crude oil, thin crude oil, and light diesel oil, compared to that without gradient wettability. The as-prepared material is robust with good repeatability for the oil absorption. The surface silane modification was also demonstrated to help prevent the oxidation of MXene, facilitating the long-term stability of the material. This study will enlighten the development of fast and highly selective liquid absorbents. Full article

The liver orchestrates metabolic homeostasis through dynamic post-translational modifications. β-hydroxybutyrylation (Kbhb), a ketone body-driven modification, regulates epigenetics and metabolism in humans and mice but remains unexplored in livestock. Here, we characterize the porcine hepatic β-hydroxybutyrylome using high-resolution mass spectrometry, identifying 4982 Kbhb sites on 2122 proteins—the largest dataset to date. β-hydroxybutyrylation predominantly targets non-histone proteins (99.68%), with enrichment in fatty acid β-oxidation, TCA cycle, and oxidative phosphorylation pathways. Subcellular localization revealed cytoplasmic (38.1%), mitochondrial (18.1%), and nuclear (15.3%) dominance, reflecting BHB-CoA synthesis sites. Motif analysis identified conserved leucine, phenylalanine, and valine residues at modified lysines, suggesting enzyme-substrate specificity. β-hydroxybutyrate treatment elevated global Kbhb levels, increasing TCA intermediates (e.g., α-ketoglutarate, +9.56-fold) while reducing acetyl-CoA, indicating enhanced mitochondrial flux. Cross-species comparisons showed tissue-specific Kbhb distribution (nuclear in human cells vs. mitochondrial in mice), highlighting metabolic adaptations. This study establishes pigs as a model for Kbhb research, linking it to energy regulation and providing insights into metabolic reprogramming. Full article

RNA modifications regulate diverse aspects of transcripts’ function and stability. Among these, N1-methyladenine (m¹A) is a reversible mark primarily installed by the TRMT6/TRMT61A methyltransferase on tRNA, though it is also found on other RNA types. m¹A has been implicated in protecting mRNAs during acute protein misfolding stress. However, the role of m¹A under chronic proteotoxic conditions, such as intracellular amyloid aggregation, remains poorly understood. To address this gap, we examined the effects of reduced N1-adenine methylation in human cells undergoing amyloidogenesis. Suppression of the methyltransferase TRMT61A or overexpression of the m¹A-specific demethylase ALKBH3 enhanced amyloid aggregation. A deficiency of N1-adenine methylation also impaired the expression of a reporter mRNA-encoded protein, highlighting the protective role of m¹A in safeguarding transcript functionality. Proteomic analysis of amyloid aggregates from TRMT61A-deficient cells revealed increased co-aggregation of bystander proteins, particularly those with known RNA-binding activity. At the same time, the aggregates from methylation-deficient cells contained elevated levels of mRNAs. Collectively, our findings support a role for m¹A in preventing RNA entanglement within aggregates and limiting RNA-mediated propagation of protein co-aggregation. Full article

Collective robotics systems hold great potential for future education and public engagement; however, only a few are utilized in these contexts. One reason is the lack of accessible tools to convey their complex, embodied interactions. In this work, we introduce the Light-Augmented Reality System (LARS), an open-source, marker-free, cross-platform tool designed to support experimentation, education, and outreach in collective robotics. LARS employs Extended Reality (XR) to project dynamic visual objects into the physical environment. This enables indirect robot–robot communication through stigmergy while preserving the physical and sensing constraints of the real robots, and enhances robot–human interaction by making otherwise hidden information visible. The system is low-cost, easy to deploy, and platform-independent without requiring hardware modifications. By projecting visible information in real time, LARS facilitates reproducible experiments and bridges the gap between abstract collective dynamics and observable behavior. We demonstrate that LARS can serve both as a research tool and as a means to motivate students and the broader public to engage with collective robotics. Its accessibility and flexibility make it an effective platform for illustrating complex multi-robot interactions, promoting hands-on learning, and expanding public understanding of collective, embodied intelligence. Full article

Extensive studies about the human immunodeficiency virus type 1 (HIV-1) have allowed the generation of lentiviral vectors as gene delivery vehicles with enhanced safety and efficacy features. In this review, several strategies for controlling the molecular mechanisms occurring during the lentiviral vector manufacturing process are presented. Specifically, modifications focused on LVV manufacturing components, such as plasmids or the producer cell line, that enable increased safety, integrity, and potency of the produced LVV, as well as manufacturing efficiency. Considering the stochasticity of the LVV manufacturing process from plasmid transfection until the budding of the virus from the target cell, minimal modifications might have a huge impact on the final LVV yield. Indeed, the extent of a potential impact may vary depending on the specificities of each LVV regarding the particular genetic payload or the envelope protein. Thus, the feasibility of each of the optimizations described herein requires thorough evaluation. The second part of the review examines the potential multi-purpose nature of the LVV. Growing research in the field has enabled the development of new engineered modalities of LVV, expanding their application scope beyond the traditional ex vivo DNA delivery approach. LVVs are becoming a versatile tool for the packaging or delivery of cargo in the form of DNA, RNA, or protein, allowing their use for in vivo approaches, vaccinology, or gene editing, among others. Full article