Search Results (128)

Environmental concerns about the widespread use of non-biodegradable plastic have generated interest in developing quick and effective methods to degrade synthetic polymers. With millions of tons of plastic waste generated annually, biodegradation by microorganisms presents a promising and eco-friendly solution. However, a bottleneck has arisen due to the lack of standardized methods for verification of the biodegradation process. Based on this literature review, he techniques most commonly employed for this purpose currently include measuring mass loss, examining the surface of plastic fragments by scanning electron microscopy (SEM) and atomic force microscopy (AFM), and using analytical methods such as Fourier transform infrared spectroscopy (FTIR), pyrolysis–gas chromatography–mass spectrometry (Pyr-GC/MS) or high-performance liquid chromatography (HPLC). Each of these methods has its advantages and disadvantages. Nevertheless, currently, there is no universal approach to accurately assess the ability of individual microorganisms to degrade plastics. In this review, we summarize the latest advances in techniques for detecting biodegradation of synthetic polymers and future directions in the development of sustainable strategies for mitigating plastic pollution. Full article

The use of insect sex pheromones as an alternative technology for pest control in agriculture and forestry offers a promising solution. The development of a novel technology for the biological production of pheromones through yeast fermentation significantly lowers production costs, enabling the adoption of sustainable pest control practices in field crops, a strategy previously reserved for high-value crops. Over three years of monitoring and mating disruption trials in Greek cotton fields, focusing on the cotton bollworm Helicoverpa armigera (Hübner) (Lepidoptera: Noctuidae), it was confirmed that yeast-derived pheromones exhibit equal efficacy compared to their chemically synthesized counterparts. For the mating disruption of H. armigera, a biodegradable, flowable, and paraffin-based matrix was developed. The matrix adheres to plants, protects the labile pheromone molecules (Z)-11-hexadecenal and (Z)-9-hexadecenal, and controls their gradual release into the environment. These biodegradable polymer blobs act as non-retrievable dispensers and can be deployed manually or via unmanned aerial vehicles (UAVs), ensuring efficient and accurate application. This precise, time-efficient, and economically sound technology aligns with European Commission initiatives, such as the Green Deal’s Farm to Fork Strategy and the Biodiversity Strategy, contributing to food sustainability while respecting biodiversity. Full article

‘Blood stasis’ (syndrome) (BSS) is a fundamental concept in Traditional Chinese Medicine (TCM), where it is known as Xue Yu (血瘀). Similar concepts exist in Traditional Korean Medicine (‘Eohyul’) and in Japanese Kampo medicine (Oketsu). Blood stasis is considered to underpin a large variety of inflammatory diseases, though an exact equivalent in Western systems medicine is yet to be described. Some time ago we discovered that blood can clot into an anomalous amyloid form, creating what we have referred to as fibrinaloid microclots. These microclots occur in a great many chronic, inflammatory diseases are comparatively resistant to fibrinolysis, and thus have the ability to block microcapillaries and hence lower oxygen transfer to tissues, with multiple pathological consequences. We here develop the idea that it is precisely the fibrinaloid microclots that relate to, and are largely mechanistically responsible for, the traditional concept of blood stasis (a term also used by Virchow). First, the diseases known to be associated with microclots are all associated with blood stasis. Secondly, by blocking red blood cell transport, fibrinaloid microclots provide a simple mechanistic explanation for the physical slowing down (‘stasis’) of blood flow. Thirdly, Chinese herbal medicine formulae proposed to treat these diseases, especially Xue Fu Zhu Yu and its derivatives, are known mechanistically to be anticoagulatory and anti-inflammatory, consistent with the idea that they are actually helping to lower the levels of fibrinaloid microclots, plausibly in part by blocking catalysis of the polymerization of fibrinogen into an amyloid form. We rehearse some of the known actions of the constituent herbs of Xue Fu Zhu Yu and specific bioactive molecules that they contain. Consequently, such herbal formulations (and some of their components), which are comparatively little known to Western science and medicine, would seem to offer the opportunity to provide novel, safe, and useful treatments for chronic inflammatory diseases that display fibrinaloid microclots, including Myalgic Encephalopathy/Chronic Fatigue Syndrome, long COVID, and even ischemic stroke. Full article

The purpose of this study was to assess the ability of Bacillus aryabhattai RAF 5 to produce P(3HB) under conditions of periodic medium renewal (PMR). The producer was isolated and confirmed using transmission electron microscopy (TEM), which revealed the presence of more than 10 dense P(3HB) granules per cell. The purity of the isolated polymer was evaluated using Fourier transform infrared spectroscopy (FTIR). The maximum concentration of P(3HB) reached 18.70 g/L with biomass accumulation of 21.44 g/L after 120 h of incubation under PMR conditions, which is 6.61 g/L higher than the concentration of P(3HB) obtained with the standard cultivation method. The resulting polymer was later used to create a membrane, which was then tested for permeability to water vapor, oxygen, carbon dioxide, and a biofilm puncture test. The resulting P(3HB)-based membranes have promising barrier properties, indicating their suitability for various industrial applications, including biomedical devices. Full article

Fungal infections of crops pose a threat to global agriculture. Fungi of the genus Fusarium cause widespread diseases in cereal crops. Fusarium graminearum reduces yields and produces harmful mycotoxins such as deoxynivalenol (DON). Plants mitigate DON toxicity through glucose conjugation mediated by UDP-glycosyltransferases (UGTs), forming deoxynivalenol-3-O-glucoside (DON-3-Glc). Few such UGTs have been identified, predominantly from Fusarium-susceptible crops. Given that the presence of this activity in diverse plants and across broader UGT subfamilies and groups was underexplored, we screened a library of 380 recombinant plant UGTs and identified and characterized eight novel enzymes glycosylating DON in vitro. Among these, ZjUGT from Ziziphus jujuba stood out with the highest activity, showing an apparent k_cat of 0.93 s⁻¹ and k_cat/K_m of 2450 M⁻¹ s⁻¹. Interestingly, four enzymes produced primarily a novel, still uncharacterized glucoside. Furthermore, we evaluated the in vivo resistance provided by these UGTs when expressed in a DON-sensitive yeast strain. At least six of the novel UGTs conferred some level of resistance, allowing growth at concentrations of up to 120 mg/L of DON. This study contributes to potential strategies to enhance DON resistance in cereal crops in the future. Full article

A recent analysis compared the proteome of (i) blood clots seen in two diseases—sepsis and long COVID—when blood was known to have clotted into an amyloid microclot form (as judged by staining with the fluorogenic amyloid stain thioflavin T) with (ii) that of those non-amyloid clots considered to have formed normally. Such fibrinaloid microclots are also relatively resistant to fibrinolysis. The proteins that the amyloid microclots contained differed markedly both from the soluble proteome of typical plasma and that of normal clots, and also between the diseases studied (an acute syndrome in the form of sepsis in an ITU and a chronic disease represented by Long COVID). Many proteins in the amyloid microclots were low in concentration in plasma and were effectively accumulated into the fibres, whereas many other abundant plasma proteins were excluded. The proteins found in the microclots associated with the diseases also tended to be themselves amyloidogenic. We here ask effectively the inverse question. This is: can the clot proteome tell us whether the clots associated with a particular disease contained proteins that are observed uniquely (or are highly over-represented) in known amyloid clots relative to normal clots, and thus were in fact amyloid in nature? The answer is in the affirmative in a variety of major coagulopathies, viz., venous thromboembolism, pulmonary embolism, deep vein thrombosis, various cardiac issues, and ischaemic stroke. Galectin-3-binding protein and thrombospondin-1 seem to be especially widely associated with amyloid-type clots, and the latter has indeed been shown to be incorporated into growing fibrin fibres. These may consequently provide useful biomarkers with a mechanistic basis. Full article

A human epidermal growth factor receptor 2 (HER2)-specific nanobody called 2Rs15d, containing a His3LysHis6 segment at the C-terminus, was recombinantly produced. Subsequent site-selective acylation on the C-terminally activated lysine residue allowed installation of the cytotoxin monomethyl auristatin E-functionalized cathepsin B-sensitive payload to provide a highly homogenous nanobody–drug conjugate (NBC), which demonstrated high potency and selectivity for HER2-positive breast cancer models. Full article

Nanoparticles (NPs) have emerged as a potent choice for various applications, from drug delivery to agricultural studies, serving as an alternative and promising methodology for future advancements. They have been widely explored in delivery systems, demonstrating immense promise and high efficiency for the delivery of numerous biomolecules such as proteins and anticancer agents, either solely or modified with other compounds to enhance their capabilities. In addition, the utilization of NPs extends to antimicrobial studies, where they are used to develop novel antibacterial, antifungal, and antiviral formulations with advanced characteristics. Lactoferrin (Lf) is a glycoprotein recognized for its significant multifunctional properties, such as antimicrobial, antioxidant, anti-inflammatory, anticancer, and neuroprotective effects. Its activity has a broad distribution in the human body, with Lf receptors present in multiple regions. Current research shows that Lf is utilized in NP technology as a surface material, encapsulated biomolecule, and even as an NP itself. Due to the abundance of Lf receptors in various regions, Lf can be employed as a surface material in NPs for targeted delivery strategies, particularly in crossing the BBB and targeting specific cancers. Furthermore, Lf can be synthesized in an NP structure, positioning it as a strong candidate in future NP-related applications. In this article, we explore the highlighted and underexplored areas of Lf applications in NPs research. Full article

Metabolic pathway modeling, essential for understanding organism metabolism, is pivotal in predicting genetic mutation effects, drug design, and biofuel development. Enhancing these modeling techniques is crucial for achieving greater prediction accuracy and reliability. However, the limited experimental data or the complexity of the pathway makes it challenging for researchers to predict phenotypes. Deep learning (DL) is known to perform better than other Machine Learning (ML) approaches if the right conditions are met (i.e., a large database and good choice of parameters). Here, we use a knowledge-based model to massively generate synthetic data and extend a small initial dataset of experimental values. The main objective is to assess if DL can perform at least as well as other ML approaches in flux prediction, using 68,950 instances. Two processing methods are used to generate DL models: cross-validation and repeated holdout evaluation. DL models predict the metabolic fluxes with high precision and slightly outperform the best-known ML approach (the Cubist model) with a lower RMSE (≤0.01) in both cases. They also outperform the PLS model (RMSE ≥ 30). This study is the first to use DL to predict the overall flux of a metabolic pathway only from variations of enzyme concentrations. Full article

Iron oxide nanoparticles (IONPs) have garnered significant attention in biomedical applications due to their unique magnetic properties, biocompatibility, and versatility. This review comprehensively examines the synthesis methods, surface functionalization techniques, and diverse biomedical applications of IONPs. Various chemical and physical synthesis techniques, including coprecipitation, sol–gel processes, thermal decomposition, hydrothermal synthesis, and sonochemical routes, are discussed in detail, highlighting their advantages and limitations. Surface functionalization strategies, such as ligand exchange, encapsulation, and silanization, are explored to enhance the biocompatibility and functionality of IONPs. Special emphasis is placed on the role of IONPs in biosensing technologies, where their magnetic and optical properties enable significant advancements, including in surface-enhanced Raman scattering (SERS)-based biosensors, fluorescence biosensors, and field-effect transistor (FET) biosensors. The review explores how IONPs enhance sensitivity and selectivity in detecting biomolecules, demonstrating their potential for point-of-care diagnostics. Additionally, biomedical applications such as magnetic resonance imaging (MRI), targeted drug delivery, tissue engineering, and stem cell tracking are discussed. The challenges and future perspectives in the clinical translation of IONPs are also addressed, emphasizing the need for further research to optimize their properties and ensure safety and efficacy in medical applications. This review aims to provide a comprehensive understanding of the current state and future potential of IONPs in both biosensing and broader biomedical fields. Full article

In classical amyloidoses, amyloid fibres form through the nucleation and accretion of protein monomers, with protofibrils and fibrils exhibiting a cross-β motif of parallel or antiparallel β-sheets oriented perpendicular to the fibre direction. These protofibrils and fibrils can intertwine to form mature amyloid fibres. Similar phenomena can occur in blood from individuals with circulating inflammatory molecules (and also some originating from viruses and bacteria). Such pathological clotting can result in an anomalous amyloid form termed fibrinaloid microclots. Previous proteomic analyses of these microclots have shown the presence of non-fibrin(ogen) proteins, suggesting a more complex mechanism than simple entrapment. We thus provide evidence against such a simple entrapment model, noting that clot pores are too large and centrifugation would have removed weakly bound proteins. Instead, we explore whether co-aggregation into amyloid fibres may involve axial (multiple proteins within the same fibril), lateral (single-protein fibrils contributing to a fibre), or both types of integration. Our analysis of proteomic data from fibrinaloid microclots in different diseases shows no significant quantitative overlap with the normal plasma proteome and no correlation between plasma protein abundance and their presence in fibrinaloid microclots. Notably, abundant plasma proteins like α-2-macroglobulin, fibronectin, and transthyretin are absent from microclots, while less abundant proteins such as adiponectin, periostin, and von Willebrand factor are well represented. Using bioinformatic tools, including AmyloGram and AnuPP, we found that proteins entrapped in fibrinaloid microclots exhibit high amyloidogenic tendencies, suggesting their integration as cross-β elements into amyloid structures. This integration likely contributes to the microclots’ resistance to proteolysis. Our findings underscore the role of cross-seeding in fibrinaloid microclot formation and highlight the need for further investigation into their structural properties and implications in thrombotic and amyloid diseases. These insights provide a foundation for developing novel diagnostic and therapeutic strategies targeting amyloidogenic cross-seeding in blood clotting disorders. Full article

Kynurenic acid (KYNA) is an antioxidant degradation product of tryptophan that has been shown to have a variety of cytoprotective, neuroprotective and neuronal signalling properties. However, mammalian transporters and receptors display micromolar binding constants; these are consistent with its typically micromolar tissue concentrations but far above its serum/plasma concentration (normally tens of nanomolar), suggesting large gaps in our knowledge of its transport and mechanisms of action, in that the main influx transporters characterized to date are equilibrative, not concentrative. In addition, it is a substrate of a known anion efflux pump (ABCC4), whose in vivo activity is largely unknown. Exogeneous addition of L-tryptophan or L-kynurenine leads to the production of KYNA but also to that of many other co-metabolites (including some such as 3-hydroxy-L-kynurenine and quinolinic acid that may be toxic). With the exception of chestnut honey, KYNA exists at relatively low levels in natural foodstuffs. However, its bioavailability is reasonable, and as the terminal element of an irreversible reaction of most tryptophan degradation pathways, it might be added exogenously without disturbing upstream metabolism significantly. Many examples, which we review, show that it has valuable bioactivity. Given the above, we review its potential utility as a nutraceutical, finding it significantly worthy of further study and development. Full article

The vast array of omics data in microbiology presents significant opportunities for studying bacterial pathogenesis and creating computational tools for predicting pathogenic potential. However, the field lacks a comprehensive, curated resource that catalogs bacterial strains and their ability to cause human infections. Current methods for identifying pathogenicity determinants often introduce biases and miss critical aspects of bacterial pathogenesis. In response to this gap, we introduce BacSPaD (Bacterial Strains’ Pathogenicity Database), a thoroughly curated database focusing on pathogenicity annotations for a wide range of high-quality, complete bacterial genomes. Our rule-based annotation workflow combines metadata from trusted sources with automated keyword matching, extensive manual curation, and detailed literature review. Our analysis classified 5502 genomes as pathogenic to humans (HP) and 490 as non-pathogenic to humans (NHP), encompassing 532 species, 193 genera, and 96 families. Statistical analysis demonstrated a significant but moderate correlation between virulence factors and HP classification, highlighting the complexity of bacterial pathogenicity and the need for ongoing research. This resource is poised to enhance our understanding of bacterial pathogenicity mechanisms and aid in the development of predictive models. To improve accessibility and provide key visualization statistics, we developed a user-friendly web interface. Full article

Clozapine is an antipsychotic drug whose accumulation in white cells can sometimes prove toxic; understanding the transporters and alleles responsible is thus highly desirable. We used a strategy in which a yeast (Saccharomyces cerevisiae) CRISPR-Cas9 knock-out library was exposed to cytotoxic concentrations of clozapine to determine those transporters whose absence made it more resistant; we also recognised the structural similarity of the fluorescent dye safranin O (also known as safranin T) to clozapine, allowing it to be used as a surrogate marker. Strains lacking the mitochondrial ABC transporter MDL1 (encoded by YLR188W) showed substantial resistance to clozapine. MDL1 overexpression also conferred extra sensitivity to clozapine and admitted a massive increase in the cellular and mitochondrial uptake of safranin O, as determined using flow cytometry and microscopically. Yeast lacking mitochondria showed no such unusual accumulation. Mitochondrial MDL1 is thus the main means of accumulation of clozapine in S. cerevisiae. The closest human homologue of S. cerevisiae MDL1 is ABCB10. Full article