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Journal articleRueda-Maíllo F, Garrido-Jurado I, Kotta-Loizou I, et al., 2025,
A mycoviral infection drives virulence and ecological fitness of the entomopathogenic fungus Beauveria bassiana
, Journal of Invertebrate Pathology, Vol: 209, ISSN: 0022-2011Entomopathogenic ascomycetes are important natural regulators of insect pest populations and an increasingly adopted microbial control option. Fungal virulence in entomopathogenic ascomycetes can be modified by mycoviruses, viruses that infect fungi, whereas the possible role of these viruses on the physical and biochemical properties of the virus-containing fungal strains and on their ecological fitness has remained largely unexplored. Here, utilizing a Beauveria bassiana strain naturally infected with two mycoviruses, Beauveria bassiana partitivirus 2 (BbPV-2) and Beauveria bassiana polymycovirus 1 (BbPmV-1), we found that the mycovirus-containing strain is hypervirulent towards the experimental insect Galleria mellonella and shows major physical and biochemical changes in spore size, isoelectric point, and Pr1 activity, but even more impactful, the mycoviral infection confers a significant environmental- abiotic and biotic stress tolerance to the fungus. Hence, mycovirus infection expanded the temperature range for fungal growth and germination, and improved tolerance to osmotic stress, water stress, and UV-B radiation. Similarly, the antagonistic activity of the mycovirus-containing strain against Trichoderma harzianum was increased as compared to the mycovirus-free one. Taken together, these data suggest for the first time a mycovirus related adaptation of key traits indicators of environmental competence of a beneficial fungus, rendering these mycoviruses as potent tools for entomopathogenic fungal strain selection and development as mycoinsecticides.
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Journal articleHernandez B, Ming DK, Rawson TM, et al., 2025,
Advances in diagnosis and prognosis of bacteraemia, bloodstream infection, and sepsis using machine learning: A comprehensive living literature review
, Artificial Intelligence in Medicine, Vol: 160, ISSN: 0933-3657Background: Blood-related infections are a significant concern in healthcare. They can lead to serious medical complications and even death if not promptly diagnosed and treated. Throughout time, medical research has sought to identify clinical factors and strategies to improve the management of these conditions. The increasing adoption of electronic health records has led to a wealth of electronically available medical information and predictive models have emerged as invaluable tools. This manuscript offers a detailed survey of machine-learning techniques used for the diagnosis and prognosis of bacteraemia, bloodstream infections, and sepsis shedding light on their efficacy, potential limitations, and the intricacies of their integration into clinical practice. Methods: This study presents a comprehensive analysis derived from a thorough search across prominent databases, namely EMBASE, Google Scholar, PubMed, Scopus, and Web of Science, spanning from their inception dates to October 25, 2023. Eligibility assessment was conducted independently by investigators, with inclusion criteria encompassing peer-reviewed articles and pertinent non-peer-reviewed literature. Clinical and technical data were meticulously extracted and integrated into a registry, facilitating a holistic examination of the subject matter. To maintain currency and comprehensiveness, readers are encouraged to contribute manuscript suggestions and/or reports for integration into this living registry. Results: While machine learning (ML) models exhibit promise in advanced disease stages such as sepsis, early stages remain underexplored due to data limitations. Biochemical markers emerge as pivotal predictors during early stages such as bacteraemia, or bloodstream infections, while vital signs assume significance in sepsis prognosis. Integrating temporal trend information into conventional machine learning models appears to enhance performance. Unfortunately, sequential deep learning models face chal
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Journal articleDobra R, Short C, Wong K, et al., 2025,
Utility and interpretation of multiple breath washout in children with cystic fibrosis
, Archives of disease in childhood - Education & practice edition, ISSN: 1743-0585<jats:p>Transformative changes in the health of children with cystic fibrosis (CF) mean that more sensitive outcome measures are needed to monitor paediatric CF lung disease. Multiple breath washout (MBW) and its primary readout lung clearance index are gaining increasing traction as an endpoint for clinical trials in the CF space and show promise as a clinical investigation. In this article, we use four clinically based questions to explore what MBW can and cannot (yet) do and highlight some of its strengths and weaknesses as an investigation. We end by discussing how we can increase the utility of MBW as an investigation in children with CF.</jats:p>
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Journal articleBrożek A, Ceccarelli A, Jørgensen ACS, et al., 2025,
Inference of a three-gene network underpinning epidermal stem cell development in Caenorhabditis elegans
, iScience, ISSN: 2589-0042 -
Journal articleXu X, Lv X, Liu Y, et al., 2025,
CRISPR/Cas13X-assisted programmable and multiplexed translation regulation for controlled biosynthesis.
, Nucleic Acids Res, Vol: 53Developing efficient gene regulation tools is essential for optimizing microbial cell factories, but most existing tools only modulate gene expression at the transcriptional level. Regulation at the translational level provides a faster dynamic response, whereas developing a programmable, efficient and multiplexed translational regulation tool remains a challenge. Here, we have developed CRISPRi and CRISPRa systems based on hfCas13X that can regulate gene translation in Bacillus subtilis. First, we constructed a CRISPRi system to regulate gene translation based on catalytically deactivated hfCas13X (dhfCas13X). Second, we designed unique mRNA-crRNA pairs to construct DiCRISPRa (degradation-inhibited CRISPRa) and TsCRISPRa (translation-started CRISPRa) systems, which can activate downstream gene translation by enhancing mRNA stability or initiating mRNA translation. In addition, we found that fusing dhfCas13X with the RNA-binding chaperone BHfq significantly improved the activation efficiency of the DiCRISPRa and TsCRISPRa systems (43.2-fold). Finally, we demonstrated that the constructed CRISPR systems could be used to optimize the metabolic networks of two biotechnologically relevant compounds, riboflavin and 2'-fucosyllactose, increasing their titers by 3- and 1.2-fold, respectively. The CRISPRa and CRISPRi systems developed here provide new tools for the regulation of gene expression at the translation level and offer new ideas for the construction of CRISPRa systems.
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Journal articleLedesma-Amaro R, Zhou T, Park Y-K, et al., 2025,
Metabolic engineering of Yarrowia lipolytica for the production and secretion of the saffron ingredient crocetin
, Biotechnology for Biofuels and Bioproducts, Vol: 18, ISSN: 2731-3654Background: Crocetin is a multifunctional apocarotenoid natural product derived from saffron, holding significant promises for protection against various diseases and other nutritional applications. Historically, crocetin has been extracted from saffron stigmas, but this method is hindered by the limited availability of high-quality raw materials and complex extraction processes. To overcome these challenges, metabolic engineering and synthetic biology can be applied to the sustainable production of crocetin. Results: We constructed a Yarrowia lipolytica strain using hybrid promoters and copy number adjustment, which was able to produce 2.66 g/L of β-carotene, the precursor of crocetin. Next, the crocetin biosynthetic pathway was introduced, and we observed both the production and secretion of crocetin. Subsequently, the metabolite profiles under varied temperatures were studied and we found that low temperature was favorable for crocetin biosynthesis in Y. lipolytica. Therefore, a two-step temperature-shift fermentation strategy was adopted to optimize yeast growth and biosynthetic enzyme activity, bringing a 2.3-fold increase in crocetin titer. Lastly, fermentation media was fine-tuned for an optimal crocetin output of 30.17 mg/L, bringing a 51% higher titer compared with the previous highest report in shake flasks. Concomitantly, we also generated Y . lipolytica strains capable of achieving substantial zeaxanthin production, yielding 1575.09 mg/L, doubling the previous highest reported titer. Conclusions: Through metabolic engineering and fermentation optimization, we demonstrated the first de novo biosynthesis of crocetin in the industrial yeast Yarrowia lipolytica. In addition, we achieved a higher crocetin titer in flasks than all our known reports. This work not only represents a high production of crocetin but also entails a significant simultaneous zeaxanthin production, setting the stage for sustainable and cost-effective production of these valuabl
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Journal articleJalali Kandeloos A, Eder T, Hetey D, et al., 2025,
Expanding Transparent Covalently Attached Liquid-Like Surfaces for Icephobic Coatings with Broad Substrate Compatibility
, Advanced Materials InterfacesIce accretion causes significant energy losses and safety risks across various sectors. Recent research shows that liquid-like surfaces (LLS) with ice-shedding properties can be created by covalently attaching linear polymer chains onto smooth substrates with sufficient hydroxyl group densities. To expand the substrate scope for LLS, a novel system using non-halogenated organosilanes attached to a commercial epoxy-silicon (EpSi) coating is proposed. The EpSi layer, easily applied using simple methods, serves as a smooth intermediate layer (Ra = 0.94 nm and Rq = 0.76 nm). Air plasma activation increases hydroxyl density on EpSi, enabling LLS formation via simple immersion in an organosilane solution. The resulting coating exhibits low contact angle hysteresis (<10°), sliding angle (SA < 14°), and ice adhesion strength (τice < 20 kPa). Effective LLS is generated regardless of substrate type, coating thickness, or application method. The coating retains its slippery properties after exposure to harsh conditions, including icing/deicing cycles, organic solvents, and acidic environment. It is also highly transparent (Tave = 84.5%, t = 500 µm) with self-cleaning and anti-staining capabilities. This methodology broadens the substrate scope of LLS, offering a sustainable solution to ice accretion challenges.
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Journal articleOrzan E, Barrio A, Biegler V, et al., 2025,
Foaming and cross-linking of cellulose fibers using phytic acid
, CARBOHYDRATE POLYMERS, Vol: 347, ISSN: 0144-8617 -
Journal articleRowland SN, Green CG, Halliwill JR, et al., 2025,
Gut feelings on short-chain fatty acids to regulate respiratory health
, Trends in Endocrinology and Metabolism, ISSN: 1043-2760Respiratory infections and diseases pose significant challenges to society and healthcare systems, underscoring the need for preventative and therapeutic strategies. Recent research in rodent models indicates that short-chain fatty acids (SCFAs), metabolites produced by gut bacteria, may offer medicinal benefits for respiratory conditions. In this opinion, we summarize the current literature that highlights the potential of SCFAs to enhance immune balance in humans. SCFAs have demonstrated the potential to decrease the risk of primary and secondary respiratory infections, modulate allergic airway exacerbations, and improve overall epithelial pathogen defenses. Therefore, we suggest that systemic SCFA levels could be targeted to support gut and respiratory health in specific groups, such as patients in hospital, women and their offspring, children, older adults, and athletes/military personnel.
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Journal articleChalmers JD, Mall MA, Chotirmall SH, et al., 2025,
Targeting neutrophil serine proteases in bronchiectasis.
, Eur Respir J, Vol: 65Persistent neutrophilic inflammation is a central feature in both the pathogenesis and progression of bronchiectasis. Neutrophils release neutrophil serine proteases (NSPs), such as neutrophil elastase (NE), cathepsin G and proteinase 3. When chronically high levels of free NSP activity exceed those of protective antiproteases, structural lung destruction, mucosal-related defects, further susceptibility to infection and worsening of clinical outcomes can occur. Despite the defined role of prolonged, high levels of NSPs in bronchiectasis, no drug that controls neutrophilic inflammation is licensed for the treatment of bronchiectasis. Previous methods of suppressing neutrophilic inflammation (such as direct inhibition of NE) have not been successful; however, an emerging therapy designed to address neutrophil-mediated pathology, inhibition of the cysteine protease cathepsin C (CatC, also known as dipeptidyl peptidase 1), is a promising approach to ameliorate neutrophilic inflammation, since this may reduce the activity of all NSPs implicated in bronchiectasis pathogenesis, and not just NE. Current data suggest that CatC inhibition may effectively restore the protease-antiprotease balance in bronchiectasis and improve disease outcomes as a result. Clinical trials for CatC inhibitors in bronchiectasis have reported positive phase III results. In this narrative review, we discuss the role of high NSP activity in bronchiectasis, and how this feature drives the associated morbidity and mortality seen in bronchiectasis. This review discusses therapeutic approaches aimed at treating neutrophilic inflammation in the bronchiectasis lung, summarising clinical trial outcomes and highlighting the need for more treatment strategies that effectively address chronic neutrophilic inflammation in bronchiectasis.
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