Implant-associated infections (IAI) are a considerable burden for healthcare systems globally. While novel anti-infective biomaterials are being pursued, prophylactic antibiotic treatment remains the most important intervention for mitigating IAI. The antibiotic tolerance of bacteria has been widely studied, but until recently, the contributions of biomaterial-pathogen interactions have been overlooked. In the present study, we investigate how material electrostatic charge influences the physiological state of the most clinically challenging pathogen—Staphylococcus aureus, and the implications on its antibiotic tolerance. We utilized a combination of techniques, including quantitative gene expression and synchrotron-sourced attenuated total reflectance Fourier-transform microspectroscopy, to characterize this phenomenon – elucidating how surface attachment to differently charged substrates drives the pathogen to modify its phenotype. Subsequently, we found a direct relationship between the activity of oppositely charged antibiotics (vancomycin and cefazolin) and the biomaterial-pathogen interface, which we determined to be governed by material electrostatic properties. The findings of the present study have the potential to inform the development of enhanced procedures of antibiotic prophylaxis by instructing personalized biomaterial-antibiotic pairing strategies. These new insights hold promise to contribute to reducing the rate of IAI by enabling clinicians and surgeons to maximize the efficacy of prophylactic antibiotic treatments during implant placement procedures.
Recent advancements in molecular engineering have established RNA-based technologies as powerful tools for both fundamental research and translational applications. Among the various RNA-based technologies developed, RNA base editing has recently emerged as a groundbreaking advancement. It primarily involves the conversion of adenosine (A) to inosine (I) and cytidine (C) to uridine (U), which are mediated by ADAR and APOBEC enzymes, respectively. RNA base editing has been applied in both biological research and therapeutic contexts. It enables site-directed editing within target transcripts, offering reversible, dose-dependent effects, in contrast to the permanent or heritable changes associated with DNA base editing. Additionally, RNA editing-based profiling of RNA-binding protein (RBP) binding sites facilitates transcriptome-wide mapping of RBP-RNA interactions in specific tissues and at the single-cell level. Furthermore, RNA editing-based sensors have been utilized to express effector proteins in response to specific RNA species. As RNA base editing technologies continue to evolve, we anticipate that they will significantly drive advancements in RNA therapeutics, synthetic biology, and biological research.
Chitinases play critical roles in plant-pathogen/insect interactions by degrading chitin, a key structural component of fungal cell walls and insect exoskeletons. However, current research lacks comprehensive studies on the broad-spectrum disease resistance of chitinases, and novel chitinases with higher enzymatic activity remain underexplored. Here, we report the prokaryotic expression and functional characterization of Nepenthes khasiana-derived chitinase NkChit2b-1, demonstrating its capacity to confer broad-spectrum resistance against chitin-containing phytopathogenic fungi and insect pests. Biochemical assays revealed that NkChit2b-1 exhibits high enzymatic activity within the optimal temperature range (28–42°C) for terrestrial plant growth and the pH range (5.0–6.0) encompassing pathogen-induced apoplastic alkalization in plants. This enzymatic profile correlates with its effective inhibition of mycelial growth in major phytopathogens including Sclerotinia sclerotiorum, Botrytis cinerea, and Magnaporthe oryzae. Exogenous application of NkChit2b-1 conferred enhanced resistance to these pathogens in both model species (e.g., Arabidopsis) and crop species (e.g., tobacco, tomato, and rice). Intriguingly, NkChit2b-1 pretreatment suppressed feeding activity of brown planthopper (BPH, Nilaparvata lugens) nymphs on rice phloem sap and induced mortality in adult BPH upon ingestion. Furthermore, NkChit2b-1 accelerated beet armyworm (Spodoptera exigua) egg hatching while delaying larval development. In addition, foliar application of NkChit2b-1 on Arabidopsis leaves conferred antifeedant activity against beet armyworm larvae in dual-choice assays. These results collectively indicate the exceptional potential of NkChit2b-1 as an eco-friendly “green pesticide”. The exploration of novel chitinases and combinatorial chitinase strategies may overcome the limitations of single-enzyme formulations, thereby advancing chitinase applications in sustainable agriculture and plant protection.
The homeostatic balance of the lung microbiota is important for the maintenance of normal physiological function of the lung, but its role in pathological processes such as severe pneumonia is poorly understood.
We screened 34 patients with community-acquired pneumonia (CAP) and 12 patients with hospital-acquired pneumonia (HAP), all of whom were admitted to the respiratory intensive care unit. Clinical samples, including bronchoalveolar lavage fluid (BALF), sputum, peripheral blood, and tissue specimens, were collected along with traditional microbiological test results, routine clinical test data, and clinical treatment information. The pathogenic spectrum of lower respiratory tract pathogens in critically ill respiratory patients was characterized through metagenomic next-generation sequencing (mNGS). Additionally, we analyzed the composition of the commensal microbiota and its correlation with clinical characteristics.
The sensitivity of the mNGS test for pathogens was 92.2% and the specificity 71.4% compared with the clinical diagnosis of the patients. Using mNGS, we detected more fungi and viruses in the lower respiratory tract of CAP-onset severe pneumonia patients, whereas bacterial species were predominant in HAP-onset patients. On the other hand, using mNGS data, commensal microorganisms such as Fusobacterium yohimbe were observed in the lower respiratory tract of patients with HAP rather than those with CAP, and most of these commensal microorganisms were associated with hospitalization or the staying time in ICU, and were significantly and positively correlated with the total length of stay.
mNGS can be used to effectively identify pathogenic pathogens or lower respiratory microbiome associated with pulmonary infectious diseases, playing a crucial role in the early and accurate diagnosis of these conditions. Based on the findings of this study, it is possible that a novel set of biomarkers and predictive models could be developed in the future to efficiently identify the cause and prognosis of patients with severe pneumonia.
Nanotechnology has emerged as a revolutionary force in modern agriculture, opening new avenues for crop enhancement and sustainable farming practices. This review systematically evaluates the roles of silica nanoparticles (SiO2 NPs) in agricultural applications, with particular emphasis on their biosynthesis pathways and functional mechanisms. SiO2 NPs have demonstrated considerable potential to enhance crop resilience against both biotic (pathogens, pests) and abiotic (heavy metals, salinity, drought) stresses through phytohormonal regulation, defense gene activation, and metabolic modulation. As nanocarriers, these particles enhance pesticide and fertilizer delivery accuracy, reduce environmental contamination, and promote plant growth. Biosynthesis methods of SiO2 NPs range from conventional physical–chemical techniques to eco-friendly green approaches, including the utilization of biological cells/extracts, natural biomaterials, and peptide templates. Although green synthesis offers sustainability advantages, the agricultural adoption of SiO2 NPs faces critical challenges, such as insufficient understanding of their long-term environmental persistence and ecotoxicological impacts, high production costs related to green synthesis, and incomplete regulatory frameworks. Addressing these challenges is essential to enable their broader use in agriculture.
Gas vesicles (GVs) produced by microorganisms are genetically engineered, air-filled protein nanostructures that have widespread applications in ultrasound imaging and ultrasound-mediated drug delivery. However, constrained by the shape and size, most of them are difficult to be imaged by clinical ultrasound machines, which limits their biomedical applications. Here, we constructed a hybrid gene cluster of the structural gene cluster from Serratia sp. ATCC 39006 and the accessory gene cluster from Bacillus megaterium in Escherichia coli to synthesize a novel gene-encoded gas vesicle with a width of approximately 70 nm and a length of about 100 nm, using a synthetic biology strategy, termed as ARGS1B. This new type of GVs can be stably produced in bacteria and is able to be imaged by clinical ultrasound machines in vivo and in vitro. Furthermore, the novel nanostructure can be easily engineered for different particle sizes through point saturation mutation, expanding the sources of GVs and providing new insights into the biosynthesis mechanism of GVs.
The sex chromosomes of fish are usually homomorphic and recently derived, making them an ideal model to understand the origin and evolution of sex chromosomes in vertebrates. Here, combined Pacbio, Hi-C, and Illumina sequencing of the male mandarin fish (Siniperca chuatsi) genome enabled the assembly of a high-quality chromosome-level genome, including highly resolved X and Y chromosome assemblies. Genome wide association study (GWAS) and coverage information analysis revealed a 2.0 Mbp sex determining region (SDR). A Y-specific duplication of the anti-Müllerian hormone (amh) gene, amhy, was identified that encoded a truncated AMH protein. Loss of function and overexpression experiments demonstrated that amhy may act as a male sex-determining gene (SDG). GWAS led to the identification of a common sex chromosome (Chr24) and SDG (amhy) in S. scherzeri, while another sex chromosome (Chr11) was identified in Coreoperca whiteheadi. Interestingly, completely conserved protein coding sequences of amhy were commonly identified in male S. chuatsi, S. scherzeri, and S. knerii. These results support a classic model for the origin and evolution of early sex chromosomes and suggest that amhy is a super SDG that can drive the origin and turnover of sex chromosome in vertebrates.
Metabolic Syndrome (MetS) is a globally prevalent condition with unclear underlying mechanisms. Current treatments primarily focus on alleviating individual symptoms, lacking long-term therapeutic strategies that target the disease’s endotypes. In this study, we found that Yinling Qushi Granule (YLQSG), a formulated prescription for treating Dampness Syndrome (DS) in Traditional Chinese Medicine (TCM), effectively attenuated hypertension associated with MetS. After 12 weeks of YLQSG treatment, MetS patients showed significant reduction in systolic and diastolic blood pressure, body mass index (BMI) and glycated hemoglobin (HbA1c). Chemical analysis has identified a total of 96 components of YLQSG, alongside with 27 serum absorbed prototypes and 13 metabolites. In vivo metabolic profiling revealed critical Phase I metabolism including dehydration, demethylation, and oxidation. By integrating network pharmacology and molecular docking, we proposed 11 triterpenoids from the sovereign herb Poria cocos (Schw.) Wolf as active constituents of YLQSG. These triterpenoids showed potent binding affinities with AGTR1 and 11β-HSD1, two crucial druggable targets in the renin–angiotensin–aldosterone system. Pharmacokinetics of these 11 lanosterol-type triterpenoids in rat serum indicated their good drug likeness properties. In summary, our findings highlight the potential of YLQSG in treating MetS, particularly hypertension, and identify its active compounds and potential molecular targets, offering a promising alternative strategy for the long-term management of MetS.
Trial registration
ChiCTR, ChiCTR2200063506. Registered 9 September 2022, https://www.chictr.org.cn/showproj.html?proj=174653.