An antimony(III) dication for styrene hydroamination
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Therapeutic vulnerabilities and pan-cancer landscape of BRAF class III mutations in epithelial solid tumors
Kinase-impaired class III BRAF mutations have recently received attention as a possible prognostic factor and therapeutic target. Class III BRAF variants differ from class I and class II mutations in terms of mechanism of pathway activation and therapeutic vulnerabilities. Genomic landscape analyses of tumors in large real-world cohorts represent a great opportunity to further characterize tumor-related molecular events and treatment vulnerabilities, however, such data is not yet available for tumors with BRAF class III mutations.
Trace metals induce microbial risk and antimicrobial resistance in biofilm in drinking water
This study investigated the changes in water quality and microbial risks resulting from trace metal pollutants in stagnant drinking water conditions using a 168-h experimental simulation and a metagenomic approach. The results showed that Fe(III) increased the water turbidity. Stagnation also caused significant biofilm growth, which was increased by trace metal pollutants, resulting in a higher production of extracellular polymeric substances (EPS). Adaptive mechanisms of bacterial communities dominated by Pseudomonadota in response to trace metal pollutant stress were discovered. Pathogenic bacteria, particularly Salmonella enterica and Pseudomonas aeruginosa, were found in stagnant drinking water, potentially exacerbated by Al(III). The overall exposure risk of antibiotic resistance genes (ARGs) increased, whereas Fe(III) enhanced the co-occurrence of ARGs and pathogens, potentially leading to serious hidden microbial risks. This study reveals imperceptible microbial risks posed by trace metal pollutants in stagnant drinking water, providing scientific warning and advice for drinking water safety.
Two-tiered mutualism improves survival and competitiveness of cross-feeding soil bacteria
Metabolic cross-feeding is a pervasive microbial interaction type that affects community stability and functioning and directs carbon and energy flows. The mechanisms that underlie these interactions and their association with metal/metalloid biogeochemistry, however, remain poorly understood. Here, we identified two soil bacteria, Bacillus sp. BP-3 and Delftia sp. DT-2, that engage in a two-tiered mutualism. Strain BP-3 has low utilization ability of pyruvic acid while strain DT-2 lacks hexokinase, lacks a phosphotransferase system, and is defective in glucose utilization. When strain BP-3 is grown in isolation with glucose, it releases pyruvic acid to the environment resulting in acidification and eventual self-killing. However, when strain BP-3 is grown together with strain DT-2, strain DT-2 utilizes the released pyruvic acid to meet its energy requirements, consequently rescuing strain BP-3 from pyruvic acid-induced growth inhibition. The two bacteria further enhance their collective competitiveness against other microbes by using arsenic as a weapon. Strain DT-2 reduces relatively non-toxic methylarsenate [MAs(V)] to highly toxic methylarsenite [MAs(III)], which kills or suppresses competitors, while strain BP-3 detoxifies MAs(III) by methylation to non-toxic dimethylarsenate [DMAs(V)]. These two arsenic transformations are enhanced when strains DT-2 and BP-3 are grown together. The two strains, along with their close relatives, widely co-occur in soils and their abundances increase with the soil arsenic concentration. Our results reveal that these bacterial types employ a two-tiered mutualism to ensure their collective metabolic activity and maintain their ecological competitive against other soil microbes. These findings shed light on the intricateness of bacterial interactions and their roles in ecosystem functioning.
Non-invasive in vivo imaging of changes in Collagen III turnover in myocardial fibrosis
Heart failure (HF) affects 64 million people globally with enormous societal and healthcare costs. Myocardial fibrosis, characterised by changes in collagen content drives HF. Despite evidence that collagen type III (COL3) content changes during myocardial fibrosis, in vivo imaging of COL3 has not been achieved. Here, we discovered the first imaging probe that binds to COL3 with high affinity and specificity, by screening candidate peptide-based probes. Characterisation of the probe showed favourable magnetic and biodistribution properties. The probe’s potential for in vivo molecular cardiac magnetic resonance imaging was evaluated in a murine model of myocardial infarction. Using the new probe, we were able to map and quantify, previously undetectable, spatiotemporal changes in COL3 after myocardial infarction and monitor response to treatment. This innovative probe provides a promising tool to non-invasively study the unexplored roles of COL3 in cardiac fibrosis and other cardiovascular conditions marked by changes in COL3.
Triple-negative breast cancer modifies the systemic immune landscape and alters neutrophil functionality
Cancer disrupts intratumoral innate-adaptive immune crosstalk, but how the systemic immune landscape evolves during breast cancer progression remains unclear. We profiled circulating immune cells in stage I–III and stage IV triple-negative breast cancer (TNBC) patients and healthy donors (HDs). Metastatic TNBC (mTNBC) patients had reduced T cells, dendritic cells, and differentiated B cells compared to non-metastatic TNBC patients and HDs, partly linked to prior chemotherapy. Vδ1 γδ T cells from mTNBC patients produced more IL17 than those from HDs. Chemotherapy-naïve mTNBC patients showed increased classical monocytes and neutrophils. Transcriptional, proteomic, and functional analyses revealed that neutrophils in mTNBC exhibited enhanced migratory capacity, elevated granule proteins, and higher ROS production. Some immune changes, such as reduced non-switched B cells and heightened neutrophil migration, were evident in earlier TNBC stages. This study comprehensively maps systemic immunity in TNBC, guiding future research on patient stratification and immunomodulation strategies.
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