Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoid malignancy in adults. Although significant progress has been made in recent years to treat DLBCL patients, 30%–40% of the patients eventually relapse or are refractory to first line treatment, calling for better therapeutic strategies for DLBCL. Long non-coding RNAs (lncRNAs) have emerged as a highly diverse group of non-protein coding transcripts with intriguing molecular functions in human disease, including cancer. Here, we review the current understanding of lncRNAs in the pathogenesis and progression of DLBCL to provide an overview of the field. As the current knowledge of lncRNAs in DLBCL is still in its infancy, we provide molecular signatures of lncRNAs in DLBCL cell lines to assist further lncRNA research in DLBCL.

Since 2012, Denmark has seen a significant rise in vancomycin-resistant Enterococcus faecium (VREfm) cases, mirroring trends in other countries, though exceptions occurred during the coronavirus disease 2019 (COVID-19) lockdown and between 2022 and 2023. This rise has been accompanied by ongoing changes in the endemic VREfm clones, reflecting the species’ high genetic plasticity. VREfm rapidly acquires plasmids and mobile genetic elements, enriching it with putative virulence markers (PVMs), including surface proteins, pili, and factors encoding biofilm production and adhesion. L. Roer, H. Kaya, A.P. Tedim, C. Novias, et al. (Microbiol Spectr 12:e0372423, 2024, https://doi.org/10.1128/spectrum.03724-23 ) released a database of 27 PVMs for Enterococcus faecium and Enterococcus lactis . In this study, we examined 516 VREfm bloodstream isolates from 2015 to 2023, identifying eight new putative virulence genes added to the database, bringing the total to 35 PVMs. Using whole-genome sequencing (WGS) and single linkage clustering, we identified six dominant VREfm clusters: ST80-CT14 vanA , ST117-CT24 vanA , ST203-CT859 vanA , ST1421-CT1134 vanA , ST117-CT36 vanB , and ST80-CT2406 vanB . We observed significant differences in the distribution of PVMs, particularly in pilin, gene clusters (PGC-1, PGC-2, and PGC-4), genes involved in carbohydrate metabolism (e.g., orf1481 , ccpA ), and biofilm production (e.g., hylEfm , capD , lysM3 ). These differences could explain variability in pathogenicity, metabolism, and adaptation to stress, contributing to shifts in endemic clones. IMPORTANCE: The newly developed and now updated database, VirulenceFinder, features 35 potential virulence markers for E. faecium and E. lactis , is highly scalable and provides a valuable tool for the in-depth analysis of closely related species using whole-genome sequencing (WGS) data. It holds considerable promise for a range of public health applications, such as hospital outbreak investigations, surveillance, and assessment of pathogenicity of bacterial species.

Serovar detector is a new bioinformatic tool for determining the serovar of Actinobacillus pleuropneumoniae using whole genome sequencing. The composition of cps genes of isolates is compared to those of the serovar reference strains, and the outcome is determined both by the number of common genes and the similarities between the homologous genes. The validation of the bioinformatic tool utilized a broad collection of 732 isolates, including representatives from all described serovars. The isolates included had been characterized by conventional serotyping, PCR tests or different bioinformatic tools. The collection also includes isolates that have been difficult to allocate to a serovar using serology to test the performance of the Serovar detector when potential new varieties or combinations of cps genes are present. Out of the 732 isolates included in the investigation, only 36 isolates (4.9%) could not be allocated to the 19 recognized serovars. The validation showed that the Serovar detector is a robust method for determining the serovar of an isolate and a valuable tool for further characterization of the genetic heterogeneity both within serovars and within the A. pleuropneumoniae species.

Background: Carbapenem-resistant Enterobacterales (CRE) represent a major therapeutic challenge, driven in part by serine β-lactamases (SBLs) and metallo-β-lactamases (MBLs). APC24-7 is a broad-spectrum β-lactamase inhibitor (BLI) designed to inhibit enzymes from both groups. Here, we evaluated the ability of APC24-7 to potentiate meropenem (MEM) activity against meropenem-resistant Escherichia coli and Klebsiella pneumoniae. Methods & Results: Checkerboard assays were performed against 31 K. pneumoniae and 17 E. coli isolates harboring a range of clinically relevant SBL and/or MBL genes. APC24-7 reduced meropenem minimum inhibitory concentrations (MICs) in an isolate- and concentration-dependent manner. At 32 mg/L APC24-7, meropenem MICs fell within the CLSI susceptible range for meropenem in 11 of 17 E. coli isolates, whereas 16 of 31 K. pneumoniae isolates remained resistant. Time-kill experiments with nine selected isolates showed bactericidal activity under active combination conditions, defined as a ≥3 log10 CFU/mL reduction from the initial bacterial count, within 3–5 h. Pharmacokinetic evaluation in infected mice showed less-than-dose-proportional systemic exposure following subcutaneous administration of APC24-7, with a maximum plasma concentration of approximately 26 mg/L after a 30 mg/kg dose. In a neutropenic murine thigh infection model, APC24-7 increased meropenem activity against four selected in vitro-responsive isolates in a dose-dependent manner. Conclusions: These findings provide preclinical proof of concept for APC24-7 as a broad-spectrum BLI capable of potentiating meropenem against Enterobacterales harboring diverse β-lactamases, while highlighting substantial isolate-dependent variability that warrants further pharmacokinetic/pharmacodynamic and resistance-mechanism studies.