Microorganisms

The perioperative management of biologic and immunomodulatory therapies in patients undergoing orthopedic surgery poses a clinical challenge, primarily due to the increased risk of postoperative infections. Biologic agents, particularly TNF inhibitors and interleukin-targeting drugs, may impair host immune responses, potentially increasing the risk of surgical site infections (SSIs), delayed wound healing, and systemic infections. However, abrupt discontinuation of these therapies can lead to disease flare-ups, which themselves may complicate recovery and rehabilitation. In addition, discontinuation of biologics can lead to drug tolerance and unresponsiveness when they are restarted and thereby need switching to another biologic. Recent studies suggest that the infection risk is particularly elevated with ongoing biologic therapy during major surgeries, especially in procedures involving prosthetic implants. Guidelines generally recommend withholding biological disease-modifying antirheumatic drugs (bDMARDs) for at least one dosing cycle prior to surgery, when feasible, while maintaining non-biologic DMARDs in most cases. The decision must be individualized, taking into account the pharmacokinetics of each drug, the type of surgery, the patient’s comorbidities, and the activity of the underlying disease. Close coordination among rheumatologists, orthopedic surgeons, and infectious disease specialists is essential to minimize perioperative complications and optimize patient outcomes.

While intensive aquaculture has developed rapidly, the consequent buildup of nitrogenous compounds, poses a critical threat to aquatic organisms. Microbial degradation offers an environmentally sustainable solution. We investigated the metabolic regulatory capacity of Priestia megaterium BZ-95 under four nitrogen regimes—ammonium (NH₄⁺-N), nitrite (NO₂⁻-N), nitrate (NO₃⁻-N), and a mixture of them (Mix)—using comparative transcriptomics. We revealed that BZ-95 in NH₄⁺-N activated a direct assimilation program prioritizing branched-chain amino acid biosynthesis. Conversely, under nitrate, BZ-95 enhanced membrane transport and 2-oxocarboxylic acid metabolism to facilitate the rapid incorporation of nitrate-derived ammonium into biomass. Nitrite stress triggered a coordinated response involving the assimilatory nir module (nirC-nirB-nirD) and enhanced energy metabolism to meet the heightened demand for reducing power during its rapid reduction. Under mixed nitrogen sources, BZ-95 established a highly synergistic carbon-nitrogen network, simultaneously processing multiple nitrogen inputs without a hierarchical preference, highlighting its remarkable metabolic plasticity. Intersection analysis defined a refined core of 692 nitrite-specific DEGs and revealed broad transcriptional activation under nitrite stress. Analysis of the NO₂⁻-specific core identified enhanced transmembrane transport capacity, coupled with auxiliary metabolic tuning, as central adaptive strategies for nitrite processing. Collectively, these findings provide crucial insights into the molecular basis of nitrogen coordination in P. megaterium BZ-95.

Human metapneumovirus genotype B (HMPV-B) is an important respiratory pathogen, requiring detailed elucidation of the evolutionary and antigenic features of its fusion (F) gene. Using 500 sequences collected between 1982 and 2024, we investigated the molecular evolution, phylodynamics, and structural epitope landscape of the HMPV-B F gene. Time-scaled phylogeny dated the divergence of sublineages B1 and B2 to around 1937, and Bayesian Skyline Plot analysis showed that these sublineages exhibited distinct demographic trajectories over time. The F gene evolved at a rate of 1.01 × 10⁻³ substitutions/site/year; however, amino acid variation remained limited, consistent with pervasive purifying selection, with 39% of codons under strong negative selection and little consensus evidence for positive selection. Conformational B-cell epitope prediction demonstrated a high degree of conservation across neutralizing antibody binding regions (sites Ø and I–V), and amino acid substitutions occurring within these sites were not predicted to substantially alter epitope architecture. Together, these findings indicate that the HMPV-B F gene evolves under strong evolutionary constraint while maintaining stable antigenic features, supporting the potential for antibody-based strategies that target neutralizing antibody binding regions of the F protein.