Xianfeng Zhou

Since its formal description in 2016, Lawsonella clevelandensis —a strictly anaerobic, partially acid-fast bacterium—has been increasingly recognized as a cause of deep-seated abscesses, yet its fastidious nature and absence from routine diagnostic databases contribute to significant underdiagnosis. This narrative review synthesizes current knowledge on its microbiology, expanding clinical spectrum, diagnostic strategies, and treatment, based on a literature search of PubMed and Web of Science up to April 2026. Analysis of 27 documented publications, comprising 18 clinical cases, reveals a potential association with host risk factors including diabetes, immunosuppression, and prior surgical procedures, alongside a notable predilection for fat-rich tissues such as the breast and abdomen. While metagenomic next-generation sequencing and 16S rRNA gene amplification have become indispensable for definitive identification, antimicrobial susceptibility data—derived primarily from a single strain—demonstrate uniformly low minimum inhibitory concentrations for penicillins, carbapenems, clindamycin, and metronidazole, with no acquired resistance genes identified by whole-genome sequencing. However, the absence of established clinical breakpoints and limited tested isolates precludes definitive conclusions about universal susceptibility. Clinicians should maintain a high index of suspicion for L. clevelandensis in culture-negative deep abscesses, particularly those with acid-fast rods, as prompt diagnosis and empirical therapy with β-lactam/β-lactamase inhibitors or carbapenems appear reasonable based on current in vitro and clinical evidence, though further susceptibility surveillance is essential.

Graphical Molecular surveillance, phylogeny and co-evolution analyses suggest that high entropy codons in the CVA6 VP1 protein are associated with global genotype replacement and conformational changes, offering potential insights for vaccine design.

Coxsackievirus A6 (CVA6) has emerged as a predominant causative agent of hand, foot, and mouth disease worldwide. Efficient genomic surveillance is crucial for understanding its evolution and spread. Nanopore sequencing presents a promising platform for rapid and cost-effective viral genome sequencing directly from clinical samples. We developed a tiling amplicon-based nanopore sequencing protocol for CVA6. Eight clinical CVA6-positive samples, spanning a wide range of Ct values (15.54–25.28), were each serially diluted to three concentrations (undiluted, 10⁻¹, and 10⁻²), generating a total of 24 libraries. These libraries were sequenced using a PromethION flow cell and a MinION flow cell on PromethION and GridION platforms, respectively. Sensitivity was assessed across the dilution series, and accuracy was benchmarked against Illumina sequencing. The protocol demonstrated high sensitivity and speed, achieving >10× average sequencing depth within 5 mins using a PromethION flow cell. High genome coverage (≥96.5%) was consistently achieved across all samples, including serial dilutions, with minimal genetic divergence: only one to five single-nucleotide variants were observed between different dilution levels of the same specimen. Complete assembly was obtained from all test samples in the 10 ⁻² dilutions (Ct: 21.73–32.7). Comparative genomic analysis revealed 99.81%–99.98% identity between Nanopore- and Illumina-derived consensus sequences, with sequences from the same sample clustering together phylogenetically. This study establishes a sensitive, accurate, and cost-effective nanopore sequencing workflow for CVA6 genomic surveillance directly from clinical specimens. The workflow delivers clear, data-informed implementation guidance, making it a practical tool for outbreak response and evolutionary tracking. IMPORTANCE: Coxsackievirus A6 (CVA6) has become a predominant cause of hand, foot, and mouth disease worldwide, necessitating rapid and accessible genomic surveillance. This study establishes a tiling amplicon-based nanopore sequencing protocol that delivers complete CVA6 genomes directly from clinical samples within hours. The workflow demonstrates high sensitivity across a wide range of Ct values, achieves >99.8% consensus accuracy compared to Illumina sequencing, and offers clear, data-driven guidelines for implementation. By enabling same-day, cost-effective genomic analysis, this approach equips public health laboratories with a practical tool for real-time outbreak response and tracking of viral evolution.

SUMMARY: In recent years, coxsackievirus A6 (CVA6) has become a predominant cause of hand, foot, and mouth disease (HFMD) worldwide, surpassing enterovirus A71 (EV-A71) and CVA16. The rise of CVA6 is of particular public health concern due to its association with atypical and severe clinical presentations, including extensive vesiculobullous eruptions and neurological complications. These diverse and often non-classical manifestations, which also occur in adults, complicate clinical diagnosis and highlight the need for enhanced molecular surveillance. Furthermore, the potential impact of enteroviral infection during pregnancy and on neonatal outcomes remains an important clinical consideration. While both structural and non-structural proteins of CVA6 are known to contribute to viral virulence, the underlying pathogenic mechanisms are not fully understood. Continuous evolution of CVA6 through genetic variation and frequent recombination has led to the emergence of distinct lineages and recombinants, posing substantial challenges to the development of effective antivirals and vaccines. To address these gaps, this review systematically examines the global epidemiology, pathogenic mechanisms, evolutionary dynamics, current diagnostic tools, and antiviral strategies for CVA6. By integrating these perspectives, this work aims to inform public health preparedness and guide future research toward mitigating outbreaks driven by emerging recombinants and novel enterovirus serotypes.

MicroRNAs (miRNAs) are pivotal post‐transcriptional regulators of gene networks in development and disease, with their functional output critically dependent on dynamic turnover. Dysregulation of miRNA turnover disrupts signaling fidelity and contributes to pathologies such as cancer and infection. This review synthesizes recent advances in understanding miRNA turnover, focusing on key degradation pathways—including ZSWIM8‐mediated target‐directed miRNA decay (TDMD), TUT4/7‐DIS3L2‐driven uridylation, and nuclease cleavage—and how they integrate with stability factors such as AGO association, terminal modifications, and sequence features to orchestrate global miRNA abundance and health status. From these insights, critical unresolved questions are delineated, such as identifying nucleases responsible for degrading TDMD‐liberated miRNAs and elucidating compartment‐specific degradation mechanisms in physiological contexts like the gut lumen and circulation. Addressing these questions will facilitate innovative strategies for targeting miRNA stability within precision medicine. This article is categorized under: RNA Turnover and Surveillance > Turnover/Surveillance Mechanisms RNA Turnover and Surveillance > Regulation of RNA Stability Regulatory RNAs/RNAi/Riboswitches > RNAi: Mechanisms of Action

Merkel cell polyomavirus (MCPyV) has been identified as the causative agent of Merkel cell carcinoma, and its non-coding control region (NCCR) has been dem