Biomedical Journal最新文献

Bacterial infections have posed a serious threat globally. The discovery of new targets and the development of novel antimicrobial agents are urgently needed to combat these bacterial infections. The bacterial membrane is a dynamic and essential structure that not only fortifies cellular integrity but also maintains bacterial core metabolism and environmental adaptation. Phospholipids constitute the primary building blocks of the bacterial membrane. The structural variability of phospholipids in both their head groups and acyl chains enables them to dynamically adjust the membrane's biophysical characteristics such as fluidity, curvature and surface charge, thereby directly shaping membrane functionality. In bacteria, these chemo-diverse phospholipids are tightly controlled by their conserved biosynthetic pathways. In this review, we summarize the structural diversity of bacterial phospholipids and their physicochemical implications, describe the biosynthesis and modification mechanisms, and discuss the critical roles of phospholipid diversity in bacterial stress adaptation and antibiotic resistance. Moreover, we highlight emerging antimicrobial strategies that directly target bacterial phospholipids or inhibit key enzymes in phospholipid biosynthetic pathways. These findings will shed light on the discovery of antibacterial targets to develop novel antibacterial agents.

Background: Programmed death ligand 1 (PD-L1) was found to play an important role in maintaining tolerance and immune balance, and its mechanism of action on asthma still needs to be further clarified. We aim to block P MATERIAL AND METHODS: in a juvenile asthma model, PD-L1 blockers were used to inhibit the expression of PD-L1 in vivo. By evaluating parameters that reflect airway hyperresponsiveness, airway inflammation, tissue damage, intestinal barrier function, and microbiome changes in mice, the impact of PD-L1 blockade on various physiological and immune indicators in asthma models is fully revealed.

Results: PD-L1 blockade reduces leukocyte infiltration in the lungs, including eosinophils, decreased levels of IgE and IgG1, and restored Th1/Th2 imbalance by reducing IL-4, IL-13, and GATA-3 while increasing IFN-γ. In addition, PD-L1 blockade significantly decreased levels of IL-17A/F and increased IL-10. Histological analysis of the lungs showed that PD-L1 blockade attenuated airway inflammatory cell infiltration and mucus hyperproduction. Further testing showed that the intestinal barrier function was improved after PD-L1 blockade. Mechanistic studies revealed that PD-L1 blockade improved microbiota composition in the lungs and gut, increased Lactobacillus, SCFA, and reduced LPS. As well as induced the downregulation of CD103⁺ DCs in lung. Correlation analysis showed that airway inflammation is negatively correlated with SCFA and positively correlated with LPS, and barrier function is negatively correlated with LPS.

Conclusions: PD-L1 blockade alleviated asthmatic airway inflammation by modulating gut and lung microbiota, improving intestinal barrier function, increasing SCFA levels, reducing LPS and CD103⁺ DCs activity.

While solid-state NMR has become renowned over the past three decades for its ability to study membrane and fibrillar proteins in their native states, determine high-resolution 3D structures, and identify docking sites between proteins and ligands, most studies have focused on the protein perspective by using isotopically labeled proteins. More recently, lipid-protein interactions are increasingly being examined from the lipid perspective, utilizing lipids and fatty acids, either isotopically labeled or unlabeled. In parallel, the development of in vivo solid-state NMR now enables the adoption of this approach within cellular membrane contexts, particularly in live bacteria. Here, we present examples utilizing ²H, ³¹P, ¹³C, ¹⁵N, ¹H and ¹⁹F NMR, with special emphasis on experiments conducted on bacteria or model membranes comprising bacterial lipids. Beyond the technological advancements, this approach enables the investigation of the molecular mechanisms of action of antimicrobial peptides, an area of crucial importance for the development of effective therapeutics.

Background: Serratia marcescens is a known cause of nosocomial outbreaks in neonatal intensive care units (NICUs). In early 2021, an outbreak occurred in our NICUs, prompting the implementation of rigorous infection control measures. This study aimed to assess whether the outbreak strain was eliminated or persisted with sporadic transmission.

Methods: Ongoing surveillance for S. marcescens infections was conducted in the NICUs and pediatric intensive care unit (PICU) through June 2023. Nosocomial cases were defined as infections diagnosed more than three days after hospitalization. Whole-genome sequencing, average nucleotide identity and minimum spanning tree analyses were employed to assess genetic relatedness.

Results: A total of 44 infections were identified: 2 pre-outbreak, 14 during the outbreak, and 28 post-outbreak. Phylogenetic analysis of 35 isolates revealed six distinct clusters. Cluster 1 included pre-outbreak cases; Cluster 2 encompassed outbreak isolates, with one sporadic isolate detected in the PICU 18 months later. Clusters 3-6 emerged post-outbreak period and were genetically unrelated to the outbreak strain. The outbreak strain harbored multiple resistance genes, including kpnH, which potentially contributed to carbapenem resistance. Only one infection over the subsequent two years was genetically linked to the original outbreak strain, supporting the effectiveness of infection control interventions.

Conclusions: Prompt and stringent infection control measures effectively contained the S. marcescens outbreak. Continued genomic surveillance is essential to trace transmission and prevent recurrence.

Background: Colorectal cancer (CRC) is one of the most prevalently diagnosed malignancies. Frequent metastasis and recurrence render treatments ineffective. The accumulation of omics data has helped develop a comprehensive functional regulatory network underlying tumorigenesis, causing significant breakthroughs in cancer therapy.

Methods: Systematic transcriptomic analysis of CRC tissues and matched normal samples identified miR-7974 as a novel miRNA with distinct expression pattern in CRC. Independent RT-qPCR assays further validated its tumor-biased expression. To investigate the role of miR-7974 in tumor progression, a series of cell-based assays and xenograft models were conducted. Additionally, RNA sequencing, reporter assays, and functional rescue experiments were performed to delineate the downstream regulatory network, with specific focuses on the miR-7974/CDKN1A and miR-7974/MYO1E axes involved in tumor growth and metastasis.

Results: MiR-7974 demonstrated high expression in early CRC but decreased abundance in later stages. We uncover that miR-7974 augments cancer growth by mitigating the expression of the cell cycle regulator, CDKN1A, through in vitro assays. Concurrently, miR-7974 reduces cellular migration and invasion by targeting MYO1E. In-depth transcriptomic investigations revealed miR-7974's role in repressing the epithelial-to-mesenchymal transition (EMT) in CRC cells, thereby maintaining the tumor in a highly proliferative epithelial state. This result is congruent with miR-7974's pronounced expression in early-stage CRC and its attenuation in advanced, metastatic stages. Such dynamic changes in expression patterns elucidate miR-7974's prognostic significance. Despite its abundant expression in CRC tissues, patients with heightened miR-7974 levels achieved more favorable survival outcomes.

Conclusions: Our findings demonstrate that miR-7974 regulates EMT plasticity, promoting a rapidly proliferating epithelial phenotype while reducing metastatic potential in CRC. Dynamic miR-7974 expression, coupled with its associated target gene regulation, provides the mechanistic foundation for understanding the acquisition of metastatic potential. This emphasizes the functional effect of miR-7974 on CRC growth and provides a deeper understanding of miRNome dynamics during cancer development.