MF-59 (MF59)

In vitro priming with Mycobacterium fortuitum induces trained immunity-associated phenotypes in caprine alveolar macrophages and enhances phagosomal maturation and antimicrobial functions upon homologous re-stimulation.

Blay-Benach Miriam M, Cuenca-Lara Patricia P, Moraleda Julia J, Cervera Zoraida Z et al.

Trained immunity refers to the stimuli-induced epigenetic and metabolic reprogramming of innate immune cells, enabling enhanced non-specific responses upon secondary stimulation. Alveolar macrophages (AMs) constitute the primary immune barrier in the lung and represent a key target in enhancing protection against pulmonary pathogens. In this study, an in vitro priming-resting-re-stimulation protocol was used to characterise the ability of Mycobacterium fortuitum (MF) to induce functional features of trained immunity in caprine AMs in vitro. Pro-inflammatory cytokines (TNFα, IL-1β, IL-6) and nitric oxide synthase (iNOS)-positive cells were quantified by multiplex assay and flow cytometry, respectively. Phagosomal acidification was detected by flow cytometry and live-cell fluorescent microscopy after MF-challenge using pH-sensitive labelled bacteria. MF-trained AMs displayed significantly elevated TNFα and IL-1β production and a higher frequency of inducible iNOS-producing cells compared to non-stimulated controls, consistent with a trained immunity-associated pro-inflammatory and antimicrobial phenotype. Phagosomal acidification was enhanced and sustained in MF-trained AMs following homologous challenge with MF, suggesting enhanced phagocytic activity against mycobacteria. These findings provide evidence that M. fortuitum induces trained immunity-associated functional responses in caprine AMs and support further trained immunity studies in the caprine lung mucosa against pulmonary infections.

Integrative analyses of metabolome and transcriptome reveal differences in terpenoids and identify the genes involved in the synthesis of terpenoids in Magnoliae Flos from different varieties.

Ma Rui R, Liu Hongdan H, Feng Weimeng W, Liu Xiuyu X et al.

Magnoliae Flos (MF), the dried flower buds of Magnolia denudata Desr., Magnolia biondii Pamp., and Magnolia sprengeri Pamp., is a crucial East Asian medicinal herb used to treat allergic rhinitis and other ailments. However, the molecular basis for its quality differences remains unclear. This study integrates GC-MS-based volatile metabolomics, high-throughput RNA sequencing, and RT-qPCR validation to elucidate the terpenoid metabolic differences and their regulatory mechanisms among the three MF varieties. The metabolomic analysis screened 55 differential terpenoids (15 key markers) that distinguish the MF varieties, with terpenoids being the primary metabolic category and the M. sprengeri vs. M. biondii group exhibiting the most differential metabolites. The transcriptomic analysis revealed TPS26 as key candidate genes involved in monoterpene synthesis, while IMPMBI2G0000034954 and IMPMBI2G0000034957 were identified as candidate genes for sesquiterpene synthesis. The expression abundances of these genes exhibited significant linear correlations with the accumulation levels of differential terpenoids, though such coordinated variation does not confirm direct causal regulation. Collectively, this work reveals the molecular basis of terpenoid diversity in MF, and provides theoretical references for germplasm discrimination, quality evaluation and genetic improvement of medicinal magnolia resources.

When membranes fail: FAP-1 and the mega roots of MF.

Branfield Siobhan S, Italiano Joseph J

Semi-quantitative assessment of paraspinal muscle fat infiltration in single-level C5-6 cervical spondylosis using gray-level thresholding on conventional MRI: associations with disc degeneration and posture-related segmental angular change.

Li Yifei Y, Zhao Liang L, Zhang Wei W, Ge Xiubo X et al.

Cervical spondylosis at C5-6 is common, but conventional imaging may not fully capture paraspinal muscle composition or posture-related segmental angular behavior. This study assessed layer-specific paraspinal muscle fat infiltration (FI) and cross-sectional area (CSA) on conventional MRI and examined their associations with C5-6 disc degeneration and posture-related angular change (PAC). In this retrospective cross-sectional study, 94 patients with single-level C5-6 cervical spondylosis who underwent cervical MRI and standing lateral radiography between January 2023 and December 2025 were included. At the C5-6 disc level, bilateral splenius capitis (SPL), semispinalis capitis (SCap), and combined multifidus plus semispinalis cervicis (MF + SCer) were manually segmented. FI was calculated as a semi-quantitative area percentage using a fixed 8-bit gray-level threshold (79-255), and CSA was measured on calibrated axial T2-weighted images. PAC was defined as the absolute difference between standing radiographic and supine MRI local C5-6 Cobb angles; patients were classified as low-PAC/relatively stiff (|PAC| ≤ 5°) or high-PAC/relatively mobile (|PAC| > 5°). FI in all three muscle groups increased with higher Pfirrmann grades, whereas CSA did not differ significantly across grades. Pfirrmann grade was independently associated with FI in the SPL, SCap, and MF + SCer after adjustment for age and sex. Compared with the high-PAC group, the low-PAC group showed higher FI in the SPL, SCap, and MF + SCer, and these differences remained significant after adjustment for age, sex, BMI, and Pfirrmann grade. CSA did not differ significantly between PAC phenotypes. In patients with single-level C5-6 cervical spondylosis, paraspinal muscle alteration was characterized primarily by increased FI, whereas CSA reduction was not evident. Compared with CSA, semi-quantitative FI measured on conventional MRI may be more sensitive for detecting observable changes in muscle composition. Higher FI in the superficial and intermediate posterior extensor muscles was associated with a low-PAC/relatively stiff phenotype. Combining PAC with paraspinal muscle FI may provide supplementary imaging information on segmental angular differences between weight-bearing and non-weight-bearing positions; however, the clinical relevance of this combined assessment requires prospective validation using quantitative fat imaging and clinical or functional outcomes.