Yu Liu

Proper organization of the enteric nervous system (ENS) is critical for normal gastrointestinal (GI) physiology. Inflammatory bowel disease (IBD) disrupts key GI functions, including bowel motility. However, in many IBD patients, motility disorders persist even during remission, suggesting an irreversible ENS defect secondary to IBD. Here, we show that postinflammatory GI motility dysfunction arises from structural remodeling of the ENS, driven by a combination of neuronal loss and neurogenesis. During mucosal inflammation, enteric neurons upregulate CCL2 expression, facilitating the recruitment of monocytes into the myenteric plexus within the intestinal muscle. Monocyte-derived macrophages infiltrate the myenteric ganglia, contributing to excessive ENS remodeling and postinflammatory motility dysfunction. This neuroimmune axis is counterbalanced by a hypoxia-induced stress response in enteric neurons mediated by HIF1α. Enhancing the neuron-intrinsic hypoxia pathway limits ENS remodeling and preserves motility. In summary, this study presents a mechanistic model of postinflammatory GI motility dysfunction and proposes a therapeutic strategy to maintain ENS integrity and function during inflammation.

Both bone mineral density (BMD) and lean body mass (LBM) are important physiological measures with strong genetic determination. Besides, BMD and LBM might have common genetic factors. Aiming to identify pleiotropic genomic loci underlying BMD and LBM, we performed bivariate genome-wide association study meta-analyses of femoral neck bone mineral density and LBM at arms and legs, and replicated in the large-scale UK Biobank cohort sample. Combining the results from discovery meta-analysis and replication sample, we identified three genomic loci at the genome-wide significance level (p < 5.0 × 10^–8): 2p23.2 (lead SNP rs4477866, discovery p = 3.47 × 10^–8, replication p = 1.03 × 10^–4), 16q12.2 (rs1421085, discovery p = 2.04 × 10^–9, replication p = 6.47 × 10^–14) and 18q21.32 (rs11152213, discovery p = 3.47 × 10^–8, replication p = 6.69 × 10^–6). Our findings not only provide useful insights into lean mass and bone mass development, but also enhance our understanding of the potential genetic correlation between BMD and LBM.

Ion. Methods: Two healthy cohorts of 200 Chinese minors (0.1–18.0 years) and 200 adults (18.0–88.0 years) were recruited. Then, they were further categorized into eight age groups. The absolute mtDNA copy number per cell was measured by a quantitative real-time polymerase chain reaction. We subsequently used this range to evaluate mtDNA content in four patients (0.5–4.0 years) with molecularly proven mitochondrial depletion syndromes (MDSs) and 83 cases of mitochondrial disease patients harboring the m.3243A>G mutation. Results: The reference range of mtDNA copy number in peripheral blood was 175–602 copies/cell (mean: 325 copies/cell) in minors and 164–500 copies/cell (mean: 287 copies/cell) in adults. There was a decreasing trend in mtDNA copy number in blood with increasing age, especially in 0–2-year-old and >50-year-old donors. The mean mtDNA copy number level among the mitochondrial disease patients with m.3243A>G mutation was significantly higher than that of healthy controls. The mtDNA content of POLG, DGUOK, TK2, and SUCLA2 genes in blood samples from MDS patients was reduced to 25%, 38%, 32%, and 24%, respectively. Conclusions: We primarily establish the reference intervals of mtDNA copy number, which might contribute to the clinical diagnosis and monitoring of mitochondrial disease....