Bone marrow-derived exosomes promote inflammation and osteoclast differentiation in high-turnover renal osteodystrophy

Introduction: Renal osteodystrophy (ROD) is a type of bone metabolic disorder in patients with chronic kidney disease (CKD). Inflammation is associated with bone loss in ROD. However, its precise mechanism has not yet been elucidated. The present study was conducted to investigate whether exosomes (Exos) in bone marrow (BM) are involved in the pathogenesis of high-turnover ROD. Methods: Bone mass, osteoclast number, and pro-inflammatory cytokines levels of BM supernatant were detected in adenine-induced ROD rats. The effect of Exos derived from BM (BM-Exos) of ROD (ROD-Exos) on inflammatory genes and osteoclast differentiation of BM-derived macrophages (BMMs) were further examined. Then, exosomal miRNA sequencing was performed and an miRNA-mRNA-pathway network was constructed. Results: we found increased osteoclasts and decreased bone mass in ROD rats, as well as inflammatory activation in the BM niche. Furthermore, BMMs from ROD rats displayed overproduction of proinflammatory cytokines and increased osteoclast differentiation, accompanied by nuclear factor κB (NF-κB) signaling activation. Mechanistically, we found that ROD-Exos activates NF-κB signaling to promote the release of proinflammatory cytokines and increase osteoclast differentiation of BMMs. Meanwhile, a total of 24 differentially expressed miRNAs were identified between BM-Exos from ROD and normal control (NC). The miRNA-mRNA-pathway network suggests that rno-miR-9a-5p, rno-miR-133a-3p, rno-miR-30c-5p, rno-miR-206-3p, and rno-miR-17-5p might play pivotal roles in inflammation and osteoclast differentiation. Additionally, we validated that the expression of miR-9a-5p is upregulated in ROD-Exos. Conclusion: The BM niche of ROD alters the miRNA cargo of BM-Exos to promote inflammation and osteoclast differentiation of BMMs, at least partially contributing to the pathogenesis of high-turnover ROD.</p

Controllable Fabrication of Poly(Arylene Ether Nitrile) Dielectrics for Thermal-Resistant Film Capacitors

High-temperature-resistant dielectric films, the heart of energy storage components in film capacitors, are key elements to ensure that the capacitors operate properly in harsh environments. Herein, a kind of flexible thermal-resistant poly­(arylene ether nitrile) (TR-PEN) dielectric film with controllable high-temperature resistance is fabricated through post self-crosslinking of PEN at different temperatures for different times. The dielectric films can present extremely high thermal stability (Tg > 370 °C), a long service life at 300 °C (4.5 × 104 min, 95 wt % of the residual weight), and a low temperature coefficient of dielectric constant from 50 to 300 °C (–4 °C–1). The retention of the energy density of TR-PEN350 at 300 °C is higher than 80% compared with that at room temperature. These results indicate that the TR-PEN films can be used over a long term as capacitor films at temperatures up to 300 °C. Besides, the simple and controllable fabrication technique for the TR-PEN can be easily industrialized

Additional file 2 of Association of gut microbiota with idiopathic membranous nephropathy

Additional file 2: Supplemental Table 2. α-Diversity was assessed with 4 different diversity analysis methods

Additional file 6 of Association of gut microbiota with idiopathic membranous nephropathy

Additional file 6: Supplemental Table 6. Bacterial species that differed significantly between the IMN patients and HC by LEfSe

Additional file 5 of Association of gut microbiota with idiopathic membranous nephropathy

Additional file 5: Supplemental Table 5. KEGG level 3 pathways of abundance changed intestinal flora

Additional file 1 of Association of gut microbiota with idiopathic membranous nephropathy

Additional file 1: Supplemental Table 1. Baseline characteristics of participants

Additional file 4 of Association of gut microbiota with idiopathic membranous nephropathy

Additional file 4: Supplemental Table 4. Gut microbiota and clinical biomarkers evaluated by Spearson correlation analysis at the genus level

Additional file 3 of Association of gut microbiota with idiopathic membranous nephropathy

Additional file 3: Supplemental Table 3. Gut microbiota and clinical biomarkers evaluated by Spearson correlation analysis at the phylum level

Data_Sheet_1_Application of Angiotensin Receptor–Neprilysin Inhibitor in Chronic Kidney Disease Patients: Chinese Expert Consensus.docx

Chronic kidney disease (CKD) is a global public health problem, and cardiovascular disease is the most common cause of death in patients with CKD. The incidence and prevalence of cardiovascular events during the early stages of CKD increases significantly with a decline in renal function. More than 50% of dialysis patients die from cardiovascular disease, including coronary heart disease, heart failure, arrhythmia, and sudden cardiac death. Therefore, developing effective methods to control risk factors and improve prognosis is the primary focus during the diagnosis and treatment of CKD. For example, the SPRINT study demonstrated that CKD drugs are effective in reducing cardiovascular and cerebrovascular events by controlling blood pressure. Uncontrolled blood pressure not only increases the risk of these events but also accelerates the progression of CKD. A co-crystal complex of sacubitril, which is a neprilysin inhibitor, and valsartan, which is an angiotensin receptor blockade, has the potential to be widely used against CKD. Sacubitril inhibits neprilysin, which further reduces the degradation of natriuretic peptides and enhances the beneficial effects of the natriuretic peptide system. In contrast, valsartan alone can block the angiotensin II-1 (AT1) receptor and therefore inhibit the renin–angiotensin–aldosterone system. These two components can act synergistically to relax blood vessels, prevent and reverse cardiovascular remodeling, and promote natriuresis. Recent studies have repeatedly confirmed that the first and so far the only angiotensin receptor–neprilysin inhibitor (ARNI) sacubitril/valsartan can reduce blood pressure more effectively than renin–angiotensin system inhibitors and improve the prognosis of heart failure in patients with CKD. Here, we propose clinical recommendations based on an expert consensus to guide ARNI-based therapeutics and reduce the occurrence of cardiovascular events in patients with CKD.</p