Acute kidney injury (AKI) is a serious renal dysfunction syndromes, which predominantly correlates with the excess production of endogenous reactive oxygen/nitrogen species (RO/NSs), triggering a series of pathological processes including cellular apoptosis, renal fibrosis, and ferroptosis. Ferroptosis as an iron‐dependent nonapoptotic regulated cell death is extensively involved in renal damage. Herein, the authors report the engineering of ultrasmall KCa(H2O)2[FeIII(CN)6]·H2O nanoparticles as multienzyme mimetics, termed as CaPB nanozymes, for effectively scavenging RO/NSs and further inhibiting ferroptosis for the treatment of AKI. CaPB nanoparticles can effectively mimic the activity of multienzymes including superoxide dismutase, catalase, peroxidase, and glutathione peroxidase. Furthermore, CaPB nanozymes serving as a robust ferroptosis inhibitor significantly increase the expression of ferroptosis regulator glutathione peroxidase 4 in vitro. Furthermore, the renal accumulation of CaPB nanozymes effectively protects the kidney from oxidative injury and alleviated ferroptosis after intravenous administration. Additionally, the abnormal expression of inflammatory factors is further inhibited by CaPB nanozymes. The results demonstrate that the engineered ultrasmall CaPB nanozyme as a multienzyme mimetic features high potential for RO/NSs scavenging and treating AKI via inhibiting ferroptosis, which promises the clinical translation on the treatment of AKI and other RO/NSs‐related renal diseases.

Background Multiple sclerosis (MS) and inflammatory bowel disease (IBD) are two autoimmune diseases that seriously affect patients' quality of life. Previous studies have established an association between MS and IBD, including Crohn's disease (CD) and ulcerative colitis (UC), but the results were inconsistent. The aim of this study was to quantify the prevalences of and the association between MS and IBD. Methods The PubMed, Web of Science, and Embase databases were searched through November 2020 for studies reporting data on MS among patients with IBD and vice versa. The main outcomes were the proportion of MS in patients with IBD and vice versa, as well as the association (risk ratio [RR]) of IBD in MS and that of MS in IBD. Results Based on the analysis of 17 studies, the prevalence of MS in patients with IBD was 0.2% (95% CI 0.1–0.4%), while the prevalence of IBD in patients with MS was 0.6% (95% CI 0.4–0.9%). Patients with MS had a higher prevalence of IBD than controls (RR = 1.53, 95% CI 1.38–1.70, p < 0.00001). There was a similarly high risk of developing CD (RR 1.41, 95% CI 1.14–1.74, p = 0.001) or UC (RR 1.42, 95% CI 1.17–1.71, p = 0.0003) in patients with MS (p for subgroup differences: 0.97). Patients with IBD had a higher prevalence of MS than controls (RR = 1.91, 95% CI 1.06–3.45, p = 0.03). Conclusions Clinicians should be aware of the increased risk of IBD or MS comorbidity during the diagnostic process. Systematic diagnosis and management at an earlier stage are suggested.