Significance of Mannan Binding Lectin-Associated Serine Protease 2 in Urinary Extracellular Vesicles in IgA Nephropathy

Purpose: Immunoglobulin A (IgA) nephropathy (IgAN) is a common chronic glomerulonephritis and the main cause of end-stage renal diseases. Recent evidence suggests that mannan binding lectin associated serine proteases 2 (MASP2) is related to IgAN; therefore, we investigated the expression and significance of MASP2 in serum and urinary extracellular vesicles (UEVs) in patients with IgAN.Methods: Thirty-eight patients with IgAN and 17 healthy controls were enrolled in this study. UEVs were extracted by ultracentrifugation. The separation by ultra-high-speed centrifuge was verified by transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). Candidate internal references (TSG101, CD9, flotillin, β-actin and GAPDH) were identified by western blotting in the control group, and the expression of MASP2 in the UEVs was compared. The levels of MASP2 in the serum and UEVs in the IgAN and control groups were determined by enzyme-linked immunosorbent assay (ELISA).Results: TEM and NTA results demonstrated that UEVs were successfully extracted. Western blotting results confirmed that TSG101 was suitable as an internal reference for this study. Compared with the control group, the IgAN group showed positive expression of MASP2. MASP2 levels in the UEVs, determined by ELISA, showed significant differences between IgAN and control groups, which were significantly positively correlated with the level of urinary microalbumin.Conclusions: The level of MASP2 in UEVs was related to IgAN and shows promise as a biomarker for evaluating the severity of renal injury and prognosis of IgAN, thereby helping to elucidate the role of MASP2 in the mannan-binding lectin pathway

Smoking and smoking cessation in relation to risk of diabetes in Chinese men and women: a 9-year prospective study of 0·5 million people

Summary: Background: In developed countries, smoking is associated with increased risk of diabetes. Little is known about the association in China, where cigarette consumption has increased (first in urban, then in rural areas) relatively recently. Moreover, uncertainty remains about the effect of smoking cessation on diabetes in China and elsewhere. We aimed to assess the associations of smoking and smoking cessation with risk of incident diabetes among Chinese adults. Methods: The prospective China Kadoorie Biobank enrolled 512 891 adults (59% women) aged 30–79 years during 2004–08 from ten diverse areas (five urban and five rural) across China. Participants were interviewed at study assessment clinics, underwent physical measurements, and had a non-fasting blood sample taken. Participants were separated into four categories according to smoking history: never-smokers, ever-regular smokers, ex-smokers, and occasional smokers. Incident diabetes cases were identified through linkage with diabetes surveillance systems, the national health insurance system, and death registries. All analyses were done separately in men and women and Cox regression was used to yield adjusted hazards ratios (HRs) for diabetes associated with smoking. Findings: 68% (n=134 975) of men ever smoked regularly compared with 3% (n=7811) of women. During 9 years' follow-up, 13 652 new-onset diabetes cases were recorded among 482 589 participants without previous diabetes. Among urban men, smokers had an adjusted HR of 1·18 (95% CI 1·12–1·25) for diabetes. HRs increased with younger age at first smoking regularly (1·12, 1·20, and 1·27 at ≥25 years, 20–24 years, and <20 years, respectively; p for trend=0·00073) and with greater amount smoked (1·11, 1·15, 1·42, and 1·63 for <20, 20–29, 30–39 and ≥40 cigarettes per day; p for trend<0·0001). Among rural men, similar, albeit more modest, associations were seen. Overall, HRs were more extreme at higher levels of adiposity. Among men who stopped by choice, there was no excess risk within 5 years of cessation, contrasting with those who stopped because of illness (0·92 [0·75–1·12] vs 1·42 [1·23–1·63]). Among the few women who ever smoked regularly, the excess risk of diabetes was significant (1·33 [1·20–1·47]). Interpretation: Among Chinese adults, smoking was associated with increased risk of diabetes, with no significant excess risk following voluntary smoking cessation. Funding: Wellcome Trust, Medical Research Council, British Heart Foundation, Cancer Research UK, Kadoorie Charitable Foundation, Ministry of Science and Technology, National Natural Science Foundation of China, and China Scholarship Council

The Phycodnaviridae: The Story of How Tiny Giants Rule the World

The family Phycodnaviridae encompasses a diverse and rapidly expanding collection of large icosahedral, dsDNA viruses that infect algae. These lytic and lysogenic viruses have genomes ranging from 160 to 560 kb. The family consists of six genera based initially on host range and supported by sequence comparisons. The family is monophyletic with branches for each genus, but the phycodnaviruses have evolutionary roots that connect them with several other families of large DNA viruses, referred to as the nucleocytoplasmic large DNA viruses (NCLDV)