Milk fat globule epidermal growth factor 8 alleviates liver injury in severe acute pancreatitis by restoring autophagy flux and inhibiting ferroptosis in hepatocytes

BACKGROUND Liver injury is common in severe acute pancreatitis(SAP).Excessive autophagy often leads to an imbalance of homeostasis in hepatocytes,which induces lipid peroxidation and mitochondrial iron deposition and ultimately leads to ferroptosis.Our previous study found that milk fat globule epidermal growth factor 8(MFG-E8)alleviates acinar cell damage during SAP via binding toαvβ3/5 integrins.MFG-E8 also seems to mitigate pancreatic fibrosis via inhibiting chaperone-mediated autophagy.AIM To speculate whether MFG-E8 could also alleviate SAP induced liver injury by restoring the abnormal autophagy flux.METHODS SAP was induced in mice by 2 hly intraperitoneal injections of 4.0 g/kg L-arginine or 7 hly injections of 50μg/kg cerulein plus lipopolysaccharide.mfge8-knockout mice were used to study the effect of MFG-E8 deficiency on SAPinduced liver injury.Cilengitide,a specificαvβ3/5 integrin inhibitor,was used to investigate the possible mechanism of MFG-E8.RESULTS The results showed that MFG-E8 deficiency aggravated SAP-induced liver injury in mice,enhanced autophagy flux in hepatocyte,and worsened the degree of ferroptosis.Exogenous MFG-E8 reduced SAP-induced liver injury in a dose-dependent manner.Mechanistically,MFG-E8 mitigated excessive autophagy and inhibited ferroptosis in liver cells.Cilengitide abolished MFG-E8’s beneficial effects in SAP-induced liver injury.CONCLUSION MFG-E8 acts as an endogenous protective mediator in SAP-induced liver injury.MFG-E8 alleviates the excessive autophagy and inhibits ferroptosis in hepatocytes by binding to integrinαVβ3/5.

Quantitative Trait Loci Mapping of Maize Yield and Its Components Under Different Water Treatments at Flowering Time

Drought or water stress is a serious agronomic problem resulting in maize （Zea mays L.） yield loss throughout the world. Breeding hybrids with drought tolerance is one important approach for solving this problem. However, lower efficiency and a longer period of breeding hybrids are disadvantages of traditional breeding programs. It is generally recognized that applying molecular marker techniques to traditional breeding programs could improve the efficiency of the breeding of drought-tolerant maize. To provide useful information for use in studies of maize drought tolerance, the mapping and tagging of quantitative trait loci （QTL） for yield and its components were performed in the present study on the basis of the principle of a mixed linear model. Two hundred and twenty-one recombinant inbred lines （RIL） of Yuyu 22 were grown under both well-watered and water-stressed conditions. In the former treatment group, plants were well irrigated, whereas those in the latter treatment group were stressed at flowering time. Ten plants of each genotype were grown in a row that was 3.00 m × 0.67 m （length × width）. The results show that a few of the QTL were the same （one additive QTL for ear length, two additive QTL and one pair of epistatic QTL for kernel number per row, one additive QTL for kernel weight per plant）, whereas most of other QTL were different between the two different water treatment groups. It may be that genetic expression differs under the two different water conditions. Furthermore, differences in the additive and epistatic QTL among the traits under water-stressed conditions indicate that genetic expression also differs from trait to trait. Major and minor QTL were detected for the traits, except for kernel number per row, under water-stressed conditions. Thus, the genetic mechanism of drought tolerance in maize is complex because the additive and epistatic QTL exist at the same time and the major and minor QTL all contribute to phenotype under water-stressed conditions. In particular, epidemic QTL under water-stressed conditions suggest that it is important to investigate the drought tolerance of maize from a genetic viewpoint.

Clinical epidemiological survey of gallbladder carcinoma in northwestern China, 2009-2013: 2379 cases in 17 centers

Objective: To analyze the clinical epidemiological characteristics of patients with gallbladder carcinoma recruited from 17 hospitals in five northwestern provinces of China (Shaanxi Province, Gansu Province, Qinghai Province, Ningxia Hui Autonomous Region, and Xinjiang Uygur Autonomous Region) from 2009 to 2013, and to summarize the clinical diagnosis and treatment data of gallbladder carcinoma. Methods: Clinical information of 2379 patients with gallbladder carcinoma from 17 hospitals in five northwestern provinces of China was retrospectively collected and analyzed using the 'Questionnaire for Gallbladder Carcinoma Patients in Northwestern Area of China.' All information was verified with EpiData software and analyzed with SPSS 13.0 software. Results: (1) Gallbladder carcinoma accounted for 2.7% (2379/86,609) of all biliary tract diseases during the study period, which was significantly higher than that from 1986 to 1998 (P < 0.001). (2) Gallbladder carcinoma was more prone to occur in elderly women. The male:female incidence ratio was 1.0:2.1, the average age of onset of disease was 63.7 ± 11.3 years, and the incidence was higher in farmers than in other occupational groups. (3) A total of 57.2% (1360/2379) of patients with gallbladder carcinoma also had gallstones. (4) Abdominal pain (1796/2379, 75.5%) and jaundice (727/2379, 30.6%) were the most common clinical manifestations, 81.2% (1527/1881) were positive in those receiving B ultrasound examinations and 90.7% (1567/1727) were positive in those undergoing computed tomography, and 64.5% (1124/1742) of patients with gallbladder carcinoma were positive for carbohydrate antigen (CA) 19-9. (5) The pathological type of gallbladder carcinoma was mainly moderately and poorly differentiated adenocarcinoma with a high degree of malignancy. At admission, 55.1% (1091/1981) of patients had stage Ⅳ cancer among patients with TNM staging information; 55.9% (1331/2379) had lymphatic metastasis, 29.7% (706/2379) had bile duct metastasis, and 53.1% (1263/2379) had liver metastasis. (6) A total of 283 patients (283/2379, 11.9%) had incidentally detected gallbladder carcinoma. (7) The rate of radical surgical resection was 30.4% (723/2379). Conclusion: The proportion of gallbladder carcinoma in biliary tract diseases in the northwestern area of China was significantly higher from 2009 to 2013 than from 1986 to 1998. Gallbladder carcinoma was common in older women and mainly diagnosed at an advanced stage. Compared with other surveys in different regions, the rate of metastasis in this survey was high, leading to a low resection rate. Populations at high risk should undergo B-ultrasound examinations at regular follow-up intervals to increase the rate of early diagnosis of gallbladder carcinoma.