Emerging evidences have indicated the role of ferroptosis in the progression of metabolic-associated fatty liver disease (MAFLD); thus, inhibiting ferroptosis is a promising strategy for the development of MAFLD therapeutics. Recent studies have demonstrated the antioxidative effect of the gut commensal bacterium Akkermansia muciniphila (A. muc); however, whether it can alleviate ferroptosis remains unclear. The current study indicates A. muc intervention efficiently reversed high-fat high-fructose diet (HFHFD)-induced lipid peroxidation and ferroptosis in the liver. These beneficial effects were mediated by activation of the hepatic AMPK/SIRT1/PGC-1α axis, as evidenced by the finding that AMPK deficiency abrogated the amelioration of lipid peroxidation in vitro and in vivo. Furthermore, the short-chain fatty acids (SCFAs) were enriched upon A. muc treatment, and acetate was identified as a key activator of hepatic AMPK signalling. Mechanistically, microbiota-derived acetate was transported to the liver and metabolized to adenosine monophosphate (AMP), which triggered AMPK activation. Furthermore, a colonization assay in germ-free mice confirmed that A. muc mediated antiferroptotic effects in the absence of other microbes. These data indicated that A. muc exerts antiferroptotic effects against MAFLD, at least partially by producing acetate, which activates the hepatic AMPK/SIRT1/PGC-1α axis to alleviate ferroptosis via the inhibition of polyunsaturated fatty acid (PUFA) synthesis.

We reported a women with omithine carbamoyltransferase deficiency who delivered a healthy boy after two pregnancies with adverse outcome with the help of a multidiscipline team.The woman was admitted to Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine with an acute prenatal hyperammonemic episode at 28 gestational weeks of her first pregnancy in 2013 and was diagnosed with ornithine transcarbamylase deficiency.Her hyperammonemic complications were controlled under a well-planned multidisciplinary management including a low-protein diet and appropriate medications assisting nitrogen removal.A boy was delivered by cesarean section at 32 weeks of gestation but died three days later.Mutation analysis revealed a hemizygous c.583G＞A (G195R) mutation in the neonatal omithine carbamyltransferase gene and his mother was a heterozygous carrier with the same mutation.Two years later in 2015,the patient was pregnant spontaneously.However,she received an induced abortion at 21 weeks of gestation because amniocentesis and DNA analysis showed that the male fetus had the same omithine transcarbamylase gene mutation.The index pregnancy was assisted by in vitro fertilization-embryo transfer and preimplantation genetic diagnosis in 2017 and the woman delivered a healthy boy with the management ofa multidisciplinary team.

Objective To examine the distribution,volume and glucose-uptake activity of brown adipose tissue (BAT) in adults and investigate their correlations with metabolic indicators.Methods 18F-flurodeoxyglucose (FDG) PET/CT was used to analyze the distribution,volume and glucose-uptake activity of BAT.The clinical and metabolic differences between BAT positive group (n =121) and BAT negative group (n=257) were compared.The influences of metabolic indicators (fast blood glucose (FBG),triglyceride (TG),total cholesterol (TC),high density lipoprotein cholesterol (HDL-C),low density lipoprotein cholesterol (LDL-C),uric acid (UA)) on the distribution,volume and activity of BAT were investigated.Logistic regression analysis,two-sample t test,x2 test and multiple linear regression were used to analyze the data.Results The distribution,volume and glucose-uptake activity of BAT were found to be significantly higher in subjects being tested in colder seasons than those who were tested in warmer seasons:2.91％ (87/2 991) vs 1.68％(34/2018),(433±402) vs (329±298) ml,(212±183) vs (169±145) g (x2=7.66,t values:3.36 and 2.98,all P＜0.05).The female proportion was significantly higher in BAT positive group than that in BAT negative group:68.60％ (83/121) vs 31.91％ (82/257) (x2 =16.10,P＜0.01).The average levels of age,body mass index (BMI),FBG,TG,TC,LDL-C and UA in BAT positive group were significantly low-er than those in BAT negative group:(41.30±10.90) vs (48.70±9.60) years,(21.30±2.40) vs (24.50± 3.10) kg/m2,(4.56±0.74) vs (5.34±1.33) mmol/L,(0.94±0.36) vs (2.06±1.64) mmol/L,(4.42± 0.79) vs (4.88±0.87) mmol/L,(1.99±0.58) vs (3.10±0.77) mmol/L,(285.11±70.00) vs (347.70± 101.10) μmol/L (t values:from-6.25 to-2.94,all P＜0.01).Logistic regression analysis revealed that season,gender,age,BMI,FBG,TG and LDL-C levels were all independent influencing factors of BAT distribution in adults (odds ratios:5.36,2.06,0.95,0.79,0.49,0.23,0.02;P＜0.01 or P＜0.05).Among BAT positive adults,gender and FBG levels were found to be strongly affected by the volume and glucose-uptake activity of BAT (β values:0.28,-0.21,both P＜0.05).Conclusions The distribution,volume and glucose-uptake activity of BAT in adults are associated with multiple metabolic indicators including BMI,levels of glucose,lipid and UA.The distribution of BAT is affected by gender,age,season,BMI,blood glucose,and blood lipids.

Congenital diaphragmatic hernia (CDH) is caused by unilateral or bilateral diaphragmatic hypoplasia allowing abdominal organs to move into the thoracic,resulting in a series of pathophysiological changes,high mortality and poor prognosis.Therefore,earlier diagnosis is conducive to prenatal intervention and postnatal treatment.At present,prenatal ultrasonography is the most common used examination for CDH due to its convenience and low cost.MRI is complementary to ultrasound examination as it can evaluate both pulmonary development and maturity.Fetal echocardiography is a newly developed method in recent years which helps to indicate the prognosis through observation of hemodynamics and pulmonary vessels development.