Protective effect of brain and muscle arnt-like protein-1 against ethanol-induced ferroptosis by activating Nrf2 in mice liver and HepG2 cells

Alcohol abuse has recently become a serious health concern worldwide,and the incidence of alcoholic liver disease(ALD)is rapidly increasing with high morbidity and mortality.Ferroptosis is a newly recognized form of regulated cell death caused by the iron-dependent accumulation of lipid peroxidation.Here we showed that the circadian clock protein brain and muscle arnt-like protein-1(BMAL1)in hepatocytes is both necessary and sufficient to protect against ALD by mitigating ferroptosis.U pon exposure to alcohol(5%Lieber-DeCarli liquid alcohol diet for 10 days before binged alcohol with 5 g/kg body weight in vivo,300 mmol/L for 12 h in vitro,respectively),the content of iron,reactive oxygen species(ROS)and malondialdehyde(MDA)was boosted signifi cantly while glutathione(GSH)was decreased that mainly based on the downregulated protein expression of ferritin heavy chain(FTH),ferroportin(FPN),heme oxygenase1(HO-1)and anti-cystine/glutamate antiporter(SLC7A11),while these changes could be abolished by ferroptosis inhibitor Ferrostatin-1[Fer-1(5 mg/kg body weight for 10 days in vivo,10μmol/L for 2 h in vitro,respectively)].Further study indicated that the alcohol could activate the protein expression of BMAL1 which exerts a protective effect against ferroptosis through promoting nuclear factor erythroid 2-related factor 2(Nrf2)translocation into nuclear and subsequently stimulating its downstream proteins FTH,FPN,glutathione peroxidase 4 activity(GPX4),HO-1,SLC7A11,while knockdown of BMAL1 and Nrf2 by RNA interference further downregulated the expression of these protein and thus promoting ferroptosis in response to alcohol.Collectively,our results unveiled that the protective action of BMAL1 during alcohol challenge depends on its ability to activate Nrf2-ARE antiferroptosis pathway and targeting hepatic BMAL1 to dampen hepatic ferroptosis signaling may have therapeutic potential for ALD.

Hofmeister Effect-Assisted Strong Natural Biopolymer-Based Hydrogels with Multi-Functions

Natural biopolymer-based hydrogels have been extensively studied in recent years due to their excellent biocompatibility.However,the preparation of multi-functional and tough natural biopolymer-based hydrogels is still a challenging problem.Herein,a natural biopolymer-based hydrogel is prepared using gelatin and carboxymethyl chitosan(CMCS)through a one-step soaking method.The prepared hydrogel without any synthetic polymers and crosslinking agents has a fully physical crosslinking structure.Due to the hydrophobic interaction brought by the Hofmeister effect,the mechanical properties of soaked hydrogels(tensile stress and strain can reach 3.77 MPa and 1082%)are superior to conventional protein hydrogels.In addition,the prepared gelatin/carboxymethyl chitosan(Gel/CMCS)hydrogels exhibit a variety of appealing properties,including good shape memory,fatigue resistance,electrical conductivity,water retention,drug releasing,antibacterial property,and recyclability.This strategy opens up a new horizon to fabricate hydrogels with excellent mechanical properties and multiple functions,which can extend their applications in the biomedicine area and other related fields.

Damage characteristics of dual-band high reflectors affected by nodule defects in the femtosecond regime

The influence of nodule defects on the characteristics of femtosecond laser-induced damage has not been fully investigated.In this study,two types of 800 nm/1064 nm dual-band HfO_(2)=Si O_(2) high-reflection films with different configurations were analyzed.Combined with finite-difference time-domain electric field simulation and focused ion beam analysis,the initial state and growth process of femtosecond laser damage of nodules were explored.In particular,the sequence of blister damage determined by the film design and the inner damage caused by nodules were clarified.The rule of the laser-induced damage threshold of different size nodules was obtained.The difference in the damage behavior of nodules in the two types of films was elucidated.