Genetically predicted fatty liver disease and risk of psychiatric disorders: A mendelian randomization study

BACKGROUND Non-alcoholic fatty liver disease(NAFLD)and alcohol-related liver disease(Ar-LD)constitute the primary forms of chronic liver disease,and their incidence is progressively increasing with changes in lifestyle habits.Earlier studies have do-cumented a correlation between the occurrence and development of prevalent mental disorders and fatty liver.AIM To investigate the correlation between fatty liver and mental disorders,thus ne-cessitating the implementation of a mendelian randomization(MR)study to elu-cidate this association.METHODS Data on NAFLD and ArLD were retrieved from the genome-wide association studies catalog,while information on mental disorders,including Alzheimer's disease,schizophrenia,anxiety disorder,attention deficit hyperactivity disorder(ADHD),bipolar disorder,major depressive disorder,multiple personality dis-order,obsessive-compulsive disorder(OCD),post-traumatic stress disorder(PTSD),and schizophrenia was acquired from the psychiatric genomics consor-tium.A two-sample MR method was applied to investigate mediators in signifi-cant associations.RESULTS After excluding weak instrumental variables,a causal relationship was identified between fatty liver disease and the occurrence and development of some psychia-tric disorders.Specifically,the findings indicated that ArLD was associated with a significantly elevated risk of developing ADHD(OR:5.81,95%CI:5.59-6.03,P<0.01),bipolar disorder(OR:5.73,95%CI:5.42-6.05,P=0.03),OCD(OR:6.42,95%CI:5.60-7.36,P<0.01),and PTSD(OR:5.66,95%CI:5.33-6.01,P<0.01).Meanwhile,NAFLD significantly increased the risk of developing bipolar disorder(OR:55.08,95%CI:3.59-845.51,P<0.01),OCD(OR:61.50,95%CI:6.69-565.45,P<0.01),and PTSD(OR:52.09,95%CI:4.24-639.32,P<0.01).CONCLUSION Associations were found between genetic predisposition to fatty liver disease and an increased risk of a broad range of psychiatric disorders,namely bipolar disorder,OCD,and PTSD,highlighting the significance of preven-tive measures against psychiatric disorders in patients with fatty liver disease.

Green Synthesis of Chemically Recyclable Polyesters via Dehydrogenative Copolymerization of Diols

Preparation of chemically recyclable polyesters by ring-opening polymerization(ROP)has made a considerable progress over the past few years.However,this method involves cumbersome synthesis and minimal functional diversity of cyclic monomers.Therefore,it is of great significance to develop novel polymerization methods for direct polymerization of commercially available monomers to prepare recyclable polyesters with versatile functionalities.In present work,we report dehydrogenative copolymerization of commercialα,ω-diols to afford high molecular weight chemically recyclable aliphatic copolyesters(65.7 kg·mol^(-1))by using commercially available Milstein catalyst precursor.The thermal properties of the obtained copolymers could be finely tuned by simply adjusting the feeding ratio of two monomers.The incorporation of aliphatic or aromatic rings into polyester mainchain via copolymerization of 1,10-decanediol with 1,4-cyclohexanedimethanol and 1,4-benzenedimethanol could significantly improve the thermal properties of the resulting copolymers.More importantly,the obtained copolyesters were able to completely depolymerize back to original diols via hydrogenation by the same catalyst in solvent-free and mild conditions,thus offering a green and cost-effective route toward the preparation of widely used polyesters.

MicroRNA-23a reduces lipopolysaccharide-induced cellular apoptosis and inflammatory cytokine production through Rho-associated kinase 1/sirtuin-1/nuclear factor-kappa B crosstalk

Background:MicroRNAs are closely associated with the progression and outcomes of multiple human diseases,including sepsis.In this study,we examined the role of miR-23a in septic injury.Methods Lipopolysaccharide(LPS)was used to induce sepsis in a rat model and H9C2 and HK-2 cells.miR-23a expression was evaluated in rat myocardial and kidney tissues,as well as H9C2 and HK-2 cells.A miR-23a mimic was introduced into cells to identify the role of miR-23a in cell viability,apoptosis,and the secretion of inflammatory cytokines.Furthermore,the effect of Rho-associated kinase 1(ROCK1),a miR-23a target,on cell damage was evaluated,and molecules involved in the underlying mechanism were identified.Results:In the rat model,miR-23a was poorly expressed in myocardial(sham vs.sepsis 1.00±0.06 vs.0.27±0.03,P<0.01)and kidney tissues(sham vs.sepsis 0.27±0.03 vs.1.00±0.06,P<0.01).Artificial overexpression of miR-23a resulted in increased proliferative activity(DNA replication rate:Control vs.LPS vs.LPS+Mock vs.LPS+miR-23a:H9C2 cells:34.13±3.12 vs.12.94±1.21 vs.13.31±1.43 vs.22.94±2.26,P<0.05;HK-2 cells:15.17±1.43 vs.34.52±3.46 vs.35.19±3.12 vs.19.87±1.52,P<0.05),decreased cell apoptosis(Control vs.LPS vs.LPS+Mock vs.LPS+miR-23a:H9C2 cells:11.39±1.04 vs.32.57±2.29 vs.33.08±3.12 vs.21.63±2.35,P<0.05;HK-2 cells:15.17±1.43 vs.34.52±3.46 vs.35.19±3.12 vs.19.87±1.52,P<0.05),and decreased production of inflammatory cytokines,including interleukin-6(Control vs.LPS vs.LPS+Mock vs.LPS+miR-23a:H9C2 cells:59.61±5.14 vs.113.54±12.30 vs.116.51±10.69 vs.87.69±2.97 ng/mL;P<0.05,F=12.67,HK-2 cells:68.12±6.44 vs.139.65±16.62 vs.143.51±13.64 vs.100.82±9.74 ng/mL,P<0.05,F=9.83)and tumor necrosis factor-α(Control vs.LPS vs.LPS+Mock vs.LPS+miR-23a:H9C2 cells:103.20±10.31 vs.169.67±18.84 vs.173.61±15.91 vs.133.36±12.32 ng/mL,P<0.05,F=12.67,HK-2 cells:132.51±13.37 vs.187.47±16.74 vs.143.51±13.64 vs.155.79±15.31 ng/mL,P<0.05,F=9.83)in cells.However,ROCK1 was identified as a miR-23a target,and further up-regulation of ROCK1 mitigated the protective function of miR-23a in LPS-treated H9C2 and HK-2 cells.Moreover,ROCK1 suppressed sirtuin-1(SIRT1)expression to promote the phosphorylation of nuclear factor-kappa B(NF-κB)p65,indicating the possible involvement of this signaling pathway in miR-23a-mediated events.Conclusion:Our results indicate that miR-23a could suppress LPS-induced cell damage and inflammatory cytokine secretion by binding to ROCK1,mediated through the potential participation of the SIRT1/NF-κB signaling pathway.