MANF brakes TLR4 signaling by competitively binding S100A8 with S100A9 to regulate macrophage phenotypes in hepatic fibrosis

The mesencephalic astrocyte-derived neurotrophic factor(MANF)has been recently identified as a neurotrophic factor,but its role in hepatic fibrosis is unknown.Here,we found that MANF was upregulated in the fibrotic liver tissues of the patients with chronic liver diseases and of mice treated with CCl4.MANF deficiency in either hepatocytes or hepatic mono-macrophages,particularly in hepatic mono-macrophages,clearly exacerbated hepatic fibrosis.Myeloid-specific MANF knockout increased the population of hepatic Ly6C^(high)macrophages and promoted HSCs activation.Furthermore,MANF-sufficient macrophages(from WT mice)transfusion ameliorated CCl4-induced hepatic fibrosis in myeloid cells-specific MANF knockout(MKO)mice.Mechanistically,MANF interacted with S100A8 to competitively block S100A8/A9 heterodimer formation and inhibited S100A8/A9-mediated TLR4-NF-κB signal activation.Pharmacologically,systemic administration of recombinant human MANF significantly alleviated CCl_(4)-induced hepatic fibrosis in both WT and hepatocytes-specific MANF knockout(HKO)mice.This study reveals a mechanism by which MANF targets S100A8/A9-TLR4 as a“brake”on the upstream of NF-κB pathway,which exerts an impact on macrophage differentiation and shed light on hepatic fibrosis treatment.

Boosting charge separation of BiVO_(4)photoanode modified with 2D metal-organic frameworks nanosheets for high-performance photoelectrochemical water splitting

Water splitting by photoelectrochemical(PEC)processes to convert solar energy into hydrogen energy using semiconductors is regarded as one of the most ideal methods to solve the current energy crisis and has attracted widespread attention.Herein,Co-based metal-organic framework(Co(bpdc)(H_(2)O)_(4)(CoMOF)nanosheets as passivation layers were in-situ constructed on the surface of Bi VO_(4)films through an uncomplicated hydrothermal method(Co-MOF/Bi VO_(4)).Under AM 1.5G illumination,synthesized CoMOF/BiVO_(4)electrode exhibited a 4-fold higher photocurrent than bare Bi VO_(4),measuring 6.0 m A/cm^(2)at 1.23 V vs.RHE in 1 mol/L potassium borate electrolyte(pH 9.5)solution.Moreover,the Co-MOF/BiVO_(4)film demonstrated a 96%charge separation efficiency,a result caused by an inhibited recombination rate of photogenerated electrons and holes by the addition of Co-MOF nanosheets.This work provides an idea for depositing inexpensive 2D Co-MOF nanosheets on the photoanode as an excellent passivation layer for solar fuel production.

Identification of molecular markers linked to rice bacterial blight resistance genes from Oryza meyeriana

Y73 is a progeny of asymmetric somatic hybridization between Oryza sativa cv.Dalixiang and the wild rice species Oryza meyeriana.Inoculation with a range of strains of Xanthomonas oryzae pv.oryzae showed that Y73 had inherited a high level of resistance to rice bacterial blight(BB)from its wild parent.An F2 population of 7125 individuals was constructed from the cross between Y73 and a BB-susceptible cultivar IR24.After testing 615 SSR and STS markers covering the 12 rice chromosomes,186 markers were selected that showed polymorphism between Y73 and IR24.Molecular markers linked to the BB resistance genes in Y73 were scanned using the F2 population and the polymorphic markers.The SSR marker RM128 on chromosome 1,the STS marker R03D159 on chromosome 3 and the STS marker R05D104 on chromosome 5 were found to be linked to the rice BB resistance genes in Y73.

Unravelling the effects of complexation of transition metal ions on the hydroxylation of catechol over the whole pH region

Catechol pollutants(CATPs)serving as chelating agents could coordinate with many metal ions to form various CATPs-metal complexes.Little information is available on the effects of complexation of metal ions on CATPs degradation.This work presents a systematical study of·OH-mediated degradation of catechol and catechol-metal complexes over the whole pH range in advanced oxidation processes(AOPs).Results show that the pH-dependent complexation of metal ions(Zn^(2+),Cu^(2+),Ti^(4+)and Fe^(3+))promotes the deprotonation of catechol under neutral and even acidic conditions.The radical adduct formation(RAF)reactions are both thermodynamically and kinetically favorable for all dissociation and complexa-tion species,and-OH/-O-group-containing C positions are more vulnerable to·OH attack.The kinetic results show that the complexation of the four metal ions offers a wide pH range of effectiveness for catechol degradation.At pH 7,the apparent rate constant(k_(app))values for different systems follow the order of catechol+Ti^(4+)≈catechol+Zn^(2+)>catechol+Cu^(2+)>catechol+Fe^(3+)>catechol.The mechanistic and kinetic results would greatly improve our understanding of the degradation of CATPs-metal and other organics-metal complexes in AOPs.The toxicity assessment indicates that the·OH-based AOPs have the ability for decreasing the toxicity and increasing the biodegradability during the processes of catechol degradation.

Palladium-catalyzed amination of chloro-substituted 5-nitropyrimidines with amines

A concise and efficient approach was developed for the synthesis of mono-substituted and di-substituted pyrimidines products via palladium-catalyzed amination of chloro-substituted 5-nitropyrimidines and amines. This synthetic methodology can produce various di-substituted pyrimidines in high yields with good functional group tolerance, and provide a complementary tool for the syntheses of important intermediates of nucleosides and purines with bioactivities.