Targeting the intestinal circadian clock by meal timing ameliorates gastrointestinal inflammation

The expression of clock genes has been observed to be impaired in biopsies from patients with inflammatory bowel disease(IBD).Disruption of circadian rhythms,which occurs in shift workers,has been linked to an increased risk of gastrointestinal diseases,including IBD.The peripheral circadian clock in intestinal epithelial cells(IECs)was previously shown to balance gastrointestinal homeostasis by regulating the microbiome.Here,we demonstrated that the intestinal clock is disrupted in an IBD-relevant mouse model(IL-10−/−).A lack of the intestinal clock gene(Bmal1)in intestinal epithelial cells(IECs)in a chemically and a novel genetically induced colitis model(DSS,Bmal1IEC−/−xIL-10−/−)promoted colitis and dramatically reduced survival rates.Germ-free Bmal1IEC−/−mice colonized with disease-associated microbiota from IL-10−/−mice exhibited increased inflammatory responses,highlighting the importance of the local intestinal clock for microbiota-induced IBD development.Targeting the intestinal clock directly by timed restricted feeding(RF)in IL-10−/−mice restored intestinal clock functions,including immune cell recruitment and microbial rhythmicity;improved inflammatory responses;dramatically enhanced survival rates and rescued the histopathological phenotype.In contrast,RF failed to improve IBD symptoms in Bmal1IEC−/−xIL-10−/−mice,demonstrating the significance of the intestinal clock in determining the beneficial effect of RF.Overall,we provide evidence that intestinal clock dysfunction triggers host immune imbalance and promotes the development and progression of IBD-like colitis.Enhancing intestinal clock function by RF modulates the pathogenesis of IBD and thus could become a novel strategy to ameliorate symptoms in IBD patients.

Theoretical prediction,synthesis,and crystal structure determination of new MAX phase compound V2SnC

Guided by the theoretical prediction,a new MAX phase V2SnC was synthesized experimentally for the first time by reaction of V,Sn,and C mixtures at 1000°C.The chemical composition and crystal structure of this new compound were identified by the cross-check combination of first-principles calculations,X-ray diffraction(XRD),energy dispersive X-ray spectroscopy(EDS),and high resolution scanning transmission electron microscopy(HR-STEM).The stacking sequence of V2C and Sn layers results in a crystal structure of space group P63/mmc.The a-and c-lattice parameters,which were determined by the Rietveld analysis of powder XRD pattern,are 0.2981(0)nm and 1.3470(6)nm,respectively.The atomic positions are V at 4f(1/3,2/3,0.0776(5)),Sn at 2d(2/3,1/3,1/4),and C at 2a(0,0,0).A new set of XRD data of V2SnC was also obtained.Theoretical calculations suggest that this new compound is stable with negative formation energy and formation enthalpy,satisfied Born-Huang criteria of mechanical stability,and positive phonon branches over the Brillouin zone.It also has low shear deformation resistance c44(second-order elastic constant,cij)and shear modulus(G),positive Cauchy pressure,and low Pugh’s ratio(G/B=0.500<0.571),which is regarded as a quasi-ductile MAX phase.The mechanism underpinning the quasi-ductility is associated with the presence of a metallic bond.

Synthesis,microstructure,and properties of high purity Mo_(2)TiAlC_(2) ceramics fabricated by spark plasma sintering

The synthesis,microstructure,and properties of high purity dense bulk Mo_(2)TiAlC_(2) ceramics were studied.High purity Mo_(2)TiAlC_(2) powder was synthesized at 1873 K starting from Mo,Ti,Al,and graphite powders with a molar ratio of 2:1:1.25:2.The synthesis mechanism of Mo_(2)TiAlC_(2) was explored by analyzing the compositions of samples sintered at different temperatures.It was found that the Mo_(2)TiAlC_(2) phase was formed from the reaction among Mo3Al2C,Mo2C,TiC,and C.Dense Mo_(2)TiAlC_(2) bulk sample was prepared by spark plasma sintering(SPS)at 1673 K under a pressure of 40 MPa.The relative density of the dense sample was 98.3%.The mean grain size was 3.5μm in length and 1.5μm in width.The typical layered structure could be clearly observed.The electrical conductivity of Mo_(2)TiAlC_(2) ceramic measured at the temperature range of 2-300 K decreased from 0.95×10^(6) to 0.77×10^(6)Ω^(-1)·m^(-1).Thermal conductivity measured at the temperature range of 300-1273 K decreased from 8.0 to 6.4 W·(m·K)^(-1).The thermal expansion coefficient(TEC)of Mo_(2)TiAlC_(2) measured at the temperature of 350-1100 K was calculated as 9.0×10^(-6) K^(-1).Additionally,the layered structure and fine grain size benefited for excellent mechanical properties of low intrinsic Vickers hardness of 5.2 GPa,high flexural strength of 407.9 MPa,high fracture toughness of 6.5 MPa·m^(1/2),and high compressive strength of 1079 MPa.Even at the indentation load of 300 N,the residual flexural strength could hold 84% of the value of undamaged one,indicating remarkable damage tolerance.Furthermore,it was confirmed that Mo_(2)TiAlC_(2) ceramic had a good oxidation resistance below 1200 K in the air.