Intestinal IgA, which is regulated by gut microbiota, has a crucial role in maintenance of intestinal homeostasis and in protecting the intestines from inflammation. However, the means by which ...microbiota promotes intestinal IgA responses remain unclear. Emerging evidence suggests that the host can sense gut bacterial metabolites in addition to pathogen-associated molecular patterns and that recognition of these small molecules influences host immune response in the intestines and beyond. We reported here that microbiota metabolite short-chain fatty acid acetate promoted intestinal IgA responses, which was mediated by "metabolite-sensing" GPR43. GPR43
mice demonstrated lower levels of intestinal IgA and IgA
gut bacteria compared with those in wild type (WT) mice. Feeding WT but not GPR43
mice acetate but not butyrate promoted intestinal IgA response independent of T cells. Acetate promoted B-cell IgA class switching and IgA production in vitro in the presence of WT but not GPR43
dendritic cells (DCs). Mechanistically, acetate-induced DC expression of Aldh1a2, which converts Vitamin A into its metabolite retinoic acid (RA). Moreover, blockade of RA signaling inhibited the acetate induction of B-cell IgA production. Our studies thus identified a new pathway by which microbiota promotes intestinal IgA response through its metabolites.
The mechanism of superconductivity in cuprates remains one of the big challenges of condensed matter physics. High-Tc
cuprates crystallize into a layered perovskite structure featuring copper oxygen ...octahedral coordination. Due to the Jahn Teller effect in combination with the strong static Coulomb interaction, the octahedra in high-Tc
cuprates are elongated along the c axis, leading to a 3dx²-y² orbital at the top of the band structure wherein the doped holes reside. This scenario gives rise to 2D characteristics in high-Tc
cuprates that favor d-wave pairing symmetry. Here, we report superconductivity in a cuprate Ba₂CuO4-y, wherein the local octahedron is in a very exceptional compressed version. The Ba₂CuO4-y compound was synthesized at high pressure at high temperatures and shows bulk superconductivity with critical temperature (Tc
) above 70 K at ambient conditions. This superconducting transition temperature is more than 30 K higher than the Tc
for the isostructural counterparts based on classical La₂CuO₄. X-ray absorption measurements indicate the heavily doped nature of the Ba₂CuO4-y superconductor. In compressed octahedron, the 3d3z²-r² orbital will be lifted above the 3dx²-y² orbital, leading to significant 3D nature in addition to the conventional 3dx²-y² orbital. This work sheds important light on advancing our comprehensive understanding of the superconducting mechanism of high Tc
in cuprate materials.
Abstract Previous data demonstrate that traumatic brain injury (TBI) activates autophagy, and increases microtubule-associated protein 1 light chain 3 (LC3) immunostaining mainly in neurons. However, ...the role of autophagy in traumatic brain damage remains elusive. The aim of the present study was to investigate the autophagic mechanisms participating in traumatic brain injury. The autophagy inhibitors 3-methyladenine (3-MA) and bafliomycin A1 (BFA) were administered with a single i.c.v. injection before TBI. We first examined the protein levels of Beclin-1 and LC3 II, which have been found to promote autophagy previously. Immunoblotting analysis showed that 3-MA pretreatment reduced post-TBI Beclin-1 and LC3-II levels, and maintained p62/SQSTM1 (p62) levels. In addition, double immunolabeling showed that the increased punctate LC3-II dots colocalizing with Propidium Iodide (PI)-stained nuclei at 24 h after injury, were partially inhibited by 3-MA pretreatment. Furthermore, inhibition of autophagy could reduce TBI-induced cell injury assessed with i.p. injection of PI and lesion volume, and attenuate behavioral outcome evaluated by motor test and Morris water maze. The neuroprotective effects were associated with an inhibition on TBI-induced up-regulation of LC3, Beclin-1, cathepsin B, caspase-3 and the Beclin-1/Bcl-2 ratio. Taken together, these data imply that the autophagy pathway is involved in the pathophysiologic responses after TBI, and inhibition of this pathway may help attenuate traumatic damage and functional outcome deficits.
Altered aerobic glycolysis is a well-recognized characteristic of cancer cell energy metabolism, known as the Warburg effect. Even in the presence of abundant oxygen, a majority of tumor cells ...produce substantial amounts of energy through a high glycolytic metabolism, and breast cancer (BC) is no exception. Breast cancer continues to be the second leading cause of cancer-associated mortality in women worldwide. However, the precise role of aerobic glycolysis in the development of BC remains elusive. Therefore, the present review attempts to address the implication of key enzymes of the aerobic glycolytic pathway including hexokinase (HK), phosphofructokinase (PFK) and pyruvate kinase (PK), glucose transporters (GLUTs), together with related signaling pathways including protein kinase B(PI3K/AKT), mammalian target of rapamycin (mTOR) and adenosine monophosphate-activated protein kinase (AMPK) and transcription factors (c-myc, p53 and HIF-1) in the research of BC. Thus, the review of aerobic glycolysis in BC may evoke novel ideas for the BC treatment.
Aim The aim of the study was to evaluate the efficacy and safety of fast‐track rehabilitation in elderly patients over 65 years of age, following laparoscopic surgery to remove colorectal cancer.
...Method A total of 78 elderly patients with colorectal cancer who underwent laparoscopic colorectal resection were randomly assigned to receive either the fast‐track care programme (n = 40) or the conventional perioperative care protocol (control group, n = 38). Medical personnel conducting the study were blinded to patients’ clinical outcomes prior to statistical analysis. The fast‐track protocol included no preoperative mechanical bowel irrigation, immediate oral alimentation and earlier postoperative ambulation exercise. The length of postoperative hospital stay, the length of time to regain bowel function and the rate of postoperative complications were compared between the two groups.
Results The length of time to regain bowel function, including the passage of flatus31 (26–40) h vs 38 (32–51) h, P = 0.001, to the first bowel movement 55 (48–63) h vs 64 (48–71) h, P = 0.009 and to start a liquid diet (12 11–16 h vs 47 35–50 h, P = 0.000) were significantly shorter in patients receiving the fast‐track care protocol compared with those receiving the conventional care protocol. A shorter duration of postoperative hospital stay was recorded in patients receiving the fast‐track program than in those receiving conventional care (P = 0.0001). A reduced percentage of patients who developed general complications was also observed in the fast‐track group (5.0%vs 21.1%, P = 0.045).
Conclusion This randomized controlled trial has shown that in the elderly undergoing laparoscopic colorectal surgery, the fast‐track recovery programme resulted in a more rapid postoperative recovery, earlier discharge from hospital and fewer general complications compared with a conventional postoperative protocol.
Stress waves, known as acoustic emissions (AEs), are released by localized inelastic deformation events during the progressive failure of brittle rocks. Although several numerical models have been ...developed to simulate the deformation and damage processes of rocks, such as non-linear stress-strain behaviour and localization of failure, only a limited number have been capable of providing quantitative information regarding the associated seismicity. Moreover, the majority of these studies have adopted a pseudo-static approach based on elastic strain energy dissipation that completely disregards elastodynamic effects. This paper describes a new AE modelling technique based on the combined finite-discrete element method (FEM/DEM), a numerical tool that simulates material failure by explicitly considering fracture nucleation and propagation in the modelling domain. Given the explicit time integration scheme of the solver, stress wave propagation and the effect of radiated seismic energy can be directly captured. Quasi-dynamic seismic information is extracted from a FEM/DEM model with a newly developed algorithm based on the monitoring of internal variables (e.g. relative displacements and kinetic energy) in proximity to propagating cracks. The AE of a wing crack propagation model based on this algorithm are cross-analysed by traveltime inversion and energy estimation from seismic recordings. Results indicate a good correlation of AE initiation times and locations, and scaling of energies, independently calculated with the two methods. Finally, the modelling technique is validated by simulating a laboratory compression test on a granite sample. The micromechanical parameters of the heterogeneous model are first calibrated to reproduce the macroscopic stress-strain response measured during standard laboratory tests. Subsequently, AE frequency-magnitude statistics, spatial clustering of source locations and the evolution of AE rate are investigated. The distribution of event magnitude tends to decay as power law while the spatial distribution of sources exhibits a fractal character, in agreement with experimental observations. Moreover, the model can capture the decrease of seismic b value associated with the macrorupture of the rock sample and the transition of AE spatial distribution from diffuse, in the pre-peak stage, to strongly localized at the peak and post-peak stages, as reported in a number of published laboratory studies. In future studies, the validated FEM/DEM-AE modelling technique will be used to obtain further insights into the micromechanics of rock failure with potential applications ranging from laboratory-scale microcracking to engineering-scale processes (e.g. excavations within mines, tunnels and caverns, petroleum and geothermal reservoirs) to tectonic earthquakes triggering.
A new N-functionalized strategy of nitrogen heterocycles was utilized for the synthesis of nitroazole-based energetic materials, giving rise to a new family of highly dense and oxygen-rich energetic ...materials. They were characterized by IR spectroscopy, NMR spectroscopy, elemental analysis, DSC, and X-ray diffraction. These new molecules exhibit high densities, moderate to good thermal stabilities, acceptable impact and friction sensitivities, and excellent detonation properties, which suggest potential applications as energetic materials or oxidizers. Interestingly, among tetrazole-based CHNO energetic materials compound 5 has the highest measured density of 1.97 g cm super(-3) to date. 5c is the first and the only heterocyclic CHNO energetic salt with a positive OB until now. Compounds 5 and 6 exhibit excellent detonation properties (38.5 GPa, 9.22 km s super(-1); 37.0 GPa, 9.05 km s super(-1)), comparable to the highly explosive HMX. With high OB, the specific impulses of 5, 5b, 5c, and 6c are superior to those of AP and ADN as neat compounds, and the ratio of oxidizer/aluminium/PBAN (%) is 80 : 20 : 0 or 80 : 13 : 7. Furthermore, computational results, BDEs, Mulliken charges and Wiberg bond orders also support the superior qualities of the newly prepared compounds and the design strategy.
High-temperature superconductivity in cuprates arises from an electronic state that remains poorly understood. We report the observation of a related electronic state in a noncuprate material, ...strontium iridate (Sr2IrO4), in which the distinct cuprate fermiology is largely reproduced. Upon surface electron doping through in situ deposition of alkali-metal atoms, angle-resolved photoemission spectra of Sr2IrO4 display disconnected segments of zero-energy states, known as Fermi arcs, and a gap as large as 80 millielectron volts. Its evolution toward a normal metal phase with a closed Fermi surface as a function of doping and temperature parallels that in the cuprates. Our result suggests that Sr2IrO4 is a useful model system for comparison to the cuprates.
MicroRNA (miRNA) and long non-coding RNA (lncRNA) have been demonstrated to participate in the progression of many cancers. Hepatocellular carcinoma (HCC) is one of the most common and aggressive ...malignant tumors worldwide, while the molecular mechanisms underlying HCC tumorigenesis are not completely clear. In this study, we showed that miR-92b was significantly upregulated in tumor tissue and plasma of HCC patients, and its expression level was highly correlated with gender and microvascular invasion. Functionally, miR-92b could promote cell proliferation and metastasis of HCC in vitro and in vivo. Mechanistic investigations suggested that Smad7, which exhibited an inverse relationship with miR-92b expression in HCC, was a direct target of miR-92b and could reverse its effects on HCC tumorigenesis. Furthermore, long non-coding RNA (lncRNA) X-inactive specific transcript (XIST) and miR-92b could directly interact with and repress each other, and XIST could inhibit HCC cell proliferation and metastasis by targeting miR-92b. Taken together, our study not only revealed for the first time the importance of XIST/miR-92b/Smad7 signaling axis in HCC progression but also suggested the potential value of miR-92b as a biomarker in the clinical diagnosis and treatment of HCC.
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