Methamphetamine (METH) is an addictive and illegal psychostimulant drug that can cause multiple organ dysfunction, especially in the central nervous system (CNS). Gut microbiota have been implicated ...in development of various CNS-related diseases, via the gut-brain axis (GBA). However, effect of METH in the alteration of gut microbiota and fecal metabolites is unclear, whereas the relationship with METH-induced neurotoxicity remains unknown. In the current study, we investigated effect of METH on neurotoxicity in striatum and colonic damage by exposing BALB/c mice to an escalating dose-multiple binge regimen, and then analyzed protein expression using Western blot analysis. We further detected and sequenced the 16 S rRNA gene in fecal samples, and performed ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS)-based metabolomics to analyze gut microbes and fecal metabolites. Exposure to METH significantly downregulated tyrosine hydroxylase (TH) proteins, but upregulated MAOA, Beclin1, Atg5, and LC3-Ⅱ. METH up-regulated inflammation-related factors, such as caspase1, TNF-α and IL-18, by activating the toll-like receptors 4 (TLR4)/myeloid differentiation factor 88 (Myd88)/nuclear factor κB (NF-κB) pathway and reduced occludin protein expression. In addition, METH exposure changed α and β diversities of gut microbiota. Specifically, METH exposure elevated relative abundances of pathogenic bacteria, but reduced those of probiotics. Metabolomics, combined with enrichment analyses revealed that METH exposure altered fecal metabolites. Our findings suggest that METH exposure induced autophagy in the CNS, elevated intestinal autophagy flora, leading to accumulation of fecal metabolites in the autophagy pathway, and causing enteritis. Moreover, METH promoted intestinal inflammation by increasing the relative abundance of the pathogenic bacteria in the intestinal tract, and reduced intestinal TJ protein expression.
•Methamphetamine (METH) induces neurotoxicity and colonic inflammatory in mice.•METH-exposed altered gut microbiota and fecal metabolites.•METH-induced neurotoxicity, gut microbiota and fecal metabolites were closely related to autophagy.
Organophosphorus flame retardants (OPFRs), such as 2-ethylhexyl diphenyl phosphate (EHDPHP), are ubiquitously used, leading to pervasive environmental contamination and human health risks. While ...associations between EHDPHP and health issues such as disruption of hormones, neurotoxic effects, and toxicity to reproduction have been recognized, exposure to EHDPHP during perinatal life and its implications for the intestinal health of dams and their pups have largely been unexplored. This study investigated the intestinal toxicity of EHDPHP and the potential for which inulin was effective. Dams were administered either an EHDPHP solution or a corn oil control from gestation day 7 (GD7) to postnatal day 21 (PND21), with inulin provided in their drinking water. Our results indicate that inulin supplementation mitigates damage to the intestinal epithelium caused by EHDPHP, restores mucus-secreting cells, suppresses intestinal hyperpermeability, and abates intestinal inflammation by curtailing lipopolysaccharide leakage through reshaping of the gut microbiota. A reduction in LPS levels concurrently inhibited the inflammation-associated TLR4/NF-κB pathway. In conclusion, inulin administration may ameliorate intestinal toxicity caused by EHDPHP in dams and pups by reshaping the gut microbiota and suppressing the LPS/TLR4/NF-κB pathway. These findings underscore the efficacy of inulin as a therapeutic agent for managing health risks linked to EHDPHP exposure.
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•Inulin alleviates EHDPHP-induced intestinal dysfunction and LPS elevation.•Inulin reshapes the gut microbiota disrupted by EHDPHP in dams and pups.•Inulin mitigates intestinal toxicity by inhibiting the LPS/TLR4/NF-κB pathway.
Inherent chirality is used to describe chiral cyclic molecules devoid of central, axial, planar, or helical chirality and has tremendous applications in chiral recognition and enantioselective ...synthesis. Catalytic and divergent syntheses of inherently chiral molecules have attracted increasing interest from chemists. Herein, we report the enantioselective synthesis of inherently chiral tribenzocycloheptene derivatives via chiral phosphoric acid (CPA)‐catalyzed condensation of cyclic ketones and hydroxylamines. This chemistry paves the way to accessing the less stable derivatives of 7‐membered rings with inherent chirality. A series of chiral tribenzocycloheptene oxime ethers was synthesized in good yields (up to 97 %) with excellent enantioselectivities (up to 99 % ee).
Developing efficient protocols to construct inherent chirality is highly desirable owing to its tremendous application in chiral recognition and enantioselective synthesis. Herein, we report the first enantioselective synthesis of 7‐membered inherently chiral derivatives via chiral phosphoric acid‐catalyzed condensation. This chemistry highlights the broad substrate scope and excellent stereocontrol (up to 99 % ee).
Introduction
Heart failure (HF) is usually the end stage of the continuum of various cardiovascular diseases. However, the mechanism underlying the progression and development of HF remains poorly ...understood. The sigma-1 receptor (Sigmar1) is a non-opioid transmembrane receptor implicated in many diseases, including HF. However, the role of Sigmar1 in HF has not been fully elucidated.
Methods
In this study, we used isoproterenol (ISO) to induce HF in wild-type (WT) and Sigmar1 knockout (Sigmar1
−/−
) mice. Multi-omic analysis, including microbiomics, metabolomics and transcriptomics, was employed to comprehensively evaluate the role of Sigmar1 in HF.
Results
Compared with the WT-ISO group, Sigmar1
−/−
aggravated ISO-induced HF, including left ventricular systolic dysfunction and ventricular remodeling. Moreover, Sigmar1
−/−
exacerbated ISO-induced gut microbiota dysbiosis, which was demonstrated by the lower abundance of probiotics g_Akkermansia and g_norank_f_Muribaculaceae, and higher abundance of pathogenic g_norank_f_Oscillospiraceae and Allobaculum. Furthermore, differential metabolites among WT-Control, WT-ISO and Sigmar
−/−
-ISO groups were mainly enriched in bile secretion, tryptophan metabolism and phenylalanine metabolism, which presented a close association with microbial dysbiosis. Corresponding with the exacerbation of the microbiome, the inflammation-related NOD-like receptor signaling pathway, NF-kappa B signaling pathway and TNF signaling pathway were activated in the heart tissues.
Conclusion
Taken together, this study provides evidence that a Sigmar1 knockout disturbs the gut microbiota and remodels the serum metabolome, which may exacerbate HF by stimulating heart inflammation.
In magnetic topological insulators (TIs), the interplay between magnetic order and nontrivial topology can induce fascinating topological quantum phenomena, such as the quantum anomalous Hall effect, ...chiral Majorana fermions, and axion electrodynamics. Recently, a great deal of attention has been focused on the intrinsic magnetic TIs, where disorder effects can be eliminated to a large extent, which is expected to facilitate the emergence of topological quantum phenomena. Despite intensive efforts, experimental evidence of the topological surface states (SSs) remains elusive. Here, by combining first-principles calculations and angle-resolved photoemission spectroscopy (ARPES) experiments, we reveal thatEuSn2As2is an antiferromagnetic TI with the observation of Dirac SSs consistent with our prediction. We also observe nearly gapless Dirac SSs in antiferromagnetic TIsMnBi2nTe3n+1(n=1and 2), which are absent in previous ARPES results. These results provide clear evidence for nontrivial topology of these intrinsic magnetic TIs. Furthermore, we find that the topological SSs show no observable changes across the magnetic transition within the experimental resolution, indicating that the magnetic order has a quite small effect on the topological SSs, which can be attributed to weak hybridization between the localized magnetic moments, from either4for3dorbitals, and the topological electronic states. This finding provides insights for further research that the correlations between magnetism and topological states need to be strengthened to induce larger gaps in the topological SSs, which will facilitate the realization of topological quantum phenomena at higher temperatures.
Esophageal squamous cell carcinoma (ESCC) is one of the deadliest cancers. We performed exome sequencing on 113 tumor-normal pairs, yielding a mean of 82 non-silent mutations per tumor, and 8 cell ...lines. The mutational profile of ESCC closely resembles those of squamous cell carcinomas of other tissues but differs from that of esophageal adenocarcinoma. Genes involved in cell cycle and apoptosis regulation were mutated in 99% of cases by somatic alterations of TP53 (93%), CCND1 (33%), CDKN2A (20%), NFE2L2 (10%) and RB1 (9%). Histone modifier genes were frequently mutated, including KMT2D (also called MLL2; 19%), KMT2C (MLL3; 6%), KDM6A (7%), EP300 (10%) and CREBBP (6%). EP300 mutations were associated with poor survival. The Hippo and Notch pathways were dysregulated by mutations in FAT1, FAT2, FAT3 or FAT4 (27%) or AJUBA (JUB; 7%) and NOTCH1, NOTCH2 or NOTCH3 (22%) or FBXW7 (5%), respectively. These results define the mutational landscape of ESCC and highlight mutations in epigenetic modulators with prognostic and potentially therapeutic implications.
Electromagnetic protection in optoelectronic instruments such as optical windows and electronic displays is challenging because of the essential requirements of a high optical transmittance and an ...electromagnetic interference (EMI) shielding effectiveness (SE). Herein, we demonstrate the creation of an efficient transparent EMI shielding film that is composed of calcium alginate (CA), silver nanowires (AgNWs), and polyurethane (PU), via a facile and low-cost Mayer-rod coating method. The CA/AgNW/PU film with a high optical transmittance of 92% achieves an EMI SE of 20.7 dB, which meets the requirements for commercial shielding applications. A superior EMI SE of 31.3 dB could be achieved, whereas the transparent film still maintains a transmittance of 81%. The integrated efficient EMI SE and high transmittance are superior to those of most previously reported transparent EMI shielding materials. Moreover, our transparent films exhibit a highly reliable shielding ability in a complex service environment, with 98 and 96% EMI SE retentions even after 30 min of ultrasound treatment and 5000 bending cycles (1.5 mm radius), respectively. The comprehensive performance that is associated with the facile fabrication strategy imparts the CA/AgNW/PU film with great potential as an optimized EMI shielding material in emerging optoelectronic devices, such as flexible solar cells, displays, and touch panels.
Abstract
Effecting the synergistic function of single metal atom sites and their supports is of great importance to achieve high-performance catalysts. Herein, we successfully fabricate ...polyoxometalates (POMs)-stabilized atomically dispersed platinum sites by employing three-dimensional metal-organic frameworks (MOFs) as the finite spatial skeleton to govern the accessible quantity, spatial dispersion, and mobility of metal precursors around each POM unit. The isolated single platinum atoms (Pt
1
) are steadily anchored in the square-planar sites on the surface of monodispersed Keggin-type phosphomolybdic acid (PMo) in the cavities of various MOFs, including MIL-101, HKUST-1, and ZIF-67. In contrast, either the absence of POMs or MOFs yielded only platinum nanoparticles. Pt
1
-PMo@MIL-101 are seven times more active than the corresponding nanoparticles in the diboration of phenylacetylene, which can be attributed to the synergistic effect of the preconcentration of organic reaction substrates by porous MOFs skeleton and the decreased desorption energy of products on isolated Pt atom sites.
Efficient and selective dehydrogenation of formic acid is a key challenge for a fuel‐cell‐based hydrogen economy. Though the development of heterogeneous catalysts has received much progress, their ...catalytic activity remains insufficient. Moreover, the design principle of such catalysts are still unclear. Here, experimental and theoretical studies on a series of mono‐/bi‐metallic nanoparticles supported on a NH2‐N‐rGO substrate are combined for formic acid dehydrogenation where the surface energy of a metal is taken as a relevant indicator for the adsorption ability of the catalyst for guiding catalyst design. The AuPd/NH2‐N‐rGO catalyst shows record catalytic activity by reducing the energy barrier of rate controlling steps of formate adsorption and hydrogen desorption. The obtained excellent results both in experiments and simulations could be extended to other important systems, providing a general guideline to design more efficient catalysts.
A AuPd/NH2‐N‐rGO catalyst shows supreme catalytic performance for the decomposition of formic acid at room temperature, with a turnover frequency (TOF) of 4445.6 h−1. Developments in the experiments and simulations of high‐performance catalysts may promote the practical application of formic acid as a promising hydrogen storage material.
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