Causal relationship between gut microbiota and autoimmune thyroiditis: A mendelian study

Background: Autoimmune thyroiditis (AIT), also known as Hashimoto's thyroiditis (HT) or chronic lymphocytic thyroiditis, is a prevalent autoimmune disorder. Despite its high prevalence, the pathogenesis of AIT remains unclear. Previous studies have suggested a potential association between gut microbiota and AIT. However, whether this relationship is causal or coincidental remains uncertain. To address this gap in knowledge, our study aimed to investigate the potential causal association between gut microbiota and AIT using the two-sample Mendelian randomization (MR) method. Methods: Summary-level gut microbiota data comprising 211 taxa (131 genera, 35 families, 20 orders, 16 classes, and 9 phyla) were obtained from the comprehensive MiBioGen study. Genetic associations with 22 gastrointestinal diseases were extracted from the UK Biobank, FinnGen study, and various extensive GWAS studies. A meticulous MR analysis was conducted to evaluate the causal relationship between genetically predicted gut microbiota and these gastrointestinal diseases. Sensitivity analyses and tests for heterogeneity were systematically performed to validate the reliability of our findings. Results: Six gut microbiota species showed significant associations with AIT according to the IVW method. Among them, the following exhibited negative associations with AIT: family Alcaligenaceae, family Pasteurellaceae (ID: 3689), family Peptococcaceae, genus Lachnospira, genus Victivallis, and order Pasteurellales (ID: 3688). No evidence of pleiotropy or heterogeneity was detected. Conclusion: The MR analysis uncovered a causal relationship at the genetic prediction level between specific gut microbiota and AIT. These findings offer novel insights into the mechanisms governing the development of AIT mediated by gut microbiota. This knowledge could inform the design of future interventions, potentially involving microbiome-related strategies, to address the mechanisms associated with AIT development

Electron–Phonon Coupling-Mediated Ultralong Carrier Lifetime in an All-Inorganic Two-Dimensional Cs₂PbI₂Cl₂ Perovskite: Explanation for the High Antisite Defect Tolerance

Two-dimensional (2D) halide perovskite are appealing candidates for applications in optoelectronics and photovoltaics, but their energy conversion efficiency is severely limited by nonradiative electron–hole recombination. In most investigations, point defects with deep defect levels and deep charge-state transition levels in the band gap are treated as the carrier recombination centers. For the all-inorganic 2D Css 2PbI2Cl2, the IPb antisite defect is the most likely to form and cause nonradiative electron–hole recombination. By using density functional theory and ab initio nonradiative molecular dynamics calculations, we found that the IPb defect can introduce the deep acceptor and donor levels into the band gap. Because electron–phonon coupling gives rise to weak nonadiabatic coupling and rapid loss of electronic coherence, those levels lead to a reduction of the carrier loss and the prolongation of the excited-state carrier lifetime, thereby enhancing the photoelectric and defect tolerance properties of the Cs2PbI2Cl2 material. These results could deepen the understanding of the chemistry of defects and carrier dynamics in perovskite materials

Table1_Metabolomics in hepatocellular carcinoma: From biomarker discovery to precision medicine.docx

Hepatocellular carcinoma (HCC) remains a global health burden, and is mostly diagnosed at late and advanced stages. Currently, limited and insensitive diagnostic modalities continue to be the bottleneck of effective and tailored therapy for HCC patients. Moreover, the complex reprogramming of metabolic patterns during HCC initiation and progression has been obstructing the precision medicine in clinical practice. As a noninvasive and global screening approach, metabolomics serves as a powerful tool to dynamically monitor metabolic patterns and identify promising metabolite biomarkers, therefore holds a great potential for the development of tailored therapy for HCC patients. In this review, we summarize the recent advances in HCC metabolomics studies, including metabolic alterations associated with HCC progression, as well as novel metabolite biomarkers for HCC diagnosis, monitor, and prognostic evaluation. Moreover, we highlight the application of multi-omics strategies containing metabolomics in biomarker discovery for HCC. Notably, we also discuss the opportunities and challenges of metabolomics in nowadays HCC precision medicine. As technologies improving and metabolite biomarkers discovering, metabolomics has made a major step toward more timely and effective precision medicine for HCC patients.</p

Systemic arterial blood pressure and intracerebral hemorrhage after mechanical thrombectomy in anterior cerebral circulation

The relationship between systemic arterial blood pressure (BP) and intracerebral hemorrhage (ICH) after mechanical thrombectomy (MT) of the cerebral artery remains unclear. This study aimed to determine the effect of BP variables on ICH after MT in patients with acute occlusions of the anterior cerebral circulation. Patients undergoing MT due to acute occlusions of the anterior cerebral circulation were enrolled in this single-center study. Non-invasive BP data following MT were obtained within the first 24 hours, including mean, maximum, minimum, difference between maximum and minimum, SD and coefficient of variation for systolic BP (SBP) and diastolic BP (DBP) and mean arterial pressure. ICH was defined and classified according to the European Cooperative Acute Stroke Study-II. In 164 enrolled patients (median age 65 (IQR 56-75) years; 31.7% female), higher maximum (89.5 mm Hg vs 98.5 mm Hg, p=0.001) and SD (9.8 mm Hg vs 10.9 mm Hg, p=0.038) of DBP were associated with higher risk of ICH. The optimal cut-off values associated with ICH for maximum SBP were 155 mm Hg and for maximum DBP 92.5 mm Hg, respectively. Higher BP within 24 hours after MT in acute occlusions of the anterior cerebral circulation is associated with a greater risk of ICH. More studies are needed to further determine optimal BP goals in the acute phase after MT

MoOx nanoparticles anchored on N-doped porous carbon as Li-ion battery electrode

Transition-metal oxides based materials have recently been shown to be promising anode material for lithium ion batteries (LIBs) application to replace graphite material. In the present work, highly dispersed ultra-small MoOx nanoparticles anchored on N-doped three-dimensional (3D) hierarchically porous carbon (3D-MoOx@CN) are prepared on the basis of an efficient in-situ chelating and hard-templating strategy. The MoOx nanoparticles with particle sizes between 1.5 and 3.5 nm are observed to be anchored on the surface of the 3D N-doped carbon. The 3D-MoOx@CN composite anode electrode exhibits several appealing characteristics for lithium ion storage, including high specific capacity, good stability against cycling and fast charge transport kinetics. An optimized 3D-MoOx@CN sample (3D-MoOx@CN-700) delivers specific capacities of 742 mAh g−1 at current density of 100 mA g−1 and 431 mAh g−1 at 1000 mA g−1 after 1000 cycles, respectively. The observed excellent performance is due to the unique hierarchical pore structure with strong binding of the ultra-small MoOx nanoparticles onto N-doped carbon surface, which can avoid the agglomeration and alleviate the volume expansion of MoOx nanoparticles in the charge-discharge process. The composite electrode material described in this work holds a great potential for the development of high-performance lithium-ion batteries. Meanwhile, the synthesis method presents a common strategy to prepare other composite materials with highly dispersed metal oxide on the hierarchically porous carbon materials

Facile synthesis of N-doped carbon layer encapsulated Fe2N as an efficient catalyst for oxygen reduction reaction

Development of non-noble metal catalysts for oxygen reduction reaction (ORR) is of significant importance for the commercialization of fuel cells and metal-air batteries. Here we provide an efficient method to produce core-shell structured Fe-N-C catalyst via a facile in-situ chelating strategy by introducing ammonia iron citrate during the polymerization process of dopamine. The influence of calcination temperature and atmosphere on the physicochemical property and the activity of the catalyst are systematically evaluated. By calcination at 800 degrees C with NH3 atmosphere, Fe2N encapsulated with N doped carbon layers shows excellent activity with close onset and half wave potential (E-1/2) while better methanol crossover resistance than the Pt/C catalyst. The high activity could be due to the synergistic effect of Fe2N with the N-doped graphitic carbon layers and the mesoporous structure facilitating the mass transfer. Moreover, the simple synthesis process could provide a versatile routine to construct core-shell structured metal-N-C composite for a wild catalytic application. (C) 2017 Elsevier Ltd. All rights reserved

Periplocin suppresses the growth of colorectal cancer cells by triggering LGALS3 (galectin 3)-mediated lysophagy

Colorectal cancer (CRC) is one of the most common malignancies worldwide and remains a major clinical challenge. Periplocin, a major bioactive component of the traditional Chinese herb Cortex periplocae, has recently been reported to be a potential anticancer drug. However, the mechanism of action is poorly understood. Here, we show that periplocin exhibits promising anticancer activity against CRC both in vitro and in vivo. Mechanistically, periplocin promotes lysosomal damage and induces apoptosis in CRC cells. Notably, periplocin upregulates LGALS3 (galectin 3) by binding and preventing LGALS3 from Lys210 ubiquitination-mediated proteasomal degradation, leading to the induction of excessive lysophagy and resultant exacerbation of lysosomal damage. Inhibition of LGALS3-mediated lysophagy attenuates periplocin-induced lysosomal damage and growth inhibition in CRC cells, suggesting a critical role of lysophagy in the anticancer effects of periplocin. Taken together, our results reveal a novel link between periplocin and the lysophagy machinery, and indicate periplocin as a potential therapeutic option for the treatment of CRC.</p