Abstract
Tuning metal–support interaction has been considered as an effective approach to modulate the electronic structure and catalytic activity of supported metal catalysts. At the atomic level, ...the understanding of the structure–activity relationship still remains obscure in heterogeneous catalysis, such as the conversion of water (alkaline) or hydronium ions (acid) to hydrogen (hydrogen evolution reaction, HER). Here, we reveal that the fine control over the oxidation states of single-atom Pt catalysts through electronic metal–support interaction significantly modulates the catalytic activities in either acidic or alkaline HER. Combined with detailed spectroscopic and electrochemical characterizations, the structure–activity relationship is established by correlating the acidic/alkaline HER activity with the average oxidation state of single-atom Pt and the Pt–H/Pt–OH interaction. This study sheds light on the atomic-level mechanistic understanding of acidic and alkaline HER, and further provides guidelines for the rational design of high-performance single-atom catalysts.
Parkinson's disease (PD) is the most common movement disorder with motor and nonmotor signs. The current therapeutic regimen for PD is mainly symptomatic as the etio-pathophysiology has not been ...fully elucidated. A variety of animal models has been generated to study different aspects of the disease for understanding the pathogenesis and therapeutic development. The disease model can be generated through neurotoxin-based or genetic-based approaches in a wide range of animals such as non-human primates (NHP), rodents, zebrafish,
(
)
, and drosophila. Cellular-based disease model is frequently used because of the ease of manipulation and suitability for large-screen assays. In neurotoxin-induced models, chemicals such as 6-hydroxydopamine (6-OHDA), 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), rotenone, and paraquat are used to recapitulate the disease. Genetic manipulation of PD-related genes, such as α-Synuclein(SNCA), Leucine-rich repeat kinase 2 (LRRK2), Pten-Induced Kinase 1 (PINK1), Parkin(PRKN), and Protein deglycase (DJ-1) Are used in the transgenic models. An emerging model that combines both genetic- and neurotoxin-based methods has been generated to study the role of the immune system in the pathogenesis of PD. Here, we discuss the advantages and limitations of the different PD models and their utility for different research purposes.
Multiple lines of evidence indicate that immune system dysfunction has a role in Parkinson disease (PD); this evidence includes clinical and genetic associations between autoimmune disease and PD, ...impaired cellular and humoral immune responses in PD, imaging evidence of inflammatory cell activation and evidence of immune dysregulation in experimental models of PD. However, the mechanisms that link the immune system with PD remain unclear, and the temporal relationships of innate and adaptive immune responses with neurodegeneration are unknown. Despite these challenges, our current knowledge provides opportunities to develop immune-targeted therapeutic strategies for testing in PD, and clinical studies of some approaches are under way. In this Review, we provide an overview of the clinical observations, preclinical experiments and clinical studies that provide evidence for involvement of the immune system in PD and that help to define the nature of this association. We consider autoimmune mechanisms, central and peripheral inflammatory mechanisms and immunogenetic factors. We also discuss the use of this knowledge to develop immune-based therapeutic approaches, including immunotherapy that targets α-synuclein and the targeting of immune mediators such as inflammasomes. We also consider future research and clinical trials necessary to maximize the potential of targeting the immune system.
Abstract
The growth of atomically dispersed metal catalysts (ADMCs) remains a great challenge owing to the thermodynamically driven atom aggregation. Here we report a surface-limited ...electrodeposition technique that uses site-specific substrates for the rapid and room-temperature synthesis of ADMCs. We obtained ADMCs by the underpotential deposition of a non-noble single-atom metal onto the chalcogen atoms of transition metal dichalcogenides and subsequent galvanic displacement with a more-noble single-atom metal. The site-specific electrodeposition enables the formation of energetically favorable metal–support bonds, and then automatically terminates the sequential formation of metallic bonding. The self-terminating effect restricts the metal deposition to the atomic scale. The modulated ADMCs exhibit remarkable activity and stability in the hydrogen evolution reaction compared to state-of-the-art single-atom electrocatalysts. We demonstrate that this methodology could be extended to the synthesis of a variety of ADMCs (Pt, Pd, Rh, Cu, Pb, Bi, and Sn), showing its general scope for functional ADMCs manufacturing in heterogeneous catalysis.
Objective
Radical lymph node dissection (LND) along the bilateral recurrent laryngeal nerve (RLN) is a surgically challenging procedure with a high rate of morbidity. Here, we assessed in a ...retrospective manner the adequacy of LND along the RLN performed with robot-assisted thoracoscopic esophagectomy (RATE) versus video-assisted thoracoscopic esophagectomy (VATE) in patients with esophageal squamous cell carcinoma (ESCC).
Methods
This was a single-center, retrospective, propensity-matched study. ESCC patients who underwent McKeown esophagectomy and bilateral RLN LND with a minimally invasive approach were divided into two groups according to the use of robot-assisted surgery or not (RATE vs VATE, respectively). Using propensity score matching, 34 balanced matched pairs were identified. The number of dissected nodes as well as the rates of RLN palsy and perioperative complications served as the main outcome measures.
Results
No conversion to open thoracotomy occurred in either group. Intraoperative blood loss and the need of blood transfusions did not show significant intergroup differences. The mean number of dissected nodes was similar in the two study groups, the only exception being the left RLN area. Specifically, the mean number of nodes removed from this region was 5.32 in the RATE group and 3.38 in patients who received VATE (
p
= 0.007). Notably, the RATE and VATE groups did not differ significantly with regard to rates of both RLN palsy (20.6 vs 29.4%, respectively,
p
= 0.401) and pulmonary complications (5.9 vs 17.6%, respectively,
p
= 0.259).
Conclusions
Compared with VATE, RATE resulted in a higher lymph node yield along the left RLN without increasing morbidity.
Summary
Iron (Fe) homeostasis is essential for both plant development and human nutrition. The maintenance of Fe homeostasis involves a complex network in which Fe signaling nodes and circuits ...coordinate tightly Fe transporters, ferric reductases, H+‐ATPases, low‐molecular‐mass metal chelators, and transporters of chelators and Fe–chelate complexes. Early‐stage studies have revealed different strategies for Fe homeostasis between graminaceous and nongraminaceous plants. Recent progress has refreshed our understanding of previous knowledge, especially on the uptake, phloem transport and systemic signaling of Fe. This review attempts to summarize recent exciting and potentially influential studies on the various routes of Fe uptake and distribution in plants, focusing on breakthroughs that have changed our understanding of plant Fe nutrition.
Methanol, being electron rich and derivable from methane or CO2, is a potentially renewable one-carbon (C1) feedstock for microorganisms. Although the ribulose monophosphate (RuMP) cycle used by ...methylotrophs to assimilate methanol differs from the typical sugar metabolism by only three enzymes, turning a non-methylotrophic organism to a synthetic methylotroph that grows to a high cell density has been challenging. Here we reprogrammed E. coli using metabolic robustness criteria followed by laboratory evolution to establish a strain that can efficiently utilize methanol as the sole carbon source. This synthetic methylotroph alleviated a so far uncharacterized hurdle, DNA-protein crosslinking (DPC), by insertion sequence (IS)-mediated copy number variations (CNVs) and balanced the metabolic flux by mutations. Being capable of growing at a rate comparable with natural methylotrophs in a wide range of methanol concentrations, this synthetic methylotrophic strain illustrates genome editing and evolution for microbial tropism changes and expands the scope of biological C1 conversion.
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•E. coli was engineered to grow on methanol alone by rational design and evolution•A doubling time of 8.5 h and maximum OD of 2 were achieved•Formaldehyde-induced DNA-protein crosslinking was identified and solved•Copy number variation of a region spanning 70kb facilitates carbon source shifts
Chen et al. demonstrate genetic reprogramming of E. coli to efficiently grow with methanol as the sole carbon source.
Perampanel is an aryl substituted 2-pyridone AMPA receptor antagonist that was recently approved as a treatment for epilepsy. The drug potently inhibits AMPA receptor responses but the mode of block ...has not been characterized. Here the action of perampanel on AMPA receptors was investigated by whole-cell voltage-clamp recording in cultured rat hippocampal neurons. Perampanel caused a slow (τ∼1 s at 3 µM), concentration-dependent inhibition of AMPA receptor currents evoked by AMPA and kainate. The rates of block and unblock of AMPA receptor currents were 1.5×105 M-1 s-1 and 0.58 s-1, respectively. Perampanel did not affect NMDA receptor currents. The extent of block of non-desensitizing kainate-evoked currents (IC50, 0.56 µM) was similar at all kainate concentrations (3-100 µM), demonstrating a noncompetitive blocking action. Parampanel did not alter the trajectory of AMPA evoked currents indicating that it does not influence AMPA receptor desensitization. Perampanel is a selective negative allosteric AMPA receptor antagonist of high-affinity and slow blocking kinetics.
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