Explore the vast range of titles available.

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. Insights into the rational design of single-atom metal catalysts remains obscure in heterogeneous catalysis. Here, the authors establish the atomic-level structure–activity relationship for a wide-pH-range hydrogen evolution reaction through the electronic metal–support interaction modulation.

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, Caenorhabditis (C.) elegans, 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.In this Review, Tan et al. provide an overview of the clinical and preclinical evidence that immune system dysfunction is involved in Parkinson disease, and discuss how increasing knowledge of the underlying mechanisms is driving development of immune-based therapeutic approaches.

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. The growth of single-atom catalysts remains a great challenge owing to favorable atom aggregation. Here, the authors report a self-limiting electrodeposition method for the fast, mild, and controllable synthesis of a library of single-atom catalysts.

We prove that quantum information propagates with a finite velocity in any model of interacting bosons whose (possibly time-dependent) Hamiltonian contains spatially local single-boson hopping terms along with arbitrary local density-dependent interactions. More precisely, with the density matrixρ∝exp[−μN](withNthe total boson number), ensemble-averaged correlators of the form⟨[A0,Br(t)]⟩, along with out-of-time-ordered correlators, must vanish as the distancerbetween two local operators grows, unlesst≥r/vfor some finite speedv. In one-dimensional models, we give a useful extension of this result that demonstrates the smallness of all matrix elements of the commutator[A0,Br(t)]between finite-density states ift/ris sufficiently small. Our bounds are relevant for physically realistic initial conditions in experimentally realized models of interacting bosons. In particular, we prove thatvcan scale no faster than linear in number density in the Bose-Hubbard model: This scaling matches previous results in the high-density limit. The quantum-walk formalism underlying our proof provides an alternative method for bounding quantum dynamics in models with unbounded operators and infinite-dimensional Hilbert spaces, where Lieb-Robinson bounds have been notoriously challenging to prove.

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.

Cadmium (Cd) is a highly toxic heavy metal in nature, which causes severe damage to plant growth. The molecular mechanisms for Cd detoxification are poorly understood. Here, we report that a G-type ATP-binding cassette transporter, OsABCG36, is involved in Cd tolerance in rice. OsABCG36 was expressed in both roots and shoots at a low level, but expression in the roots rather than the shoots was greatly up-regulated by a short exposure to Cd. A spatial expression analysis showed that Cd-induced expression of OsABCG36 was found in both the root tip and the mature root region. Transient expression of OsABCG36 in rice protoplast cells showed that it was localized to the plasma membrane. Immunostaining showed that OsABCG36 was localized in all root cells except the epidermal cells. Knockout of OsABCG36 resulted in increased Cd accumulation in root cell sap and enhanced Cd sensitivity, but did not affect tolerance to other metals including Al, Zn, Cu, and Pb. The concentration of Cd in the shoots was similar between the knockout lines and wild-type rice. Heterologous expression of OsABCG36 in yeast showed an efflux activity for Cd, but not for Zn. Taken together, our results indicate that OsABCG36 is not involved in Cd accumulation in the shoots, but is required for Cd tolerance by exporting Cd or Cd conjugates from the root cells in rice.

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.

Genome duplication (or polyploidization) has occurred throughout plant evolutionary history and is thought to have driven the adaptive radiation of plants. We found that the cytotype of the root, and not the genotype, determined the majority of heritable natural variation in leaf potassium (K) concentration in Arabidopsis thaliana. Autopolyploidy also provided resistance to salinity and may represent an adaptive outcome of the enhanced K accumulation of plants with higher ploidy.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has brought an unprecedented public health crisis and persistently threatens to humanity. With tireless efforts from scientists around the world, understanding of the biology of coronavirus has been greatly enhanced over the past 2 years. Structural biology has demonstrated its powerful impact on uncovering structures and functions for the vast majority of SARS-CoV-2 proteins and guided the development of drugs and vaccines against COVID-19. In this review, we summarize current progress in the structural biology of SARS-CoV-2 and discuss important biological issues that remain to be addressed. We present the examples of structure-based design of Pfizer’s novel anti-SARS-CoV-2 drug PF-07321332 (Paxlovid), Merck’s nucleotide inhibitor molnupiravir (Lagevrio), and VV116, an oral drug candidate for COVID-19. These examples highlight the importance of structure in drug discovery to combat COVID-19. We also discussed the recent variants of Omicron and its implication in immunity escape from existing vaccines and antibody therapies.