Heteromeric nicotinic ACh receptors (nAChRs) were thought to have two orthodox agonist‐binding sites at two α/β subunit interfaces. Highly selective ligands are hard to develop by targeting orthodox ...agonist sites because of high sequence similarity of this binding pocket among different subunits. Recently, unorthodox ACh‐binding sites have been discovered at some α/α and β/α subunit interfaces, such as α4/α4, α5/α4 and β3/α4. Targeting unorthodox sites may yield subtype‐selective ligands, such as those for (α4β2)2α5, (α4β2)2β3 and (α6β2)2β3 nAChRs. The unorthodox sites have unique pharmacology. Agonist binding at one unorthodox site is not sufficient to activate nAChRs, but it increases activation from the orthodox sites. NS9283, a selective agonist for the unorthodox α4/α4 site, was initially thought to be a positive allosteric modulator (PAM). NS9283 activates nAChRs with three engineered α4/α4 sites. PAMs, on the other hand, act at allosteric sites where ACh cannot bind. Known PAM sites include the ACh‐homologous non‐canonical site (e.g. morantel at β/α), the C‐terminus (e.g. Br‐PBTC and 17β‐estradiol), a transmembrane domain (e.g. LY2087101) or extracellular and transmembrane domain interfaces (e.g. NS206). Some of these PAMs, such as Br‐PBTC and 17β‐estradiol, require only one subunit to potentiate activation of nAChRs. In this review, we will discuss differences between activation from orthosteric and allosteric sites, their selective ligands and clinical implications. These studies have advanced understanding of the structure, assembly and pharmacology of heteromeric neuronal nAChRs.
Linked Articles
This article is part of a themed section on Nicotinic Acetylcholine Receptors. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.11/issuetoc
The adverse effects of loneliness and of poor perceived social support on physical health and mortality are established, but no systematic synthesis is available of their relationship with the ...outcomes of mental health problems over time. In this systematic review, we aim to examine the evidence on whether loneliness and closely related concepts predict poor outcomes among adults with mental health problems.
We searched six databases and reference lists for longitudinal quantitative studies that examined the relationship between baseline measures of loneliness and poor perceived social support and outcomes at follow up. Thirty-four eligible papers were retrieved. Due to heterogeneity among included studies in clinical populations, predictor measures and outcomes, a narrative synthesis was conducted.
We found substantial evidence from prospective studies that people with depression who perceive their social support as poorer have worse outcomes in terms of symptoms, recovery and social functioning. Loneliness has been investigated much less than perceived social support, but there is some evidence that greater loneliness predicts poorer depression outcome. There is also some preliminary evidence of associations between perceived social support and outcomes in schizophrenia, bipolar disorder and anxiety disorders.
Loneliness and quality of social support in depression are potential targets for development and testing of interventions, while for other conditions further evidence is needed regarding relationships with outcomes.
The aim of this study was to investigate the effect of natural organic matter (NOM) including humic acid (HA) and fulvic acid (FA), intracellular organic matter (IOM) extracted from Microcystis ...aeruginosa (MA) and Chlorella sp. (CH), and their different molecular weight (MW) fractions on the aerobic denitrification performance of bacterial strain WGX-9 by monitoring nitrogen removal efficiency and testing changes in organic matter with HA, FA, MA-IOM and CH-IOM as the sole carbon source. Strain WGX-9 was identified as Acinetobacter johnsonii and exhibited excellent aerobic denitrification capability. The nitrate removal efficiency with IOM as the sole carbon source was relatively higher than that with NOM as the sole carbon source. The prepared NOM and extracted IOM samples were separated into six fractions with MW cut-offs of 100, 30, 10, 5 and 1 kDa. The fraction of MW > 100 kDa contributed the largest amount to the MW distribution, accounting for 77.11%, 29.00%, 44.97% and 24.81% of HA, FA, MA-IOM, and CH-IOM, respectively. Nitrate removal efficiency was improved with decreasing MW of organic matter. For example, nitrate removal efficiency was 26.50%, 32.41%, 27.88% and 43.89% using HA, FA, MA-IOM, and CH-IOM fractions of MW > 100 kDa as the carbon source, whereas with MW < 1 kDa, it increased to 36.67%, 37.88%, 60.90%, and 68.90%, respectively. This is probably because the smaller MW fraction is more suitable for bacterial growth. These results demonstrate that the strain WGX-9 can utilize lower MW organic matter, which lays the foundations for nitrogen removal in actual drinking water reservoirs.
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•Acinetobacter johnsonii WGX-9 has excellent aerobic denitrification performance.•IOM as carbon source show higher nitrate removal relative to NOM, but lower than sodium acetate.•The nitrate removal efficiency was improved with the MW of organic matter decrease.•The tyrosine/tryptophan-like organic matter are preferentially used by microorganisms.
In recent years, carbon neutrality has received increasing attention to alleviate climate and environmental problems. Electrocatalytic CO2 reduction towards syngas can be an efficient and sustainable ...strategy to mitigate the greenhouse gas effect. While the challenges of this technique lie in its high overpotential, poor selectivity, and difficulty of accurate regulation for syngas composition ratio. In this review, we analyze the catalytic mechanisms of electrochemical CO2-to-syngas conversion, and introduce various types of catalysts for CO2RR towards syngas. Emphatically, the effective strategies to improve the catalytic efficiency of electrochemical CO2-to-syngas conversion have been comprehensively summarized, including surface modification of catalyst, structural design of double active sites catalysts, morphology control of catalysts, anodic reaction coupling, and combination of CO2 capture and CO2 reduction. Then, the strategies for large-scale electrochemical CO2 reduction are presented, involving the scalable production of catalysts and reactor engineering strategies for industrial application. Finally, the future development guidelines for electrochemical CO2-to-syngas conversion are discussed. Our review paves the way to develop efficient electrocatalysts for enhanced CO2-to-syngas conversion and application.
•The catalytic mechanisms of CO2-to-syngas conversion are analyzed.•The various types of catalysts for CO2RR towards syngas are introduced.•The strategies to improve the catalytic efficiency have been summarized.•The future development guidelines for CO2-to-syngas conversion are discussed.
Covalent organic frameworks (COFs) represent an emerging class of organic photocatalysts. However, their complicated structures lead to indeterminacy about photocatalytic active sites and reaction ...mechanisms. Herein, we use reticular chemistry to construct a family of isoreticular crystalline hydrazide-based COF photocatalysts, with the optoelectronic properties and local pore characteristics of the COFs modulated using different linkers. The excited state electronic distribution and transport pathways in the COFs are probed using a host of experimental methods and theoretical calculations at a molecular level. One of our developed COFs (denoted as COF-4) exhibits a remarkable excited state electron utilization efficiency and charge transfer properties, achieving a record-high photocatalytic uranium extraction performance of ~6.84 mg/g/day in natural seawater among all techniques reported so far. This study brings a new understanding about the operation of COF-based photocatalysts, guiding the design of improved COF photocatalysts for many applications.
In the past two decades, single-walled carbon nanotubes (SWNTs) have been explored for electronic applications because of their high charge carrier mobility, low-temperature solution processability ...and mechanical flexibility. Semiconducting SWNTs (s-SWNTs) are also considered an alternative to traditional silicon-based semiconductors. However, large-scale, as-produced SWNTs have poor solubility, and they are mixtures of metallic SWNTs (m-SWNTs) and s-SWNTs, which limits their practical applications. Conjugated polymer wrapping is a promising method to disperse and separate s-SWNTs, due to its high selectivity, high separation yield and simplicity of operation. In this review, we summarize the recent progress of the conjugated polymer wrapping method, and discuss possible separation mechanisms for s-SWNTs. We also discuss various parameters that may affect the selectivity and sorting yield. Finally, some electronic applications of polymer-sorted s-SWNTs are introduced. The aim of this review is to provide polymer chemist a basic concept of polymer based SWNT separation, as well as some polymer design strategies, influential factors and potential applications.
China’s environmental tax aims to encourage technological innovation and achieve a win–win situation between the economy and the environment. Based on the panel data of A-share listed enterprises in ...heavy polluting industries in China from 2011 to 2019, this paper empirically examines how environmental taxes affect the development of heavy polluting enterprises. The main results are as follows: (i) Environmental taxes increase innovation and bring economic benefits to innovative enterprises, and thus, the “strong version” of the Porter hypothesis is validated. (ii) The effect on the quality of innovation is heterogeneous across tax regions. Specifically, a high environmental tax rate is more conducive to the improvement of innovation quality, and the intermediary effect of innovation quality is significant only in high tax rate regions. Further research finds that other environmental policies, such as environmental subsidies and R&D subsidies, play an important role in improving the quality of technological innovation. Well-designed policy combinations can correct the “distortion” of innovation that results from environmental taxes. A series of recommendations are proposed to improve the overall effect of environmental tax strategies.
Selenium ions are toxic at concentrations of >40ppb (40μgL−1) which has been a very challenging environmental issue. Compared to Se (IV), Se (VI) is more bioavailable and much more difficult to ...remove from water. Conventional adsorbent materials only show well defined removal capacity for Se (IV) while performing poorly for Se (VI) (typical removal percentage <50%). In this report, functionalized water-dispersible magnetic nanoparticle–graphene oxide (MGO) composites were synthesized, characterized and applied to remove selenium ions (both Se (IV) and Se (VI)) in aqueous system. MGO (dosage 1gL−1) shows removal percentage of >99.9% for Se (IV) and ∼80% for Se (VI) from water (pH 6–7) within 10s. Effect of pH ranging from 2 to 11 was investigated, and the results show that acidic pH enhances the adsorption of selenium ions on MGO resulting in an increased removal percentage of Se (VI) to >95% at pH ∼2. MGO can be separated effectively under an external magnetic field and recycled for reuse in water treatment. Our results show that MGO composites have favorable removal capability of both selenite and selenate in water with important potential practical applications in removing selenium from wastewater.
Deep neural networks (DNN) have been shown to be useful in a wide range of applications. However, they are also known to be vulnerable to adversarial samples. By transforming a normal sample with ...some carefully crafted human imperceptible perturbations, even highly accurate DNN make wrong decisions. Multiple defense mechanisms have been proposed which aim to hinder the generation of such adversarial samples. However, a recent work show that most of them are ineffective. In this work, we propose an alternative approach to detect adversarial samples at runtime. Our main observation is that adversarial samples are much more sensitive than normal samples if we impose random mutations on the DNN. We thus first propose a measure of 'sensitivity' and show empirically that normal samples and adversarial samples have distinguishable sensitivity. We then integrate statistical hypothesis testing and model mutation testing to check whether an input sample is likely to be normal or adversarial at runtime by measuring its sensitivity. We evaluated our approach on the MNIST and CIFAR10 datasets. The results show that our approach detects adversarial samples generated by state-of-the-art attacking methods efficiently and accurately.
Purpose
Social isolation and related concepts have been discussed increasingly in the field of mental health. Despite this, there is a lack of conceptual clarity and consistency in the definition and ...operationalisation of these terms. This review aimed to provide a clear framework for social isolation and related concepts, and to identify well-established measures in the field of mental health for each conceptual domain discussed.
Methods
We used an iterative strategy of expert consultation and literature searching. A multi-disciplinary group of senior academics was consulted both before and after the literature searching to identify relevant terms, conceptual papers, or recommended measures. Our conceptual framework was also validated through expert consultation. We searched the Web of Science database using terms suggested by experts and subsequently identified further relevant studies through review articles and by reading full texts and reference lists of included studies. A narrative synthesis was conducted.
Results
We developed a model with five domains incorporating all the concepts relevant to social isolation in regular use in the mental health research literature. These five domains are: social network—quantity; social network—structure; social network—quality; appraisal of relationships—emotional; and appraisal of relationships—resources. We also identified well-developed measures suitable for assessing each of the five conceptual domains or covering multi-domains.
Conclusions
Our review proposes a conceptual model to encompass and differentiate all terms relating to social isolation. Potential uses are in allowing researchers and intervention developers to identify precisely the intended outcomes of interventions, and to choose the most appropriate measures to use in mental health settings.
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