Many intercellular solute transport processes require an apoplasmic step, that is, efflux from one cell and subsequent uptake by an adjacent cell. Cellular uptake transporters have been identified ...for many solutes, including sucrose; however, efflux transporters have remained elusive for a long time. Cellular efflux of sugars plays essential roles in many processes, such as sugar efflux as the first step in phloem loading, sugar efflux for nectar secretion, and sugar efflux for supplying symbionts such as mycorrhiza, and maternal efflux for filial tissue development. Furthermore, sugar efflux systems can be hijacked by pathogens for access to nutrition from hosts. Mutations that block recruitment of the efflux mechanism by the pathogen thus cause pathogen resistance. Until recently, little was known regarding the underlying mechanism of sugar efflux. The identification of sugar efflux carriers, SWEETs (Sugars Will Eventually be Exported Transporters), has shed light on cellular sugar efflux. SWEETs appear to function as uniporters, facilitating diffusion of sugars across cell membranes. Indeed, SWEET sprobably mediate sucrose efflux from putative phloem parenchyma into the phloem apoplasm, a key step proceeding phloem loading. Engineering of SWEET mutants using transcriptional activator-like effector nuclease (TALEN)- based genomic editing allowed the engineering of pathogen resistance. The widespread expression of the SWEET family promises to provide insights into many other cellular efflux mechanisms.
High-entropy and medium-entropy alloys are presumed to have a configurational entropy as high as that of an ideally mixed solid solution (SS) of multiple elements in near-equal proportions. However, ...enthalpic interactions inevitably render such chemically disordered SSs rare and metastable, except at very high temperatures. Here we highlight the wide variety of local chemical ordering (LCO) that sets these concentrated SSs apart from traditional solvent-solute ones. Using atomistic simulations, we reveal that the LCO of the multi-principal-element NiCoCr SS changes with alloy processing conditions, producing a wide range of generalized planar fault energies. We show that the LCO heightens the ruggedness of the energy landscape and raises activation barriers governing dislocation activities. This influences the selection of dislocation pathways in slip, faulting, and twinning, and increases the lattice friction to dislocation motion via a nanoscale segment detrapping mechanism. In contrast, severe plastic deformation reduces the LCO towards random SS.
Spirooxindoles are privileged scaffolds in diverse bioactive natural products and pharmaceuticals, significant achievements for the construction of these molecules have thus been made in the past ...years. Among them, organocatalysis, in particular, nucleophilic Lewis base catalysis, has recently emerged as an efficient and reliable method for the preparation of diverse and valuable functionalized spirooxindoles. According to different kinds of nucleophilic catalysts, we summarize and classify three catalytic strategies; these are tertiary amine‐catalyzed cycloadditions, NHC‐catalyzed cycloadditions, and tertiary phosphine‐catalyzed cycloadditions, respectively. Through these methods, potential bioactive spirooxindole skeletons owning various functional groups can be produced to enrich the small organic molecule library. In this review, we describe a comprehensive and updated advances of nucleophilic Lewis base catalytic cycloaddition reactions for the construction of spirooxindoles. Meanwhile, the related mechanism and the application of these annulation strategies in natural product total synthesis will be highlighted in detail.
This study investigates the nature and the extent of adolescences’ experience of cyberbullying. A survey study of 177 grade seven students in an urban city is conducted. In this paper, ...“cyberbullying” refers to bullying via electronic communication tools. The results show that almost 54% of the students were victims of traditional bullying and over a quarter of them had been cyber-bullied. Almost one in three students had bullied others in the traditional form, and almost 15% had bullied others using electronic communication tools. Almost 60% of the cyber victims are females, while over 52% of cyber-bullies are males. Majority of the cyber-bully victims and bystanders did not report the incidents to adults.
Fluorinated ketones are widely prevalent in numerous biologically interesting molecules, and the development of novel transformations to access these structures is an important task in organic ...synthesis. Herein, we report the multicomponent radical acylfluoroalkylation of a variety of olefins in the presence of various commercially available aromatic aldehydes and fluoroalkyl reagents through N‐heterocyclic carbene organocatalysis. With this protocol, over 120 examples of functionalized ketones with diverse fluorine substituents have been synthesized in up to 99 % yield with complete regioselectivity. The generality of this catalytic strategy was further highlighted by its successful application in the late‐stage functionalization of pharmaceutical skeletons. Excellent diastereoselectivity could be achieved in the reactions forging multiple stereocenters. In addition, preliminary results have been achieved on the catalytic asymmetric variant of the olefin difunctionalization process.
Organocatalytic acylfluoroalkylation: A multicomponent radical acylfluoroalkylation of olefins through NHC organocatalysis was developed, and over 120 examples of fluoroketones were facilely accessed from simple materials. Moreover, a dearomative difunctionalization of indoles could be readily achieved in a highly diastereoselective manner. The generality and practicality were highlighted by the late‐stage modification of drug skeletons.
Over the past decades, N‐heterocyclic carbene (NHC) organocatalysis has undergone a flourish of development on the basis of closed‐shell reaction paths. By contrast, the emerging area of ...single‐electron transfer (SET) reactions enabled by NHC catalysis still remain underdeveloped, but offer plenty of opportunities to develop new catalytic modes and useful synthetic methods. A number of interesting transformations were triggered by the SET process from the electron‐rich Breslow intermediates to various single‐electron acceptors. In additions, recent studies revealed that the Breslow radical cations could also be generated by single‐electron reduction of the electron‐deficient acyl azolium intermediates. These discoveries open a new avenue for NHC organocatalysis to harness radical reactions. The present review will focus on the exciting advancements in the dynamic area of radical NHC organocatalysis.
NHC organocatalysis: The development of N‐heterocyclic carbene (NHC) organocatalysis presents new opportunities in radical reactions. The Breslow intermediate‐based radical cations, which could be generated through single‐electron oxidation or reduction, enabled a series of novel radical transformations. These advancements greatly extend the synthetic potential of N‐heterocyclic carbene catalysis.
The reduction of survival motor neuron (SMN) protein causes spinal muscular atrophy (SMA), an autosomal recessive neuromuscular disease. Nusinersen is an antisense oligonucleotide, approved by the ...FDA, which specifically binds to the repressor within SMN2 exon 7 to enhance exon 7 inclusion and augment production of functional SMN protein. Nusinersen is the first new oligonucleotide-based drug targeting the central nervous system for the treatment of SMA. This review of nusinersen will discuss its action mechanism, cellular uptake, trafficking mechanisms, and administration approaches to cross the blood-brain barrier. Furthermore, nusinersen clinical trials will be assessed in terms of pharmacokinetics, tolerability and safety, the clinical outcomes of multiple intrathecal doses, and a discussion on the primary and secondary endpoints.
We intend to explore whether sleep duration is associated with overweight and obesity among the adult American population. Furthermore, we stratified the study population by age and sex in the ...subgroup analysis to investigate the potential disparities between adults and older adults, and men and women.
In total, 2459 individuals from the 2015-2016 National Health and Nutrition Examination Survey cycle were included for analysis in this study. Sleep duration was assessed by the Sleep Disorders Questionnaire. Classification of the short-sleep, normal-sleep, and long-sleep group was based on the recommendation of the National Sleep Foundation. Bodyweight was measured during the physical examination. Multivariate logistic regression models were implemented.
We observed a significantly higher overweight incidence in the short-sleep group compared to the normal-sleep group (OR = 1.825, 95%CI: 1.251-2.661, P = 0.004). Short-sleep (OR = 1.832, 95%CI: 1.215-2.762, P = 0.007) duration and long-sleep duration (OR = 1.370, 95%CI: 1.043-1.800, P = 0.027) were associated with higher prevalence of obesity. When stratified by age, short-sleep also increased the overweight and obese incidence 1.951 and 1.475 times in the adult group. In the sex-stratified subgroup analysis, the short-sleep group showed 2.49 times higher overweight incidence among females. The prevalence of obesity was 2.59 times higher in the short-sleep group and 1.698 times higher in the long-sleep group in the female population.
Sleep duration is associated with the occurrence of overweight and obesity, with sleep duration less than 7 h increase the overweight and obesity rate nearly 2 folds comparing to sleep 7-9 h.
Hardware implementation of artificial synaptic devices that emulate the functions of biological synapses is inspired by the biological neuromorphic system and has drawn considerable interest. Here, a ...three‐terminal ferrite synaptic device based on a topotactic phase transition between crystalline phases is presented. The electrolyte‐gating‐controlled topotactic phase transformation between brownmillerite SrFeO2.5 and perovskite SrFeO3−δ is confirmed from the examination of the crystal and electronic structure. A synaptic transistor with electrolyte‐gated ferrite films by harnessing gate‐controllable multilevel conduction states, which originate from many distinct oxygen‐deficient perovskite structures of SrFeOx induced by topotactic phase transformation, is successfully constructed. This three‐terminal artificial synapse can mimic important synaptic functions, such as synaptic plasticity and spike‐timing‐dependent plasticity. Simulations of a neural network consisting of ferrite synaptic transistors indicate that the system offers high classification accuracy. These results provide insight into the potential application of advanced topotactic phase transformation materials for designing artificial synapses with high performance.
A ferrite synaptic transistor with topotactic transformation is presented. The electrolyte‐gating‐controlled topotactic phase transformation between the brownmillerite SrFeO2.5 and perovskite SrFeO3−δ is confirmed by the crystal and electronic structure measurements. This ferrite synaptic transistor can mimic important synaptic functions such as synaptic plasticity and spike‐timing‐dependent plasticity.
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