Alzheimer disease (AD) accounts for 60-70% of dementia cases. Given the seriousness of the disease and continual increase in patient numbers, developing effective therapies to treat AD has become ...urgent. Presently, the drugs available for AD treatment, including cholinesterase inhibitors and an antagonist of the N-methyl-D-aspartate receptor, can only inhibit dementia symptoms for a limited period of time but cannot stop or reverse disease progression. On the basis of the amyloid hypothesis, many global drug companies have conducted many clinical trials on amyloid clearing therapy but without success. Thus, the amyloid hypothesis may not be completely feasible. The number of anti-amyloid trials decreased in 2019, which might be a turning point. An in-depth and comprehensive understanding of the contribution of amyloid beta and other factors of AD is crucial for developing novel pharmacotherapies.In ongoing clinical trials, researchers have developed and are testing several possible interventions aimed at various targets, including anti-amyloid and anti-tau interventions, neurotransmitter modification, anti-neuroinflammation and neuroprotection interventions, and cognitive enhancement, and interventions to relieve behavioral psychological symptoms. In this article, we present the current state of clinical trials for AD at clinicaltrials.gov. We reviewed the underlying mechanisms of these trials, tried to understand the reason why prior clinical trials failed, and analyzed the future trend of AD clinical trials.
A phototransistor based on a chemical vapor deposited (CVD) MoS2 monolayer exhibits a high photoresponsivity (2200 A W−1) and an excellent photogain (5000). The presence of shallow traps contributes ...to the persistent photoconductivity. Ambient adsorbates act as p‐dopants to MoS2, decreasing the carrier mobility, photoresponsivity, and photogain.
Contact engineering is a prerequisite for achieving desirable functionality and performance of semiconductor electronics, which is particularly critical for organic–inorganic hybrid halide ...perovskites due to their ionic nature and highly reactive interfaces. Although the interfaces between perovskites and charge‐transporting layers have attracted lots of attention due to the photovoltaic and light‐emitting diode applications, achieving reliable perovskite/electrode contacts for electronic devices, such as transistors and memories, remains as a bottleneck. Herein, a critical review on the elusive nature of perovskite/electrode interfaces with a focus on the interfacial electrochemistry effects is presented. The basic guidelines of electrode selection are given for establishing non‐polarized interfaces and optimal energy level alignment for perovskite materials. Furthermore, state‐of‐the‐art strategies on interface‐related electrode engineering are reviewed and discussed, which aim at achieving ohmic transport and eliminating hysteresis in perovskite devices. The role and multiple functionalities of self‐assembled monolayers that offer a unique approach toward improving perovskite/electrode contacts are also discussed. The insights on electrode engineering pave the way to advancing stable and reliable perovskite devices in diverse electronic applications.
Rational selection of electrodes plays a critical role in perovskite‐based electronics due to the high reactivity of halide perovskite materials. A comprehensive review of perovskite/electrode interfaces, as well as, state‐of‐the‐art contact engineering, which assists the development of perovskite‐based devices with inhibited interfacial reactions, ohmic carrier transport, and non‐hysteric electronic characteristics, is presented.
Neurological complications are common in patients with COVID-19. Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causal pathogen of COVID-19, has been detected in some ...patient brains, its ability to infect brain cells and impact their function is not well understood. Here, we investigated the susceptibility of human induced pluripotent stem cell (hiPSC)-derived monolayer brain cells and region-specific brain organoids to SARS-CoV-2 infection. We found that neurons and astrocytes were sparsely infected, but choroid plexus epithelial cells underwent robust infection. We optimized a protocol to generate choroid plexus organoids from hiPSCs and showed that productive SARS-CoV-2 infection of these organoids is associated with increased cell death and transcriptional dysregulation indicative of an inflammatory response and cellular function deficits. Together, our findings provide evidence for selective SARS-CoV-2 neurotropism and support the use of hiPSC-derived brain organoids as a platform to investigate SARS-CoV-2 infection susceptibility of brain cells, mechanisms of virus-induced brain dysfunction, and treatment strategies.
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•SARS-CoV-2 minimally infects human neurons and astrocytes in 2D and brain organoids•Model developed for hiPSC-derived choroid plexus organoids (CPOs)•SARS-CoV-2 productively infects CPOs and increases cell death•SARS-CoV-2 CPO infection leads to transcriptional upregulation of inflammatory genes
SARS-CoV-2 causes neurological symptoms in a significant portion of patients with COVID-19. Ming and colleagues tested SARS-CoV-2 neurotropism by using monolayer neural cells and brain organoids generated from human pluripotent stem cells and show minimal neuron and astrocyte infection but efficient choroid plexus infection, leading to cell death and functional deficits.
The development of “anode‐free” lithium‐metal batteries with high energy densities is, at present, mainly limited by the poor control of the nucleation of lithium directly on the copper current ...collector, especially in conventional carbonate electrolytes. It is therefore essential to improve the understanding of the lithium nucleation process and its interactions with the copper substrate. In this study, it is shown that diffusion of lithium into the copper substrate, most likely via the grain boundaries, can significantly influence the nucleation process. Such diffusion makes it more difficult to obtain a great number of homogeneously distributed lithium nuclei on the copper surface and thus leads to inhomogeneous electrodeposition. It is, however, demonstrated that the nucleation of lithium on copper is significantly improved if an initial chemical prelithiation of the copper surface is performed. This prelithiation saturates the copper surface with lithium and hence decreases the influence of lithium diffusion via the grain boundaries. In this way, the lithium nucleation can be made to take place more homogenously, especially when a short potentiostatic nucleation pulse that can generate a large number of nuclei on the surface of the copper substrate is applied.
Diffusion of lithium into the copper substrate, most likely via the grain boundaries, can significantly influence the nucleation process by making it more difficult to obtain a great number of homogeneously‐distributed lithium nuclei on the copper surface and thus leads to inhomogeneous electrodeposition. This problem can be mitigated by an initial chemical prelithiation of the copper surface.
Microdroplets display distinctive interfacial chemistry, manifested as accelerated reactions relative to those observed for the same reagents in bulk. Carbon dioxide undergoes C-N bond formation ...reactions with amines at the interface of droplets to form carbamic acids. Electrospray ionization mass spectrometry displays the reaction products in the form of the protonated and deprotonated carbamic acid. Electrosonic spray ionization (ESSI) utilizing carbon dioxide as nebulization gas, confines reaction to the gas-liquid interface where it proceeds much faster than in the bulk. Intriguingly, trace amounts of water accelerate the reaction, presumably by formation of superacid or superbase at the water interface. The suggested mechanism of protonation of CO
2
followed by nucleophilic attack by the amine is analogous to that previously advanced for imidazole formation from carboxylic acids and diamines.
Microdroplets display distinctive interfacial chemistry, manifested as accelerated reactions relative to those observed for the same reagents in bulk.
Metal‐halide perovskites have drawn profuse attention during the past decade, owing to their excellent electrical and optical properties, facile synthesis, efficient energy conversion, and so on. ...Meanwhile, the development of information storage technologies and digital communications has fueled the demand for novel semiconductor materials. Low‐dimensional perovskites have offered a new force to propel the developments of the memory field due to the excellent physical and electrical properties associated with the reduced dimensionality. In this review, the mechanisms, properties, as well as stability and performance of low‐dimensional perovskite memories, involving both molecular‐level perovskites and structure‐level nanostructures, are comprehensively reviewed. The property–performance correlation is discussed in‐depth, aiming to present effective strategies for designing memory devices based on this new class of high‐performance materials. Finally, the existing challenges and future opportunities are presented.
Low‐dimensional halide perovskites are among the most rapidly emerging building blocks for optoelectronic applications. This review elucidates the advantages and the crucial role of molecular‐/structure‐level low‐dimensional halide perovskites in achieving high performance and enhanced stability in memory applications.
Although it is widely believed that early vertebrate evolution was shaped by ancient whole-genome duplications, the number, timing and mechanism of these events remain elusive. Here, we infer the ...history of vertebrates through genomic comparisons with a new chromosome-scale sequence of the invertebrate chordate amphioxus. We show how the karyotypes of amphioxus and diverse vertebrates are derived from 17 ancestral chordate linkage groups (and 19 ancestral bilaterian groups) by fusion, rearrangement and duplication. We resolve two distinct ancient duplications based on patterns of chromosomal conserved synteny. All extant vertebrates share the first duplication, which occurred in the mid/late Cambrian by autotetraploidization (that is, direct genome doubling). In contrast, the second duplication is found only in jawed vertebrates and occurred in the mid-late Ordovician by allotetraploidization (that is, genome duplication following interspecific hybridization) from two now-extinct progenitors. This complex genomic history parallels the diversification of vertebrate lineages in the fossil record.
Summary
Many plant populations exhibit synchronous flowering, which can be advantageous in plant reproduction. However, molecular mechanisms underlying flowering synchrony remain poorly understood. ...We studied the role of known vernalization‐response and flower‐promoting pathways in facilitating synchronized flowering in Arabidopsis thaliana.
Using the vernalization‐responsive Col‐FRI genotype, we experimentally varied germination dates and daylength among individuals to test flowering synchrony in field and controlled environments. We assessed the activity of flowering regulation pathways by measuring gene expression across leaves produced at different time points during development and through a mutant analysis.
We observed flowering synchrony across germination cohorts in both environments and discovered a previously unknown process where flower‐promoting and repressing signals are differentially regulated between leaves that developed under different environmental conditions. We hypothesized this mechanism may underlie synchronization. However, our experiments demonstrated that signals originating from sources other than leaves must also play a pivotal role in synchronizing flowering time, especially in germination cohorts with prolonged growth before vernalization.
Our results suggest flowering synchrony is promoted by a plant‐wide integration of flowering signals across leaves and among organs. To summarize our findings, we propose a new conceptual model of vernalization‐induced flowering synchrony and provide suggestions for future research in this field.
Oil spill accidents are a key contributor to marine pollution worldwide. Therefore, timely and effective oil spill detection is crucial for reducing marine pollution and enhancing environmental ...protection. Against this backdrop, this study explored two methods for performing nearshore on-site oil spill detection and segmentation, namely the U-net and Mask region-based convolutional neural network (R-CNN) methods. The U-net and Mask R-CNN models were revealed to exhibit acceptable and favorable performance, achieving overall accuracy of 77.01 % and 89.02 %, respectively. Subsequently, a verification system based on the Geographic Information System (GIS) was developed to improve the performance of the deep-learning model. With the integration of the verification system, the Mask R-CNN model achieved higher overall accuracy of 90.78 %. The feasibility of applying deep-learning methods to nearshore on-site oil spill monitoring was demonstrated through this study. In addition, the integration of the GIS not only assisted in the provision of oil spill information but also in the improvement of the deep-learning models. The timely, accurate, and effective method for nearshore on-site oil spill monitoring that this study explored can be applied to considerably improve traditional on-site oil spill monitoring, which has received limited academic attention in the last two decades.
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•Well-trained Deep Learning models were used to help in nearshore oil spill monitoring.•Drawbacks in traditional oil spill monitoring were solved through DL and GIS.•The importance of temporal changes in oil spill detection was determined.
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