Following the severe acute respiratory syndrome coronavirus (SARS‐CoV) and Middle East respiratory syndrome coronavirus (MERS‐CoV), another highly pathogenic coronavirus named SARS‐CoV‐2 (previously ...known as 2019‐nCoV) emerged in December 2019 in Wuhan, China, and rapidly spreads around the world. This virus shares highly homological sequence with SARS‐CoV, and causes acute, highly lethal pneumonia coronavirus disease 2019 (COVID‐19) with clinical symptoms similar to those reported for SARS‐CoV and MERS‐CoV. The most characteristic symptom of patients with COVID‐19 is respiratory distress, and most of the patients admitted to the intensive care could not breathe spontaneously. Additionally, some patients with COVID‐19 also showed neurologic signs, such as headache, nausea, and vomiting. Increasing evidence shows that coronaviruses are not always confined to the respiratory tract and that they may also invade the central nervous system inducing neurological diseases. The infection of SARS‐CoV has been reported in the brains from both patients and experimental animals, where the brainstem was heavily infected. Furthermore, some coronaviruses have been demonstrated able to spread via a synapse‐connected route to the medullary cardiorespiratory center from the mechanoreceptors and chemoreceptors in the lung and lower respiratory airways. Considering the high similarity between SARS‐CoV and SARS‐CoV2, it remains to make clear whether the potential invasion of SARS‐CoV2 is partially responsible for the acute respiratory failure of patients with COVID‐19. Awareness of this may have a guiding significance for the prevention and treatment of the SARS‐CoV‐2‐induced respiratory failure.
Research Highlights
SARS‐CoV2 causes epidemic pneumonia characterized by acute respiratory distress.
This novel coronavirus is similar to SARS‐CoV in sequence, pathogenesis, and cellular entry.
Some coronaviruses can invade brainstem via a synapse‐connected route from the lung and airways.
The potential invasion of SARS‐CoV2 may be one reason for the acute respiratory failure.
Awareness of this will have guiding significance for the prevention and treatment.
In a recent review, we have suggested a neuroinvasive potential of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and its possible role in the causation of acute respiratory failure of ...coronavirus disease 2019 (COVID‐19) patients (J Med Viol doi: 10.1002/jmv.25728), based upon the clinical and experimental data available on the past SARS‐CoV‐1 and the recent SARS‐CoV‐2 pandemic. In this article, we provide new evidence recently reported regarding the neurotropic potential of SARS‐CoV‐2 and respond to several comments on our previously published article. In addition, we also discuss the peculiar manifestations of respiratory failure in COVID‐19 patients and the possible involvement of nervous system.
Highlights
New evidence has been available for the neurotropism of SARS‐CoV‐2.
Muscular injuries and reduced sensitivity of nerves may play a role in the respiratory failure.
Potential neuroinvasion of SARS‐CoV‐2 indicates a possible involvement of central factors.
Path planning remains a challenge for Unmanned Aerial Vehicles (UAVs) in dynamic environments with potential threats. In this paper, we have proposed a Deep Reinforcement Learning (DRL) approach for ...UAV path planning based on the global situation information. We have chosen the STAGE Scenario software to provide the simulation environment where a situation assessment model is developed with consideration of the UAV survival probability under enemy radar detection and missile attack. We have employed the dueling double deep Q-networks (D3QN) algorithm that takes a set of situation maps as input to approximate the Q-values corresponding to all candidate actions. In addition, the ε-greedy strategy is combined with heuristic search rules to select an action. We have demonstrated the performance of the proposed method under both static and dynamic task settings.
The palladium‐catalyzed asymmetric carboamination reaction is one of the most significant transformations in organic chemistry. Herein, we report the first palladium‐catalyzed asymmetric ...alleneamination of β,γ‐unsaturated hydrazones with propargylic acetates. This protocol enables the efficient installation of various multisubstituted allene groups onto dihydropyrazoles in good yields with excellent enantioselectivities. The chiral sulfinamide phosphine ligand Xu‐5 exhibits highly efficient stereoselective control in this protocol. The salient features of this reaction include the readily available starting materials, a broad substrate scope, an easy scale‐up, mild reaction conditions and versatile transformations.
A new robust palladium‐catalyzed enantioselective alleneamination reaction of β,γ‐unsaturated hydrazones with propargylic acetates is described. The salient features of this reaction include general substrate scope, good functional group tolerance, good yields and high enantioselectivities.
Proton is a charge carrier with the smallest ionic size and quickest kinetics, making aqueous proton batteries (APBs), a promising technology for safe and profitable energy storage systems. Despite ...being potential electrode materials, organic compounds have not yet been fully investigated in terms of proton storage properties and APB applications due to their low capacity and unstable cycle life in aqueous electrolytes. Herein, a novel redox‐active polymer (PDPZ) with diquinoxalino‐phenazine as the structural unit has been designed, which is further integrated with MXene nanosheets to construct a flexible PDPZ@MXene electrode material with a rapid and ultra‐stable proton storage behavior. In‐operando monitoring techniques, i.e., in situ Raman and in situ FTIR, demonstrate the highly reversible redox reaction between CN and CN/NH bonds in electro‐active PDPZ molecule with the strong proton absorption ability. Theoretical calculation further proves the electron transfer from MXene to PDPZ promotes the redox reaction of the PDPZ@MXene electrode. As a result, a flexible APB device is developed with a considerable energy density (64.3 mWh cm−3), a supercapacitor‐level power density (6000 mW cm−3), and a record lifespan with ≈98.2% capacity retention over 10 000 cycles, revealing its potential applications in satisfying the various requirements of energy storage systems.
A redox‐active polymer‐based flexible electrode with excellent proton coordination ability is developed, which exhibits rapid, ultra‐stable, and efficient proton redox charge‐storage characteristics as evidenced by in‐operando monitoring techniques and theoretical calculations. For real applications, a metal‐free, quasi‐solid, and flexible aqueous proton battery is effectively fabricated with high energy/power densities and a record long lifespan over 10 000 cycles.
A TEMPO promoted oxidative aza‐Diels‐Alder reaction of ketohydrazones with 3‐methyleneoxindoles or 2‐arylidene‐1,3‐indanediones were successfully developed, This reaction provided an efficient ...synthetic protocol for novel functionalized spiroindoline‐3,3′‐pyridazines and spiroindene‐2,3′‐pyridazines. This reaction showed high diastereoselectivity and strict substituent's electron effect, which might be due to the reaction mechanisms process including sequential oxidative generation of 1,2‐diaza‐1,3‐dien and normal electron‐demand aza‐Diels‐Alder reaction.
Spiroindoline‐3,3′‐pyridazine and spiroindene‐2,3′‐pyridazine were efficiently and diastereoselective synthesized from TEMPO‐promoted oxidative aza‐Diels‐Alder reaction of ketohydrazones.
Stable representation of information in distributed neural connectivity is critical to function effectively in the world. Despite the dynamic nature of the brain’s functional architecture, ...characterizing its temporal stability within a continuous state has been largely neglected. Here we characterized stability of functional architecture at a dynamic timescale (~1 min) for each brain voxel by measuring the concordance of dynamic functional connectivity (DFC) over time, compared between association and unimodal regions, and established its reliability using test-retest resting-state fMRI data of adults from an open dataset. After the measure of functional stability was established, we further employed another fMRI open dataset which included movie-watching and resting-state data of children and adolescents, to explore how stability was modified by natural viewing from its intrinsic form, with specific focus on the associative and primary visual cortices. The results showed that high-order association regions, especially the default mode network, demonstrated high stability during resting-state scans, while primary sensory-motor cortices revealed relatively lower stability. During movie watching, stability in the primary visual cortex was decreased, which was associated with larger DFC variation with neighboring regions. By contrast, higher-order regions in the ventral and dorsal visual stream demonstrated increased stability. The distribution of functional stability and its modification describes a profile of the brain’s stability property, which may be useful reference for examining distinct mental states and disorders.
•Functional stability is the concordance of dynamic functional connectivity over time.•High-order association regions show higher intrinsic stability than unimodal regions.•Natural viewing task increases stability in associative visual areas.•Natural viewing task decreases stability in primary visual areas.
Rumination is strongly and consistently correlated with depression. Although multiple studies have explored the neural correlates of rumination, findings have been inconsistent and the mechanisms ...underlying rumination remain elusive. Functional brain imaging studies have identified areas in the default mode network (DMN) that appear to be critically involved in ruminative processes. However, a meta-analysis to synthesize the findings of brain regions underlying rumination is currently lacking. Here, we conducted a meta-analysis consisting of experimental tasks that investigate rumination by using Signed Differential Mapping of 14 fMRI studies comprising 286 healthy participants. Furthermore, rather than treat the DMN as a unitary network, we examined the contribution of three DMN subsystems to rumination. Results confirm the suspected association between rumination and DMN activation, specifically implicating the DMN core regions and the dorsal medial prefrontal cortex subsystem. Based on these findings, we suggest a hypothesis of how DMN regions support rumination and present the implications of this model for treating major depressive disorder characterized by rumination.
•Rumination is strongly and consistently correlated with depression.•Meta-analyze the findings of brain regions regarding to rumination.•Specifically examined the contribution of three DMN subsystems to rumination.•Rumination is specifically correlated with the DMN core regions and the dorsal medial prefrontal cortex subsystem.
To provide instructive clues for clinical practice and further research of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection, we analyzed the existing literature on viral ...neuroinvasion of SARS‐CoV‐2 in coronavirus disease 2019 (COVID‐19) patients. To date, SARS‐CoV‐2 has been detected in the cerebrospinal fluid (CSF) or brain parenchyma in quite a few patients, which provide undeniable evidence for the neuroinvasive potential of this novel coronavirus. In contrast with the cerebrum and cerebellum, the detection rate of SARS‐CoV‐2 was higher in the olfactory system and the brainstem, both of which also showed severe microgliosis and lymphocytic infiltrations. As compared with the number of patients who underwent viral testing in the central nervous system (CNS), the number of patients showing positive results seems very small. However, it seems too early to conclude that the neuroinvasion of SARS‐CoV‐2 is rare in COVID‐19 patients because the detection methods or sampling procedures in some studies may not be suitable or sufficient to reveal the CNS infection induced by neurotropic viruses. Moreover, the primary symptoms and/or causes of death were distinctly different among examined patients, which probably caused more conspicuous pathological changes than those due to the direct infection that usually localized to specific brain areas. Unfortunately, most autopsy studies did not provide sufficient details about neurological symptoms or suspected diagnoses of the examined patients, and the documentation of neuropathological changes was often incomplete. Given the complex pathophysiology of COVID‐19 and the characteristics of neurotropic viruses, it is understandable that any study of the CNS infection may inevitably have limitations.
Highlights
We analyzed the papers on CSF testing and brain autopsies in COVID‐19 patients.
SARS‐CoV‐2 has been detected in the CSF or brain parenchyma in a few patients.
The detection rate of SARS‐CoV‐2 is high in the olfactory system and the brainstem.
Some detection methods are not sufficient to reveal the CNS infection of SARS‐CoV‐2.
Symptoms or death causes of examined patients are not often provided in some papers.
It cannot be simply concluded that viral neuroinvasion is rare in COVID‐19 patients.