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Viologen-based porous organic polymers with a hollow structure were synthesized via a Sonogashira–Hagihara cross-coupling reaction. They showed excellent catalytic performance for the carbon-dioxide cycloaddition reaction.

Magnetic resonance imaging (MRI) studies are sensitive to biological mechanisms of neuroplasticity in white matter (WM). In particular, diffusion tensor imaging (DTI) has been used to investigate structural changes. Historically, functional MRI (fMRI) neuroplasticity studies have been restricted to gray matter, as fMRI studies have only recently expanded to WM. The current study evaluated WM neuroplasticity pre–post motor training in healthy adults, focusing on motor learning in the non-dominant hand. Neuroplasticity changes were evaluated in two established WM regions-of-interest: the internal capsule and the corpus callosum. Behavioral improvements following training were greater for the non-dominant hand, which corresponded with MRI-based neuroplasticity changes in the internal capsule for DTI fractional anisotropy, fMRI hemodynamic response functions, and low-frequency oscillations (LFOs). In the corpus callosum, MRI-based neuroplasticity changes were detected in LFOs, DTI, and functional correlation tensors (FCT). Taken together, the LFO results converged as significant amplitude reductions, implicating a common underlying mechanism of optimized transmission through altered myelination. The structural and functional neuroplasticity findings open new avenues for direct WM investigations into mapping connectomes and advancing MRI clinical applications. Supplementary Information The online version contains supplementary material available at 10.1007/s00429-021-02407-4.

HSV-1 is a typical neurotropic virus that infects the brain and causes keratitis, cold sores, and occasionally, acute herpes simplex encephalitis (HSE). The large amount of proinflammatory cytokines induced by HSV-1 infection is an important cause of neurotoxicity in the central nervous system (CNS). Microglia, as resident macrophages in CNS, are the first line of defense against neurotropic virus infection. Inhibiting the excessive production of inflammatory cytokines in overactivated microglia is a crucial strategy for the treatment of HSE. In the present study, we investigated the effect of nicotinamide n-oxide (NAMO), a metabolite mainly produced by gut microbe, on HSV-1-induced microglial inflammation and HSE. We found that NAMO significantly inhibits the production of cytokines induced by HSV-1 infection of microglia, such as IL-1β, IL-6, and TNF-α. In addition, NAMO promotes the transition of microglia from the pro-inflammatory M1 type to the anti-inflammatory M2 type. More detailed studies revealed that NAMO enhances the expression of Sirtuin-1 and its deacetylase enzymatic activity, which in turn deacetylates the p65 subunit to inhibit NF-κB signaling, resulting in reduced inflammatory response and ameliorated HSE pathology. Therefore, Sirtuin-1/NF-κB axis may be promising therapeutic targets against HSV-1 infection-related diseases including HSE.

Heterostructured non-precious metal phosphides have attracted increasing attention in the development of high-performance catalysts for hydrogen evolution reaction (HER), particularly in acidic media. Herein, a catalyst composed of ternary Ni5P4-NiP2-Ni2P nanocomposites and N-doped carbon nanotubes/carbon particulates (Ni5P4-NiP2-Ni2P/NC) was prepared from a Ni-containing hybrid precursor through approaches of a successive carbonization and phosphating reaction. Benefiting from the synergistic effect from three-component nickel phosphides and the support role of porous carbon network, the Ni5P4-NiP2-Ni2P/N-doped carbon catalyst presents the promising HER performance with overpotentials of 168 and 202 mV at the current density of 10 mA cm−2 and Tafel slopes of 69.0 and 74 mV dec−1 in both acidic and alkaline solutions, respectively, which surpasses the Ni2P/N-doped carbon counterpart. This work provides an effective strategy for the preparation and development of highly efficient HER non-precious metal electrocatalysts by creating heterostructure in acidic and alkaline media.

Polyimide covalent organic framework (PI-COF) materials that can realize intrinsic redox reactions by changing the charge state of their electroactive sites are considered as emerging electrode materials for rechargeable devices. However, the highly crystalline PI-COFs with hierarchical porosity are less reported due to the rapid reaction between monomers and the poor reversibility of the polyimidization reaction. Here, we developed a water-assistant synthetic strategy to adjust the reaction rate of polyimidization, and PI-COF (COFTPDA-PMDA) with kgm topology consisting of dual active centers of N,N,N',N'-tetrakis(4-aminophenyl)-1,4-benzenediamine (TPDA) and pyromellitic dianhydride (PMDA) ligands was successfully synthesized with high crystallinity and porosity. The COFTPDA-PMDA possesses hierarchical micro-/mesoporous channels with the largest surface area (2669 m2/g) in PI-COFs, which can promote the Li+ ions and bulky bis(trifluoromethanesulfonyl)imide (TFSI-) ions in organic electrolyte to sufficiently interact with the dual active sites on COF skeleton to increase the specific capacity of cathode materials. As a cathode material for lithium-ion batteries, COFTPDA-PMDA@50%CNT which integrated high surface area and dual active center of COFTPDA-PMDA with carbon nanotubes via π-π interactions gave a high initial charge capacity of 233 mAh/g (0.5 A/g) and maintains at 80 mAh/g even at a high current density of 5.0 A/g after 1800 cycles. This work was supported by the Jilin Province Science and Technology Development Plan (20210101112JC and 20220101048JC), the National Natural Science Foundation of China (21871104, 21621001, 22288101, and 22133005), the Natural Science foundation of Shanghai (20ZR1427600), and the Opening Project of State Key Laboratory of High Performance Ceramics and Superfine Microstructure (SKL202105SIC).

Deep learning (DL) on brain magnetic resonance imaging (MRI) data has shown excellent performance in differentiating individuals with Alzheimer's disease (AD). However, the value of DL in detecting progressive structural MRI (sMRI) abnormalities linked to AD pathology has yet to be established. In this study, an interpretable DL algorithm named the Ensemble of 3-dimensional convolutional neural network (Ensemble 3DCNN) with enhanced parsing techniques is proposed to investigate the longitudinal trajectories of whole-brain sMRI changes denoting AD onset and progression. A set of 2369 T1-weighted images from the multi-centre Alzheimer's Disease Neuroimaging Initiative and Open Access Series of Imaging Studies cohorts are applied to model derivation, validation, testing, and pattern analysis. An Ensemble-3DCNN-based P-score is generated, based on which multiple brain regions, including amygdala, insular, parahippocampal, and temporal gyrus, exhibit early and connected progressive neurodegeneration. Complex individual variability in the sMRI is also observed. This study combining non-invasive sMRI and interpretable DL in detecting patterned sMRI changes confirmed AD pathological progression, shedding new light on predicting AD progression using whole-brain sMRI.

Objectives: Psychological capital is the core element that represents individual initiative, which lays an important foundation for individual to gain competitive advantage. In the team organization, the employee’s active psychological resource is the main source of the organizational innovation power. Therefore, the factors that influence the organization innovation based on the team creativity of QCA analysis are analyzed in this paper. Methods: Based on the analysis of the basic principle of psychological capital and the atmosphere, motivation and performance of team innovation, the mechanism of interaction between mental capital and team innovation, it is found out that innovation is the embodiment of employee psychological capital are explored in this paper. Results: And a model of innovation power based on psychological capital is proposed. The validity and reliability of the model are validated by QCA analysis. Conclusion: The simulation results show that the research has found out the mechanism of team creativity on organizational innovation, and it has a good reference meaning and application value to improve the creative power of team innovation.

Microglia are the primary cellular source of type I interferons (I-IFNs) in the brain upon neurotropic virus infection. Although the I-IFN-based antiviral innate immune response is crucial for eliminating viruses, overproduction led to immune disorders. Therefore, the relatively long-lasting I-IFNs must be precisely controlled, but the regulatory mechanism for the innate antiviral response in microglia remains largely unknown. Long non-coding RNAs (lncRNAs) are being recognized as crucial factors in numerous diseases, but their regulatory roles in the innate antiviral response in microglia are undefined. Methods: The high-throughput RNA sequencing was performed to obtain differentially expressed lncRNAs (DELs) in primary microglia infected with or without the neurotropic herpes simplex virus type 1 (HSV-1). We selected four DELs ranked in the top 15 in basic level and their fold change induced by HSV-1, i.e., FPKMHSV-1/FPKMCells.We subsequently found a key lncRNA affecting the innate antiviral response of microglia significantly. We next used dual-luciferase reporter assays, bioinformatical tools, and truncation mutants of both lncRNA and targeted proteins to elucidate the downstream and upstream mechanism of action of lncRNA. Further, we established microglia-specific knock-in (KI) mice to investigate the role of lncRNA in vivo. Results: We identified a long intergenic non-coding RNA, linc-AhRA, involved in regulating the innate antiviral response in murine microglia. linc-AhRA is activated by aryl hydrocarbon receptor (AhR) and restricts I-IFN production in microglia upon neurotropic herpesvirus infection and innate immune stimulation. Mechanistically, linc-AhRA binds to both tripartite motif-containing 27 (TRIM27) and TANK-binding kinase 1 (TBK1) through its conserved 117nt fragment as a molecular scaffold to enhance TRIM27-TBK1 interaction. This interaction facilitates the TRIM27-mediated ubiquitination of TBK1 and results in ubiquitin-proteasome-dependent degradation of TBK1. Consequently, linc-AhRA suppresses I-IFN production through facilitating TBK1 degradation and limits the microglial innate immune response against neurotropic herpesvirus infection. Microglia-specific KI of linc-AhRA mice shows a weakened antiviral immune response upon neurotropic herpesvirus challenge due to a reduction of TBK1 in microglia. Conclusion: Our findings indicate that linc-AhRA is a negative regulator of I-IFN production in microglia to avoid excessive autoimmune responses. These findings uncover a previously unappreciated role for lncRNA conserved fragments in the innate antiviral response, providing a strong foundation for developing nucleotide drugs based on conserved functional fragments within lncRNAs., Theranostics, 11(19), pp. 9623-9651; 2021

Posttranslational modification (PTM) and regulation of protein stability are crucial to various biological processes. Histone deacetylase 6 (HDAC6), a unique histone deacetylase with two functional catalytic domains (DD1 and DD2) and a ZnF-UBP domain (ubiquitin binding domain, BUZ), regulates a number of biological processes, including gene expression, cell motility, immune response, and the degradation of misfolded proteins. In addition to the deacetylation of histones, other nonhistone proteins have been identified as substrates for HDAC6. Hsp90, a molecular chaperone that is a critical modulator of cell signaling, is one of the lysine deacetylase substrates of HDAC6. Intriguingly, as one of the best-characterized regulators of Hsp90 acetylation, HDAC6 is the client protein of Hsp90. In addition to regulating Hsp90 at the post-translational modification level, HDAC6 also regulates Hsp90 at the gene transcription level. HDAC6 mainly regulates the Hsp90-HSF1 complex through the ZnF-UBP domain, thereby promoting the HSF1 entry into the nucleus and activating gene transcription. The mutual interaction between HDAC6 and Hsp90 plays an important role in the regulation of protein stability, cell migration, apoptosis and other functions. Plenty of of studies have indicated that blocking HDAC6/Hsp90 has a vital regulatory role in multifarious diseases, mainly in cancers. Therefore, developing inhibitors or drugs against HDAC6/Hsp90 becomes a promising development direction. Herein, we review the current knowledge on molecular regulatory mechanisms based on the interaction of HDAC6 and Hsp90 and inhibition of HDAC6 and/or Hsp90 in oncogenesis and progression, antiviral and immune-related diseases and other vital biological processes.

TTo perform three-dimensional (3D) quantitative TProspective.Eight healthy subjects and 20 patients with symptomatic carotid atherosclerosis.3 T, SQUMA imaging TSQUMA was acquired in all subjects and multi-contrast images were acquired in healthy subjects. TPaired t or Wilcoxon signed-rank test, independent t or Mann-Whitney U test, area under the receiver operating characteristic curve (AUC), intraclass correlation coefficients, and Bland-Altman plots. Statistically significant level, P 0.05.There were no significant differences in LA (P = 0.340), WA (P = 0.317), MeanWT (P = 0.088), and NWI (P = 0.091) of carotid arteries between SQUMA and multi-contrast vessel wall images. The values of TCarotid MR 3D quantitative multi-parametric imaging of SQUMA enables acquisition of T2 TECHNICAL EFFICACY: Stage 2.

Steering photoelectrons in a well-defined spatiotemporal localization is realized by exciting with incident one-color double-pulses. We demonstrate active control of the photoemission yield for various plasmonic hot spots by tuning the polarization direction of the two orthogonally polarized laser pulses. The polarization of the pulse pair changes the plasmonic field response, corresponding to their interaction with the plasmonic hot spot. A model describes the modulation depth of the photoemission yield as a function of the difference of the photoemission response to the incident two laser pulses. Moreover, our results reveal that the proportion of photoemission yields is mainly determined by the rearrangement of the quantum pathway proportion.

On-demand manipulation of the plasmon dephasing time plays critical roles in many important applications of localized surface plasmon resonance. Here, we systemically investigate the influence of the far-field coupling on plasmon dephasing time in different nanostructure arrays supporting single or multiple modes by for the first time applying the harmonic oscillator analysis model combined with the finite-difference time-domain numerical simulation. The results show that the dephasing time of a bright mode in the nanodisk array can be well on-demand manipulated based on the far-field coupling through varying the individual nanodisk size and array period. In particular, the dephasing time of nanodisk array with adjusting periods exhibits the behavior of first increasing and then decreasing, and it is also modified to different extents under different nanodisk sizes. Furthermore, for the heptamer array supporting multiple modes, we demonstrate that the influence of array period on dephasing time also exists for a bright mode, but a negligible effect appears for dark mode due to the negligible far-field coupling. These findings provide a potential solution to manipulate the dephasing time of plasmonic nanostructure and thereby offer flexible controllability of the ultrafast on-off process of plasmonic switching and photocatalytic efficiency.

SARS-CoV-2 infection poses a global challenge to human health. Upon viral infection, host cells initiate the innate antiviral response, which primarily involves type I interferons (I-IFNs), to enable rapid elimination of the invading virus. Previous studies revealed that SARS-CoV-2 infection limits the expression of I-IFNs in vitro and in vivo, but the underlying mechanism remains incompletely elucidated. In the present study, we performed data mining and longitudinal data analysis using SARS-CoV-2-infected normal human bronchial epithelial (NHBE) cells and ferrets, and the results confirmed the strong inhibitory effect of SARS-CoV-2 on the induction of I-IFNs. Moreover, we identified genes that are negatively correlated with IFNB1 expression in vitro and in vivo based on Pearson correlation analysis. We found that SARS-CoV-2 activates numerous intrinsic pathways, such as the circadian rhythm, phosphatidylinositol signaling system, peroxisome, and TNF signaling pathways, to inhibit I-IFNs. These intrinsic inhibitory pathways jointly facilitate the successful immune evasion of SARS-CoV-2. Our study elucidates the underlying mechanism by which SARS-CoV-2 evades the host innate antiviral response in vitro and in vivo, providing theoretical evidence for targeting these immune evasion-associated pathways to combat SARS-CoV-2 infection.

In the context of carbon emission reduction, both servitization and digitalization of manufacturing enterprises are important ways to promote the high-quality development of manufacturing enterprises. The coordinated development of digitalization and servitization may provide a feasible path for enterprises to realize energy conservation and emission reduction across the value chain. Based on the 393 valid questionnaires issued by the Association of Manufacturing Enterprises and government agencies, this paper uses the methods of Grey Relational Analysis and Topsis to construct three major indicator systems of manufacturing enterprise service, digitalization and high-quality economic development. Based on the Cobb–Douglas production function regression analysis, the relevant assumptions involved in the model of promoting the service of manufacturing enterprises and the model of promoting the digitalization of manufacturing enterprises are verified. The empirical results show that, firstly, the digitalization capability of manufacturing enterprises can positively affect the servitization performance of manufacturing enterprises. Secondly, the digital capability of manufacturing enterprises has a significant positive impact on both breakthrough service innovation and incremental innovation of manufacturing enterprises. Thirdly, breakthrough service innovation and incremental service innovation play a partial mediating role. Fourthly, the degree of servitization of manufacturing enterprises has a significant positive impact on the digital demand of supporting customer behavior service business and supporting customer product service. There are three possible contributions of this paper. Firstly, it has further enriched and deepened the research on the interactive mechanism of digitalization and service of manufacturing enterprises. The second is to design a scientific and systematic evaluation system for the digitalization and service level of Chinese manufacturing enterprises, and measure and evaluate the coupling and coordination level of digitalization and service level of Chinese manufacturing enterprises based on this. Thirdly, it reveals the promotion of the coordinated development of digitalization and service in manufacturing enterprises to the high-quality development of manufacturing enterprises in China and puts forward that the coordinated development of digitalization and service in manufacturing enterprises is a way to promote the high-quality development of manufacturing enterprises.

Contextual processing (or context processing; CP) is an integral component of cognition. CP allows people to manage their thoughts and actions by adjusting to surroundings. CP involves the formation of an internal representation of context in relation to the environment, maintenance of this information over a period of time, and the updating of mental representations to reflect changes in the environment. Each of these functions can be affected by aging and associated conditions. Here, we introduced contextual processing research and summarized the literature studying the impact of normal aging and neurodegeneration-related cognitive decline on CP. Through searching the PubMed, PsycINFO, and Google Scholar databases, 23 studies were retrieved that focused on the impact of aging, mild cogniitve impairment (MCI), Alzheimer’s disease (AD), and Parkinson’s disease (PD) on CP. Results indicated that CP is particularly vulnerable to aging and neurodegeneration. Older adults had a delayed onset and reduced amplitude of electrophysiological response to information detection, comparison, and execution. MCI patients demonstrated clear signs of impaired CP compared to normal aging. The only study on AD suggested a decreased proactive control in AD participants in maintaining contextual information, but seemingly intact reactive control. Studies on PD restricted to non-demented older participants, who showed limited ability to use contextual information in cognitive and motor processes, exhibiting impaired reactive control but more or less intact proactive control. These data suggest that the decline in CP with age is further impacted by accelerated aging and neurodegeneration, providing insights for improving intervention strategies. This review highlights the need for increased attention to research this important but understudied field.

The synthesis of high-surface-area porous organic polymers (POPs) for CO2 capture and storage (CCS) has received significant attention from researchers. However, the construction of POPs with a large surface area still remains challenging in synthetic chemistry, because of the complex formation process of the porous skeletons. Herein, we developed a facile post-knitting method to increase the surface area of conjugated microporous polymers (CMPs) to improve the CO2 adsorption capacity. Four CMPs were knitted using two different cross-linkers via a Friedel–Crafts reaction to obtain eight CMP-based hyper-crosslinked polymers (KCMPs), respectively. These resulting KCMPs exhibit a high Brunauer–Emmett–Teller (BET) surface area and total pore volume up to 2267 m2 g−1 and 3.27 cm3 g−1, which are 2.3 times and 8.8 times higher than the corresponding CMPs, respectively. In addition, these KCMPs show obvious increases in the CO2 uptake with the best-performing KCMP-M4 of 3.98 mmol g−1 (89.2 cm3 g−1) at 1 bar and 273 K, an increase of 122.2% compared to the pristine CMP-4. This post-knitting method can provide more potential porous adsorbents for CCS technologies and could be used to further develop novel methods for the synthesis of high-surface-area POPs.

Background Frailty is common in older adults and associated with many adverse outcomes. To promote early detection and management of frailty outside specialized geriatric services, we developed an electronic Frailty Index based on a Comprehensive Geriatric Assessment (eFI-CGA) in electronic health records. Here, we compare the eFI-CGA assessments between family physicians (FP) and geriatricians (GM). Methods Data from community-dwelling older adults were collected as part of the collaborative effort between Fraser Health and Nova Scotia Health to validate the eFI-CGA. The eFI-CGA was created following a standard procedure based on understanding deficit accumulation. A FP and a GM assessed each patient independently. Characteristics of the eFI-CGA were examined for each physician group using descriptive statistics and correlation analysis. FP-GM inter-rater reliability was tested using Cohen’s Kappa. Results The first 30 cases were aged 80.8±5.2 years; 7% were women; with 12.9±2.8 years of education; 17% lived alone. Mild cognitive impairment or dementia was present in 20% participants. The mean clinical frailty scale (CFS) was 3 and the mean eFI-CGA was 0.20 by both FP and GM ratings. The CFS and eFI-CGA were closely correlated (r=0.76 for FP and r=0.71 for GM, p0.37, p values Conclusion Frailty data collected in primary care are highly comparable with geriatrician assessments. Ongoing work will test the generalizability of these findings using a larger sample with follow-up and outcomes evaluations.

Despite the high stability of bulk water, water microdroplets possess strikingly different properties, such as the presence of hydroxyl radicals (OH⋅) at the air-water interface. Previous studies exhibited the recombination of OH⋅ into H

Background Electrocardiogram (ECG) monitoring can quickly obtain the human body's ECG signal, and it is convenient for researchers to analyze the variability of heart rate. Some noise is often introduced in the process of signal acquisition and transmission. The existence of these noises interferes with the authenticity of the signal, and it is not conducive to the signal analysis and processing. Method In this paper, for the purpose of suppressing these noises, a sparse ECG denoising framework combining low-pass filtering and sparsity recovery is investigated. We propose a sparse ECG denoising method based on generalized entropy penalty. We use a novel denoising penalty function for sparse recovery, and compared the proposed generalized entropy penalty (GEP) with \({\ell _{\text{1}}}\)-norm penalty. Result The proposed method is evaluated on ECG signals from the MIT-BIH Arrhythmia database. The results show that the proposed method overcomes the problem of underestimation of the high-frequency components amplitude of the ECG signal. At the same time, the GEP punishes the large values less severely than \({\ell _{\text{1}}}\)-norm, and can also be used to overcome the shortcomings of "\({\ell _{\text{1}}}\)-norm" underestimating the QRS wave in ECG signal. Conclusion The proposed GEP-based penalty can be used for ECG denoising. The result of signal denoising is to remove the noise without destroying the information of the signal itself. The method has a higher restoration degree of the original signal and has relatively excellent denoising effect.

Accurate segmentation of ground-glass opacity (GGO) is an important premise for doctors to judge COVID-19. Aiming at the problem of mis-segmentation for GGO segmentation methods, especially the problem of adhesive GGO connected with chest wall or blood vessel, this paper proposes an accurate segmentation of GGO based on fuzzy c-means (FCM) clustering and improved random walk algorithm. The innovation of this paper is to construct a Markov random field (MRF) with adaptive spatial information by using the spatial gravity Model and the spatial structural characteristics, which is introduced into the FCM model to automatically balance the insensitivity to noise and preserve the effectiveness of image edge details to improve the clustering accuracy of image. Then, the coordinate values of nodes and seed points in the image are combined with the spatial distance, and the geodesic distance is added to redefine the weight. According to the edge density of the image, the weight of the grayscale and the spatial feature in the weight function is adaptively calculated. In order to reduce the influence of edge noise on GGO segmentation, an adaptive snowfall model is proposed to preprocess the image, which can suppress the noise without losing the edge information. In this paper, CT images of different types of COVID-19 are selected for segmentation experiments, and the experimental results are compared with the traditional segmentation methods and several SOTA methods. The results suggest that the paper method can be used for the auxiliary diagnosis of COVID-19, so as to improve the work efficiency of doctors.

Separation of mixture is always necessarily required in modern industry, especially in fine chemical, petrochemical, coal chemical and pharmaceutical industries. The challenge of the separation process is usually associated with small molecules with very similar physical and chemical properties. Among the separation techniques, the commonly used high-pressure cryogenic distillation process with combination of high pressure and very low temperature is heavily energy-consuming, which accounts for the major production costs as well as 10–15% of the world's energy consumption. To this end, the adsorptive separation process based on zeolite sorbents is a promising lower-energy alternative and the performance is directly determined by the zeolite sorbents. In this review, we surveyed the separation mechanisms based on the steric, equilibrium, kinetic and ‘trapdoor’ effect, and summarized the recent advances in adsorptive separation via zeolites including CO2, light olefins, C8 aromatics and hydrogen isotopes. Furthermore, we provided the perspectives on the rational design of zeolite sorbents for the absolute separation of mixtures.

Calcific aortic valve disease (CAVD) is a common heart valve disease in aging populations, and aberrant osteogenic differentiation of valvular interstitial cells (VICs) plays a critical role in the pathogenesis of ectopic ossification of the aortic valve. miR-214 has been validated to be involved in the osteogenesis process. Here, we aim to investigate the role and mechanism of miR-214 in CAVD progression. miR-214 expression was significantly downregulated in CAVD aortic valve leaflets, accompanied by upregulation of osteogenic markers. Overexpression of miR-214 suppressed osteogenic differentiation of VICs, while silencing the expression of miR-214 promoted this function. miR-214 directly targeted ATF4 and Sp7 to modulate osteoblastic differentiation of VICs, which was proved by dual luciferase reporter assay and rescue experiment. miR-214 knockout rats exhibited higher mean transvalvular velocity and gradient. The expression of osteogenic markers in aortic valve leaflets of miR-214 knockout rats was upregulated compared to that of the wild-type group. Taken together, our study showed that miR-214 inhibited aortic valve calcification via regulating osteogenic differentiation of VICs by directly targeting ATF4 and Sp7, indicating that miR-214 may act as a profound candidate of targeting therapy for CAVD., Graphical Abstract, miR-214 imbalance in aortic valve leaflets is responsible for the progress of calcific aortic valve disease (CAVD). Downregulation of miR-214 eliminates its inhibitory effect on translation of Sp7 and ATF4, thereby promoting the development of CAVD. These results suggested that miR-214 might provide an avenue for treating CAVD.

Recently developed advanced metering infrastructure in an intelligent physical system (IPS) sorts large quantities of data available in design, whereas the potential electricity system is implemented for profits and aid in the client’s transition from inactive to an active role. This paper investigates the usage of Deep Reinforcement Learning (DRL), in Intelligent Physical System for Strategic Planning in Enterprise Information (IPSSPEI) has been proposed to achieve the online schedule optimization for building energy management of Enterprise Data in an intelligent grid context. Here, two methods such as, profound R-learning and deep policy gradient, have been proposed to compute and examine the learning procedure which performs several actions simultaneously to overcome the scheduling problems. Hence, this high-dimensional database contains information about the generation and utilization of energy by photovoltaic power cars and smart buildings, with advanced metering infrastructure. Moreover, the electrical energy forecasting approaches could be used to give a real-time input to the consumers, facilitating the better application of electricity in an intelligent physical system to overcome the scheduling problems.

The lower limb exoskeleton provides assistance by following the lower limb joints’ desired motion trajectory. However, angle control is not enough to meet the requirements in some special circumstances such as encountering obstacles. In the swing phase of the attached leg with the exoskeleton, there is a different contact force between the sole and the road surface in different road conditions. Therefore, it is particularly important to control the joint angle and contact force simultaneously, that is, it is not only necessary to follow the desired angle but also to minimize the influence of external contact force. In this article, a novel scheme is proposed to adjust the trajectory dynamically in the swing phase. First of all, the physical model is streamlined and the Lagrangian principle is carried out to dynamic analysis and established a model of lower limb exoskeleton in the swing phase. Furthermore, the angle dynamics equation is transformed into a Cartesian coordinate system to calculate the end contact force for the impedance model. Finally, the impedance control strategy together with a disturbance observer is designed which is suitable for nonlinear and strong coupling characteristics. The simulation result shows that the control system can follow the angle accurately in the condition of minimizing external constraints. Hardware experiment shows that lower extremity exoskeleton can adjust motion trajectory actively when encountering obstacles and complete the movement trajectory tracking at the same time.

Breaking the morphological and compositional symmetries of metallic nanoparticle (NP) dimers provides a novel approach to modulate plasmon coupling between the NPs. In this study, we theoretically investigate the effect of symmetry breaking on the plasmonic coupling in morphologically asymmetric Au nanoring-nanodisk (NR-ND) dimer, compositionally heterogeneous Au-Ag nanoring dimer, and compositionally as well as morphologically asymmetric Au-Ag NR-ND heterodimers. It has been found that when the inner radii of symmetrical Au NR dimer is decreased, the scattering spectral intensity of coupled bonding mode and higher-order coupled bonding mode drastically decreases and increases, respectively. Besides, the effect of aspect ratio on the plasmon resonance modes is investigated. Furthermore, with fixed geometric parameters of one NR and by morphing the shape of the other NR into ND through inner radius, we show the generation and modification of a Fano resonance. As a result of introducing morphological and compositional asymmetry separately, single Fano-type spectral feature is observed in the scattering spectra. We demonstrate that the double Fano resonances can be easily achieved in compositionally and morphologically asymmetric heterodimer with double symmetry breaking. These dual modes are caused by the interference of dipolar bright mode (localized LSPR modes) of Ag NP with the quadrupole and hexapole modes (interband transitions) of the Au NP. Finally, at optimum asymmetric heterodimers, we discussed the effect of refractive index on the Fano-type resonance. These new and simple designs provide a novel insight to modulate optical response and the generation of higher-order Fano resonances, which have many potential applications such as in photonics and refractive index sensing.

Alzheimer's disease (AD) is a multifactorial disease triggered by environmental factors in combination with genetic predisposition. Infectious agents, in particular herpes simplex virus type 1 (HSV-1), are gradually being recognised as important factors affecting the development of AD. However, the mechanism linking HSV-1 and AD remains unknown. Of note, HSV-1 manipulates the activity of cofilin-1 to ensure their efficient infection in neuron cells. Cofilin-1, the main regulator of actin cytoskeleton reorganization, is implicating for the plastic of dendritic spines and axon regeneration of neuronal cells. Moreover, dysfunction of cofilin-1 is observed in most AD patients, as well as in mice with AD and ageing. Further, inhibition of cofilin-1 activity ameliorates the host cognitive impairment in an animal model of AD. Together, dysregulation of cofilin-1 led by HSV-1 infection is a potential link between HSV-1 and AD. Herein, we critically summarize the role of cofilin-1-mediated actin dynamics in both HSV-1 infection and AD, respectively. We also propose several hypotheses regarding the connecting roles of cofilin-1 dysregulation in HSV-1 infection and AD. Our review provides a foundation for future studies targeting individuals carrying HSV-1 in combination with cofilin-1 to promote a more individualised approach for treatment and prevention of AD.

Saliva is a noninvasive biofluid that can contain metabolite signatures of oral squamous cell carcinoma (OSCC). Conductive polymer spray ionization mass spectrometry (CPSI-MS) is employed to record a wide range of metabolite species within a few seconds, making this technique appealing as a point-of-care method for the early detection of OSCC. Saliva samples from 373 volunteers, 124 who are healthy, 124 who have premalignant lesions, and 125 who are OSCC patients, were collected for discovering and validating dysregulated metabolites and determining altered metabolic pathways. Metabolite markers were reconfirmed at the primary tissue level by desorption electrospray ionization MS imaging (DESI-MSI), demonstrating the reliability of diagnoses based on saliva metabolomics. With the aid of machine learning (ML), OSCC and premalignant lesions can be distinguished from the normal physical condition in real time with an accuracy of 86.7%, on a person by person basis. These results suggest that the combination of CPSI-MS and ML is a feasible tool for accurate, automated diagnosis of OSCC in clinical practice.

Construction of porous organic polymers (POPs) with high surface areas, well-defined nanopores, and excellent stability remains extremely challenging because of the unmanageable reaction process. Until now, only a few reported POPs have Brunauer-Emmett-Teller (BET) surface areas (SBET ) exceeding 3000 m2 g-1 . Herein, we demonstrate a molecular expansion strategy to integrate high surface areas, large nanopore sizes, and outstanding stability into POPs. A series of hyper-crosslinked conjugated polymers (HCCPs) with exceptional porosity are synthesized through this strategy. Specially, HCCP-6 and HCCP-11 exhibit the highest surface areas (SBET >3000 m2 g-1 ) and excellent total pore volumes (up to 3.98 cm3 g-1 ) among these HCCPs. They present decent total CH4 storage capacities of 491 and 421 mg g-1 at 80 bar and 298 K, respectively. Meanwhile, they are highly stable in harsh environments. The facile and general molecular expansion strategy would lead to improved synthetic routes of POPs for desired functions.

The article presents a full-size pole pair set-up of an MW-class direct drive (DD) high temperature superconducting (HTS) wind turbine generator. The set-up serves as a precursor to the world's first full-scale DD HTS generator developed within the EU-funded EcoSwing project. The set-up built for de-risking employs an HTS field winding in the rotor and a conventional copper armature winding in the stator, representing a minimum independent unit of the corresponding full generator. Such a prototyping approach well reflects the performance of the full generator at a low cost. The article first explains the main design considerations of the full generator, followed by designing and construction details of the set-up. Afterward, a number of tests for determining the key performance of the set-up are reported. The testing results showed that the HTS field winding ran stably at its rated current of 480 A and was well maintained below 30 K. Moreover, the tangential force in the set-up reached 29.8 kN, projecting the 2 MW target output power of the full generator. The set-up developed effectively validated the design ideas and engineering feasibilities of the full generator, leading to successful kick-off of the EcoSwing project.

High temperature superconducting (HTS) generators are being considered for large offshore direct-drive (DD) wind turbines as they are expected to be lightweight and compact. However, short circuit torques of an HTS generator with integral-slot distributed windings (ISDWs) are too high for wind turbine constructions, mainly due to the large magnetic air gap. Fractional-slot concentrated windings (FSCWs) can be considered to address this issue since their high leakage inductance can limit short circuit currents and torques. Unlike ISDWs, FSCWs produce great contents of space harmonics that induce excessive losses in rotor components. Multi-layer and stator-shifting windings have been proposed to effectively reduce such losses. Based on a conventional 12-slot 10-pole configuration, this paper evaluates the effects of multi-layer and stator-shifting FSCWs on torque production and loss reduction in a 10 MW DD HTS generator. The examined losses include eddy current losses in the rotor shields and AC losses in the HTS field winding. This paper also checks if these FSCW schemes maintain the advantage of achieving a low short circuit torque. The results show that a 6-phase stator-shifting winding is the best choice for applying FSCWs to HTS generators.

The tea plant [Camellia sinensis (L.) O. Kuntze] is a species with a high concentration of fluorine in its leaves, especially in the mature leaves. The physiological mechanisms for fluorine absorption and accumulation have been well studied, but the related molecular mechanisms are poorly understood in the tea plant. In this study, transcriptome analysis by RNA-Seq following exposure to 16 mg/L of fluorine for 0, 3, 6, and 24 h was performed to identify the candidate genes involved in the transmembrane transportation of fluorine. More than 1.23 billion high-quality reads were generated, and 259.84 million unigenes were assembled de novo, with 518 216 of them being annotated in the seven databases used. Meanwhile, a large number of transporters, transcription factors, and heat-shock proteins with differential expression in response to high levels of fluorine (P ≤ 0.05) were identified. Comparative transcriptome analysis showed that the uptake of fluorine is related to photosynthesis, plant hormone signal transduction, and glutathione metabolism. Further systematic analysis of nitrate and potassium transporter genes revealed that many of these genes regulate fluorine transportation in roots and leaves. Gene expression and fluorine content analysis in different cultivars revealed CsNRT1/PTR 3.1 and CsPT 8 as the key genes regulating the transmembrane transportation of fluorine in the tea plant.