The Altered Reconfiguration Pattern of Brain Modular Architecture Regulates Cognitive Function in Cerebral Small Vessel Disease

Background: Cerebral small vessel disease (SVD) is a common cause of cognitive dysfunction. However, little is known whether the altered reconfiguration pattern of brain modular architecture regulates cognitive dysfunction in SVD.Methods: We recruited 25 cases of SVD without cognitive impairment (SVD-NCI) and 24 cases of SVD with mild cognitive impairment (SVD-MCI). According to the Framingham Stroke Risk Profile, healthy controls (HC) were divided into 17 subjects (HC-low risk) and 19 subjects (HC-high risk). All individuals underwent resting-state functional magnetic resonance imaging and cognitive assessments. Graph-theoretical analysis was used to explore alterations in the modular organization of functional brain networks. Multiple regression and mediation analyses were performed to investigate the relationship between MRI markers, network metrics and cognitive performance.Results: We identified four modules corresponding to the default mode network (DMN), executive control network (ECN), sensorimotor network and visual network. With increasing vascular risk factors, the inter- and intranetwork compensation of the ECN and a relatively reserved DMN itself were observed in individuals at high risk for SVD. With declining cognitive ability, SVD-MCI showed a disrupted ECN intranetwork and increased DMN connection. Furthermore, the intermodule connectivity of the right inferior frontal gyrus of the ECN mediated the relationship between periventricular white matter hyperintensities and visuospatial processing in SVD-MCI.Conclusions: The reconfiguration pattern of the modular architecture within/between the DMN and ECN advances our understanding of the neural underpinning in response to vascular risk and SVD burden. These observations may provide novel insight into the underlying neural mechanism of SVD-related cognitive impairment and may serve as a potential non-invasive biomarker to predict and monitor disease progression

A Motivational Mechanism Framework for Teachers' Online Informal Learning and Innovation During the COVID-19 Pandemic

Online informal learning (IL) spreads quickly in the COVID-19 Pandemic. Studies have predicted that both online and workplace IL have potential value to individual and organization development, whereas the study on its link with innovation remains scarce. IL is an individualized learning pattern different from formal learning, and its functioning mechanism on innovation will deepen our understanding of the relationship between learning and innovation. Self-efficacy and autonomous motivation are considered as two streams of motivational mediating mechanisms to innovation. However, previous studies have proceeded largely in separation from each other. Researchers highlight the need to develop a more fine-grained theory of motivation and innovation. In addressing these literature gaps, this paper takes college teachers as the sample and focuses on the motivational mediating mechanism between online IL and innovation. The results showed that teachers IL could positively predict innovative teaching performance. Personal teaching efficacy and autonomous motivation played as sequential mediators on the link between IL and innovative teaching performance. This study extends the literature of IL–innovation relationship and enriches understanding of cognition-oriented motivation theory, highlighting one's internal autonomous construction is the key to innovation. Theoretical and practical implications for psychological empowerment are discussed.</jats:p

Multifunctional DNAzyme-Anchored Metal–Organic Framework for Efficient Suppression of Tumor Metastasis

High mortality and rapid development of metastasis requires the development of more effective antimetastasis strategies. However, conventional therapeutic methods, including surgery, radiation therapy, and chemotherapy, show less effectiveness in curbing the metastatic spread of cancer cells and the formation of metastases. A therapeutic platform, targeting the early stage of metastasis cascade, could effectively prevent metastasis dissemination. Herein, Fe/Mn-based metal–organic frameworks (FMM) were constructed for the delivery of a specific DNAzyme with high catalytic cleavage activity on the metastasis-involved Twist mRNA, thus efficiently inhibiting the invasion of cancer cells through DNAzyme-catalyzed gene silencing. Highly potent combined gene/chemodynamic therapy is achieved from the self-supplied DNAzyme cofactors and efficient glutathione depletion. Importantly, by virtue of the intrinsic photo-to-thermal conversion of the FMM nanocarriers, our combined therapeutic strategy could be further promoted under photothermal stimuli to speed up the Fenton reaction and to accelerate the release of the Twist DNAzyme with efficient gene therapy. Consequently, the effective elimination of tumors and the blockage of metastasis are simultaneously achieved under photothermal/magnetic resonance imaging guidance. This work aims at developing versatile theranostic agents to combat metastatic tumors

Simultaneously Enhancing Light Emission and Suppressing Efficiency Droop in GaN Microwire-Based Ultraviolet Light-Emitting Diode by the Piezo-Phototronic Effect

Achievement of p–n homojuncted GaN enables the birth of III-nitride light emitters. Owing to the wurtzite-structure of GaN, piezoelectric polarization charges present at the interface can effectively control/tune the optoelectric behaviors of local charge-carriers (i.e., the piezo-phototronic effect). Here, we demonstrate the significantly enhanced light-output efficiency and suppressed efficiency droop in GaN microwire (MW)-based p–n junction ultraviolet light-emitting diode (UV LED) by the piezo-phototronic effect. By applying a −0.12% static compressive strain perpendicular to the p–n junction interface, the relative external quantum efficiency of the LED is enhanced by over 600%. Furthermore, efficiency droop is markedly reduced from 46.6% to 7.5% and corresponding droop onset current density shifts from 10 to 26.7 A cm–2. Enhanced electrons confinement and improved holes injection efficiency by the piezo-phototronic effect are revealed and theoretically confirmed as the physical mechanisms. This study offers an unconventional path to develop high efficiency, strong brightness and high power III-nitride light sources

Blocking ERK-DAPK1 Axis Attenuates Glutamate Excitotoxicity in Epilepsy

Glutamate excitotoxicity induces neuronal cell death during epileptic seizures. Death-associated protein kinase 1 (DAPK1) expression is highly increased in the brains of epilepsy patients; however, the underlying mechanisms by which DAPK1 influences neuronal injury and its therapeutic effect on glutamate excitotoxicity have not been determined. We assessed multiple electroencephalograms and seizure grades and performed biochemical and cell death analyses with cellular and animal models. We applied small molecules and peptides and knocked out and mutated genes to evaluate the therapeutic efficacy of kainic acid (KA), an analog of glutamate-induced neuronal damage. KA administration increased DAPK1 activity by promoting its phosphorylation by activated extracellular signal-regulated kinase (ERK). DAPK1 activation increased seizure severity and neuronal cell death in mice. Selective ERK antagonist treatment, DAPK1 gene ablation, and uncoupling of DAPK1 and ERK peptides led to potent anti-seizure and anti-apoptotic effects in vitro and in vivo. Moreover, a DAPK1 phosphorylation-deficient mutant alleviated glutamate-induced neuronal apoptosis. These results provide novel insight into the pathogenesis of epilepsy and indicate that targeting DAPK1 may be a potential therapeutic strategy for treating epilepsy.</jats:p