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Aiming at the problem of low accuracy of traditional algorithm model, an intelligent recognition model of business English translation based on an improved GLR algorithm is proposed. Through this algorithm, the automatic sentence recognition technology is established, and according to the characteristics of business English, the improved GLR algorithm is used for collection, sorting, and analysis, so as to realize the intelligent recognition of business English. The results show that based on the improved GLR algorithm, the recognition accuracy is high, and the comprehensive score is 92.5 points, which overcomes the disadvantages of the GLR algorithm, and the operation speed and processing are improved. Based on the improved GLR algorithm, the intelligent translation of business English is realized, which is accurate and fast, and greatly promotes the learning and development of business English. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRs), a class of small non-coding RNAs, have been demonstrated to be involved in the development and progression of human malignancies, including cutaneous squamous cell carcinoma (CSCC). miR-186 serves a suppressive role in certain common types of human cancer; however, its exact function in CSCC has not been reported previously. In the present study, the expression of miR-186 was significantly increased in CSCC tissues compared with adjacent non-tumour tissues. Overexpression of miR-186 significantly promoted CSCC cell proliferation while inhibiting cell apoptosis. Reticulophagy regulator 1 (RETREG1), a gene that is significantly downregulated in CSCC tissues and cell lines, was identified as a novel target of miR-186. In addition, the expression of RETREG1 was inversely correlated with miR-186 expression in CSCC tissues. Furthermore, the expression of RETREG1 was negatively regulated by miR-186 in CSCC cells, and restoration of RETREG1 attenuated the effects of miR-186 on CSCC cells. Taken together, the results of the current study suggest that miR-186 serves an oncogenic role in CSCC and may be used as a potential therapeutic target for the treatment of this disease. [ABSTRACT FROM AUTHOR]

RNA-targeting CRISPR system Cas13 offers an efficient approach for manipulating RNA transcripts in vitro. In this perspective, we provide a proof-of-concept demonstration that Cas13-mediated Vegfa knockdown in vivo could prevent the development of laser-induced CNV in mouse model of Age-related macular degeneration. [ABSTRACT FROM AUTHOR]

The porous carbon-doped g-C 3 N 4 nanosheets photocatalysts (NSs-APAM) were synthesized using anionic polyacrylamide (APAM) as the intercalator and carbon source via the thermal treatment method. The as-prepared samples were characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), Atomic force microscopy (AFM), Fourier transform infrared spectroscopy (FT-IR), nitrogen adsorption, X-ray photoelectron spectroscopy (XPS), UV–vis diffuse reflectance absorption spectra (UV-DRS) and photoluminescence spectroscopy (PL). The results indicate that the APAM can effectively induce the formation of high-quality nanosheets (NSs) with narrowed bandgap. The specific surface area of NSs-APAM is 118.6 m 2 /g, which is 5-fold larger than bulk g-C 3 N 4 . The carbon doping could narrow the bandgap, from 2.75 eV of g-C 3 N 4 NSs without carbon doping (NSs-Water) to 2.41 eV of NSs-APAM. The two-dimensional NSs structure facilitates the charge separation by shortening the diffusion distance to the surface of photocatalysts. The synergic effects of the carbon doping and unique structural properties contributed to the superior photocatalytic activity of NSs-APAM with 95% degradation rate towards X–3 B after 30 min visible-light irradiation. [ABSTRACT FROM AUTHOR]

Radial spoke protein 3 (RSP3) was first identified in Chlamydomonas as a component of radial spoke, which is important for flagellar motility. The mammalian homolog of the Chlamydomonas RSP3 protein is found to be a mammalian protein kinase A-anchoring protein that binds ERK1/2. Here we show that mouse RSP3 is a nucleocytoplasmic shuttling protein. The full-length RSP3-EGFP fusion protein is mainly located in the cytoplasm of Chinese hamster ovary cells. However, by using deletion mutants of RSP3, we identified two nuclear localization signals and a nuclear export signal in RSP3. Moreover, using in utero electroporation, we found that overexpression of RSP3 in the developing cerebral cortex promotes neurogenesis. The layer II/III of the neocortex was much thicker in the RSP3-transfected region than that of the untransfected region in the neocortex. We also show that RSP3 is specifically located in the primary cilia of the radial glial cells, where it acts as a signaling mediator that regulates neurogenesis. Thus, our results suggest that RSP3 is a nucleocytoplasmic shuttling protein and plays an essential role in neurogenesis. [ABSTRACT FROM AUTHOR]

• AAV based-vaccine could efficiently mediate the RBD protein expression of the SARS-CoV-2 in mammalian cells. • AAV based-vaccine could rapidly induce strong immune responses in mice, which maintaining at least six months. • AAV-3xRBD vaccine could elicit the high level of neutralizing antibodies against SARS-CoV-2 in mice. • AAV-3xRBD vaccine has the ability of inducing the specific antibodies against SARS-CoV-2 in canines. The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has resulted in catastrophic damage worldwide. Accordingly, the development of powerful, safe, easily accessible vaccines with long-term effectiveness is understood as an urgently needed countermeasure against this ongoing pandemic. Guided by this strong promise of using AAVs, we here designed, optimized, and developed an AAV-based vaccines (including AAV-RBD(max), AAV-RBD(wt), AAV-2xRBD, and AAV-3xRBD) that elicit strong immune responses against the RBD domain of the SARS-CoV-2 S protein. These immunogenic responses have proven long-lived, with near peak levels for at least six months in mice. Notably, the sera immunized with AAV-3xRBD vaccine contains powerful neutralizing antibodies against the SARS-CoV-2 pseudovirus. Further evidence proven that potent specific antibodies could also be elicited in canines after vaccination with AAV-3xRBD vaccine. [ABSTRACT FROM AUTHOR]

Conversion of glial cells into functional neurons represents a potential therapeutic approach for replenishing neuronal loss associated with neurodegenerative diseases and brain injury. Previous attempts in this area using expression of transcription factors were hindered by the low conversion efficiency and failure of generating desired neuronal types in vivo. Here, we report that downregulation of a single RNA-binding protein, polypyrimidine tract-binding protein 1 (Ptbp1), using in vivo viral delivery of a recently developed RNA-targeting CRISPR system CasRx, resulted in the conversion of Müller glia into retinal ganglion cells (RGCs) with a high efficiency, leading to the alleviation of disease symptoms associated with RGC loss. Furthermore, this approach also induced neurons with dopaminergic features in the striatum and alleviated motor defects in a Parkinson's disease mouse model. Thus, glia-to-neuron conversion by CasRx-mediated Ptbp1 knockdown represents a promising in vivo genetic approach for treating a variety of disorders due to neuronal loss. • Knockdown of Ptbp1 converts Müller glia into retinal ganglion cells in mature retinas • Central projections of converted retinal ganglion cells restore visual responses • Induction of neurons with dopaminergic features in PD model mice • Induced neurons alleviated motor dysfunctions in PD mice In vivo CasRx-mediated downregulation of a single RNA-binding protein, Ptbp1, locally converts glia to neurons and shows promise for treating disorders due to neuronal loss in mice. [ABSTRACT FROM AUTHOR]

We here report a genome-editing strategy to correct spinal muscular atrophy (SMA). Rather than directly targeting the pathogenic exonic mutations, our strategy employed Cas9 and guide-sgRNA for the targeted disruption of intronic splicing-regulatory elements. We disrupted intronic splicing silencers (ISSs, including ISS-N1 and ISS + 100) of survival motor neuron (SMN) 2, a key modifier gene of SMA, to enhance exon 7 inclusion and full-length SMN expression in SMA iPSCs. Survival of splicing-corrected iPSC-derived motor neurons was rescued with SMN restoration. Furthermore, co-injection of Cas9 mRNA from Streptococcus pyogenes (SpCas9) or Cas9 from Staphylococcus aureus (SaCas9) alongside their corresponding sgRNAs targeting ISS-N1 into zygotes rescued 56% and 100% of severe SMA transgenic mice (Smn −/−, SMN2 tg/−). The median survival of the resulting mice was extended to >400 days. Collectively, our study provides proof-of-principle for a new strategy to therapeutically intervene in SMA and other RNA-splicing-related diseases. [ABSTRACT FROM AUTHOR]

Proliferation of neural stem cells and differentiation of newly generated cells are crucial steps during the development of mammalian neocortex, which are able to generate suitable number of neurons and glial cells to ensure normal formation of cortex. Any disturbance in these processes leads to structural and functional abnormalities of cerebral cortex, such as epilepsy or intellectual disability. Numerous molecules involved in the development of disorders of the nervous system have been discovered in the recent years. The PI3K/AKT signaling pathway has been shown to be widely involved in the corticogenesis. Recently we could show that overexpression of regulatory subunit P85 of PI3K disrupts neuronal migration. However, it remains unclear whether the regulatory subunit P85 plays a role in the proliferation of neural stem cells and differentiation of newly generated cells during mouse brain development. Here, by using in utero electroporation and immunohistochemistry, we show that overexpression of P85 inhibited proliferation of neural progenitor cells and neuronal differentiation. By using 5-bromo-2-deoxyuridine (BrdU) labeling, we reveal that overexpression of P85 extended the cell cycle duration, which may result in developmental retardation during mouse corticogenesis. [ABSTRACT FROM AUTHOR]

In mammalian developing embryonic cortex, projection neurons migrate from the ventricular zone to the cortical plate, guided by radial glial cells with a transformation between bipolar and multipolar morphology. Previous studies have demonstrated that the PI3K-Akt-mTOR signal plays a critical role in brain development. However, the function of P85 in cortical development is still unclear. In the present study, we found that overexpression of P85 impaired cortical neuronal migration. Using in utero electroporation, we revealed that the length of the leading process in P85 overexpressed neurons became shorter than that in the control group but with more branches. Using markers for new-born neurons, we further found that overexpression of P85 did not affect the ultimate fate of these cortical neurons. These findings indicated that the P85 subunit plays an essential role in neuronal migration and neuronal morphology during mouse corticogenesis. [ABSTRACT FROM AUTHOR]

Paraquat, a fast-acting non-selective contact herbicide, is considered an etiological factor related to Parkinson's disease. This study investigated its effects on hippocampal neurogenesis and cognition in adult mice as well as possible mechanisms for the effects. We administered paraquat (1.25 mg/kg, intraperitoneal injection, i.p.) and an equal volume of normal saline for 3 weeks to adult male C57BL/6J mice. The results showed that hippocampus-dependent spatial learning and memory was significantly impaired in paraquat-treated mice. Moreover, paraquat administration inhibited the proliferation of neural progenitor cells, and impaired the survival and altered the fate decision of newly generated cells in the hippocampus. The expression levels of caspase-3 and glial fibrillary acidic protein were significantly higher in paraquat-treated mice than in control mice. Interestingly, paraquat reduced the phosphorylation of Akt, but did not affect the total amount of Akt. In conclusion, our findings suggest that paraquat negatively affected adult hippocampal neurogenesis and cognition function. [ABSTRACT FROM AUTHOR]

The BiVO 4 /surface rough TiO 2 ceramic fibers were fabricated via a mild hydrothermal method by using surface-modified Si–TiO 2 as self-supporting substrate materials. The as-prepared fibers consisted of the needle-like or flower-like BiVO 4 uniformly assembled on surface rough TiO 2 ceramic fibers (RTF). Notably, several needle-like BiVO 4 with lengths less than 1 µm and diameters ranging from 80 to 100 nm constructed a microflower by radiating from the center, which could be controlled by adjusting the concentration of the precursor. The incorporation of monoclinic BiVO 4 in the composites was confirmed by XRD, SEM, PL and XPS. RTF was obtained through the dissolution of silicon in the surface of Si–TiO 2 ceramic fibers (STF) by HF. The photocatalytic performance of the heterostructured fibers was investigated by the degradation of X-3B in aqueous solution under both ultraviolet and visible light irradiation. The 0.2BiVO 4 /RTF with mass ratio of 20% vanadate exhibited optimized photocatalytic activity compared with pure STF, BiVO 4 , 0.2BiVO 4 /STF and mechanically mixed 0.2BiVO 4 +RTF, which might be ascribed to synergistic effect of morphology and heterostructures. Moreover, such 0.2BiVO 4 /RTF composites were easy to separate from the treated wastewater and remained stable after 10 irradiation cycles. It was proposed that electronic interactions at the interface of BiVO 4 /RTF heterostructures could effectively inhibit the charge recombination. [ABSTRACT FROM AUTHOR]

During brain development, the radial glial cell acts as a scaffold to support radial migration of postmitotic neurons. However, the morphological changes of radial glial cells during embryo development are poorly understood. We used in utero electroporation and immunohistochemistry to study the dynamics of radial glial cells accompanied by cortical development in mice from embryonic day 14 to postnatal day 0. We found that different segments of radial glial cells changed by the growth of different layers of cortex, such as marginal zone, cortical plate, intermediate zone and ventricular zone. Moreover, the length, angle and number of branches of the radial glial cell changed significantly at the late stage of neurogenesis. All these changes were consistent with the distinct phases of locomotion. Thus, we speculated that morphological changes of the radial glial cell were associated with the neuronal migration and dendritic development. [ABSTRACT FROM AUTHOR]

Macrophage migration inhibitory factor (MIF) functions as a pleiotropic protein, participating in a vast array of cellular and biological processes. Abnormal expression of MIF has been implicated in many neurological diseases, including Parkinson's disease, epilepsy, Alzheimer's Disease, stroke, and neuropathic pain. However, the expression patterns of mif transcript and MIF protein from the early postnatal period through adulthood in the mouse brain are still poorly understood. We therefore investigated the temporal and spatial expression of MIF in the mouse neocortex during postnatal development in detail and partially in posterior piriform cortices (pPC). As determined by quantitative real-time PCR (qPCR), mif transcript gradually increased during development, with the highest level noted at postnatal day 30 (P30) followed by a sharp decline at P75. In contrast, Western blotting results showed that MIF increased constantly from P7 to P75. The highest level of MIF was at P75, while the lowest level of MIF was at P7. Immunofluorescence histochemistry revealed that MIF-immunoreactive (ir) cells were within the entire depth of the developed neocortex, and MIF was heterogeneously distributed among cortical cells, especially at P7, P14, P30, and P75; MIF was abundant in the pyramidal layer within pPC. Double immunostaining showed that all the mature neurons were MIF-ir and all the intensely stained MIF-ir cells were parvalbumin positive (Pv +) at adult. Moreover, it was demonstrated that MIF protein localized in the perikaryon, processes, presynaptic structures, and the nucleus in neurons. Taken together, the developmentally regulated expression and the subcellular localization of MIF should form a platform for an analysis of MIF neurodevelopmental biology and MIF-related nerve diseases. [ABSTRACT FROM AUTHOR]

The primary objective of this investigation was to assess the neuroprotective efficacy of lithium in an acrylamide (ACR)-induced neuropathy model in mice. In this study, Kunming male mice were administered ACR (25 mg/kg bw, i.p. once a day) with or without lithium (25 mg/kg bw, i.p. once a day) for 2 weeks. All ACR-administered mice exhibited severe symptoms of neuropathy. We found that treatment with lithium effectively alleviated behavioral deficits in animals elicited by acrylamide. Interestingly, the reduction of hippocampal neurogenesis resulting from ACR injection was promoted by administration of lithium. Further, lithium treatment significantly offset ACR-induced depletion in p-GSK-3β (Ser9) levels in hippocampus. Collectively our findings suggest the propensity of lithium to attenuate ACR-induced neuropathy. Further studies are necessary to understand the precise molecular mechanism by which the lithium attenuates neuropathy. Nevertheless, our data clearly demonstrate the beneficial effects of lithium on ACR-induced neuropathy in mice and suggest its possible therapeutic application as an adjuvant in the management of other forms of neuropathy in humans. [ABSTRACT FROM AUTHOR]

In this article, a novel route for the synthesis of graphene/TiO2 continuous fibers (GTF) using force-spinning combined with water vapor annealing method is reported for the first time. The morphology, structure and optical properties of the composite were fully characterized. With a single step of heat treatment process using steam at ambient conditions, we were able to initiate a series of chemical reactions, such as reduction of graphene oxide (GO), crystallization of TiO2, formation of C-Ti bond, and introduction of oxygen vacancies into TiO2. The incorporation of graphene in TiO2 fibers facilitated bandgap narrowing and improved photo-induced charge separation in the photocatalyst. As a result of synergistic effects, TiO2 fibers-2 wt% graphene (2%GTF) showed the highest photocatalytic activities in the degradation of X-3B under UV irradiation, superior to the benchmark photocatalyst P25. Under visible light irradiation, the same catalyst was about 4 times more efficient compared to pure TiO2 fibers (PTF). A detailed study of involved active species (in particular, ·, h+ and ·OH) unraveled the mechanism regarding photocatalysis. [ABSTRACT FROM AUTHOR]