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The lateral geniculate nucleus (LGN), a retinotopic relay center where visual inputs from the retina are processed and relayed to the visual cortex, has been proposed as a potential target for artificial vision. At present, it is unknown whether optogenetic LGN stimulation is sufficient to elicit behaviorally relevant percepts and the properties of LGN neural responses relevant for artificial vision have not been thoroughly characterized. Here, we demonstrate that tree shrews pretrained on a visual detection task can detect optogenetic LGN activation using an AAV2-CamKIIα-ChR2 construct and readily generalize from visual to optogenetic detection. We also characterize how amplitude and frequency of optogenetic stimulation affect behavioral performance. Given the importance of temporal stimulation parameters, we also study tree shrew behavioral ability to discriminate among pairs of visual flicker frequencies and demonstrate performance transfer among related discrimination problems as well as limitations. Neural recordings in LGN and primary visual cortex (V1) examining two flicker discriminations reveal that while LGN neurons multiplex information about temporal stimulation discriminations, V1 neurons explicitly encode information about one or the other discriminations but not both. Our findings confirm the LGN as a potential target for visual prosthetics and introduce a distinction in stimulus encoding between thalamic and cortical representations that could be of fundamental importance in artificial vision.

From the perspective of targeting factors, iron acetylacetonate and nickel acetylacetonate were used as major materials, and oleylamine was used as a solvent. Through thermal decomposition, the uniformly distributed nanoparticle FeNi3 was obtained. Then, the α-methyltryptophan (AMT) was used to modify FeNi3, thereby the material (FeNi3-AMT) would be biocompatible. The prepared material was used as a targeting factor to explore whether it could target the epileptogenic focus in temporal lobe epilepsy model rats. In the experiment, the animal models of temporal lobe epilepsy were constructed by using the lithium chloride-pirocarpine method. According to the injection of the nuclear magnetic factor, the models were divided into the FeNi3 group, the FeNi3-AMT group, and the saline group. The model rats received intravenous injections 48 hours after the onset of epilepsy. The activity of the epileptic seizure sites before and after injection, the penetration of nanoparticles, and the toxic and side effects of the material were compared. The results showed that the rat models of temporal lobe epilepsy were successfully constructed (the success rate was more than 85%). Meanwhile, the epilepsy lesions of the rat models added with nanoparticles were darker (P < 0.05). The staining of rat brain sections confirmed the distribution of iron particles. In the FeNi3-AMT group, there were more iron particles distributed (P < 0.05). In addition, various abnormal neurons appeared in the hippocampus of the three groups, and there was no significant difference between the different groups (P < 0.05). There was no significant difference in the number of positive neurons in the CA3 region of the brain between different groups (P < 0.05). However, the imaging effect based on FeNi3-AMT was more prominent (P < 0.05), which confirmed that the FeNi3-AMT group had better targeting location effects. The study confirmed that the iron nano alloy particle material had excellent application values in the localization of temporal lobe epilepsy.

The infiltration and invasion of nerve trunks, nerve roots, and cranial nerves by lymphomatous malignant cells is defined as "neurolymphomatosis". It is mainly caused by lymphoma cells directly infiltrating the peripheral nerves, with a low incidence. Neurolymphomatosis is a rare condition of neoplastic endoneurial invasion, which is primary or secondary to non-Hodgkin's lymphoma and leukemia. We describe a case of primary peripheral neurolymphomatosis of multifocal involvement in a 77-year-old male patient. He presented with left lower limb pain and was diagnosed with CD20+ diffuse large B cell lymphoma (DLBCL). Magnetic resonance imaging (MRI), fluorine-18 fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) computed tomography (CT), and nerve biopsy contributed to the diagnosis. Genomic profiling, programmed death ligand-1 (PD-L1) expression and tumor mutational burden (TMB) were also assessed. CDKN2A/CDKN2B deletions have been identified. PD-L1 expression assessed by 28-8 antibody was 1% positivity, and TMB of the sample was 11.6 muts/Mb. The patient responded well to rituximab combined with chemotherapy, however, he died after 3 cycles of chemotherapy due to severe lung infection and subsequent complication of respiratory failure. Here we report the clinical, radiological, pathological and molecular findings of the patient affected by multifocal neurolymphomatosis without systemic involvement of other organs.

BACKGROUND Because facet joints move with the disc, changes in vertebral bodies occur simultaneously with progression of degeneration of cervical facet joints. This study investigated age-related differences in cervical facet joint abnormalities and multi-dimensional characteristics of MCs in patients with cervical spondylotic myelopathy. MATERIAL AND METHODS Forty-five patients underwent both magnetic resonance imaging (MRI) and computed tomography (CT) of the cervical spine. Axial and sagittal parameter changes from C3 to C7, including facet orientation (FO) and facet tropism (FT), and Modic changes (MCs), were evaluated and documented preoperatively, and we also measured the heights and diameters of MCs and performed correlation analysis and established linear regression models. RESULTS The axial facet orientation increased slightly from C3 66.5 (11.4) to C7 89.9 (19). The sagittal facet orientation and facet tropism increased between C3-C4 and C6-C7, but it decreased between C4 to C6. The MCs volume decreased from C3 to C4 and increased from C4 to C7. There was a gradual decrease of FO and FT from C3 to C5 and a gradual increase of these 2 angles from C5 to C7 in all age groups. The lowest values of FO and FT were detected at C5, while the highest values of FO and FT were detected at C7. CONCLUSIONS Age was negatively correlated with the axial, sagittal, and coronal cervical facet orientation, especially at C4/5 level. The FT with respect to the axial and sagittal plane from C5 to C6 increased with age.

Constructing Bi-rich photocatalysts has been regarded as a promising strategy for promoting the photocatalytic performance of bismuth oxyhalides, however, tailored fabrication of Bi-rich bismuth oxyhalides with hierarchical structure still remains unexplored. Hereof, Bi24O31Br10 hierarchical hexagonal nanoplates (HPs) are fabricated via facile co-precipitation with subsequent hydrothermal (solvothermal) treatment. The ethylene glycol coordination induced dissolving-recrystallization of one-dimensional Bi24O31Br10 nanobelts (NBs) gives rise to the construction of such unique hierarchical structure. Attributed to the compact intersecting and stacking of nanosheets in this hierarchical structure, Bi24O31Br10 HPs are rich in interfaces relative to Bi24O31Br10 hierarchical flowers (HFs) constructed by sparsely assembled nanosheets. The abundant interfaces endow hierarchical structure with enhanced charge storage ability for suppressing rapid electron-hole recombination, leading to facilitated separation of photogenerated charge carriers. Thanks to this advantage, Bi24O31Br10 HPs display standout catalytic properties in comparison with Bi24O31Br10 HFs with fewer interfaces and Bi24O31Br10 NBs without hierarchical structure, which only need 20 min and 30 min to reduce 94% of Cr(VI) and degradation of 90% OTC under visible light illumination, respectively. This work not only presents the first report about the fabrication of Bi24O31Br10 hierarchical hexagonal nanoplates, but also discloses the pivotal role of interfaces in boosting the photocatalytic performance of hierarchical photocatalysts.

Background: Several studies have substituted the T1 slope (T1S) with the C7 slope (C7S) because the C7 endplate is clearer on radiographs. Further, abnormal serum lipid levels have been proven to be related with the development of disc degeneration. The aim of this study was to explore the relationship between C7S, serum lipid levels, cervical parameters related to cervical sagittal balance and Modic changes (MCs) in patients with multisegment cervical spondylotic myelopathy (CSM). Methods: Between January 2014 and January 2017, 75 patients with multisegment CSM were enrolled in our retrospective study. Gender, age, history of smoking status and alcohol consumption, and laboratory test data were recorded. The cervical sagittal balance parameters C7S, T1S, cervical lordosis (CL), neck tilt (NT), thoracic inlet angle (TIA), C2-C7 sagittal vertical axis (SVA), and T1S-CL were analyzed with Spearman correlation tests and multiple linear regression analysis. We diagnosed MCs through computed tomography or magnetic resonance imaging of the cervical spine. Patients were divided into four subgroups according to the presence or absence of MCs and their C7S values. Results: 75 patients were included in our study. Age, gender, C7S, and T1S were significantly different between the two groups. However, there was no statistical difference with regard to smoking status, alcohol consumption, lipoprotein(a), high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, albumin, globulin, triglycerides, total cholesterol, Ca2+, CL, T1S, TIA, NT, and T1S-CL. The correlation between HDL-C, LDL-C, ALB, GLB, Ca2+, C7S, T1S, MCs, NT, TIA, and C2-C7 SVA was statistically significant. Conclusion: Significant correlations were observed between MCs and TG (as well as other preoperative sagittal parameters), which may accelerate the development of degeneration of the cervical spine. Therefore, alcohol consumption, TG, and sagittal parameters, such as C7S, and T1S could be a promising candidate for the assessment of cervical sagittal balance and predicting neck pain.

Proteinase K (PRK) is a proteolytic enzyme that has been widely used in industrial applications. However, poor stability has severely limited the uses of PRK. In this work, we used two structure-guided rational design methods, Rosetta and FoldX, to modify PRK thermostability. Fifty-two single amino acid conversion mutants were constructed based on software predictions of residues that could affect protein stability. Experimental characterization revealed that 46% (21 mutants) exhibited enhanced thermostability. The top four variants, D260V, T4Y, S216Q, and S219Q, showed improved half-lives at 69°C by 12.4-, 2.6-, 2.3-, and 2.2-fold that of the parent enzyme, respectively. We also found that selecting mutations predicted by both methods could increase the predictive accuracy over that of either method alone, with 73% of the shared predicted mutations resulting in higher thermostability. In addition to providing promising new variants of PRK in industrial applications, our findings also show that combining these programs may synergistically improve their predictive accuracy.

Oral arsenic trioxide (ATO) has demonstrated a favorable clinical efficiency in the treatment of acute promyelocytic leukemia (APL). However, the pharmacokinetic characteristics, tissue bioaccumulation, and toxicity profiles of arsenic metabolites in vivo following oral administration of ATO have not yet been characterized. The present study uses high performance liquid chromatography-hydride generation-atomic fluorescence spectrometry (HPLC-HG-AFS) to assess the pharmacokinetics of arsenic metabolites in rat plasma after oral and intravenous administration of 1 mg kg−1 ATO. In addition, the bioaccumulation of arsenic metabolites in blood and selected tissues were evaluated after 28 days oral administration of ATO in rats at a dose of 0, 2, 8, and 20 mg kg−1 d−1. The HPLC-HG-AFS analysis was complemented by a biochemical, hematological, and histopathological evaluation conducted upon completion of ATO treatment. Pharmacokinetic results showed that arsenite (AsIII) reached a maximum plasma concentration rapidly after initial dosing, and the absolute bioavailability of AsIII was 81.03%. Toxicological results showed that the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and white blood cells (WBC) in the 20 mg kg−1 d−1 ATO group were significantly increased compared to the control group (p < 0.05). The distribution trend of total arsenic in the rat was as follows: whole blood > kidney > liver > heart. Dimethylated arsenic (DMA) was the predominant bioaccumulative metabolite in the whole blood, liver, and heart, while monomethylated arsenic (MMA) was the predominant one in the kidney. Collectively, these results revealed that oral ATO was rapidly absorbed, well-tolerated, and showed organ-specific and dose-specific bioaccumulation of arsenic metabolites. The present study provides preliminary evidence for clinical applications and the long-term safety evaluation of oral ATO in the treatment of APL.

Imaging examinations methods (including US, CT, and MRI) have gotten more and more applied to liver failure. They can show the normal findings of segments of the livers, hepatic vessels, and bile ducts. They also can demonstrate the imaging findings of acute and chronic liver failure, including complications of liver failure and after liver transplant.

Background Peutz-Jeghers Syndrome (PJS) is known as a rare inherited polyposis due to the malfunction of serine/threonine kinase gene LKB1. However, not all of PJS patients carry LKB1 germline mutation. Previous researches have observed the elevated DNA methylation level in PJS polyps. Nevertheless, the mechanism of such abnormal and its impact on PJS patients remains to be fully described. Results The results proved a significant increase on the methylation level of LKB1 promoter in PJS polyps compared with normal colon biopsies through bisulfite PCR followed by Sanger sequencing. Moreover, the methylation pattern in PJS polyps could be further categorized as three different scenarios: hypermethylated, hemimethylated and hypomethylated pattern. Furthermore, immunohistochemistry of DNMT1/3a/3b suggested the up-regulation of DNMT1 and 3a might participate the epigenetic alternation of LKB1 in PJS polyps. Logistic regression suggested hypomethylated LKB1 promoter in PJS polyps as a risk factor for gastrointestinal malignancies in PJS patients. Conclusions The promoter methylation level of LKB1 gene in PJS polyps is generally elevated compared with normal colon mucosa. Yet not all of PJS polyps carry hypermethylated LKB1 promoter. Hypomethylation in this region has linked to malignant tumors in PJS patients. Given the rarity of PJS, this work together with previous researches, have proved the importance of LKB1 promoter methylation in PJS development and prognosis.

Rhodopsin S334ter-3 retinal degeneration rats have been widely used to investigate degenerative diseases of the retina. In this model, morphological and electrophysiological changes have been observed in the retina, superior colliculus and primary visual cortex (V1). However, no study so far has examined rhodopsin S334ter-3 rats with regards to their contrast response in V1 - a fundamental property of visual information processing. In this study, experimental rats (S334ter-3) carried one copy of the mutant transgene. We compared responses to spatio-temporal variations in luminance contrast in the primary visual cortex of these rats with those in Long-Evans (LE) rats to elucidate the degeneration-specific activity changes in this part of the visual pathway. We measured extracellular responses to different stimulus contrasts at the preferred parameters of each recorded cell under classical receptive field (CRF) stimulation. Our results show that V1 cells in the S334ter-3 group exhibit stronger spontaneous activity but weaker stimulus-evoked responses at medium and high contrasts. By fitting responses to a sigmoid function, we found that the S334ter-3 group had a lower Rmax but a larger exponent N than the LE group. However, we did not find a significant difference in C50 value. These results indicate the decrease in discriminating the stimuli contrast and loss in responses and lower signal to noise ratio after retinal degeneration. Our study supports the notion that a considerable degree of plasticity is found in cortex after retinal degeneration, indicating that visual restoration therapies would succeed if the retina could send useful signals to the brain.

First, this paper sorts out the theme types and patterns of Tibetan architectural colored paintings, and analyzes the artistic characteristics of Tibetan color paintings. On this basis, it focuses on studying the artistic ways to enhance the scope of Tibetan color painting art, and elaborates on the application of traditional color painting art in the design of street furniture in accordance with the current situation of urban and environmental development in Tibetan areas, so as to help to promote the regional style of urban environment in Tibetan areas.

Sanggenon C (SC), a natural flavonoid extracted from Cortex Mori (Sang Bai Pi), is reported to possess anti-inflammatory and antioxidant properties in hypoxia. The present study aimed to investigate the therapeutic potential and the underlying mechanisms of SC in cerebral ischemia-reperfusion (I/R) injury. A rat model of reversible middle cerebral artery occlusion (MCAO) was used to induce cerebral I/R injury in vivo, and SC was administrated intragastrically. Brain injuries were evaluated using Bederson scores, brain water content, and 2, 3, 5-triphenyltetrazolium chloride (TTC) staining. The levels of inflammatory factors and oxidative stress were examined using corresponding kits. Cell apoptosis was evaluated by TUNEL. Moreover, the expressions of apoptosis-related and RhoA/ROCK signaling-related proteins were detected through western blotting. In vitro, RhoA was overexpressed in oxygen-glucose deprivation and reperfusion (OGD/R)-induced PC12 cells to confirm the contribution of RhoA-ROCK signaling inhibition by SC to the neuroprotective effects post OGD/R. Pretreatment with SC significantly ameliorated the neurologic impairment, brain edema, and cerebral infarction post MCAO-reperfusion, associated with reductions of inflammation, oxidative stress, and cell apoptosis in the brain. Furthermore, SC remarkably downregulated the expression of RhoA/ROCK signaling-related proteins post MCAO-reperfusion in rats, while overexpression of RhoA reversed the beneficial effects of SC on protecting against inflammation and oxidative stress in OGD/R-induced PC12 cells. Taken together, these findings demonstrated that SC exerts neuroprotective effects after cerebral I/R injury via inhibiting inflammation and oxidative stress through regulating RhoA-ROCK signaling, suggesting a therapeutic potential of SC in cerebral I/R injury.

Superficial solid masses are common conditions in clinical practice, however, some of which can be easily diagnosed and others would be difficult. Although imaging of superficial masses is not always characteristic, it would be helpful to give a definitive diagnosis or narrow a differential diagnosis. Crossing-section imaging can depicture the masses directly, find some pathognomonic signs and demonstrate their relationship with adjacent structures, which can provide decision support for clinician’s reference. Computed tomography (CT) can be used to detect calcifications and bone erosion which could not be seen on radiographs. Magnetic resonance imaging (MRI) is the preferred way for evaluating soft tissue lesions and provides information on hemorrhage, necrosis, edema, cystic and myxoid degeneration, and fibrosis. Other advantages of MRI are its superior soft tissue resolution and any profile imaging, which can aid the assessment of extension and adjacent infiltration. Positron emission tomography (PET)/CT and PET/MRI have been increasingly used in bone and soft tissue sarcomas and provides advantages in the initial tumor staging, tumor grading, therapy assessment, and recurrence detection. Therefore, imaging examination can play an important role in treatment decision making for superficial solid tumors. Here we review the important conditions presenting as superficial mass and show the imaging of typical cases diagnosed in our hospital.

The concentrations, distribution, sources and ecological risk levels of polycyclic aromatic hydrocarbons (PAHs) in tidal creek water from coastal tidal flats of the Yellow River Delta were investigated. The concentrations of 16 PAHs ranged from 0.113 to 1.533, with a mean value of 0.496 ± 0.035 μg L−1, which indicated a moderate level of pollution. The main long-term sources of PAHs in the coastal tidal flats of the Yellow River Delta were petroleum combustion and petroleum pollution. The ecological risk assessment showed that the levels of PAHs in tidal creek water of the coastal tidal flats in the Yellow River Delta corresponded to medium to high ecological risk levels, and a high probability of potential ecological risk, posing harm to aquatic organisms. Among the 7 sampling sites, site 5, site 6, and site 7 were at high ecological risk, and the other sites were at moderate ecological risk. PAH pollution in the tidal creek water near the Yellow River Estuary and farther south, in the coastal tidal wetland of Laizhou Bay, deserves special attention, especially with respect to the prevention and control of benzo[a]pyrene (BaP) pollution in the water.

Integrin‑linked kinase (ILK) is overexpressed in ovarian cancer (OC), and ILK gene silencing results in apoptosis in OC cells. In the present study, the mechanism by which ILK induces apoptosis was explored from the perspective of microRNA (miRNA) expression. Alterations in the global miRNA expression profile were detected using a miRNA microarray after OC cells were transduced with an ILK small hairpin RNA lentivirus. ILK silencing led to a significant upregulation of 14 miRNAs by at least 1.5‑fold. These findings were validated by reverse transcription‑quantitative polymerase chain reaction. A pathway analysis of experimentally validated target genes revealed the inhibition of multiple cancer‑associated signaling pathways and the wnt signaling pathway. Compared with cells transfected with scrambled RNA, the ILK‑silenced cells had remarkably lower expression of wnt ligands (wnt3a, wnt4 and wnt5a) and downstream β‑catenin. ILK silencing led to apoptosis of OC cells and impaired the migratory ability. Taken together, the present results suggested that miRNA‑mediated wnt pathway alterations are involved in the anti‑apoptotic role of ILK in OC. It was also indicated that ILK silencing reduced the ability of OC cells to adhere to fibronectin, which may lead to unstable focal contact. Consistently, the phosphorylation levels of focal adhesion kinase and RAC‑α serine/threonine protein kinase were downregulated. The present work demonstrated the first global miRNA expression profile of OC cells when ILK was inhibited, and this expression profile may provide a basis for the development of biomarkers and therapeutic targets for OC.

Monocular visual deprivation is an excellent experimental paradigm to induce primary visual cortical response plasticity. In general, the response of the cortex to the contralateral eye to a stimulus is much stronger than the response of the ipsilateral eye in the binocular segment of the mouse primary visual cortex (V1). During the mammalian critical period, suturing the contralateral eye will result in a rapid loss of responsiveness of V1 cells to contralateral eye stimulation. With the continuing development of transgenic technologies, more and more studies are using transgenic mice as experimental models to examine the effects of specific genes on ocular dominance (OD) plasticity. In this study, we introduce detailed protocols for monocular visual deprivation and calculate the change in OD plasticity in mouse V1. After monocular deprivation (MD) for 4 days during the critical period, the orientation tuning curves of each neuron are measured, and the tuning curves of layer four neurons in V1 are compared between stimulation of the ipsilateral and contralateral eyes. The contralateral bias index (CBI) can be calculated using each cell's ocular OD score to indicate the degree of OD plasticity. This experimental technique is important for studying the neural mechanisms of OD plasticity during the critical period and for surveying the roles of specific genes in neural development. The major limitation is that the acute study cannot investigate the change in neural plasticity of the same mouse at a different time.

Background This study was conducted to summarize the clinical, magnetic resonance imaging (MRI) and pathological features of IgG4-realated hypertrophic pachymeningitis (IgG4-RHP) and its differential diagnosis from similar diseases. Methods Data of IgG4-RHP patients admitted to Department of Neurology, Neurosurgery and Infection, the First Affiliated Hospital of Medical School of Zhejiang University from January 1, 2015 to July 31, 2019 were collected and their clinical symptoms, laboratory examinations, imaging and pathological features were investigated. At the same time, the clinicopathological and imaging findings of other dura thickening diseases diagnosed in our hospital were compared and analyzed. Results The clinical symptoms of 4 IgG4-RHP patients include chronic headache and cranial nerves injury, etc. Levels of serum IgG4 and cerebrospinal fluid (CSF) IgG4 increased in all patients. Focal enhancement of dura mater could be seen on plain and enhanced cranial MRI. Pathological results were consistent with IgG4-RHP symptoms. Among other diseases that cause dural thickening, the content of serum C-reactive protein in patients with Rosai-Dorfman disease declined. Patients with intracranial hypotension syndrome often have postural headache. Patients with tuberculous meningitis can have previous pulmonary tuberculosis. The diagnosis of patients with atypical meningioma depends on the results of operation and pathology. Patients with central nervous system leukemia can be diagnosed with reference to the results of laboratory results. Conclusions The clinicopathological and imaging manifestations of IgG4-RHP are summarized in this study. Meanwhile, the clinical data of several other diseases with similar imaging characteristics are analyzed in order to clarify the diagnostic strategy of IgG4-RHP and provide help for the next treatment.

Tizoxanide, the active metabolite of nitazoxanide, has recently been reported as an effective agent for the treatment of glioma. As there had been no report about the analysis of tizoxanide in brain tissue, we established extraction and UHPLC-MS/MS methods to quantify tizoxanide in rat brain and plasma to evaluate the brain-to-plasma ratio of tizoxanide. The biological samples were mainly prepared by acetonitrile and the separation was performed on a Waters XBridge® BEH C18 column. The mobile phase was composed of water mixed with 10 mm ammonium formate (pH 3.0) and acetonitrile according a gradient volume. Tizoxanide and topiramate (internal standard) were monitored utilizing negative electron spray ionization in multiple reaction monitoring mode. The methods were validated to be precise and accurate within the dynamic range of 5-1000 ng/mL and 0.2-50 ng/g for plasma and brain tissue samples, respectively. The lower limit of quantitation of the method was 0.2 ng/g, which was far more sensitive than all existing methods to quantify tizoxanide in biological samples. Application performed on rats exhibited that the brain-to-plasma ratio of tizoxanide ranged from 3.16 to 26.86% in 1 h after administration of 10 mg/kg nitazoxanide.

Salinomycin with antibacterial and anticoccidial activities is a commercial polyether polyketide widely used in animal husbandry as a food additive. Malonyl-CoA (MCoA), methylmalonyl-CoA (MMCoA), and ethylmalonyl-CoA (EMCoA) are used as extension units in its biosynthesis. To understand how the salinomycin modular polyketide synthase (PKS) strictly discriminates among these extension units, the acyltransferase (AT) domains selecting MCoA, MMCoA, and EMCoA were structurally characterized. Molecular dynamics simulations of the AT structures helped to reveal the key interactions involved in enzyme-substrate recognitions, which enabled the engineering of AT mutants with switched specificity. The catalytic efficiencies ( k