Vision Improvement in Keratoconus Patients Trained with Perceptual Learning: A Randomized Controlled Trial.

BACKGROUND: Keratoconus (KC) is a corneal ectasia disease in which the vision of some patients cannot achieve satisfaction by spectacle corrections. However, not everyone can embrace contact lenses to achieve better vision. Perceptual learning (PL) is a potential treatment for vision improvement in such patients. PURPOSE: To investigate the effectiveness and maintenance of PL on vision improvement in KC patients corrected with spectacles. DESIGN: Randomized, double-blind clinical trial. PARTICIPANTS: Thirty-five non-progressive KC patients aged 9 years or older with unsatisfied spectacle-corrected vision were enrolled. METHODS: Non-progressive KC patients with best spectacle-corrected distance visual acuity (CDVA) of 0 to 1.0 logMAR (Snellen equivalent range 20/20 to 20/200) and contact lenses intolerant were enrolled. Eligible subjects were randomized into PL and control groups to receive PL and placebo training for 3 months, respectively. Spectacle-corrected visual acuity, contrast sensitivity function (CSF), stereoacuity, and visual functioning and quality of life questionnaires were measured at baseline, 3 months, and 6 months of follow-up. Statistics were analyzed following the intention-to-treat (ITT) principle. RESULTS: After 3 months of training, the CDVA of patients in the PL group improved as compared to the placebo group (0.17 ± 0.15 logMAR vs. 0.02 ± 0.06 logMAR; P = 0.0006). Eight out of seventeen (47.06 %) patients in the PL group reached CDVA improvement ≥ 2 lines (P=0.0010). This improvement persisted for at least 6 months (from baseline) as compared to the placebo group (0.17 ± 0.17 logMAR vs. 0.01 ± 0.07 logMAR; P = 0.0011). The increase of CSF in the PL group mainly was found for moderate spatial frequency (0.11 ± 0.17 log units at 3 cpd; 0.12 ± 0.19 log units at 6 cpd). Linear regression indicated that patients with worse initial CDVA achieved better gains in CDVA after PL (P = 0.009). No side effects were observed and no subjects quit because of training difficulties. CONCLUSION: Three-month perceptual learning improved vision in KC patients and the improvement maintained after 3 months of treatment cessation. The results indicate that perceptual learning may be a promising therapy for KC patients with unsatisfied spectacle-corrected visual acuity.

Impact of government governance and environmental taxes on sustainable energy transition in China: fresh evidence using a novel QARDL approach.

Although economies have experienced immense growth in recent times, however, it also comes with environmental and social consequences which question the current practices and threaten the well-being of current as well as the future generation. This realization, thus, pushes institutions to bring change in existing energy-related policies in order to incorporate social and environmental concerns. Clean energy transition, in this regard, is gaining attraction all over the world as it shifts away economies from non-renewable resources. The study, thereby, intends to explore the role of governance and environmental taxes in the energy transition in China economy over the period 1999-2019. The roles of industrialization and economic growth in the transition of energy are taken into consideration. The recently introduced legit quantile autoregressive distributed lag (QARDL) model and Granger causality in quantiles are applied to quarterly data spanning 1999Q1 to 2019Q4 for empirical quantile analysis. Results echoed that governance has a positive impact and environmental resources have a negative impact on energy transition across all quantiles. However, economic growth influences clean energy transition only at extremely higher quantiles (0.60-0.95), and industrialization does not have any effect on energy transition over the entire quantile range. The findings of the Granger causality analysis reveal the presence of a bidirectional causal association between clean energy transition and all the variables. Worthy policies are recommended on the basis of the findings.

The first Elcanidae (Orthoptera, Elcanoidea) from the Daohugou fossil bed of northeastern China.

A new species of Elcanidae (Orthoptera, Elcanoidea), Parelcana pulchmacula sp. nov., is described based on four new specimens from the Middle Jurassic Jiulongshan Formation of northeastern China. The new species differs from all other known Archelcaninae species by its combination of wing-venation characters. This new finding improves our knowledge of variation on wing venation in elcanid insects and constitutes the first record of Elcanidae from the Daohugou fossil bed (Yanliao Biota) of northeastern China.

Altered Regional Homogeneity in Patients With Corneal Ulcer: A Resting-State Functional MRI Study.

OBJECTIVE: To investigate the potential regional homogeneity (ReHo) brain activity changes in patients with corneal ulcer (CU) and their possible relationship with clinical symptoms. MATERIALS AND METHODS: Forty patients with CU (26 men and 14 women), and 40 healthy controls (HCs) (26 men and 14 women) closely matched in age, sex, and weight underwent resting-state functional MRI scans, respectively. The ReHo method was applied to evaluate synchronous neural activity changes. Receiver operating characteristic curve (ROC curve) was used to show high test-retest stability and high degree of sensitivity and specificity. We utilized the correlation analysis to calculate the relationship between the average ReHo signal values in different brain areas and the clinical symptoms in CU patients. RESULTS: Compared with the HCs, CU patients had significantly increased ReHo values in right cerebellum posterior lobe, left cerebellum posterior lobe, left inferior temporal gyrus, right lingual gyrus, left middle frontal gyrus, left angular gyrus, left cingulate gyrus, right angular gyrus and bilateral superior frontal gyrus, and decreased ReHo values in right anterior cingulate and left precentral gyrus. ROC curve analysis of each brain regions showed the accuracy of AUC was perfect except the right cerebellum posterior lobe. Nevertheless, there was no clear evidence of prominent relevance between the average ReHo values in brain areas and the clinical symptoms. CONCLUSION: Corneal ulcer caused dysfunctional adaption in different brain areas, which including relatively increased values and decreased values. This finding may help us take a further step in exploring the underlying pathologic mechanisms of CU.

Application of amplitude of low­frequency fluctuation to altered spontaneous neuronal activity in classical trigeminal neuralgia patients: A resting­state functional MRI study.

Recent studies have reported structural and functional abnormalities in multiple brain regions of classical trigeminal neuralgia (CTN) patients. Differences in spontaneous neuronal activity between CTN patients and healthy subjects, however, remain unknown. The aim of the present study was to investigate alterations in brain activity by application of amplitude of low frequency fluctuation (ALFF), thus analyzing the correlation between durations of spontaneous pain intensity and ALFF values in CTN patients. A total of 28 CTN patients (male, n=12; female, n=16) and 28 healthy controls (HCs; male, n=12; female, n=16) matched for age and sex were enrolled. All subjects underwent resting­state functional magnetic resonance imaging and changes in spontaneous brain activity were investigated using an ALFF method. Receiver operating characteristic (ROC) curve analysis was applied to differentiate ALFF values of CTN patients from HCs. Altered ALFF values and clinical manifestations were evaluated using Pearson's correlation analysis. ALFF values of the bilateral inferior cerebellum, bilateral fusiform gyrus, right precentral gyrus, left inferior temporal gyrus, right superior cerebellum, left inferior occipital gyrus and right superior occipital gyrus were significantly higher in CTN patients when compared to HCs. ROC curve analysis of each brain revealed a near­perfect AUC accuracy. Pearson's correlation analysis revealed the visual analog scale of the right eye to be positively correlated with both left inferior temporal and occipital gyral findings, while episode duration likewise was positively associated with left inferior temporal gyral findings. CTN patients exhibited abnormal spontaneous activity in multiple brain regions closely related to pain regulation and perception, while VAS and CTN episode duration were positively correlated with ALFF signal values in some brain regions. The present findings provide further insight into the pathological mechanisms underlying CTN.

The levels and significance of inflammasomes in the mouse retina following optic nerve crush.

Inflammasomes play an important role in neuroinflammation. However, their function during the secondary death of retinal cells after traumatic optic neuropathy and their dependence on pathogen stimuli remains unclear. Therefore, we evaluated the expression profiles of 10 different inflammasome-related mRNAs in the retina following an optic nerve crush (OPC) injury under both conventional sterile as well as non-sterile conditions, and validated two significantly varied ones on a protein level. While most factors were much more highly elevated in non-sterile conditions, both Nlrp1b and Nlrp3 inflammasome mRNAs were increased significantly on postoperative day 1 to day 7 in the mouse sterile OPC injury model. While production of the inflammation-associated cytokines IL-1ß and IL-18 could be continuously detected on an mRNA level postoperatively, a clear peak could be seen on day 7 that coincided with maximal expression of caspase-1 mRNA and with observation of retinal ganglion cells death, despite the mice being held in specific-pathogen free conditions. As such, the pro-inflammatory cytokines activated by inflammasome activation during OPC injury may drive secondary cell death through pyroptosis, and inhibition of these delayed responses may be an important means of preventing worsened injury and loss of vision in trauma patients.

Increased serum bile acid level is associated with high-risk coronary artery plaques in an asymptomatic population detected by coronary computed tomography angiography.

BACKGROUND: There are limited data on the association between serum total bile acid level and coronary plaque characteristics. This study investigated the relationship between serum total bile acid level and the severity of coronary stenosis and coronary plaque features in an asymptomatic population using coronary computed tomography angiography (CTA). METHODS: A total of 1,137 consecutive participants with no known coronary artery disease (CAD) undergoing CTA as part of a general routine health evaluation were recruited. Serum total bile acid level and clinical parameters were assayed. Coronary stenosis and high-risk plaques features (napkin-ring sign, low-attenuation plaque, spotty calcification, positive remodelling) were evaluated. Associations between serum total bile acid concentration and high-risk coronary plaques was tested through univariate and multivariate analyses. RESULTS: A total of 101 high-risk coronary plaques subjects and 93 controls were eligible for study inclusion. The severity of coronary artery stenosis and high-risk coronary plaques increased with serum total bile acid level quartiles (all P<0.001). The independent predictor of high-risk coronary plaques in multivariate analysis was serum total bile acid level (P<0.001). Receiver operating characteristic (ROC) confirmed that serum total bile acid concentration significantly differentiated high-risk coronary plaques [the area under the curve (AUC) =0.876; P<0.001, with a sensitivity of 87.13% and a specificity of 86.02%]. CONCLUSIONS: Higher serum total bile acid level was associated with the severity of coronary artery stenosis and high-risk coronary artery plaques detected by CTA in asymptomatic populations.

Altered Spontaneous Brain Activity in Patients with Classical Trigeminal Neuralgia Using Regional Homogeneity: A Resting-State Functional MRI Study.

OBJECTIVE: Neuroimaging studies have shown that patients with pain-related conditions have altered neuronal activity and structural functions. The purpose of this study was to investigate whether patients with classical trigeminal neuralgia (CTN) exhibit changes in corresponding neuronal activity via analysis of neuronal activity regional homogeneity (ReHo). METHODS: A total of 28 patients presenting with sore eyes (12 men and 16 women) were matched with 28 healthy controls (12 men and 16 women). All participants underwent functional magnetic resonance imaging (fMRI). This ReHo method was used to assess the consistency of changes in neural activity in various brain regions. The receiver operating characteristic (ROC) curve was applied to differentiate ReHo values of patients with CTN from ReHo values of healthy controls. Pearson's correlation analysis was applied to evaluate the correlation between ReHo values of different brain regions of patients with CTN and clinical manifestations. RESULTS: Compared with healthy controls, patients with CTN were found to have increased ReHo values in the inferior cerebellum bilaterally, right inferior temporal gyrus, right middle occipital gyrus, right fusiform gyrus, right superior frontal gyrus, and right precentral gyrus. ROC curve analysis of each brain region revealed near-perfect accuracy regarding the area under the curve. However, no correlation between ReHo values and clinical manifestations in patients with CTN was found. CONCLUSIONS: CTN is associated with altered neuronal networks in different areas of the brain. ReHo values all possess different degrees of change, implying that CTN has a certain impact on cerebral function.

Hemin induces necroptosis of neurons through interleukin -1 receptor after intracerebral hemorrhage / 中华神经医学杂志

Objective To investigate the effect of hemin on neuronal necroptosis and its mechanism in mice after intracerebral hemorrhage.Methods (1) Experiment one: 24 C57BL/6 mice were divided into sham-operated group, saline control group, 5 mmol/L hemin group, and 10 mmol/L hemin group (n=6); mice in the latter two groups were injected 20μL 5 mmol/L or 10 mmol/L heme solution into the corpus striatum to prepare cerebral hemorrhage models, and the normal saline group was injected 20μL normal saline; Western blotting was used to detect the protein expressions of heme oxygenase-1 (HO-1), receptor-interacting protein (RIP)1, RIP3, and mixed lineage kinase domain like protein (MLKL). Three C57BL/6 mice were injected 20μL 10 mmol/L heme solution into the corpus striatum to prepare cerebral hemorrhage models; 24 h after that, double-labelling immunofluorescence was used to detect the expressions of Caspases-3 and neuron-specific nuclear protein (NeuN) in the hippocampus tissues. (2) Experiment two: the primary cultured hippocampal neurons were stimulated with 0, 10, 20, 40 and 80μmol/L heme for 6 h and 40μmol/L heme for 0, 1, 2, 4 and 6 h, respectively; lactic dehydrogenase (LDH) method was used to determine the neuron damage. After the primary cultured hippocampal neurons being stimulated with 40μmol/L heme for 0, 1, 2, 4 and 6 h, respectively, the protein expressions of interleukin-1 receptor (IL-1R)1, RIP1, RIP3, MLKL and caspase-3 in the neurons were detected by Western blotting, and the level of inflammatory factor interleukin-1β(IL-1β) was detected by ELISA. After primary cultured hippocampal neurons being stimulated with 0, 40μmol/L heme for 6 h, the expressions of NeuN and Caspase-3 in the neurons were detected by double-labelling immunofluorescence. (3) Experiment three: the primary cultured hippocampal neurons were pre-incubated with 0, 0.5, 1.0, and 1.5μg/mL IL-1R antagonist for one h, and then, stimulated with 40μmol/L heme for 6 h; the toxic injury of neurons was detected by LDH method, and the protein expressions of IL-1R1, RIP1, RIP3 and MLKL in neurons were detected by Western blotting.Results (1) As compared with those in the sham-operated group and saline control group, protein expressions of HO-1, RIP1, RIP3 and MLKL in the 5 mmol/L heme group and 10 mmol/L heme group were significantly increased (P<0.05); at 24 h after 10 mmol/L heme injection, Caspase-3 expression was found in frozen sections of hippocampal tissues of mice, but no co-localization of Caspase-3 and NeuN was found. (2) As compared with those in the 0μmol/L heme group, LDH release rates in the heme groups of different concentrations were significantly increased and concentration-dependent (P<0.05); as compared with the heme group of 0 h stimulation, the heme groups of different times of stimulation had significantly increased release rates of LDH in time dependent manner (P<0.05). As compared with the heme group of 0 h stimulation, the heme groups of different times of stimulation had significantly increased IL-1R1, RIP1, RIP3, and MLKL protein expressions (P<0.05); Caspase-3 showed no obvious changes. As compared with the heme group of 0 h stimulation, the heme groups of different times of stimulation had significantly increased IL-1βlevels in time dependent manner (P<0.05). No obvious Caspase-3 expression was noted in the heme group of 6 h stimulation. (3) As compared with the 40μmol/L heme group, pre-incubation groups of 0.5, 1.0, and 1.5μg/mL IL-1R antagonist had significantly reduced LDH release rates and protein expressions of IL-1R1, RIP1, RIP3 and MLKL (P<0.05).Conclusion sHemin could induce neuron cell death directly via a necroptosis pathway rather than Caspase3-mediated apoptosis. The cytotoxicity of hemin could be alleviated by blocking IL-1R.

Luteolin alleviates NLRP3 inflammasome activation and directs macrophage polarization in lipopolysaccharide-stimulated RAW264.7 cells.

Pure plant extract luteolin has been demonstrated to possess numerous biological effects. However, the specific effect of luteolin on macrophage polarization and NOD-like receptor protein 3 (NLRP3) inflammasome activation has not been documented. In this study, Cultured RAW264.7 cells were treated with or without luteolin in the presence or absence of LPS. Subsequently, cell viability was tested by CCK-8 assay. Total reactive oxygen species (ROS) were measured by flow cytometry. NLRP3, apoptosis-associated speck-like protein containing CARD (ASC), caspase-1, inducible nitric oxide synthase (iNOS) and Arginase (Arg-1) protein expression was detected using western blotting. Enzyme-linked immunosorbent assay (ELISA) kits were used to detect the level of TNF-α, IL-18, and Interleukin-1ß (IL-1ß). Increased production of ROS and expression of NLRP3, ASC, caspase-1, IL-18 and IL-1ß proteins were observed in RAW264.7 cells incubated with LPS and were effectively inhibited by 2 µM luteolin. Furthermore, 2 µM luteolin pretreatment enhanced the expression of M2 macrophage markers (Arg-1 and IL-10), and decreased the expression of markers associated with M1 macrophage polarization (TNF-α, IL-6 and iNOS). These results indicated that low-dose luteolin inhibits NLRP3 inflammasomes activation and promotes macrophage polarization toward an M2 phenotype, which provides new evidence for the anti-inflammation activity of luteolin.

Recent progress on the effects of microRNAs and natural products on tumor epithelial-mesenchymal transition.

Epithelial-mesenchymal transition (EMT) is a biological process of phenotypic transition of epithelial cells that can promote physiological development as well as tissue healing and repair. In recent years, cancer researchers have noted that EMT is closely related to the occurrence and development of tumors. When tumor cells undergo EMT, they can develop enhanced migration and local tissue invasion abilities, which can lead to metastatic growth. Nevertheless, two researches in NATURE deny its necessity in specific tumors and that is discussed in this review. The degree of EMT and the detection of EMT-associated marker molecules can also be used to judge the risk of metastasis and to evaluate patients' prognosis. MicroRNAs (miRNAs) are noncoding small RNAs, which can inhibit gene expression and protein translation through specific binding with the 3' untranslated region of mRNA. In this review, we summarize the miRNAs that are reported to influence EMT through transcription factors such as ZEB, SNAIL, and TWIST, as well as some natural products that regulate EMT in tumors. Moreover, mutual inhibition occurs between some transcription factors and miRNAs, and these effects appear to occur in a complex regulatory network. Thus, understanding the role of miRNAs in EMT and tumor growth may lead to new treatments for malignancies. Natural products can also be combined with conventional chemotherapy to enhance curative effects.

The complete mitochondrial genome of Humphaplotropis culaishanensis sp. nov. (Orthoptera: Acridoidea: Pamphagidae: Pamphaginae).

The complete mitochondrial genome of Humphaplotropis culaishanensis sp. nov., which was collected from the Shandong Province of China, is reported here. It was 15,659 bp in length and contained 72.3% AT. All Humphaplotropis culaishanensis protein-coding sequences started with a typical ATN codon, excluding cox1 and nad6. The usual termination codon (TAN) and incomplete stop codons (T, TA) were found from 13 protein-coding genes. All tRNA genes could be folded into the typical cloverleaf secondary structure, excluding trnS(AGN) which forms another structure. The sizes of the large and small ribosomal RNA genes were 1322 and 852 bp, respectively. The AT content of the A+T-rich region was 81.3%.

The complete mitochondrial genome of Asiotmethis jubatus (Uvarov, 1926) (Orthoptera: Acridoidea: Pamphagidae).

The complete mitochondrial genome of Asiotmethis jubatus (Uvarov, 1926), which was collected from the Xinjiang Uygur Autonomous Region of China, is reported here. It is 15,669 bp in length and contains 72.3% AT. All Asiotmethis jubatus protein-coding sequences start with a typical ATN codon, excluding cox1 and nad6. The usual termination codon (TAN) and incomplete stop codons (T) were found from 13 protein-coding genes. All tRNA genes could be folded into the typical cloverleaf secondary structure, excluding trnS(AGN) which forms another structure. The sizes of the large and small ribosomal RNA genes are 1315 and 852 bp, respectively. The AT content of the A + T-rich region is 81.9%.

N-methyl-D-aspartic acid receptor 1 (NMDAR1) aggravates secondary inflammatory damage induced by hemin-NLRP3 pathway after intracerebral hemorrhage / 中华创伤杂志(英文版)

<p><b>OBJECTIVE</b>Inflammation plays a critical role in secondary brain damage after intracerebral hemorrhage (ICH). However, the mechanisms of inflammatory injury following ICH are still unclear, particularly the involvement of NLRP3 inflammasome, which are crucial to sterile inflammatory responses. In this study, we aim to test the hypothesis that NLRP3 signaling pathway takes a vital position in ICH-induced secondary inflammatory damage and detect the role of N-methyl-D-aspartic acid receptor 1 (NMDAR1) in this progress.</p><p><b>METHODS</b>ICH was induced in mice by microinjection of hemin into the striatum. The protein levels of NMDAR1, NMDAR1 phosphorylation, NLRP3 and IL-1b were measured by Western blot. The binding of NMDAR1 to NLRP3 was detected by immunoprecipitation.</p><p><b>RESULTS</b>The expression of NMDAR1, NMDAR1 phosphorylation, NLRP3 and IL-1b were rapidly increased after ICH. Hemin treatment enhanced NMDAR1 expression and NMDAR1 phosphorylation, as well in cultured microglial cells treated by hemin. Hemin up regulated NLRP3 and IL-1b level, which was reversed by MK801 (NMDAR antagonist) in vitro. Hemin also promoted the binding of NMDAR1 to NLRP3.</p><p><b>CONCLUSION</b>Our findings suggest that NMDAR1 plays a pivotal role in hemin-induced NLRP3-mediated inflammatory damage through synergistic activation.</p>

The complete mitochondrial genome of Filchnerella beicki Ramme, 1931 (Orthoptera: Acridoidea: Pamphagidae).

Abstract The complete mitochondrial genome of Filchnerella beicki Ramme, 1931, which was collected from the Ningxia Hui Autonomous Region of China, is reported here. It is 15,658 bp in length and contains 72.3% AT. All Filchnerella beicki protein-coding sequences start with a typical ATN codon, excluding cox1. The usual termination codon (TAN) and incomplete stop codons (T) were found from 13 protein-coding genes. All tRNA genes could be folded into the typical cloverleaf secondary structure, excluding trnS(AGN) which forms another structure. The sizes of the large and small ribosomal RNA genes are 1315 and 853 bp, respectively. The AT content of the A+T-rich region is 83.1%.

Fractional-order anisotropic diffusion for image denoising.

This paper introduces a new class of fractional-order anisotropic diffusion equations for noise removal. These equations are Euler-Lagrange equations of a cost functional which is an increasing function of the absolute value of the fractional derivative of the image intensity function, so the proposed equations can be seen as generalizations of second-order and fourth-order anisotropic diffusion equations. We use the discrete Fourier transform to implement the numerical algorithm and give an iterative scheme in the frequency domain. It is one important aspect of the algorithm that it considers the input image as a periodic image. To overcome this problem, we use a folded algorithm by extending the image symmetrically about its borders. Finally, we list various numerical results on denoising real images. Experiments show that the proposed fractional-order anisotropic diffusion equations yield good visual effects and better signal-to-noise ratio.

[Molecular phylogeny of some species of the acridoidea based on 16S rDNA].

Based on the 16S rDNA of 8 species (belonging to 8 families of Acridoidea) from China and keyed to 8 relative species of Orthoptera from GenBank, the homologus sequences were compared. The used frequency of nucleotide was calculated and the molecular phylogenetic tree constructed by MEGA microsoft. In the 480 bp fragment of mitochondial 16S rDNA, A + T was about 70.7% and G + C only 29.3%. The sequence data revealed considerable variation in 188 nucleotide sites among the analyzed individuals from 8 different families. The variation rate of transversion was larger than or approach to transition. The results showed that the ranges of the 16S rDNA nucleotide divergence within species, among species of a genus, among genera of a family, and among the same family and suborder were 1.5%, 3.5%-3.6%, 4.8%-15.8% and 15.2%-25.6%, respectively. The members of the same genus and family were grouped together. The phylogenetic relationships of 8 families were Pyrgomorphidae-->Chrotogonidae-->Pamphagidae-->Oedipodidae-->Acrididae--> Arcypteridae-->Gomphoceridae-->Catantopidae. Pyrgomorphidae had closer relationships with Chrotogonidae as well as being the most ancestral group. Arcypteridae and Gomphoceridae were the sister groups and had closer relationships with most evolutionary Catantopidae. Tridactylidae was divided firstly as a suborder, which differs from the recent taxonomy distinctly. Haglidae (Tettigonoidea) and Gryllidae were grouped into suborder Ensifera, Tetrigidae and 8 families of Acridoidea were grouped into suborder Caelifera, as same as recent taxonomy.