Space-time mapping on the sagittal axis in congenital blindness.

Previous evolutionary perspectives proposed that the space-time mapping on the sagittal axis originates from visuo-locomotion coupling when walking/running forward. Accordingly, the congenitally blind could not have developed a sagittal mental timeline if the latter depends on such a visuo-locomotion coupling. However, this conclusion was reached in only a single empirical study (Rinaldi et al. in J Exp Psychol General 147:444-450, 2018), and its theoretical underpinnings are not entirely convincing as locally static and continuous auditory input undergoes a relatively similar change as function of self-locomotion, but this type of sensory-locomotion coupling is spared even in congenital blindness. Therefore, the present study systematically explored whether the congenitally blind show space-time mappings on the sagittal axis using different paradigms in three experiments. In Experiment 1, using a typical implicit RT task, the congenitally blind showed the same preferred space-time mapping in the sagittal dimension as normally sighted participants did. In Experiment 2, this space-time mapping occurred even automatically when temporal relations were task-irrelevant in a naming task. In Experiment 3, in an explicit space-time mapping task, the congenitally blind were more likely to locate the past behind and the future in front of their bodies. Moreover, most blind participants used spatial metaphors for their space-time mapping on the sagittal axis. These results supported the conclusion that the congenitally blind have a sagittal mental timeline, and that their sensory-locomotion coupling experience was either more similar to that of sighted participants or not critical for the space-time mapping. The present study, thus, also helps to clarify the origin of the sagittal mental timeline.

Japanese medaka Olpax6.1 mutant as a potential model for spondylo-ocular syndrome.

pax6 is a canonic master gene for eye formation. Knockout of pax6 affects the development of craniofacial skeleton and eye in mice. Whether pax6 affects the development of spinal bone has not been reported yet. In the present study, we used CRISPR/Cas9 system to generate Olpax6.1 mutant in Japanese medaka. Phenotype analysis showed that ocular mutation caused by the Olpax6.1 mutation occurred in the homozygous mutant. The phenotype of heterozygotes is not significantly different from that of wild-type. In addition, knockout Olpax6.1 resulted in severe curvature of the spine in the homozygous F2 generation. Comparative transcriptome analysis and qRT-PCR revealed that the defective Olpax6.1 protein caused a decrease in the expression level of sp7, col10a1a, and bglap, while the expression level of xylt2 did not change significantly. The functional enrichment of differentially expressed genes (DEGs) using the Kyoto Encyclopedia of Genes and Genomes database showed that the DEGs between Olpax6.1 mutation and wild-type were enriched in p53 signaling pathway, extracellular matrix (ECM) -receptor interaction, et al. Our results indicated that the defective Olpax6.1 protein results in the reduction of sp7 expression level and the activation of p53 signaling pathway, which leads to a decrease in the expression of genes encoding ECM protein, such as collagen protein family and bone gamma-carboxyglutamate protein, which further inhibits bone development. Based on the phenotype and molecular mechanism of ocular mutation and spinal curvature induced by Olpax6.1 knockout, we believe that the Olpax6.1-/- mutant could be a potential model for the study of spondylo-ocular syndrome.

Does walking/running experience shape the sagittal mental time line?

A growing body of evidence suggested that time could be separately represented either on the lateral or sagittal axis. And the lateral mental time line has an origin associated with sensorimotor experience, e.g., reading/writing. However, it is still not clear whether the sagittal mental time line also originates from sensorimotor experience, e.g., walking/running. To address this question, we examined how the movement experience affected the space-time mapping on the lateral and sagittal axes using the virtual reality technique in two experiments. The results showed that the virtual movement experience had significant effects on the space-time mapping on the lateral axis (Experiment 1), but not on the sagittal axis (Experiment 2). This finding supported that the space-time mapping on the lateral axis does originate from sensorimotor experience, while the space-time mapping on the sagittal axis more likely originates from spatial metaphors in languages or other cultural experiences.

Long-term prediction for temporal propagation of seasonal influenza using Transformer-based model.

Influenza is one of the most common infectious diseases worldwide, which causes a considerable economic burden on hospitals and other healthcare costs. Predicting new and urgent trends in epidemiological data is an effective way to prevent influenza outbreaks and protect public health. Traditional autoregressive(AR) methods and new deep learning models like Recurrent Neural Network(RNN) have been actively studied to solve the problem. Most existing studies focus on the short-term prediction of influenza. Recently, Transformer models show superior performance in capturing long-range dependency than RNN models. In this paper, we develop a Transformer-based model, which utilizes the potential of the Transformer to increase the prediction capacity. To fuse information from data of different sources and capture the spatial dependency, we design a sources selection module based on measuring curve similarity. Our model is compared with the widely used AR models and RNN-based models on USA and Japan datasets. Results show that our approach provides approximate performance in short-term forecasting and better performance in long-term forecasting.

Propagation source identification of infectious diseases with graph convolutional networks.

Source identification in networks has drawn considerable interest to understand and control the infectious disease propagation processes. It is usually difficult to achieve both high accuracy and short error distance when we try to solve the problem. This study attempts to introduce the graph convolutional network for the problem of source identification in a given network with different infection rates. First, we put forward a label propagation framework, which can locate the infection source based on both infected and uninfected nodes. Then, a novel Source Identification Graph Convolutional Network (SIGN) framework is proposed inspired by label propagation. Third, we modify the classical cross-entropy loss function and presented neighborhood loss to optimize the average error distance. Finally, extensive experiments are performed on eight datasets with different topologies and varying infection sizes to demonstrate the effectiveness of the proposed algorithms. We compare the proposed method with four mainstream approaches, and our method shows strong performances especially under the large infection size.

Gonadal, Not Maternal, Acquisition of Duplicated pax6 Orthologs in Megalobrama Amblycephala.

: The highly conserved transcription factor Pax6 is involved in the development of the eyes, brain, and pancreas in vertebrates and invertebrates, whereas the additional expression pattern in other organs is still elusive. In this study, we cloned and characterized two pax6 homologs in blunt snout bream (Megalobrama amblycephala), named Mapax6a and Mapax6b. The protein alignment and phylogenetic tree showed that Mapax6a and Mapax6b were highly conserved compared with their counterparts in other species. Genomic information analysis revealed that the synteny conservation of Wilms tumor, Aniridia, genitourinary abnormalities, and mental retardation loci was also maintained in this species. By reverse transcription polymerase chain reaction, the expression of Mapax6a was later than that of Mapax6b which was found in the blastula stage, while the expression of Mapax6a started from the somite stage, and both of them persisted in a subsequent stage during the embryonic development. By RNA and protein detection, Mapax6a and Mapax6b were detected in the eye and brain as canonic patterns, and most importantly, they were also enriched in germ cells of the testis and ovary. Therefore, our findings validate the duplication of pax6 in fish, confirm the classical expression patterns in the brain and eye, and, for the first time, present a new acquisition of Mapax6a and Mapax6b in gonadal germ cells in particular. Therefore, our results enrich the expression pattern and evolutionary relationship of pax6 by suggesting that duplicated Mapax6 is involved in gametogenesis in Megalobrama amblycephala.

[Chinese Medical Syndrome Distribution Laws of Mitochondrial Diseases Based on Combination of Disease and Syndrome].

Clinical manifestations of mitochondrial genetic disease and mitochondria related disor- ders have involved many aspects of Chinese medical syndromes. Combination of disease and syndrome based studies on mitochondrial disease related Chinese medical syndromes are quite less. Authors be- lieved mitochondrial diseases were mainly manifested as qi deficiency, involving related symptoms of five zang-organs, blood and qi, meridian disease by analyzing their clinical manifestations from the angle of Chinese medicine, and exploring their distribution laws.

A parallel algorithm for the two-dimensional time fractional diffusion equation with implicit difference method.

It is very time consuming to solve fractional differential equations. The computational complexity of two-dimensional fractional differential equation (2D-TFDE) with iterative implicit finite difference method is O(M(x)M(y)N(2)). In this paper, we present a parallel algorithm for 2D-TFDE and give an in-depth discussion about this algorithm. A task distribution model and data layout with virtual boundary are designed for this parallel algorithm. The experimental results show that the parallel algorithm compares well with the exact solution. The parallel algorithm on single Intel Xeon X5540 CPU runs 3.16-4.17 times faster than the serial algorithm on single CPU core. The parallel efficiency of 81 processes is up to 88.24% compared with 9 processes on a distributed memory cluster system. We do think that the parallel computing technology will become a very basic method for the computational intensive fractional applications in the near future.

A domain decomposition method for time fractional reaction-diffusion equation.

The computational complexity of one-dimensional time fractional reaction-diffusion equation is O(N²M) compared with O(NM) for classical integer reaction-diffusion equation. Parallel computing is used to overcome this challenge. Domain decomposition method (DDM) embodies large potential for parallelization of the numerical solution for fractional equations and serves as a basis for distributed, parallel computations. A domain decomposition algorithm for time fractional reaction-diffusion equation with implicit finite difference method is proposed. The domain decomposition algorithm keeps the same parallelism but needs much fewer iterations, compared with Jacobi iteration in each time step. Numerical experiments are used to verify the efficiency of the obtained algorithm.

Nonlinear correlation and mediation effects between serum 25-hydroxyvitamin D levels and all-cause mortality in COPD patients.

Background: Numerous studies have shown that low levels of vitamin D are linked to a higher risk of inflammatory diseases and their progression. However, how vitamin D levels affect mortality in chronic obstructive pulmonary disease (COPD) patients is still unclear. Thus, this study aimed to explore the relationship between serum 25-hydroxyvitamin D [25(OH)D] levels and the risk of death from all causes in U.S. adults with COPD. Methods: This study analyzed 1,876 adults with COPD from the National Health and Nutrition Examination Survey (2005-2018). Mortality data up to December 31, 2019, were obtained from the National Death Index (NDI) records. Participants were categorized into three groups according to their 25(OH)D levels: Q1 (<50.0 nmol/L) for deficiency; Q2 (50.0-74.9 nmol/L) for insufficiency; and Q3 (≥75.0 nmol/L) for adequacy. A weighted Cox regression model assessed the link between 25(OH)D levels and mortality. Kaplan-Meier survival curves, subgroup, and sensitivity analyses were conducted. Additionally, the relationship between 25(OH)D and the hazard ratio (HR) was detailed through restricted cubic spline analysis. Mediation analysis revealed how 25(OH)D mediates the relationship between Dietary Inflammatory Index and mortality. Results: There were 395 all-cause deaths during the follow-up, resulting in a mortality rate of 21.06%. After adjusting for potential confounders, higher 25(OH)D levels significantly correlated with a lower risk of all-cause mortality in COPD patients (HR = 0.52, 95% CI: 0.37-0.72, p < 0.001). Restricted cubic spline analysis indicated a non-linear relationship between 25(OH)D levels and all-cause mortality (p for nonlinear = 0.023), with levels below 63.4 nmol/L posing an independent risk for all-cause mortality in COPD patients (HR = 0.98, 95% CI: 0.97-0.99, p = 0.005). Sensitivity and subgroup analyses confirmed our results' robustness, with mediation analysis showing 25(OH)D's 22% mediating effect on diet-induced inflammation and all-cause mortality in COPD patients. Conclusion: 25(OH)D independently lowers the risk of all-cause mortality in COPD patients, with a non-linear L-shaped correlation, and mediates the effect of Dietary Inflammatory Index on mortality, suggesting new therapeutic possibilities.

Medaka (Oryzias latipes) Olpax6.2 acquires maternal inheritance and germ cells expression, but functionally degenerate in the eye.

Gene duplication provides raw material for the evolution of genetic and phenotypic complexity. It has remained a long-standing mystery how duplicated genes evolve into new genes by neofunctionalization via the acquisition of new expression and/or activity and simultaneous loss of the old expression and activity. Fishes have many gene duplicates from whole genome duplication, making them excellent for studying the evolution of gene duplicates. In the fish medaka (Oryzias latipes), an ancestral pax6 gene has given rise to Olpax6.1 and Olpax6.2. Here we report that medaka Olpax6.2 is evolving towards neofunctionalization. A chromosomal syntenic analysis indicated that Olpax6.1 and Olpax6.2 are structurally co-homologous to the single pax6 in other organisms. Interestingly, Olpax6.2 maintains all conserved coding exons but loses the non-coding exons of Olpax6.1, and has 4 promoters versus 8 in Olpax6.1. RT-PCR revealed that Olpax6.2 maintains expression in the brain eye, pancreas as Olpax6.1. Surprisingly, Olpax6.2 also exhibits maternal inheritance and gonadal expression by RT-PCR, in situ hybridization and RNA transcriptome analysis. The expression and distribution of Olpax6.2 is not different from Olpax6.1 in the adult brain, eye and pancreas, but exhibited overlapping and distinct expression in early embryogenesis. We show that ovarian Olpax6.2 expression occurs in female germ cells. Olpax6.2 knockout shows no obvious defect in eye development, while Olpax6.1 F0 mutant have severe defects in eye development. Thus, Olpax6.2 acquires maternal inheritance and germ cell expression, but functionally degenerates in the eye, making this gene as an excellent model to study the neofunctionalization of duplicated genes.

[Protective effect of combined administration blood-activating drug and sedative drug on acute myocardial infarction rats].

OBJECTIVE: To observe the protective effect of combined administration of blood-activating drug and sedative drug on myocardial injury of acute myocardial infarction (AMI) rats. METHOD: The acute myocardial infarction (AMI) model was established by occluding the left descending coronary artery of Wistar rats. These rats were further divided into four groups (n = 15 per group): the sham-operated group, the AMI model group, the blood-activating drug group and the combined administration group. RESULT: Compared with the sham-operated group, the AMI model group showed significant decrease in ejection fraction (EF) and fractional shortening (FS) (P < 0.001) and notable increase in the left ventricular end-diastolic internal diameter (LVIDd) and left ventricular end-systolic internal diameter (LVIDs) (P < 0.01), with the infarct area of left ventricular front wall up to about 70%-90%. Besides, tissue was severely replaced by collagen deposition and fibrosis, the sarcomeres disorganized and mitochondrial abnormalized. Compared with the AMI model group, the blood-activating drug group and the combined administration group showed significant increase in the values of EF and FS (P < 0.05 or P < 0.01) and obvious reduction in LVIDd and LVIDs (P < 0.05 or P < 0.01), with the infarction area of left ventricular front wall up to about 40%-60%. The collagen deposition and myocardium fibrosis, the disorganized sarcomeres and mitochondrial abnormalities relieved significantly. And compared with blood-activating drug group, the combined administration group demonstrated further increase in the values of EF and FS and further decrease in LVIDd and LVIDs (P < 0.05), the collagen deposition and myocardium fibrosis, the disorganized sarcomeres and mitochondrial abnormalities relieved even more in Huoxue plus Anshen prescription group. CONCLUSION: The combined administration of blood-activating drug and sedative drug can further improve cardiac structure and function after myocardial ischemia infarction and have an obvious synergistic effect which may be related to sedative drug's effect of resisting lipid peroxide, stabling myocardial cell membrane and mitochondrial membrane and relieving cardiac cell injury.

Efficient gene editing in a medaka (Oryzias latipes) cell line and embryos by SpCas9/tRNA-gRNA.

Generation of mutants with clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) is commonly carried out in fish species by co-injecting a mixture of Cas9 messenger RNA (mRNA) or protein and transcribed guide RNA (gRNA). However, the appropriate expression system to produce functional gRNAs in fish embryos and cells is rarely present. In this study, we employed a poly-transfer RNA (tRNA)-gRNA (PTG) system driven by cytomegalovirus (CMV) promoter to target the medaka (Oryzias latipes) endogenous gene tyrosinase(tyr) or paired box 6.1 (pax6.1) and illustrated its function in a medaka cell line and embryos. The PTG system was combined with the CRISPR/Cas9 system under high levels of promoter to successfully induce gene editing in medaka. This is a valuable step forward in potential application of the CRISPR/Cas9 system in medaka and other teleosts.

Source identification of infectious diseases in networks via label ranking.

BACKGROUND: Outbreaks of infectious diseases would cause great losses to the human society. Source identification in networks has drawn considerable interest in order to understand and control the infectious disease propagation processes. Unsatisfactory accuracy and high time complexity are major obstacles to practical applications under various real-world situations for existing source identification algorithms. METHODS: This study attempts to measure the possibility for nodes to become the infection source through label ranking. A unified Label Ranking framework for source identification with complete observation and snapshot is proposed. Firstly, a basic label ranking algorithm with complete observation of the network considering both infected and uninfected nodes is designed. Our inferred infection source node with the highest label ranking tends to have more infected nodes surrounding it, which makes it likely to be in the center of infection subgraph and far from the uninfected frontier. A two-stage algorithm for source identification via semi-supervised learning and label ranking is further proposed to address the source identification issue with snapshot. RESULTS: Extensive experiments are conducted on both synthetic and real-world network datasets. It turns out that the proposed label ranking algorithms are capable of identifying the propagation source under different situations fairly accurately with acceptable computational complexity without knowing the underlying model of infection propagation. CONCLUSIONS: The effectiveness and efficiency of the label ranking algorithms proposed in this study make them be of practical value for infection source identification.

Analysis of COVID-19 Prevention and Control Effects Based on the SEITRD Dynamic Model and Wuhan Epidemic Statistics.

Since December 2019, millions of people worldwide have been diagnosed with COVID-19, which has caused enormous losses. Given that there are currently no effective treatment or prevention drugs, most countries and regions mainly rely on quarantine and travel restrictions to prevent the spread of the epidemic. How to find proper prevention and treatment methods has been a hot topic of discussion. The key to the problem is to understand when these intervention measures are the best strategies for disease control and how they might affect disease dynamics. In this paper, we build a transmission dynamic model in combination with the transmission characteristics of COVID-19. We thoroughly study the dynamical behavior of the model and analyze how to determine the relevant parameters, and how the parameters influence the transmission process. Furthermore, we subsequently compare the impact of different control strategies on the epidemic, the variables include intervention time, control duration, control intensity, and other model parameters. Finally, we can find a better control method by comparing the results under different schemes and choose the proper preventive control strategy according to the actual epidemic stage and control objectives.

Constructing HLM to examine multi-level poverty-contributing factors of farmer households: Why and how?

Accurately identifying poverty-contributing factors of farmer households in an all-round way is the critical prerequisite and guarantee for taking targeted measures in poverty alleviation. From the combined perspectives of multi-level comprehensive detection and human-nature sustainable development, this study has designed a multi-level index system of household-level, village-level, and town-level, and constructed a nested three-level hierarchical linear model to examine the poverty-contributing factors of farmer households, and to reveal the significant ones and their multi-level interaction mechanism. The case test from Fugong County shows that: (1) Poverty-contributing factors are multi-level, showing both individual and background effects. 77.14% of the poverty is caused by household-level factors, 6.24% by village-level ones and 16.62% by town-level factors. (2) Significant poverty-contributing factors at different levels are different, identifying different contribution degrees to poverty gaps of farmer households. Five household-level factors show significant influence on poverty degree and account for 70.95% of the overall poverty gap among poor households, 11.70% for four village-level significant factors and 86.80% for two town-level ones, respectively. (3) Higher-level factors have different degrees of influence on the contribution difference of lower-level ones. The two town-level factors, terrain relief and town per capita annual income have explained 59.38% of the difference of village-level proportion of migrant workers' contribution to poverty degree among towns and 89.89% of the difference of household-level per capita annual income's contribution to poverty degree among towns respectively. (4) Measures such as improving the type of access to roads, developing characteristic planting and breeding, and implementing relocation projects, can help poor households in the study area to reduce poverty. This study provides a new perspective for identifying farmers' poverty-contributing factors and technical reference and decision support for local departments to plan and implement targeted assistance and household-specific development policies.