Complete genome sequencing and analysis of six enterovirus 71 strains with different clinical phenotypes

BACKGROUND: Hand, foot and mouth diseases (HFMD) caused by enterovirus 71(EV71) presents a broad spectrum of clinical manifestations ranging from mild febrile disease to fatal neurolocal disease. However, the mechanism of virulence is unknown. METHODS: We isolated 6 strains of EV71 from HFMD patients with or without neurological symptoms, and sequenced the whole genomes of the viruses to reveal the virulence factors of EV71. RESULTS: Phylogenetic tree based on VP1 region showed that all six strains clustered into C4a of C4 sub-genotype. In the complete polypeptide, 298 positions were found to be variable in all strains, and three of these positions (Val(P814)/Ile(P814) in VP1, Val(P1148)/Ile(P1148) in 3A and Ala (P1728)/Cys (P1728)/Val (P1728) in 3C) were conserved among the strains with neurovirulence, but variable in strains without neurovirulence. In the 5(′)-UTR region, it showed that the first 10 nucleotides were mostly conserved, however from the 11th nucleotide, nucleotide insertions and deletions were quite common. The secondary structure prediction of 5(′)-UTR sequences showed that two of three strains without neurovirulence (SDLY11 and SDLY48) were almost the same, and all strains with neurovirulence (SDLY96, SDLY107 and SDLY153) were different from each other. SDLY107 (a fatal strain) was found different from other strains on four positions (C(P241)/T(P241), A(P571)/T(P571), C(P579)/T(P579) in 5(′)-UTR and T(P7335)/C(P7335) in 3(′)-UTR). CONCLUSIONS: The three positions (Val(P814)/Ile(P814) in VP1, Val(P1148)/Ile(P1148) in 3A and Ala (P1728)/Cys (P1728)/Val (P1728) in 3C), were different between two phenotypes. These suggested that the three positions might be potential virulent positions. And the three varied positions were also found to be conserved in strains with neurovirulence, and variable in strains without neurovirulence. These might reveal that the conservation of two of the three positions or the three together were specific for the strains with neurovirulence. Varation of secondary structure of 5(′)-UTR, might be correlated to the changes of viral virulence. SDLY107 (a fatal strain) was found different from other strains on four positions, these positions might be related with death

Enkephalin-Encoding Herpes Simplex Virus-1 Decreases Inflammation and Hotplate Sensitivity in a Chronic Pancreatitis Model

Background: A chronic pancreatitis model was developed in young male Lewis rats fed a high-fat and alcohol liquid diet beginning at three weeks. The model was used to assess time course and efficacy of a replication defective herpes simplex virus type 1 vector construct delivering human cDNA encoding preproenkephalin (HSV-ENK). Results: Most surprising was the relative lack of inflammation and tissue disruption after HSV-ENK treatment compared to the histopathology consistent with pancreatitis (inflammatory cell infiltration, edema, acinar cell hypertrophy, fibrosis) present as a result of the high-fat and alcohol diet in controls. The HSV-ENK vector delivered to the pancreatic surface at week 3 reversed pancreatitis-associated hotplate hypersensitive responses for 4-6 weeks, while control virus encoding beta-galactosidase cDNA (HSV-beta-gal) had no effect. Increased Fos expression seen bilaterally in pain processing regions in control animals with pancreatitis was absent in HSV-ENK-treated animals. Increased met-enkephalin staining was evident in pancreas and lower thoracic spinal cord laminae I-II in the HSV-ENK-treated rats. Conclusion: Thus, clear evidence is provided that site specific HSV-mediated transgene delivery of human cDNA encoding preproenkephalin ameliorates pancreatic inflammation and significantly reduces hypersensitive hotplate responses for an extended time consistent with HSV mediated overexpression, without tolerance or evidence of other opiate related side effects

Enkephalin-encoding herpes simplex virus-1 decreases inflammation and hotplate sensitivity in a chronic pancreatitis model

<p>Abstract</p> <p>Background</p> <p>A chronic pancreatitis model was developed in young male Lewis rats fed a high-fat and alcohol liquid diet beginning at three weeks. The model was used to assess time course and efficacy of a replication defective herpes simplex virus type 1 vector construct delivering human cDNA encoding preproenkephalin (HSV-ENK).</p> <p>Results</p> <p>Most surprising was the relative lack of inflammation and tissue disruption after HSV-ENK treatment compared to the histopathology consistent with pancreatitis (inflammatory cell infiltration, edema, acinar cell hypertrophy, fibrosis) present as a result of the high-fat and alcohol diet in controls. The HSV-ENK vector delivered to the pancreatic surface at week 3 reversed pancreatitis-associated hotplate hypersensitive responses for 4–6 weeks, while control virus encoding β-galactosidase cDNA (HSV-β-gal) had no effect. Increased Fos expression seen bilaterally in pain processing regions in control animals with pancreatitis was absent in HSV-ENK-treated animals. Increased met-enkephalin staining was evident in pancreas and lower thoracic spinal cord laminae I–II in the HSV-ENK-treated rats.</p> <p>Conclusion</p> <p>Thus, clear evidence is provided that site specific HSV-mediated transgene delivery of human cDNA encoding preproenkephalin ameliorates pancreatic inflammation and significantly reduces hypersensitive hotplate responses for an extended time consistent with HSV mediated overexpression, without tolerance or evidence of other opiate related side effects.</p

A study of suicidal ideation in acute ischemic stroke patients

Background Increasing evidences indicate that stroke confers a substantial risk for suicidal ideation. The aim of this study was to identify risk factors of suicidal ideation in acute ischemic stroke patients. Method A total of 271 consecutive patients with acute ischemic stroke were recruited in Huai-He hospital or the First People’s Hospital, Kaifeng City, China. Demographic and clinical variables were collected and evaluated. Suicidal ideation was assessed using the Beck Scale for Suicide Ideation (BSI). Multivariate logistic regression was applied to determine the risk factors of suicidal ideation. Results Suicidal ideation was identified in 29 patients (10.7%). It was more frequent in patients who lived in rural region, with pre-/post-stroke depression or diabetes, had a higher NIHSS score, had no confidence in disease treatment, or had a poor coping style. Living in rural region (OR 2.59, 95% CI 1.02-6.58), the presence of pre-stroke depression (OR 11.74, 95% CI 4.45-31.01), stroke severity (OR 1.20, 95% CI 1.08-1.33), having no confidence in disease treatment (OR 14.70, 95% CI 2.60-83.15), and post-stroke depression (OR 16.22, 95% CI 6.40-41.10) were independent risk factors of suicidal ideation. Conclusion Several factors may be associated with an increased risk of suicidal ideation in acute ischemic stroke patients, including pre-/post-stroke depression, more severe stroke, having no confidence in treatment, as well as living in rural region. Our findings may have implication in risk assessment and intervention for acute ischemic stroke patients in reducing the burdens of suicidal ideation.Published versio

Data-Centric Financial Large Language Models

Large language models (LLMs) show promise for natural language tasks but struggle when applied directly to complex domains like finance. LLMs have difficulty reasoning about and integrating all relevant information. We propose a data-centric approach to enable LLMs to better handle financial tasks. Our key insight is that rather than overloading the LLM with everything at once, it is more effective to preprocess and pre-understand the data. We create a financial LLM (FLLM) using multitask prompt-based finetuning to achieve data pre-processing and pre-understanding. However, labeled data is scarce for each task. To overcome manual annotation costs, we employ abductive augmentation reasoning (AAR) to automatically generate training data by modifying the pseudo labels from FLLM's own outputs. Experiments show our data-centric FLLM with AAR substantially outperforms baseline financial LLMs designed for raw text, achieving state-of-the-art on financial analysis and interpretation tasks. We also open source a new benchmark for financial analysis and interpretation. Our methodology provides a promising path to unlock LLMs' potential for complex real-world domains

Effect of total flavones of buckwheat flowers and leaves on protein tyrosine phosphatase 1B expression in type 2 diabetic rats

The total flavone content was obtained from flowers and leaf of buckwheat (Fagopyrum esculentum Moench) by heating reflux method. The effects of the total flavone extract on the protein tyrosine phosphatase 1B (PTP1B) expression in type 2 diabetic rats were evaluated by immunofluorescence, western blotting and real-time quantitative PCR. The results suggested that the total flavone fraction from buckwheat flowers and leaves can significantly decrease the PTP1B expression in liver.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Aerial Violence Recognition Based on Spatial-Temporal Graph Convolutional Networks and Attention Model

The violence in public areas occurs frequently and video surveillance is of great significance for maintaining public safety.Compared with fixed cameras,unmanned aerial vehicles (UAVs) have surveillance mobility.However,in aerial images,the rapid movement of UAVs as well as the change of posture and height cause the problem of motion blur and large-scale change of target.To solve this problem,an attention spatial-temporal convolutional network (AST-GCN) combining attention mechanism is designed to realize the identification of violent behavior in aerial video.The proposed method is divided into two steps:the key frame detection network completes the initial positioning,and the AST-GCN network completes the behavior identification through the sequence features.Firstly,aiming at video violence localization,a key frame cascade detection network is designed to realize violence key frame detection based on human posture estimation,and preliminarily judge the occurrence time of violence.Secondly,the skeleton information of multiple frames around key frames is extracted from the video sequence,and the skeleton data is pre-processed,including normalization,screening and completion,so as to improve the robustness of different scenes and the partial missing of key nodes.And the skeleton temporal-spatial representation matrix is constructed according to the extracted skeleton information.Finally,AST-GCN network analyzes and identifies multiple frames of human skeleton information,to integrate attention module,improve feature expression ability,and complete the recognition of violent behavior.The method is validated on self-built aerial violence data set,and experimental results show that the AST-GCN can realize the recognition of aerial scene violence,and the recognition accuracy is 86.6%.The proposed method has important engineering value and scientific signifi-cance for the realization of aerial video surveillance and human pose understanding applications