Braswellduelund5333
Porcine extraintestinal pathogenic Escherichia coli (ExPEC) is occurring with increasing frequency in China, which causes acute septicemia and sudden death in pigs leading to significant economic losses. Bacterial survival and even proliferation within host bloodstream are a common manifestation of a number of bacterial septicemias, including porcine ExPEC diseases. However, the underlying pathogenesis for this novel pathotype of ExPEC has not been explored deeply. Here, we used a conjunction with transposon mutagenesis to identify the mechanisms of bacterial fitness involved in optimal growth of porcine ExPEC in swine serum ex vivo under static culture. Our work identified 28 genes involved in nucleotide biosynthesis, extracellular polysaccharide biosynthesis, regulators Fur and FNR, acid/zinc resistance, and Deley-Douderoff carbon metabolism that are required for the serum fitness. Subsequent functional analyses revealed that either interruption of de novo nucleotide biosynthesis or blocking of several extracellular polysaccharide biosynthesis including O2-antigen, Lipid A-core, and ECA significantly affect porcine ExPEC's growth in swine serum and proliferation in host bloodstream. Furthermore, the reasonable regulations of iron and anaerobic metabolisms in response to host stimuli by global regulators Fur and FNR also play key roles during systemic infection of porcine ExPEC. These findings provide compelling evidences that de novo nucleotide biosynthesis may enable porcine ExPEC to adapt to swine blood-specific nutrient availability, and the effective assembly of O-antigen, lipid A-core, and ECA is required to resist the bactericidal activity of swine serum. These studies contribute to better understand the underlying mechanisms employed by porcine ExPEC to survive, grow in the swine bloodstream, and cause disease. Selleck FTY720 These related factors may serve as therapeutic targets for countering or preventing ExPEC serum resistance in the clinic.
How spinal cord stimulation (SCS) in its different modes suppresses pain is poorly understood. Mechanisms of action may reside locally in the spinal cord, but also involve a larger network including subcortical and cortical brain structures. Tonic, burst, and high-frequency modes of SCS can, in principle, entrain distinct temporal activity patterns in this network, but finally have to yield specific effects on pain suppression. Here, we employ high-density electroencephalography (EEG) and recently developed spatial filtering techniques to reduce SCS artifacts and to enhance EEG signals specifically related to neuromodulation by SCS.
We recorded high-density resting-state EEGs in patients suffering from pain of various etiologies under different modes of SCS. We established a pipeline for the robust spectral analysis of oscillatory brain activity during SCS, which includes spatial filtering for attenuation of pulse artifacts and enhancement of brain activity potentially modulated by SCS.
In sensor regions responsive to SCS, neuromodulation strongly reduced activity in the theta and low alpha range (6-10 Hz) in all SCS modes. Results were consistent in all patients, and in accordance with thalamocortical dysrhythmia hypothesis of pain. Only in the tonic mode showing paresthesia as side effect, SCS also consistently and strongly reduced high-gamma activity (>84 Hz).
EEG spectral analysis combined with spatial filtering allows for a spatially and temporally specific assessment of SCS-related, neuromodulatory EEG activity, and may help to disentangle therapeutic and side effects of SCS.
EEG spectral analysis combined with spatial filtering allows for a spatially and temporally specific assessment of SCS-related, neuromodulatory EEG activity, and may help to disentangle therapeutic and side effects of SCS.Understanding the particular mechanisms by which vulnerability and capability factors influence cognitive reactivity (CR) can contribute to an enhanced capacity to adequately react to depression. However, few studies have explored the CR model. The main aim of the present study was to develop a model that specifies the predictive effects of CR for depression among individuals at high risk for first-episode and recurrent depression. A national cross-sectional, online study using convenience sampling was conducted among 587 vulnerable healthy individuals and 224 depressed patients in China. A battery of indices, including measures of CR, social support, resilience, self-compassion, life events, neuroticism, sleep condition, and negative emotion, were collected. A structural equation model was applied to analyse the data. The final first-episode and recurrent depressive symptoms of the CR models showed good model fit. According to the models, 45%-52% of the variance in depressive symptom was predicted by CR. Social support, self-compassion, resilience, and positive life events directly influenced CR, with β values ranging from -0.18 to -0.24 (P less then 0.01). Neuroticism, negative emotion, poor sleep conditions, and negative life events also directly and positively influenced CR (P less then 0.01). The relationship between these negative or positive contributing factors and depression was also indirectly influenced by CR (P less then 0.01). Our findings demonstrate the role of CR in the prevention and treatment of depression. The first-episode and recurrent depressive symptoms of the CR models considering both vulnerabilities and capabilities of CR in the psychopathology of depression provide a theoretical basis for interventions that reduce CR in high-risk populations.
Thiopurine methyltransferase (TPMT) polymorphism is one of the causes for the toxicity of thiopurines, but rarely seen in Asian populations. Rather, nucleoside diphosphate-linked X-component motif 15 (NUDT15) gene is frequently linked to mercaptopurine (MP) intolerance and myelotoxicity in children with acute lymphoblastic leukemia (ALL) in East Asians, however little is known about the NUDT15 polymorphism in healthy children, especially in ethnic minorities of China.
Totally 162 cases of healthy children with Bai nationality were enrolled for NUDT15 genotyping.
Three coding variants were identified in the NUDT15 gene including rs186364861, rs746071566 and rs116855232. Notably, the rs746071566 and rs116855232 in NUDT15 showed much higher frequencies in healthy children with Bai nationality compared with healthy East Asian populations, suggesting a concentrated distribution of these variants in the Bai ethnic group.
This finding reveals the genetic polymorphism of NUDT15 in children with Chinese Bai nationality, providing a biological genetic background for the individualized therapy of thiopurines for children with Bai nationality in China.
