Slit3 along with Slit1 and Slit2 comprise the Slit family of proteins. The latter two proteins are known to be involved in axon guidance and cell migration during animal development. However, little is know about the functions of Slit3. We created a Slit3-deficient mouse model from an OmniBank ES cell line with a Slit3 allele trapped by insertional mutagenesis to analyze the in vivo functions of this protein. In this model, congenital diaphragmatic hernia is the most obvious phenotype. Herniation was found to be caused by a defective central tendon (CT) of the diaphragm that remained fused with the liver. Electron microscopic analyses of the defective CT revealed disorganized collagen fibrils that failed to form tight collagen bundles. The hearts of Slit3-deficient mice have an enlarged right ventricle. In addition, 20% of homozygous mice also showed a range of kidney defects that include unilateral or bilateral agenesis of the kidney and ureter, or varying degrees of renal hypoplasia. Thus, we concluded that Slit3 is involved in the development of multiple organ systems that include the diaphragm and the kidney. Slit3-deficient mice represent a genetic animal model for physiological and pathological studies of congenital diaphragmatic hernia.
bDetection of Toxoplasma gondii infection with sensitive and specific methods is a key step in the prevention and treatment of toxoplasmosis. Among the available diagnostic tests, serology is commonly used. Although serological tests give satisfactory results, the production of reliable reagents remains laborious and expensive. There is therefore a real need to acquire specific and effective recombinant antigens for the serodiagnosis of T. gondii infection. In this study, a multiepitope peptide was designed and successfully expressed in Escherichia coli, and then IgG and IgM enzyme-linked immunosorbent assays (ELISAs) were developed and evaluated. Our results showed that the new multiepitope antigen is one of the most promising recombinant antigens which could be used in routine screening of human toxoplasmosis.
Chronic
hepatitis B virus (HBV) infection is a serious public health
burden, and current therapies cannot achieve satisfactory cure rate.
There are high unmet medical needs of novel therapeutic agents with
differentiated mechanism of action (MOA) from the current standard
of care. RG7834, a compound from the dihydroquinolizinone (DHQ) chemical
series, is a first-in-class highly selective and orally bioavailable
HBV inhibitor which can reduce both viral antigens and viral DNA with
a novel mechanism of action. Here we report the discovery of RG7834
from a phenotypic screening and the structure–activity relationship
(SAR) of the DHQ chemical series. RG7834 can selectively inhibit HBV
but not other DNA or RNA viruses in a virus panel screening. Both
in vitro and in vivo profiles of RG7834 are described herein, and
the data support further development of this compound as a chronic
HBV therapy.
Hemodynamic alteration with postural change from supine to sitting has been unclear in the young. In the cross-sectional study, 686 participants (371 boys and 315 girls, aged 6-18 years) were recruited from 4 schools in Kaifeng city, the central area of China. The active sitting test was performed to obtain heart rate (HR) and blood pressure (BP) changes from supine to sitting in children and adolescents. Hemodynamic change-associated sitting intolerance was analyzed. In the study participants, the 95th percentile (P 95) values of changes in HR and BP within 3 min from supine to sitting were 25 beats/min and 18/19 mm Hg, respectively. Sixty-six participants had sitting intolerance symptoms. Compared with participants without sitting intolerance symptoms, those with symptoms more frequently had HR increase ≥ P 95 or BP increase ≥ P 95 within 3 min from supine to sitting (P < 0.001). Risk factors for sitting intolerance were age (odds ratio 1.218, 95% confidence interval 1.072-1.384, P = 0.002) and changes in HR or BP ≥ P 95 within 3 min after sitting (odds ratio 2.902, 95% confidence interval 1.572-5.357, P = 0.001). We firstly showed hemodynamic changing profiles from supine to sitting and their association with sitting intolerance in children and adolescents. Sitting tachycardia is likely suggested with a change in HR ≥ 25 beats/min and sitting hypertension with a change in BP ≥ 20/20 mm Hg when changing from supine to sitting within 3 min. The age and changes in HR or BP were independent risk factors for sitting intolerance. Lying, sitting and standing are inevitable postures in daily life, and blood distribution changes are accompanied by postural changes. Physiologically, changing from the supine to the orthostatic position induces an instantaneous and large shift of 10% to 25% of blood volume from the thorax to the lower extremities and splanchnic organs and a transfer from the vasculature to the interstitial tissues. This redistribution causes an immediate decrease in venous return to the heart, resulting in a transient decline in cardiac filling and blood pressure. Then, positive chronotropic and inotropic cardiac effects are stimulated by activation of the sympathetic nervous system and withdrawal of the parasympathetic nervous system to maintain a relatively stable circulatory condition,
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