miR-181a Post-Transcriptionally Downregulates Oncogenic RalA and Contributes to Growth Inhibition and Apoptosis in Chronic Myelogenous Leukemia (CML)

MicroRNAs (miRNAs) are a class of short RNAs that regulate gene expression through either translational repression or mRNA cleavage. miRNA-181a (miR-181a), one of the many miRNAs conserved among vertebrates, is differentially expressed in a variety of leukemia. However, its function in leukemia, particularly chronic myelogenous leukemia (CML), is poorly understood. Here we have reported the identification of miR-181a targets by combining TargetScan software prediction and expression profiling through overexpression of miR-181a mimic in leukemic K562 cells. Four overlapping genes were found to be the likely targets of miR-181a. Among the four genes, RalA is a downstream molecule of bcr-abl fusion protein in ras signaling pathway. However, its role in CML remains elusive. Luciferase reporter and Western blot assays confirmed that RalA is a direct target of miR-181a. overexpression of miR-181a effectively suppresses cell growth and induces G2-phase arrest and apoptosis partially by targeting RalA in leukemic K562 cells. Using the KEGG database combined with recent publications, downstream signaling pathway of RalA was graphed by cytoscape software. Therefore, our study is the first to report that RalA is directly regulated by miR-181a and plays an important role in CML. The approach of computational prediction combined with expression profiling might be valuable for the identification of miRNA targets in animal

Where to serve and return in Badminton Men's Double?

This study aims to analyze the service and return landing areas in badminton men's double, based on data extracted from 20 badminton matches. We find that most services land near the center-line, while returns tend to land in the crossing areas of the serving team's court. Using generalized logit models, we are able to predict the return landing area based on features of the service and return round. We find that the direction of the service and the footwork and grip of the receiver could indicate his intended return landing area. Additionally, we discover that servers tend to intercept in specific areas based on their serving position. Our results offer valuable insights into the strategic decisions made by players in the service and return of a badminton rally

In vivo assessment of the mechanical properties of the child cortical bone using quantitative computed tomography

The mechanical properties of the rib cortical bone are extremely rare on children due to difficulties to obtain specimens to perform conventional tests. Some recent studies used cadaveric bones or bone tissues collected during surgery but are limited by the number of samples that could be collected. A non-invasive technique could be extremely valuable to overcome this limitation. It has been shown that a relationship exists between the mechanical properties (apparent Young’s modulus and ultimate strength) and the bone mineral density (assessed using Quantitative Computed Tomography, QCT), for the femur and recently by our group for the adult ribs ex vivo. Thus the aim of this study was to assess the mechanical properties of the child rib cortical bone using both QCT images in vivo and the previous relationship between bone mineral density and mechanical properties of the rib cortical bone. Twenty-eight children were included in this study. Seven age-groups have been considered (1, 1.5, 3, 6, 10, 15, 18 years old). The QCT images were prescribed for various thoracic pathologies at the pediatric hospital in Lyon. A calibration phantom was added to the clinical protocol without any modifications for the patient. The protocol was approved by the ethical committee. A 3D reconstruction of each thorax was performed using the QCT images. A custom software was then used to obtain cross-sections to the rib midline. The mean bone mineral density was then computed by averaging the Hounsfield Units in a specific cross-section and by converting the mean value (Hounsfield Units) in bone mineral density using the calibration phantom. This bone mineral density was assessed for the 6th rib of each subject. Our relationship between the bone mineral density and the mechanical properties of the rib cortical bone was used to derive the mechanical properties of the child ribs in vivo. The results give values for the apparent Young’s modulus and the ultimate strength. The mechanical properties increase along growth. As an example the apparent Young’s modulus in the lateral region ranges from 7 GPa +/-3 at 1 year old up to 13 GPa +/- 2 at 18 years old. These data are in agreement with the few previous values obtained from child tissues. This methodology opens the way to in vivo measurement of the mechanical properties of the child cortical bone based on calibrated QCT images

Novelties of solid-liquid phase transfer catalyzed synthesis of benzyl diethyl phosphate from the sodium salt of diethyl phosphate

Solid-liquid phase transfer catalysis coupled with mixed solvents, which could be recycled, as a green chemistry procedure, was applied to the synthesis of phosphate from the sodium salt of diethyl phosphate. The benzyl diethyl phosphate was synthesized in good yield via one-pot method from the reaction of the industrial by-product sodium salt of diethyl phosphate with benzyl chloride in solid-liquid phase transfer catalysis and toluene-water mixed solvents. The effects of catalyst structure, the amounts of catalyst, the raw material molar ratio, water loading, and reaction temperature on the conversion of the reaction were investigated. The structure of the benzyl diethyl phosphate generated was confirmed by Elemental Analysis, IR, 1H NMR and GC/MS

Molecular epidemiology of hepatitis E virus infections in Shanghai, China

<p>Abstract</p> <p>Background</p> <p>Hepatitis E virus (HEV) causes acute or fulminant hepatitis in humans and is an important public health concern in many developing countries. China has a high incidence of HEV epidemics, with at least three genotypes (1, 3 and 4) and nine subtypes (1b, 1c, 3b, 4a, 4b, 4d, 4g, 4h and 4i) so far identified. Since genotype 3 and the newly identified subtype 4i have been exclusively limited geographically to Shanghai and its neighboring provinces, the epidemiology of HEV infections within the municipality, a major industrial and commercial center, deserves closer attention.</p> <p>Findings</p> <p>A total of 65 sequences, 60 located within the HEV SH-SW-zs1 genome [GenBank:<ext-link ext-link-id="EF570133" ext-link-type="gen">EF570133</ext-link>], together with five full-length swine and human HEV genomic sequences, all emanating from Shanghai, were retrieved from GenBank. Consistent with the primary role of genotype 4 in China overall, analysis of the sequences revealed this to have been the dominant genotype (58/65) in Shanghai. Six HEV subtypes (3b, 4a, 4b, 4d, 4h and 4i) were also represented. However, although subtype 4a is the dominant subtype throughout China, subtype 4i (29/65) was the most prevalent subtype among the Shanghai sequences, followed by subtypes 4d (10/65) and 4h (9/65). Subtypes 4h, 4i and 4d were found in both swine and humans, whereas 4b was found only in swine and subtype 4a only in humans.</p> <p>Conclusions</p> <p>Six different swine and human HEV subtypes have so far been documented in Shanghai. More molecular epidemiological investigations of HEV in swine, and particularly among the human population, should be undertaken.</p

Effect of void-carbon on blue-shifted luminescence in TADF molecules by theoretical simulations

Thermally activated delayed fluorescence (TADF) molecules have a theoretical 100% photoluminescence quantum yield in comparison with traditional fluorescent materials, leading to broad application in organic light-emitting diode (OLED). However, the application of TADF molecules with conjugated donor-acceptor structures in blue OLED remains a challenge due to their generally narrow energy gap between frontier molecular orbitals. Recently, a strategy has been approved in the improvement of the performance in TADF, in which void-carbon atoms between donor and acceptor fragments (donor-void-acceptor (D-v-A)) could regulate blue light emission. In this study, we first select three reported isomers followed by two proposed D-v-A TADF isomers to verify the feasibility of the void-carbon strategy through evaluation of the electronic structures in the excited state and photophysical properties. We further proposed a series of TADF molecules by replacing different donor and acceptor fragments to assess the applicability of the void-carbon strategy from the aspect of simulations in electronic structures, different properties of donor and acceptor fragments, photophysical properties, and analysis in the molecular conjugation. The results indicate that void-carbon strategy has conditional feasibility and applicability. Donor-acceptor molecular properties could be tuned through void-carbon strategy on aromatic acceptor fragments during the selection of promising candidates of TADF molecules. However, the void-carbon strategy does not work for the molecules with antiaromatic acceptor fragments, where the steric hindrance of the molecules plays a dominant role. Our work provides insightful guidance for the design of the blue-emission TADF molecules

Coronary angiography review in 21 children with Kawasaki disease complicated with coronary artery disease

Objective·To analyze the progression of children with severe coronary artery lesions due to Kawasaki disease by coronary artery angiography, and evaluate the diagnostic value of echocardiography in these children.Methods·A retrospective analysis was performed to enroll children with Kawasaki disease whose coronary artery lesions were graded Ⅳ or above from Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, from January 2013 to January 2023. The subjects were required to have received at least 2 times of coronary angiogram, and their clinical and imaging data were collected to analyze the progression of the lesions. Echocardiography results were compared with the results of the coronary angiogram.Results·A total of 21 children were included, including 15 males and 6 females, with a median age at onset of 3 years and 6 months, a median age at initial coronary angiography of 7 years and 11 months, a median interval of 4 years and 5 months between the time of onset and initial angiography, a median age at angiographic review of 9 years and 2 months, and a median interval of 1 year and 3 months between the time of initial angiography and review. Coronary stenosis or occlusion was detected in 13 children in the initial angiography, of whom 6 underwent coronary artery bypass grafting (CABG) and had their angiography reviews 1 year later. The review results showed that the bridging vessels were unobstructed and no obvious stenosis was observed. Fifteen children had progression of the lesions detected by echocardiography in the subsequent follow-up and had their angiogram reviews, of whom 8 had significant progression of the coronary lesions. Intracoronary balloon dilatation was performed in 1 case, and CABG was performed in another case. Sixteen lesions of coronary stenosis or occlusion were detected in the initial angiography in 21 children, while only 1 lesion of coronary stenosis was detected by echocardiography during the same period of time. Twenty-eight medium- to large-sized coronary aneurysms were detected in the initial angiography in the 21 children, and the diameters of the 28 aneurysms measured by echocardiography and coronary angiogram were subjected to the Bland-Altman analysis. The Bland-Altman analysis showed that the difference in maximum diameter between 2 methods was (1.63±2.33) mm, with 95%CI of -2.95‒6.21 mm.Conclusion·Coronary artery lesions due to Kawasaki disease may be progressive; in the children with severe lesions, coronary artery stenosis or occlusion may be missed or misdiagnosed and some errors may exist in the measurement of diameters of aneurysms by echocardiography. Regular review of coronary angiography is needed

Differential Impacts of Soybean and Fish Oils on Hepatocyte Lipid Droplet Accumulation and Endoplasmic Reticulum Stress in Primary Rabbit Hepatocytes

Parenteral nutrition-associated liver disease (PNALD) is a severe ailment associated with long-term parenteral nutrition. Soybean oil-based lipid emulsions (SOLE) are thought to promote PNALD development, whereas fish oil-based lipid emulsions (FOLE) are thought to protect against PNALD. This study aimed to investigate the effects of SOLE and FOLE on primary rabbit hepatocytes. The results reveal that SOLE caused significant endoplasmic reticulum (ER) and mitochondrial damage, ultimately resulting in lipid droplets accumulation and ER stress. While these deleterious events induce hepatocyte injury, FOLE at high doses cause only minor ER and mitochondrial damage, which has no effect on hepatic function. SOLE also significantly upregulated glucose-regulated protein 94 mRNA and protein expression. These data indicate that SOLE, but not FOLE, damage the ER and mitochondria, resulting in lipid droplets accumulation and ER stress and, finally, hepatocyte injury. This likely contributes to the differential impacts of SOLE and FOLE on PNALD development and progression