Crack assessment has remained one of the high‐priority research topics for structural health monitoring. However, the current research mainly focuses on the crack assessment at some point, but pays ...relatively less attention to the long‐term development of cracks, which is important for structure health monitoring. In this paper, a new method based on dual‐convolutional neural network (CNN) (well over 94% accuracy), digital image processing technology and shape context is proposed, which achieves a fully automated process composed of crack detection, crack measurement, and quantitative crack growth monitoring. In crack growth monitoring, an algorithm to label each crack is put forward for the first time, which is able to reflect the sequential order of the occurrence of cracks. Therefore, each skeleton point of cracks will be assigned an ID which contains information about its identity and width in order to monitor cracks at both a global and local level. Experimental studies of a concrete member with complex cracks are utilized for the illustration and validation of the proposed methodology.
The existence of breast cancer stem cells (BCSCs) is a major reason underlying cancer metastasis and recurrence after chemotherapy and radiotherapy. Targeting BCSCs may ameliorate breast cancer ...relapse and therapy resistance. Here we report that expression of the pseudokinase Tribble 3 (TRIB3) positively associates with breast cancer stemness and progression. Elevated TRIB3 expression supports BCSCs by interacting with AKT to interfere with the FOXO1-AKT interaction and suppress FOXO1 phosphorylation, ubiquitination, and degradation by E3 ligases SKP2 and NEDD4L. The accumulated FOXO1 promotes transcriptional expression of SOX2, a transcriptional factor for cancer stemness, which in turn, activates FOXO1 transcription and forms a positive regulatory loop. Disturbing the TRIB3-AKT interaction suppresses BCSCs by accelerating FOXO1 degradation and reducing SOX2 expression in mouse models of breast cancer. Our study provides insights into breast cancer development and confers a potential therapeutic strategy against TRIB3-overexpressed breast cancer.
A pandemic of severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) infection broke out all over the world; however, epidemiological data and viral shedding in pediatric patients are limited. ...We conducted a retrospective, multicenter study, and followed‐up with all children from the families with SARS‐CoV‐2 infected members in Zhejiang Province, China. All infections were confirmed by testing the SARS‐CoV‐2 RNA with real‐time reverse transcription PCR method, and epidemiological data between children and adults in the same families were compared. Effect of antiviral therapy was evaluated observationally and fecal‐viral excretion times among groups with different antiviral regiments were compared with Kaplan‐Meier plot. By 29 February 2020, 1298 cases from 883 families were confirmed with SARS‐CoV‐2 infection and 314 of which were families with children. Incidence of infection in child close contacts was significantly lower than that in adult contacts (13.2% vs 21.2%). The mean age of 43 pediatric cases was 8.2 years and mean incubation period was 9.1 days. Forty (93.0%) were family clustering. Thirty‐three children had coronavirus disease 2019 (20 pneumonia) with mild symptoms and 10 were asymptomatic. Fecal SARS‐CoV‐2 RNA detection was positive in 91.4% (32/35) cases and some children had viral excretion time over 70 days. Viral clearance time was not different among the groups treated with different antiviral regiments. No subsequent infection was observed in family contacts of fecal‐viral‐excreting children. Children have lower susceptibility of SARS‐CoV‐2 infection, longer incubation, and fecal‐viral excretion time. Positive results of fecal SARS‐CoV‐2 RNA detection were not used as indication for hospitalization or quarantine.
Highlights
Children had lower susceptibility for SARS‐CoV‐2 infection than adults.
Children had longer incubation period and fecal viral excretion time after infected by SARS‐CoV‐2.
Viral clearance time was not different among the groups treated with different antiviral regiments.
Children had milder clinical symptoms, better clinical outcome, and more common fecal viral excretion.
Positive results of fecal SARS‐CoV‐2 RNA detection are not used as indication for hospitalization or quarantine.
Background： Nontraumatic osteonecrosis of the femoral head （NONFH） is a debilitating disease that represents a significant financial burden for both individuals and healthcare systems. Despite its ...significance, however, its prevalence in the Chinese general population remains unknown. This study aimed to investigate the prevalence of NONFH and its associated risk factors in the Chinese population. Methods： A nationally representative survey of 30,030 respondents was undertaken from June 2012 to August 2013. All participants underwent a questionnaire investigation, physical examination of hip, and bilateral hip joint X-ray and/or magnetic resonance imaging exalnination. Blood samples were taken after overnight fasting to test serum total cholesterol, triglyceride, and high-density lipoprotein （HDL） and low-density lipoprotein （LDL） levels. We then used multivariate logistic regression analysis to investigate the associations between various metabolic, demographic, and lifestyle-related variables and NONFH. Results： NONFH was diagnosed in 218 subjects （0.725%） and the estimated NONFH cases were 8.12 million among Chinesepeople aged 15 years and over. The prevalence of NONFH was significantly higher in males than in females （1.02% vs. 0.51%, x^2 = 24.997, P 〈 0.001 ）. Among NONFH patients, North residents were subjected to higher prevalence of NONFH than that of South residents （0.85% vs. 0.61%,x^2= 5.847, P = 0.016）. Our multivariate regression analysis showed that high blood levels oftriglycerides, total cholesterol, LDL-cholesterol, and non-H DL-cholesterol, male, urban residence, family history of osteonecrosis of the femoral head. heavy smoking, alcohol abuse and glucocorticoid intake, overweight, and obesity were all significantly associated with an increased risk of NONFH. Conclusions： Our findings highlight that NONFH is a significantpublic health challenge in China and underscore the need for policy measures on the national level. Furthermore, NONFH shares a number of risk factors with atherosclerosis.
Obesity and related metabolic diseases are becoming worldwide epidemics that lead to increased death rates and heavy health care costs. Effective treatment options have not been found yet. Here, ...based on the observation that baicalin, a flavonoid from the herbal medicine Scutellaria baicalensis, has unique antisteatosis activity, we performed quantitative chemoproteomic profiling and identified carnitine palmitoyltransferase 1 (CPT1), the controlling enzyme for fatty acid oxidation, as the key target of baicalin. The flavonoid directly activated hepatic CPT1 with isoform selectivity to accelerate the lipid influx into mitochondria for oxidation. Chronic treatment of baicalin ameliorated diet-induced obesity (DIO) and hepatic steatosis and led to systemic improvement of other metabolic disorders. Disruption of the predicted binding site of baicalin on CPT1 completely abolished the beneficial effect of the flavonoid. Our discovery of baicalin as an allosteric CPT1 activator opens new opportunities for pharmacological treatment of DIO and associated sequelae.
A novel ratiometric fluorescence molecularly imprinted sensor based on a dual-emission quantum dot hybrid was fabricated and used as an alternative analytical tool for the detection of tetracycline. ...In the synthesis process, red-emitting quantum dots (r-QDs) and green-emitting quantum dots (g-QDs) were modified by two different methods. Afterward, a stepwise precipitation polymerization imprinting reaction was performed to prepare the novel ratiometric fluorescence molecularly imprinted sensor (MIP–g/r-QD sensor). The MIP–g/r-QD sensor integrated the advantages of molecularly imprinted polymers and ratiometric fluorescence probes. The specific recognition sites in the polymer layers could adsorb tetracycline molecules, and then they caused fluorescence quenching behavior of g-QDs via an electron transfer process. Under the optimal conditions, a linear relationship was obtained covering the range from 10 to 160 μmol/L, with a correlation coefficient of 0.9976 and a high imprinting factor of about 3.3. Moreover, the novel MIP–g/r-QD sensor was successfully applied to detect tetracycline in milk samples. This work provides a new way to fabricate an efficient ratiometric fluorescence molecularly imprinted sensor based on quantum dots for convenient, fast, and highly selective and sensitive detection of organic molecules.
Graphical abstract
A novel ratiometric fluorescence molecularly imprinted sensor based on a dual-emission quantum dot hybrid was fabricated and used as an alternative analytical tool for the detection of tetracycline. AIBN azoisobutyronitrile, EGDMA ethylene glycol dimethacrylate, KH-570 3-(methacryloyloxy)propyltrimethoxysilane, OVDAC octadecyl-4-vinylbenzyldimethylammonium chloride, PDDA poly(diallyldimethylammonium chloride), QD quantum dot, TEOS tetraethoxysilane
The transcription factor MYC is deregulated in almost all human cancers, especially in aggressive lymphomas, through chromosomal translocation, amplification, and transcription hyperactivation. Here, ...we report that high expression of tribbles homologue 3 (TRIB3) positively correlates with elevated MYC expression in lymphoma specimens; TRIB3 deletion attenuates the initiation and progression of MYC-driven lymphoma by reducing MYC expression. Mechanistically, TRIB3 interacts with MYC to suppress E3 ubiquitin ligase UBE3B-mediated MYC ubiquitination and degradation, which enhances MYC transcriptional activity, causing high proliferation and self-renewal of lymphoma cells. Use of a peptide to disturb the TRIB3-MYC interaction together with doxorubicin reduces the tumor burden in Myc
mice and patient-derived xenografts. The pathophysiological relevance of UBE3B, TRIB3 and MYC is further demonstrated in human lymphoma. Our study highlights a key mechanism for controlling MYC expression and a potential therapeutic option for treating lymphomas with high TRIB3-MYC expression.
Glucose and fatty acids are the major sources of energy for human body. Cholesterol, the most abundant sterol in mammals, is a key component of cell membranes although it does not generate ATP. The ...metabolisms of glucose, fatty acids and cholesterol are often intertwined and regulated. For example, glucose can be converted to fatty acids and cholesterol through de novo lipid biosynthesis pathways. Excessive lipids are secreted in lipoproteins or stored in lipid droplets. The metabolites of glucose and lipids are dynamically transported intercellularly and intracellularly, and then converted to other molecules in specific compartments. The disorders of glucose and lipid metabolism result in severe diseases including cardiovascular disease, diabetes and fatty liver. This review summarizes the major metabolic aspects of glucose and lipid, and their regulations in the context of physiology and diseases.
Basal-like breast cancer (BLBC) is an aggressive subtype with a strong tendency to metastasize. Due to the lack of effective chemotherapy, BLBC has a poor prognosis compared with luminal subtype ...breast cancer. MicroRNA-221 and -222 (miR-221/222) are overexpressed in BLBC and associate with metastasis as well as poor prognosis; however, the mechanisms by which miR-221/222 function as oncomiRs remain unknown. Here, we report that miR-221/222 expression is inversely correlated with Notch3 expression in breast cancer cell lines. Notch3 is known to be overexpressed in luminal breast cancer cells and inhibits epithelial to mesenchymal transition (EMT). We demonstrate that miR-221/222 target Notch3 by binding to its 3' untranslated region and suppressing protein translation. Ectopic expression of miR-221/222 significantly promotes EMT, whereas overexpression of Notch3 intracellular domain attenuates the oncogenic function of miR-221/222, suggesting that miR-221/222 exerts its oncogenic role by negatively regulating Notch3. Taken together, our results elucidated that miR-221/222 promote EMT via targeting Notch3 in breast cancer cell lines suggesting that miR-221/222 can serve as a potential therapeutic target in BLBC.
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