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.
Exosomes are cell-derived vesicles and are abundant in biological fluids; they contain RNA molecules which may serve as potential diagnostic biomarkers in 'precision medicine'. To promote the ...clinical application of exosomal RNA (exoRNA), many isolation methods must be compared and validated. Exosomes in cell culture medium (CCM) and serum may be isolated using ultracentrifugation (UC), ExoQuick or Total Exosome Isolation Reagent (TEI), and exoRNA may be extracted using TRIzol-LS, SeraMir, Total Exosome RNA Isolation (TER), HiPure Liquid RNA/miRNA kit (HLR), miRNeasy or exoRNeasy. ExoRNA was assessed using NanoDrop, Bioanalyzer 2100, quantitative polymerase chain reaction and high-throughput sequencing. UC showed the lowest recovery of particles, but the highest protein purity for exosome isolation. For isolation of exoRNA, we found that combinations of the TEI and TER methods resulted in high extraction efficiency and purity of small RNA obtained using CCM. High yield and a narrow size distribution pattern of small RNA were shown in exoRNA isolated by exoRNeasy from serum. In RNA profile analysis, the small RNA constituent ratio, miRNA content and amount varied as a result of methodological differences. This study showed that different methods may introduce variations in the concentration, purity and size of exosomes and exoRNA. Herein we discuss the advantages and disadvantages of each method and their application to different materials, therefore providing a reference according to research design.
According to guidelines, endoscopic resection should only be performed for patients whose early gastric cancer invasion depth is within the mucosa or submucosa of the stomach regardless of lymph node ...involvement. The accurate prediction of invasion depth based on endoscopic images is crucial for screening patients for endoscopic resection. We constructed a convolutional neural network computer-aided detection (CNN-CAD) system based on endoscopic images to determine invasion depth and screen patients for endoscopic resection.
Endoscopic images of gastric cancer tumors were obtained from the Endoscopy Center of Zhongshan Hospital. An artificial intelligence–based CNN-CAD system was developed through transfer learning leveraging a state-of-the-art pretrained CNN architecture, ResNet50. A total of 790 images served as a development dataset and another 203 images as a test dataset. We used the CNN-CAD system to determine the invasion depth of gastric cancer and evaluated the system’s classification accuracy by calculating its sensitivity, specificity, and area under the receiver operating characteristic curve.
The area under the receiver operating characteristic curve for the CNN-CAD system was .94 (95% confidence interval CI, .90-.97). At a threshold value of .5, sensitivity was 76.47%, and specificity 95.56%. Overall accuracy was 89.16%. Positive and negative predictive values were 89.66% and 88.97%, respectively. The CNN-CAD system achieved significantly higher accuracy (by 17.25%; 95% CI, 11.63-22.59) and specificity (by 32.21%; 95% CI, 26.78-37.44) than human endoscopists.
We constructed a CNN-CAD system to determine the invasion depth of gastric cancer with high accuracy and specificity. This system distinguished early gastric cancer from deeper submucosal invasion and minimized overestimation of invasion depth, which could reduce unnecessary gastrectomy.
The present study was focused on the preparation and characterization of the antioxidant peptides by microwave-assisted enzymatic hydrolysis of collagen from sea cucumber
(ASC-Am) obtained from ...Zhejiang Province in China. The results exhibited the effects of microwave irradiation on hydrolysis of ASC-Am with different protease. Neutrase was selected from the four common proteases (papain, pepsin, trypsin, and neutrase) based on the highest content and DPPH scavenging activity of hydrolysate Fa (Molecular weight < 1 kDa). The content and 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity of Fa obtained by hydrolysis of neutrase increased by 100% and 109% respectively at a microwave power of 300 W compared with no microwave irradiation. Five subfractions were obtained after performing the gel filtration chromatography, and the Fa.2 exhibited the highest DPPH scavenging activity. The amino acid analysis showed that the contents of Glutamic acid, Alanine, Tyrosine, and Phenylalanine in fraction Fa.2 increased significantly, but an obvious decrease in the content of Glycine was observed compared to Fa. Four peptides (Fa.2-A, Fa.2-B, Fa.2-C, and Fa.2-D) were purified from Fa.2 by high performance liquid chromatography, and Fa.2-C showed the highest DPPH scavenging activity. The sequence of Fa.2-C was identified as Phenylalanine-Leucine- Alanine-Proline with a half elimination ratio (EC
) of 0.385 mg/mL. The antioxidant activity of Fa.2-C was probably attributed to the small molecular sizes and the presence of hydrophobic amino acid residues in its sequence. This report provided a promising method for the preparation of antioxidant peptides from collagen for food and medicinal purposes.
A direct hydroalkylation of disubstituted alkynes with unfunctionalized ethers and amides was achieved in an atom-efficient and additive-free manner through the synergistic combination of photoredox ...and nickel catalysis. The protocol was effective with a wide range of internal alkynes, providing products in a highly selective fashion. Notably, the observed regioselectivity is complementary to conventional radical addition processes. Mechanistic investigations suggest that the photoexcited iridium catalyst facilitated the nickel activation via single-electron transfer.
Six flavonoids, namely, three undescribed biflavonoids, one undescribed 8-aryl flavonoid, and two known compounds, were isolated from Selaginella tamariscina (P.Beauv.) Spring. The structures and ...absolute configurations of those undescribed compounds were established by NMR spectroscopy data, HRESIMS analyses and electronic circular dichroism (ECD) analyses. In addition, all the isolates were evaluated for their hypoglycemic activity in HepG2 cells. Involvenflavone H, I, and J significantly increased glucose consumption in both normal and insulin-resistant HepG2 cells. Interestingly, these three compounds can effectively upregulate the protein expression of glucokinase (GCK) and adenylate cyclases (ADCYs). These results suggested that involvenflavone H, I, and J (especially involvenflavone J) may have potent hypoglycemic activity, which also provided promising molecular targets for the treatment of diabetes.
Display omitted
•Four undescribed flavonoids were isolated from Selaginella tamariscina (P.Beauv.) Spring.•Involvenflavone H, I, and J significantly increased the glucose consumption in insulin-resistant HepG2 cells.•Involvenflavone J up-regulated the protein expression of glucokinase and adenylate cyclases effectively.
Yes‐associated protein (YAP) is a component of the canonical Hippo signaling pathway that is known to play essential roles in modulating organ size, development, and tumorigenesis. Activation or ...upregulation of YAP1, which contributes to cancer cell survival and chemoresistance, has been verified in different types of human cancers. However, the molecular mechanism of YAP1 upregulation in cancer is still unclear. Here we report that the E3 ubiquitin ligase STUB1 ubiquitinates and destabilizes YAP1, thereby inhibiting cancer cell survival. Low levels of STUB1 expression were correlated with increased protein levels of YAP1 in human gastric cancer cell lines and patient samples. Moreover, we revealed that STUB1 ubiquitinates YAP1 at the K280 site by K48‐linked polyubiquitination, which in turn increases YAP1 turnover and promotes cellular chemosensitivity. Overall, our study establishes YAP1 ubiquitination and degradation mediated by the E3 ligase STUB1 as an important regulatory mechanism in gastric cancer, and provides a rationale for potential therapeutic interventions.
Our study establishes YAP1 ubiquitination and degradation mediated by the E3 ligase STUB1 as an important regulatory mechanism in gastric cancer, and provides a rationale for potential therapeutic interventions.
Display omitted
•A deep neural network method is proposed to study the interaction of microcracks.•The method predicts the strengths of specimens containing a number of microcracks.•Both open and ...closed microcracks are considered under arbitrary biaxial loading.
The strengths of brittle or quasi-brittle materials strongly depend on the interaction of distributed microcracks. Traditional micromechanics methods are difficult to exactly predict the strengths of materials containing a large number of microcracks. In this paper, a micromechanics-based deep learning method is proposed to predict the strengths of two-dimensional microcracked brittle materials. Utilizing a numerical method based on Kachanov’s theory of microcrack interaction, we generate a data set containing a large number of images of two-dimensional microcracked specimens and their load-bearing capacity under various in-plane loading. A deep neural network is formulated based on this data set to establish the implicit mapping between the load-bearing capacity of the specimens and the spatial distribution of microcracks. Numerical experiments demonstrate that the trained deep neural network can accurately and efficiently predict the load-bearing capacity of microcracked brittle materials.
Herein, a photocatalytic system for defluorinative 4+2 annulation of gem‐difluoroalkenes with unactivated alkenes is realized. This protocol was compatible with a broad scope of unactivated alkenes, ...affording the diverse monofluorocyclohexene products in 30–95% yields. Furthermore, the value of this method was demonstrated by the gram‐scale synthesis, late‐stage functionalization and synthesis of various valuable and complex monofluorocyclohexene derivatives.
The study of pathophysiological mechanisms in human liver disease has been constrained by the inability to expand primary hepatocytes in vitro while maintaining proliferative capacity and metabolic ...function. We and others have previously shown that mouse mature hepatocytes can be converted to liver progenitor-like cells in vitro with defined chemical factors. Here we describe a protocol achieving efficient conversion of human primary hepatocytes into liver progenitor-like cells (HepLPCs) through delivery of developmentally relevant cues, including NAD
-dependent deacetylase SIRT1 signaling. These HepLPCs could be expanded significantly during in vitro passage. The expanded cells can readily be converted back into metabolically functional hepatocytes in vitro and upon transplantation in vivo. Under three-dimensional culture conditions, differentiated cells generated from HepLPCs regained the ability to support infection or reactivation of hepatitis B virus (HBV). Our work demonstrates the utility of the conversion between hepatocyte and liver progenitor-like cells for studying HBV biology and antiviral therapies. These findings will facilitate the study of liver diseases and regenerative medicine.
PDF
