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Mitochondrial genomes (mitogenomes) are valuable resources in molecular and evolutionary studies, such as phylogeny and population genetics. The complete mitogenomes of two crocodile newts, Tylototriton broadoridgus and Tylototriton gaowangjienensis, were sequenced, assembled, and annotated for the first time using next-generation sequencing. The complete mitogenomes of T. broadoridgus and T. gaowangjienensis were 16,265 bp and 16,259 bp in lengths, which both composed of 13 protein-coding genes (PCGs), 2 rRNA genes, 22 tRNA genes, and 1 control region. The two mitogenomes had high A + T content with positive AT-skew and negative GC-skew patterns. The ratio of non-synonymous and synonymous substitutions showed that, relatively, the ATP8 gene evolved the fastest and COI evolved the slowest among the 13 PCGs. Phylogenetic trees from BI and ML analyses resulted in identical topologies, where the Tylototriton split into two groups corresponding to two subgenera. Both T. broadoridgus and T. gaowangjienensis sequenced here belonged to the subgenus Yaotriton, and these two species shared a tentative sister group relationship. The two mitogenomes reported in this study provided valuable data for future molecular and evolutionary studies of the genus Tylotoriton and other salamanders.

This document discusses the challenges and methods for constructing fluorinated quaternary stereogenic centers in organic molecules, which are important in pharmaceuticals. The authors present a Pd-catalyzed allylic C–H alkylation method using an α-fluoroester for the construction of a C–F quaternary stereogenic center. They found that using a chiral phosphoramidite-palladium catalyst and 2,5-diphenylhydroquinone as an oxidant resulted in high yields and selectivities. The researchers also explored the substrate scope and proposed a plausible reaction mechanism. Overall, this study provides an efficient method for synthesizing fluorinated quaternary stereogenic centers. [Extracted from the article]

In this paper, the L-ascorbic acid (L-AA) biosensor based on magnetic beads-ascorbate oxidase/graphene oxide/indium gallium zinc oxide/aluminum (MBs-AOX/GO/IGZO/Al) membrane was integrated with the potentiometric measurement system with the microfluidic framework in order to investigate the different sensing characteristics under the static condition and the dynamic condition. The L-AA biosensor showed the average sensitivity of 78.9 mV/decade (25 °C) under the static condition, and it showed the average sensitivity of 81.7 mV/decade (25 °C) at the optimal flow rate (25 μl/min). Besides, the XBee module was used to apply in the remote detection for the L-AA biosensor, and the experimental results were shown the average sensitivity of 78.7 mV/decade (25 °C). Moreover, we also investigated various experiments, such as temperature effect, hysteresis effect, and lifetime. These experimental results would be beneficial to the development of the L-AA biosensor based on electrochemical detection.

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Drug-coated balloon (DCB) is a therapeutic method that can effectively deliver antiproliferative drugs such as paclitaxel and rapamycin (RAPA) with no permanent implants left behind. However, delayed reendothelialization due to the toxicity of the delivered drugs leads to poor therapeutic effects. Here, we propose a new design of DCB coating, which incorporates both vascular endothelial growth factor (VEGF)-encoding plasmid DNA (pDNA) that can promote endothelial repair and RAPA into protamine sulfate (PrS). We demonstrate that the PrS/pDNA/RAPA coating had stability and good anticoagulation properties in vitro. We further show that the coating exhibited excellent transfer capacity from balloon substrates to vessel walls both in vitro and in vivo. Furthermore, the PrS/pDNA/RAPA coating effectively inhibited neointimal hyperplasia after balloon-induced vascular injuries through the down-regulation of the mammalian target of Rapamycin (mTOR) and promoted endothelium regeneration through increased expression of VEGF in vivo. These data indicate that our nanocomposite coating has great potential for use as a novel coating of DCB to treat neointimal hyperplasia after vascular injuries. [ABSTRACT FROM AUTHOR]

Bolted spherical joints, due to their prominent merits in installation, have been widely used in modern spatial structures. Despite significant research, there is a lack of understanding of their flexural fracture behaviour, which is important for the catastrophe prevention of the whole structure. Given the recent development to fill this knowledge gap, it is the objective of this paper to experimentally investigate the flexural bending capacity of the overall fracture section featured by a heightened neutral axis and fracture behaviour related to variable crack depth in screw threads. Accordingly, two full-scale bolted spherical joints with different bolt diameters were evaluated under three-point bending. The fracture behaviour of bolted spherical joints is first revealed with respect to typical stress distribution and fracture mode. A new theoretical flexural bending capacity expression for the fracture section with a heightened neutral axis is proposed and validated. A numerical model is then developed to estimate the stress amplification and stress intensity factors related to the crack opening (mode-I) fracture for the screw threads of these joints. The model is validated against the theoretical solutions of the thread-tooth-root model. The maximum stress of the screw thread is shown to take place at the same location as the test bolted sphere, while its magnitude can be greatly reduced with an increased thread root radius and flank angle. Finally, different design variants related to threads that have influences on the SIFs are compared, and the moderate steepness of the flank thread has been found to be efficient in reducing the joint fracture. The research findings could thus be beneficial for further improving the fracture resistance of bolted spherical joints. [ABSTRACT FROM AUTHOR]

Simple Summary: Soybean is a prominent grain and oil crop in the world. The production of soybean is threatened by weed competition. Recently, CRISPR/Cas9-mediated base editing, which can cause irreversible nucleotide changes in target loci, has been widely used in basic plant science and breeding. However, until now, herbicide-resistant traits in soybean have not been created by the base editor. The objective of this study was to modify different AHAS homologous alleles by base editor to generate a novel AHAS-inhibiting herbicide-resistant soybean. Our results showed that the GmAHAS4 P180S mutants have apparent resistance to AHAS-inhibiting herbicides, which will be beneficial for weed control in soybean production. Weeds cause the largest yield loss in soybean production. The development of herbicide-resistant soybean germplasm is of great significance for weed control and yield improvement. In this study, we used the cytosine base editor (BE3) to develop novel herbicide-resistant soybean. We have successfully introduced base substitutions in GmAHAS3 and GmAHAS4 and obtained a heritable transgene-free soybean with homozygous P180S mutation in GmAHAS4. The GmAHAS4 P180S mutants have apparent resistance to chlorsulfuron, flucarbazone-sodium, and flumetsulam. In particular, the resistance to chlorsulfuron was more than 100 times that of with wild type TL-1. The agronomic performance of the GmAHAS4 P180S mutants showed no significant differences to TL-1 under natural growth conditions. In addition, we developed allele-specific PCR markers for the GmAHAS4 P180S mutants, which can easily discriminate homozygous, heterozygous mutants, and wild-type plants. This study demonstrates a feasible and effective way to generate herbicide-resistant soybean by using CRISPR/Cas9-mediated base editing. [ABSTRACT FROM AUTHOR]

Background: The endovascular strategy of the huge dissecting aneurysms involving the basilar artery (BA) is controversial and challenging. This study was to investigate the clinical and angiographic outcomes of the treatment of the huge dissecting aneurysms involving the BA by the internal trapping (IT) technique. Methods: We retrospectively studied 15 patients with the huge dissecting aneurysms involving the BA treated by the IT technique between September 2005 and September 2014 in Department of Interventional Neuroradiology of Beijing Tiantan Hospital. Clinical and angiographic data were reviewed and evaluated. Results: All patients were treated by the IT technique. That meant the dissecting artery and aneurysm segments were completed occlusion. After the procedure, the angiography demonstrated that all the dissecting artery and aneurysm segments were completed occlusion. Follow-up angiography was performed at 3-6 months or 12-18 months after the endovascular treatment (median 8 months), 14 patients had a good recovery. Re-canalization occurred in one patient whose aneurysm involved in bilateral vertebral arteries and the two third of the middle-lower BA. After the second treatment, the patient died by the ventricular tachycardia. Conclusions: The IT technique is a technically feasible and safe alternative for the treatment of BA dissecting aneurysms, but it is not necessarily the safest or most definitive treatment modality. The ideal treatment of the huge dissecting aneurysms involving the BA remains debatable and must be investigated on a case-by-case basis.

Omalizumab is widely used in clinical practice; however, knowledge gaps in the dosage of omalizumab for children aged 2–6 years with moderate‐to‐severe persistent allergic asthma have been identified. The aim of this study was to explore dosing regimens for moderately‐to‐severely allergic pediatric patients aged 2–6 years. The physiologically‐based pharmacokinetic (PBPK) model of omalizumab was developed and verified in adult patients, extrapolated to pediatric patients, and simulated for omalizumab by adding two observation chambers (free IgE and total IgE). The simulation results showed that the fold errors of the predicted and observed values of the area under the curve (AUC) and peak plasma concentration (Cmax) were between 0.5 and 2.0, and the average folding error and the absolute average folding error values for all concentration‐time data points were 1.09 and 1.48, respectively. The PBPK model combined with pharmacokinetic/pharmacodynamic analysis of omalizumab demonstrated that both the model‐derived dose and the original dose could control the average free IgE of 2–6‐year‐old children with moderate‐to‐severe allergic asthma below 25 ng/mL, and some of the model‐derived doses were lower. This conclusion provides a basis for the selection of dosage in clinical practice reference. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC) is a highly prevalent malignancy with a poor prognosis. USP20 can support progression of variety of tumors. USP20 was shown to promote breast tumor metastasis, and proliferation of oral squamous carcinoma cells. However, the role of USP20 in CRC remains unclear. Methods: We used bioinformatics to analyze the expression and prognosis of USP20 in pan-cancer and explore the relationship between USP20 expression and immune infiltration, immune checkpoints, and chemotherapy resistance in CRC. The differential expression and prognostic role of USP20 in CRC was validated by qRT-PCR and immunohistochemistry. Cox univariate and multivariate analyses were performed to assess risk factors for poor prognosis of CRC, and new prognostic prediction models were constructed and evaluated by decision curve analysis (ROC) and receiver operating characteristic (DCA). USP20 was overexpressed in CRC cell lines to explore the effect of USP20 on the functionalities of CRC cells. Enrichment analyses were used to explore the possible mechanism of USP20 in CRC. Results: The expression of USP20 was lower in CRC tissues than adjacent normal tissues. Compared with low USP20 expression patients, CRC patients with high USP20 expression level had shorter OS. Correlation analysis showed that USP20 expression was associated with lymph node metastasis. Cox regression analysis revealed USP20 as an independent risk factor for poor prognosis in CRC patients. ROC and DCA analyses showed that the performance of the newly constructed prediction model was better than the traditional TNM model. Immune infiltration analysis shown that USP20 expression is closely associated with T cell infiltration in CRC. A co-expression analysis showed that USP20 expression was positively correlated with several immune checkpoint genes including ADORA2A, CD160, CD27 and TNFRSF25 genes and positively associated with multiple multi-drug resistance genes such as MRP1, MRP3, and MRP5 genes. USP20 expression positively correlated with the sensitivity of cells to multiple anticancer drugs. Overexpression of USP20 enhanced the migration and invasive ability of CRC cells. Enrichment pathway analyses showed the USP20 may play a role via the Notch pathway, Hedgehog pathway and beta-catenin pathway. Conclusion: USP20 is downregulated in CRC and associated with prognosis in CRC. USP20 enhances CRC cells metastasis and is associated with immune infiltration, immune checkpoints, and chemotherapy resistance. [ABSTRACT FROM AUTHOR]

Based on planned behavior theory (TPB), this study aims to explore the direct or indirect impacts of entrepreneurship education on entrepreneurial intentions through entrepreneurial self-efficacy and explore the moderating role of psychological capital. Sample data were collected by sending online electronic questionnaires to university students in some universities in Guangxi. A structural equation model was used to test the 757 valid sample data. The results showed that: (1) college students of different genders and those with or without family business experience have significant differences in terms of their entrepreneurial intentions; (2) entrepreneurship education has a significant positive impact on entrepreneurial intentions; (3) entrepreneurial self-efficacy plays a complete mediating role; and (4) higher psychological capital can positively regulate the impact of entrepreneurial self-efficacy on entrepreneurial intention. The findings help explain the need for entrepreneurship education. In order to increase students' participation in entrepreneurship education courses, different innovative technology-based curricula and educational methods can be used at higher educational levels. In addition, this study constructs a mediation and moderation model influencing entrepreneurial intention based on TPB, which further tests and enriches the research perspective of this theory from the perspective of positive psychology. [ABSTRACT FROM AUTHOR]

Two types of urea biosensors were integrated with a wireless measurement system and microfluidic measurement system. The two biosensors used were (i) a magnetic beads (MBs)-urease/graphene oxide (GO)/titanium dioxide (TiO2)-based biosensor and (ii) an MBs-urease/GO/ nickel oxide (NiO)-based biosensor, respectively. The wireless measurement system work exhibited the feasibility for the remote detection of urea, but it will require refinement and modification to improve stability and precision. The microchannel fluidic system showed the measurement reliability. The sensing properties of urea biosensors at different flow rates were investigated. From the measurement results, the decay of average sensitivity may be attributed to the induced vortex-induced vibrations (VIV) at the high flow rate. In the aspect of wireless monitoring, the average sensitivity of the urea biosensor based on MBs-urease/GO/NiO was 4.780 mV/(mg/dl) and with the linearity of 0.938. In the aspect of measurement under dynamic conditions, the average sensitivity of the urea biosensor based on MBs-urease/GO/NiO were 5.582 mV/(mg/dl) and with the linearity of 0.959. Both measurements performed NiO was better than TiO2 according to the comparisons.

Hereditary hemorrhagic telangiectasis (HHT) and juvenile polyposis syndrome (JPS) are both relatively rare hereditary disorders. It has been reported that patients with SMAD4 mutations may suffer from both HHT and JPS, defined as JPS/HHT. To improve the understanding and diagnosis of these diseases, we herein report a case of a 17-year-old male with abdominal pain and hematochezia. Low-tension computed tomography (CT) of the small intestine showed intussusception. Combined with the patient's medical history of nasal bleeding and pulmonary arteriovenous fistula (pAVF) embolism, a final diagnosis of JPS/HHT was reached, according to the Curaçao Diagnostic Criteria. The possibility of JPS/HHT should be considered in patients with epistaxis and intussusception. [ABSTRACT FROM AUTHOR]