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1.
Brief Bioinform ; 24(4)2023 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-37287133

RESUMO

MicroRNAs (miRNAs) are a family of non-coding RNA molecules with vital roles in regulating gene expression. Although researchers have recognized the importance of miRNAs in the development of human diseases, it is very resource-consuming to use experimental methods for identifying which dysregulated miRNA is associated with a specific disease. To reduce the cost of human effort, a growing body of studies has leveraged computational methods for predicting the potential miRNA-disease associations. However, the extant computational methods usually ignore the crucial mediating role of genes and suffer from the data sparsity problem. To address this limitation, we introduce the multi-task learning technique and develop a new model called MTLMDA (Multi-Task Learning model for predicting potential MicroRNA-Disease Associations). Different from existing models that only learn from the miRNA-disease network, our MTLMDA model exploits both miRNA-disease and gene-disease networks for improving the identification of miRNA-disease associations. To evaluate model performance, we compare our model with competitive baselines on a real-world dataset of experimentally supported miRNA-disease associations. Empirical results show that our model performs best using various performance metrics. We also examine the effectiveness of model components via ablation study and further showcase the predictive power of our model for six types of common cancers. The data and source code are available from https://github.com/qwslle/MTLMDA.


Assuntos
MicroRNAs , Neoplasias , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Algoritmos , Biologia Computacional/métodos , Neoplasias/genética , Software
2.
Funct Integr Genomics ; 23(1): 52, 2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36717528

RESUMO

Oral squamous cell carcinoma (OSCC) is a common malignant tumor with high recurrence, metastasis rates, and poor prognosis. Numerous studies discover that circular RNA (circRNA) is closely associated with OSCC progression. Hsa_circ_0020377 has been aberrantly expressed in OSCC, but its role in tumor growth and metastasis remains largely unclear. Hsa_circ_0020377, microRNA-194-5p (miR-194-5p), and Krüppel-like factor 7 (KLF7) contents were determined by real-time quantitative polymerase chain reaction (RT-qPCR). Cell proliferative, cycle progression migration, and invasion were measured using 5-ethynyl-2'-deoxyuridine (EdU), Cell Counting Kit-8 (CCK-8), flow cytometry, wound healing, and Transwell assays. The glycolysis level was detected via specific kits. Cyclin D1, E-cadherin, hexokinase 2 (HK2), and KLF7 protein levels were detected via western blot. Using predicting bioinformatics software, the binding between miR-194-5p and hsa_circ_0020377 or KLF7 was verified using a dual-luciferase reporter and RNA Immunoprecipitation (RIP). Beyond that, a xenograft tumor model was used to analyze the role of hsa_circ_0020377 on tumor cell growth in vivo. Increased hsa_circ_0020377 and KLF7 and reduced miR-194-5p were found in OSCC tissues and cell lines. Loss-of-function experiments proved that hsa_circ_0020377 depletion might block OSCC cell proliferation, cycle progression, migration, invasion, and glycolysis in vitro. In xenograft mouse models, hsa_circ_0020377 silencing might suppress tumor growth. In addition, mechanism research suggested that hsa_circ_0020377 could bind with miR-194-5p and enhance its target gene (KLF7), thereby affecting OSCC development. These results broaden our insights regarding the regulation of OSCC progression via circRNA and act as a reference for future clinical studies in OSCC diagnosis and treatment.


Assuntos
Fatores de Transcrição Kruppel-Like , MicroRNAs , Neoplasias Bucais , RNA Circular , Carcinoma de Células Escamosas de Cabeça e Pescoço , Animais , Humanos , Camundongos , Linhagem Celular Tumoral , Proliferação de Células , Fatores de Transcrição Kruppel-Like/genética , MicroRNAs/genética , Neoplasias Bucais/genética , RNA Circular/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética
3.
Small ; 19(34): e2300384, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37116117

RESUMO

Prussian blue analogs (PBAs) represent a crucial class of intercalation electrode materials for electrochemical water desalination. It is shown here that structural/compositional tailoring of PBAs, the nickel hexacyanoferrate (NiHCF) electrodes in particular, can efficiently modulate their capacitive deionization (CDI) performance (e.g., desalination capacity, cyclability, selectivity, etc.). Both the desalination capacity and the cyclability of NiHCF electrodes are highly dependent on their structural/compositional features such as crystallinity, morphology, hierarchy, and coatings. It is demonstrated that the CDI cell with hierarchically structured NiHCF nanoframe (NiHCF-NF) electrode exhibits a superior desalination capacity of 121.38 mg g-1 , a high charge efficiency of up to 82%, and a large capacity retention of 88% after 40 cycles intercalation/deintercalation. In addition, it is discovered that coating of carbon (C) film over NiHCF can lower its desalination capacity owing to the partial blockage of diffusion openings by the coated C film. Moreover, the hierarchical NiHCF-NF electrode also demonstrates a superior selectivity toward monovalent sodium ions (Na+ ) over divalent calcium (Ca2+ ) and magnesim (Mg2+ ) ions, allowing it to be a promising platform for preferential capturing Na+ ions from brines. Overall, the structural/compositional tailoring strategies would offer a viable option for the rational design of other intercalation electrode materials applied in CDI techniques.

4.
Plant Biotechnol J ; 21(4): 698-710, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36529909

RESUMO

Although plant secondary metabolites are important source of new drugs, obtaining these compounds is challenging due to their high structural diversity and low abundance. The roots of Astragalus membranaceus are a popular herbal medicine worldwide. It contains a series of cycloartane-type saponins (astragalosides) as hepatoprotective and antivirus components. However, astragalosides exhibit complex sugar substitution patterns which hindered their purification and bioactivity investigation. In this work, glycosyltransferases (GT) from A. membranaceus were studied to synthesize structurally diverse astragalosides. Three new GTs, AmGT1/5 and AmGT9, were characterized as 3-O-glycosyltransferase and 25-O-glycosyltransferase of cycloastragenol respectively. AmGT1G146V/I variants were obtained as specific 3-O-xylosyltransferases by sequence alignment, molecular modelling and site-directed mutagenesis. A combinatorial synthesis system was established using AmGT1/5/9, AmGT1G146V/S and the reported AmGT8 and AmGT8A394F . The system allowed the synthesis of 13 astragalosides in Astragalus root with conversion rates from 22.6% to 98.7%, covering most of the sugar-substitution patterns for astragalosides. In addition, AmGT1 exhibited remarkable sugar donor promiscuity to use 10 different donors, and was used to synthesize three novel astragalosides and ginsenosides. Glycosylation remarkably improved the hepatoprotective and SARS-CoV-2 inhibition activities for triterpenoids. This is one of the first attempts to produce a series of herbal constituents via combinatorial synthesis. The results provided new biocatalytic tools for saponin biosynthesis.


Assuntos
COVID-19 , Plantas Medicinais , Saponinas , Triterpenos , Astragalus propinquus/química , Astragalus propinquus/genética , Astragalus propinquus/metabolismo , Saponinas/química , Saponinas/metabolismo , Glicosiltransferases/genética , SARS-CoV-2 , Triterpenos/metabolismo , Engenharia de Proteínas , Açúcares/metabolismo
5.
Org Biomol Chem ; 21(42): 8467-8470, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37842833

RESUMO

The bacterial glycosyltransferase YjiC1 was used to glycosylate triterpenoids from the medicinal fungus Antrodia camphorata. Eleven new compounds were obtained from enzymatic reactions. Glucosylation could increase the inhibitory activities against COX-2, and improve the anti-inflammatory activities of Antrodia ergostanes on acute lung injury mice, especially (25R)-antcin C 7-O-ß-D-glucoside.


Assuntos
Antrodia , Polyporales , Triterpenos , Camundongos , Animais , Triterpenos/farmacologia
6.
Environ Sci Technol ; 57(34): 12741-12751, 2023 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-37578487

RESUMO

Marine biological activities make a non-negligible contribution to atmospheric aerosols, leading to potential impacts on the regional atmospheric environment and climate. The eastern China seas are highly productive with significant emissions of biogenic substances, but the spatiotemporal variations of marine biogenic aerosols are not well known. Air mass exposure to chlorophyll a (AEC) can be used to indicate the influence of biogenic sources on the atmosphere to a certain degree. In this study, the 12 year (2009-2020) daily AEC were calculated over the eastern China seas, showing the spatial and seasonal patterns of marine biogenic influence intensity which were co-controlled by surface phytoplankton biomass and boundary layer height. By combining the AEC values, relevant meteorological parameters, and extensive observations of a typical biogenic secondary aerosol component, methanesulfonate (MSA), a parameterization scheme for MSA simulation was successfully constructed. This AEC-based approach with observation constraints provides a new insight into the distribution of marine biogenic aerosols. Meanwhile, the wintertime air mass retention over land exhibited a significant decrease, showing a decadal weakening trend of terrestrial transport, which is probably related to the weakening of the East Asian winter monsoon. Thus, marine biogenic aerosols may play an increasingly important role in the studied region.


Assuntos
Poluentes Atmosféricos , Poluentes Atmosféricos/análise , Clorofila A , Oceanos e Mares , China , Atmosfera/análise , Estações do Ano , Aerossóis/análise , Monitoramento Ambiental
7.
Zhongguo Zhong Yao Za Zhi ; 48(18): 4967-4973, 2023 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-37802838

RESUMO

A field experiment was conducted to measure the physiological characteristics, yield, active ingredient content, and other indicators of Carthamus tinctorius leaves undergoing 13 sowing date treatments. The principal component analysis(PCA) and redundancy analysis were used to analyze the correlation between these indicators to explore the effect of sowing date on the yield and active ingredient content of C. tinctorius in Liupanshan of Ningxia. The results illustrated that the early sowing in autumn and spring had significant effects on leaf photosynthetic parameters, SPAD value, antioxidant enzyme activity, nitrogen metabolism enzyme activity, filament yield, grain yield, and hydroxy safflower yellow A(HYSA) of C. tinctorius. Sowing in mid-November and late March had the best effect. Leaf transpiration rate, stomatal conductance, nitrate reductase, nitrite reductase, glutamine synthetase, and glutamate synthase increased by 44.9%, 52.4%, 15.9%, 60.8%, 10.3%, and 38.3%, respectively. The activities of superoxide dismutase, peroxidase, and catalase decreased by 10.8%, 4.1%, and 20.9%, respectively. The improvement of photosynthetic physiological characteristics promoted the dry matter accumulation and reproductive growth of C. tinctorius. The yield of filaments and seeds increased by 15.5% and 11.7%, and the yield of HYSA and kaempferol increased by 17.9% and 20.0%. In short, the suitable sowing date can promote the growth and development of C. tinctorius in Liupanshan of Ningxia, and significantly improve the yield and quality, which is conducive to the high quality and efficient production of C. tinctorius.


Assuntos
Carthamus tinctorius , Sementes , Peroxidase/metabolismo , Folhas de Planta/metabolismo , Antioxidantes
8.
Angew Chem Int Ed Engl ; 62(35): e202308041, 2023 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-37428115

RESUMO

While chain-walking stimulates wide interest in both polymerization and organic synthesis, site- and stereoselective control of chain-walking on rings is still a challenging task in the realm of organometallic catalysis. Inspired by a controllable chain-walking on cyclohexane rings in olefin polymerization, we have developed a set of chain-walking carboborations of cyclohexenes based on nickel catalysis. Different from the 1,4-trans-selectivity disclosed in polymer science, a high level of 1,3-regio- and cis-stereoselectivity is obtained in our reactions. Mechanistically, we discovery that the base affects the reduction ability of B2 pin2 and different bases lead to different catalytic cycles and different regioselective products (1,2- Vs 1,3-addition). This study provides a concise and modular method for the synthesis of 1,3-disubstituted cyclohexylboron compounds. The incorporation of a readily modifiable boronate group greatly enhances the value of this method, the synthetic potential of which was highlighted by the synthesis of a series of high-valued commercial chemicals and pharmaceutically interesting molecules.

9.
J Cell Mol Med ; 26(10): 2881-2894, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35415942

RESUMO

Hypoxic resistance is the main obstacle to radiotherapy for laryngeal carcinoma. Our previous study indicated that hypoxia-inducible factor 1α (HIF-1α) and glucose transporter 1 (Glut-1) double knockout reduced tumour biological behaviour in laryngeal carcinoma cells. However, their radioresistance mechanism remains unclear. In this study, cell viability was determined by CCK8 assay. Glucose uptake capability was evaluated by measurement of 18 F-fluorodeoxyglucose radioactivity. A tumour xenograft model was established by subcutaneous injection of Tu212 cells. Tumour histopathology was determined by haematoxylin and eosin staining, immunohistochemical staining, and TUNEL assays. Signalling transduction was evaluated by Western blotting. We found that hypoxia induced radioresistance in Tu212 cells accompanied by increased glucose uptake capability and activation of the PI3K/Akt/mTOR pathway. Inhibition of PI3K/Akt/mTOR activity abolished hypoxia-induced radioresistance and glucose absorption. Mechanistic analysis revealed that hypoxia promoted higher expressions of HIF-1α and Glut-1. Moreover, the PI3K/Akt/mTOR pathway was a positive mediator of HIF-1α and/or Glut-1 in the presence of irradiation. HIF-1α and/or Glut-1 knockout significantly reduced cell viability, glucose uptake and PI3K/Akt/mTOR activity, all of which were induced by hypoxia in the presence of irradiation. In vivo analysis showed that knockout of HIF-1α and/or Glut-1 also inhibited tumour growth by promoting cell apoptosis, more robustly compared with the PI3K inhibitor wortmannin, particularly in tumours with knockout of both HIF-1α and Glut-1. HIF-1α and/or Glut-1 knockout also abrogated PI3K/Akt/mTOR signalling transduction in tumour tissues, in a manner similar to wortmannin. HIF-1α and/or Glut-1 knockout facilitated radiosensitivity in laryngeal carcinoma Tu212 cells by regulation of the PI3K/Akt/mTOR pathway.


Assuntos
Carcinoma , Transportador de Glucose Tipo 1 , Subunidade alfa do Fator 1 Induzível por Hipóxia , Neoplasias Laríngeas , Animais , Sistemas CRISPR-Cas , Carcinoma/genética , Carcinoma/metabolismo , Carcinoma/radioterapia , Linhagem Celular Tumoral , Glucose , Transportador de Glucose Tipo 1/genética , Transportador de Glucose Tipo 1/metabolismo , Humanos , Hipóxia , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Neoplasias Laríngeas/genética , Neoplasias Laríngeas/metabolismo , Neoplasias Laríngeas/radioterapia , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Tolerância a Radiação/genética , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo , Wortmanina
10.
BMC Anesthesiol ; 22(1): 208, 2022 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-35794540

RESUMO

BACKGROUND: Either neuraxial anesthesia or general anesthesia can be performed for cesarean delivery. Generally, neuraxial anesthesia is the first choice with the risk and benefit balance for both the mother and fetus. However, general anesthesia is also applicable most commonly in the emergent setting. This study analyzed maternal complications associated with general anesthesia for cesarean delivery and suggested lowering pregnancy-related maternal and newborn adverse outcomes. METHODS: With the approval of the Institutional Ethics Review Board (No: 2017016), data on cesarean delivery and related anesthesia were collected from the Electronic Health Record System from 1/1/2013 to 12/31/2016. Statistical software STATA version 15.1 was used for data analyses. All statistical tests were two-sided, and a level significance of 0.05 was assumed. RESULTS: The rate of general anesthesia for cesarean delivery increased steadily during 2013-2016, 3.71% in 2013 to 10.23% in 2016 (p < 0.001). Repeat cesarean delivery among general anesthesia group increased significantly from 16.22% in 2013 to 54.14% in 2016 (p < 0.001). Morbidly adherent placenta (MAP) was the first reason among pregnancy-related complications, which accounted for 33% in total in general anesthesia group (38% in 2013 to 44% in 2016). The laryngeal mask airway (LMA) was used in airway management, and the proportion of LMA increased from 28.38% in 2013 to 92.99% in 2016 (p < 0.001). There were significant differences in newborn outcomes between general anesthesia and neuraxial anesthesia groups, including newborn weight, newborn Apgar score at 1 min and 5 min and newborn admission to the NICU (p < 0.001). CONCLUSIONS: The growing incidence of general anesthesia was consistent with the trend of rising repeat cesarean delivery and MAP. low newborn Apgar score and high newborn admission to the NICU in general anesthesia group compared with neuraxial anesthesia group. The LMA was performed safely for airway management with enough fasting and careful gastric volume evaluation.


Assuntos
Máscaras Laríngeas , Complicações na Gravidez , Anestesia Geral/efeitos adversos , Cesárea/efeitos adversos , Feminino , Humanos , Recém-Nascido , Gravidez , Estudos Retrospectivos , Centros de Atenção Terciária
11.
Eur Arch Otorhinolaryngol ; 279(3): 1413-1424, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34800155

RESUMO

PURPOSE: We investigated the role of Glut-1 and H+/K+-ATPase expression in pepsin-induced development of human vocal cord leukoplakia cells (HVCLCs). Next, we analyzed the relationship between Glut-1 and H+/K+-ATPase expression with the clinicopathological features of laryngeal carcinoma. METHODS: Glut-1 and H+/K+-ATPase expression levels in HVCLCs were determined after treatment with artificial gastric juice containing pepsin and laryngeal carcinoma tissues. RESULTS: Exposure to pepsin-containing artificial gastric juice significantly enhanced the migration and proliferation of VSCLCs in a time-dependent manner. The apoptotic rate of VSCLCs decreased over time after exposure to pepsin and reached a nadir on day 7 (p < 0.01). With increasing duration of exposure to pepsin, the proportion of VSCLCs in G0/G1 phase decreased and the proportions in the S and G2/M phases significantly increased (p < 0.05). After treatment with pepsin-containing artificial gastric juice, RT-PCR and Western blotting showed that the expression of Glut-1 and H+/K+-ATPase α, ß significantly increased in HVCLCs compared to in the absence of pepsin (p < 0.05). The expression of Glut-1 and H+/K+-ATPase α, ß gradually increased from vocal cord leukoplakia (VLC) to laryngeal carcinoma (p < 0.05). Lentivirus-mediated inhibition of Glut-1 expression in VCL significantly inhibited the cells' migration and proliferation (p < 0.05) but enhanced their apoptosis (p < 0.05). Also, inhibition of Glut-1 expression resulted in an increased proportion of cells in G0/G1 phase and a significantly decreased proportion in G2/M phase (p < 0.05). CONCLUSIONS: Elevated Glut-1 expression may promote the development of VCL by upregulating laryngeal H+/K+-ATPase expression to reactivate absorbed pepsin, thus damaging the laryngeal mucosa.


Assuntos
Transportador de Glucose Tipo 1 , ATPase Trocadora de Hidrogênio-Potássio , Neoplasias Laríngeas , Refluxo Laringofaríngeo , Leucoplasia , Prega Vocal , Adenosina Trifosfatases/metabolismo , Transportador de Glucose Tipo 1/biossíntese , ATPase Trocadora de Hidrogênio-Potássio/biossíntese , Humanos , Neoplasias Laríngeas/patologia , Refluxo Laringofaríngeo/patologia , Leucoplasia/patologia , Pepsina A/análise , Pepsina A/farmacologia , Prega Vocal/patologia
12.
Eur Arch Otorhinolaryngol ; 279(6): 2981-2987, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35083516

RESUMO

PURPOSE: To explore the role played by Glut-1 and H+/K+-ATPase in pepsin-induced, mouse laryngeal epithelial proliferation, growth, and development. METHODS: We established a mouse model of laryngopharyngeal reflux and measured Glut-1 and H+/K+-ATPase expression levels in mouse laryngeal epithelium treated with artificial gastric juice containing pepsin. RESULTS: Artificial pepsin-containing gastric juice induced significant hyperplastic changes in mouse laryngeal epithelium compared to control mice at 15, 30, and 45 days. Inhibition of Glut-1 expression by 2-DG significantly suppressed such hyperplasia compared to mice exposed to artificial gastric juice containing pepsin at 15, 30, and 45 days. After treatment with pepsin-containing artificial gastric juice, RT-PCR and Western blotting showed that the levels of Glut-1 and H+/K+-ATPase α, ß increased significantly. CONCLUSIONS: Pepsin-containing artificial gastric juice promoted mouse laryngeal epithelial hyperplasia associated with abnormal expression of Glut-1 and H+/K+-ATPase α, ß.


Assuntos
Refluxo Laringofaríngeo , Pepsina A , Adenosina Trifosfatases , Animais , Humanos , Hiperplasia/patologia , Mucosa Laríngea/patologia , Refluxo Laringofaríngeo/patologia , Camundongos , Pepsina A/análise
13.
Sensors (Basel) ; 22(19)2022 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-36236722

RESUMO

Model assisted probability of detection (MAPoD) is crucial for quantifying the inspection capability of a nondestructive testing (NDT) system which uses the coil or probe to sense the size and location of the cracks. Unfortunately, it may be computationally intensive for the simulation models. To improve the efficiency of the MAPoD, in this article, an efficient 3D eddy current nondestructive evaluation (ECNDE) forward solver is proposed to make estimations for PoD study. It is the first time that singular value decomposition (SVD) is used as the recompression technique to improve the overall performance of the adaptive cross approximation (ACA) algorithm-based boundary element method (BEM) ECNDE forward solver for implementation of PoD. Both the robustness and efficiency of the proposed solver are demonstrated and testified by comparing the predicted impedance variations of the coil with analytical, semi-analytical and experimental benchmarks. Calculation of PoD curves assisted by the proposed simulation model is performed on a finite thickness plate with a rectangular surface flaw. The features, which are the maximum impedance variations of the coil for various flaw lengths, are obtained entirely by the proposed model with selection of the liftoff distance as the uncertain parameter in a Gaussian distribution. The results show that the proposed ACA-SVD based BEM fast ECNDE forward solver is an excellent simulation model to make estimations for MAPoD study.

14.
Nano Lett ; 21(20): 8800-8807, 2021 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-34644096

RESUMO

Memristor devices that exhibit high integration density, fast speed, and low power consumption are candidates for neuromorphic devices. Here, we demonstrate a filament-based memristor using p-type SnS as the resistive switching material, exhibiting superlative metrics such as a switching voltage ∼0.2 V, a switching speed faster than 1.5 ns, high endurance switching cycles, and an ultralarge on/off ratio of 108. The device exhibits a power consumption as low as ∼100 fJ per switch. Chip-level simulations of the memristor based on 32 × 32 high-density crossbar arrays with 50 nm feature size reveal on-chip learning accuracy of 87.76% (close to the ideal software accuracy 90%) for CIFAR-10 image classifications. The ultrafast and low energy switching of p-type SnS compared to n-type transition metal dichalcogenides is attributed to the presence of cation vacancies and van der Waals gap that lower the activation barrier for Ag ion migration.

15.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 44(6): 1049-1055, 2022 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-36373645

RESUMO

Coronaviruses are a major source of emerging infectious diseases in recent years.With a variety of family members,wide host spectrum,and diverse mutant strains,coronaviruses have demonstrated unique advantages in evolution.This paper reviews the research progress of coronaviruses from genome characteristics,host animals,distribution of receptorsand gene mutations,summarizes the advantages of coronaviruses in evolution and transmission,aiming to draw attention to the prevention and control of such viruses.


Assuntos
Infecções por Coronavirus , Coronavirus , Animais , Coronavirus/genética , Filogenia
16.
Angew Chem Int Ed Engl ; 61(8): e202113587, 2022 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-34894044

RESUMO

Engineering the function of triterpene glucosyltransferases (GTs) is challenging due to the large size of the sugar acceptors. In this work, we identified a multifunctional glycosyltransferase AmGT8 catalyzing triterpene 3-/6-/2'-O-glycosylation from the medicinal plant Astragalus membranaceus. To engineer its regiospecificity, a small mutant library was built based on semi-rational design. Variants A394F, A394D, and T131V were found to catalyze specific 6-O, 3-O, and 2'-O glycosylation, respectively. The origin of regioselectivity of AmGT8 and its A394F variant was studied by molecular dynamics and hydrogen deuterium exchange mass spectrometry. Residue 394 is highly conserved as A/G and is critical for the regiospecificity of the C- and O-GTs TcCGT1 and GuGT10/14. Finally, astragalosides III and IV were synthesized by mutants A394F, T131V and P192E. This work reports biocatalysts for saponin synthesis and gives new insights into protein engineering of regioselectivity in plant GTs.


Assuntos
Glicosiltransferases/metabolismo , Engenharia de Proteínas , Saponinas/biossíntese , Triterpenos/metabolismo , Astragalus propinquus/enzimologia , Biocatálise , Glicosiltransferases/química , Conformação Proteica , Saponinas/química , Estereoisomerismo , Triterpenos/química
17.
J Cell Mol Med ; 2021 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-33955148

RESUMO

In this study, we investigated the ability of curcumin alone or in combination with GLUT1 siRNA to radiosensitize laryngeal carcinoma (LC) through the induction of autophagy. Protein levels in tumour tissues and LC cells were measured by immunohistochemistry and Western blotting. In vitro, cell proliferation, colony formation assays, cell death and autophagy were detected. A nude mouse xenograft model was established through the injection of Tu212 cells. We found that GLUT1 was highly expressed and negatively associated with autophagy-related proteins in LC and that curcumin suppressed radiation-mediated GLUT1 overexpression in Tu212 cells. Treatment with curcumin, GLUT1 siRNA, or the combination of the two promoted autophagy. Inhibition of autophagy using 6-amino-3-methypourine (3-MA) promoted apoptosis after irradiation or treatment of cells with curcumin and GLUT1 siRNA. 3-MA inhibited curcumin and GLUT1 siRNA-mediated non-apoptotic programmed cell death. The combination of curcumin, GLUT1 siRNA and 3-MA provided the strongest sensitization in vivo. We also found that autophagy induction after curcumin or GLUT1 siRNA treatment implicated in the AMP-activated protein kinase-mTOR-serine/threonine-protein kinase-Beclin1 signalling pathway. Irradiation primarily caused apoptosis, and when combined with curcumin and GLUT1 siRNA treatment, the increased radiosensitivity of LC occurred through the concurrent induction of apoptosis and autophagy.

18.
Philos Trans A Math Phys Eng Sci ; 378(2182): 20190583, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-32921240

RESUMO

The eddy current non-destructive evaluation (NDE) modelling using Stratton-Chu formulation-based fast algorithm is analysed. Stratton-Chu formulations, which have no low frequency breakdown issue, are selected for modelling electromagnetic NDE problems with low frequency and high conductivity approximations. As the main contribution of this article, the robustness and efficiency of the approximations, which result in big savings in both memory and CPU time, are validated and analysed using examples from practical EC testing. The boundary element method (BEM) is used to discretize the integral equations into a linear system of equations: the first order Rao-Wilton-Glisson (RWG) vector basis functions with the flat triangle meshes of the object and pulse basis functions are selected to expand the equivalent surface currents and the normal component of magnetic fields, respectively. Then the multilevel adaptive cross approximation (MLACA) algorithm is applied to accelerate the iterative solution process. The performance and efficiency of adaptively applying a multi-stage (level) algorithm based on the criteria concluded for the operators are shown. This article is part of the theme issue 'Advanced electromagnetic non-destructive evaluation and smart monitoring'.

19.
BMC Anesthesiol ; 20(1): 134, 2020 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-32487070

RESUMO

BACKGROUND: Abnormal laryngeal structures are likely to be associated with a difficult laryngoscopy procedure. Currently, laryngeal structures can be measured by ultrasonography, however, little research has been performed on the potential role of ultrasound on the evaluation of a difficult laryngoscopy. The present study investigated the value of laryngeal structure measurements for predicting a difficult laryngoscopy. OBJECTIVE: The main objective of this study was to explore the value of laryngeal structure measurements for predicting a difficult laryngoscopy. METHODS: Two hundred and eleven adult patients (over 18 years old) were recruited to undergo elective surgery under general anesthesia via endotracheal intubation. Ultrasound was utilized to measure the distance between the skin and thyroid cartilage (DST), the distance between the thyroid cartilage and epiglottis (DTE), and the distance between the skin and epiglottis (DSE) in the parasagittal plane. These metrics were then investigated as predictors for classifying a laryngoscopy as difficult vs easy, as defined by the Cormack and Lehane grading scale. RESULTS: Multivariate logistic regression showed that the DSE, but not DST or DTE, was significantly related to difficult laryngoscopies. Specifically, a DSE ≥ 2.36 cm predicted difficult laryngoscopies with a sensitivity and specificity of 0.818 (95% CI: 0.766-0.870) and 0.856 (95% CI: 0.809-0.904). Furthermore, when combining the best model constructed of other indicators (i.e. sex, body mass index, modified Mallampati test) to predict the difficult laryngoscopy, the AUC reached 93.28%. CONCLUSION: DSE is an independent predictor of a difficult laryngoscopy; a DSE cutoff value of 2.36 cm is a better predictor of a difficult laryngoscope than other ultrasound or physiological measurements for predicting a difficult laryngoscope. Nevertheless, it's more valuable to apply the best model of this study, composed of various physiological measurements, for this prediction purpose.


Assuntos
Laringoscopia/métodos , Laringe/diagnóstico por imagem , Ultrassonografia , Adulto , Idoso , Feminino , Humanos , Intubação Intratraqueal/métodos , Laringe/anatomia & histologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade
20.
Proc Natl Acad Sci U S A ; 114(45): 11974-11979, 2017 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-29078333

RESUMO

Pluripotency of embryonic stem cells (ESCs) can be functionally assessed according to the developmental potency. Tetraploid complementation, through which an entire organism is produced from the pluripotent donor cells, is taken as the most stringent test for pluripotency. It remains unclear whether ESCs of other species besides mice can pass this test. Here we show that the rat ESCs derived under 2i (two small molecule inhibitors) conditions at very early passages are able to produce fertile offspring by tetraploid complementation. However, they lose this capacity rapidly during culture due to a nearly complete loss of genomic imprinting. Our findings support that the naïve ground state pluripotency can be captured in rat ESCs but also point to the species-specific differences in its regulation and maintenance, which have implications for the derivation and application of naïve pluripotent stem cells in other species including human.


Assuntos
Embrião de Mamíferos/citologia , Desenvolvimento Embrionário/fisiologia , Células-Tronco Embrionárias/citologia , Células-Tronco Pluripotentes/citologia , Animais , Diferenciação Celular , Células Cultivadas , Feminino , Teste de Complementação Genética , Camundongos , Ratos , Ratos Endogâmicos F344 , Tetraploidia
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