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1.
Plant Physiol ; 2020 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-32732350

RESUMEN

Epidemics of obesity and type 2 diabetes drive strong consumer interest in plant-based low calorie sweeteners. Trilobatin (phloretin-4'-O-glucoside) is a sweetener found at high concentrations in the leaves of a range of crabapple (Malus) species, but not in domesticated apple (M. × domestica) leaves, which contain trilobatin's bitter positional isomer phloridzin (phloretin-2'-O-glucoside). Variation in trilobatin content was mapped to the Trilobatin locus on linkage group 7 in a segregating population developed from a cross between domesticated apples and crabapples. Phloretin glycosyltransferase 2 (PGT2) was identified by activity-directed protein purification and differential gene expression analysis in samples high in trilobatin but low in phloridzin. Markers developed for PGT2 co-segregated strictly with the Trilobatin locus. Biochemical analysis showed PGT2 efficiently catalyzed 4'-O-glycosylation of phloretin to trilobatin as well as 3-hydroxyphloretin to sieboldin (3-hydroxyphloretin-4'-O-glucoside). Transient expression of MdDBR (double bond reductase), MdCHS (chalcone synthase) and PGT2 genes reconstituted the apple pathway for trilobatin production in Nicotiana benthamiana. Transgenic M. × domestica plants over-expressing PGT2 produced high concentrations of trilobatin in young leaves. Transgenic plants were phenotypically normal, and no differences in disease susceptibility were observed compared to wildtype plants grown under simulated field conditions. Sensory analysis indicated that apple leaf teas from PGT2 transgenics were readily discriminated from control leaf teas and were perceived as significantly sweeter. Identification of PGT2 allows marker-aided selection to be developed to breed apples containing trilobatin, and for high amounts of this natural low calorie sweetener to be produced via biopharming and metabolic engineering in yeast.

2.
Cell Death Dis ; 11(7): 605, 2020 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-32732872

RESUMEN

Hepatocellular carcinoma (HCC) is a more common malignancy than the majority of cancers and ranks second in the world's top causes of cancer-related mortality. The objective of the study was to investigate and explain how circularRNA-9119 (circ9119) regulated the properties of HCC cell lines. Cancer cells isolated from HCC patients and HCC cell lines showed clearly upregulated expression of circ9119 and Janus kinase 1 (JAK1) with decreased levels of miR-26a compared to healthy controls and normal hepatic cells. To determine the function of circ9119, circ9119 was silenced in HCC cells, resulting in significantly less proliferation of HCC cells and increasing apoptosis. Circ9119 silencing also resulted in the upregulation of miR-26a. Bioinformatics prediction and dual-luciferase reporter assays showed that circ9119 targeted miR-26a. Further studies revealed that miR-26a had the opposite effect on circ9119; the inhibition of miR-26a antagonized circ9119 silencing, leading to reduced cell proliferation and increased apoptosis, while the ectopic overexpression of miR-26a impaired cell growth. Additionally, we found that the JAK1 3'-UTR was targeted by miR-26a; a decrease in the levels of JAK1 protein and mRNA followed transfection of a miR-26a mimic. Administration of the JAK1 inhibitor, baricitinib, caused the activation of signal transducer and activator of transcription 3 (STAT3) and revealed an effect similar to that of circ9119 silencing on cell proliferation and apoptosis. These results showed that circ9119 could modulate apoptosis, and broadly, cell proliferation by competitively binding miR-26a, which targeted JAK1-STAT3, in HCC cell lines. This study is a novel description of circ9119 regulation of HCC.

3.
Biomed Res Int ; 2020: 8607418, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32733959

RESUMEN

Advanced glycation end products (AGEs) have been widely regarded as an important inducing factor in the pathogenesis of diabetic arteriosclerosis, and the proliferation and migration of vascular smooth muscle cells (VSMCs) are also involved in this process. However, it is not clear whether AGEs promote atherosclerosis by inducing the proliferation and migration of VSMCs. To figure out this question, this study investigated the effects of AGEs on the proliferation and migration of human aorta vascular smooth muscle cells (HASMCs) and the underlying mechanisms. This study evaluated the effects of different concentrations of AGEs on cell proliferation and migration. CCK8, transwell, and western blotting assays demonstrated that AGEs significantly increased cell proliferation and migration in a concentration-dependent manner and that the optimal proproliferative and promigratory concentrations of AGEs were 10 mg/L and 20 mg/L, respectively. AGE-induced cell proliferation, migration, and expression of filament actin (F-actin) were markedly attenuated by a PI3K inhibitor (LY2940002). Additionally, the phosphorylation of AKT was reduced when the receptor of advanced glycation end product (RAGE) gene was silenced by lentivirus transfection, which led to a concomitant reduction of the expression of proliferation and migration-related proteins. These data indicate that AGEs may activate the PI3K/AKT pathway through RAGE and thus facilitate the proliferation and migration of HASMCs.

4.
Stem Cell Reports ; 2020 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-32735821

RESUMEN

Recent studies have demonstrated that fibroblasts can be directly converted into functional Leydig cells by transcription factors. However, the transgenic approach used in these studies raises safety concerns for its future application. Here, we report that fibroblasts can be directly reprogrammed into Leydig-like cells by exposure to a combination of forskolin, 20α-hydroxycholesterol, luteinizing hormone, and SB431542. These chemical compound-induced Leydig-like cells (CiLCs) express steroidogenic genes and have a global gene expression profile similar to that of progenitor Leydig cells, although not identical. In addition, these cells can survive in testis and produce testosterone in a circadian rhythm. This induction strategy is applicable to reprogramming human periodontal ligament fibroblasts toward Leydig-like cells. These findings demonstrated fibroblasts can be directly converted into Leydig-like cells by pure chemical compounds. This strategy overcomes the limitations of conventional transgenic-based reprogramming and provides a simple, effective approach for Leydig cell-based therapy while simultaneously preserving the hypothalamic-pituitary-gonadal axis.

5.
J Mol Endocrinol ; 2020 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-32755999

RESUMEN

White adipose tissue (WAT) browning may have beneficial effects for treating metabolic syndrome. MicroRNAs are important regulators of the differentiation, development, and function of brown and beige adipocytes. Here, we found that the cold-inducible microRNA (miR) 17-92 cluster is enriched in brown adipose tissue (BAT) compared with WAT. Overexpression of the miR17-92 cluster in C3H10T1/2 cells, a mouse mesenchymal stem cell line, enhanced the thermogenic capacity of adipocytes. Furthermore, we observed a significant reduction in adiposity in adipose tissue-specific miR17-92 cluster transgenic (TG) mice. This finding is partly explained by dramatic increases in white fat browning and energy expenditure. Interestingly, the miR17-92 cluster stimulated WAT browning without altering BAT activity in mice. In addition, when we removed the intrascapular BAT (iBAT), the TG mice could maintain their body temperature well under cold exposure. At the molecular level, we found that the miR17-92 cluster targets Rb1, a beige cell repressor in WAT. The present study reveals a critical role for the miR17-92 cluster in regulating WAT browning. These results may be helpful for better understanding the function of beige fat, which could compensate for the lack of BAT in humans, and may open new avenues for combats metabolic syndrome.

6.
Medicine (Baltimore) ; 99(31): e21538, 2020 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-32756205

RESUMEN

BACKGROUND: With the increase in the incidence of premature ovarian insufficiency (POI) over the years, the ovarian function has become one of the integral aspects of research in reproductive medicine today. POI seriously affects the physical and mental health of women, especially reproductive health. Studies show both complementary and alternative therapies to be effective in treating POIs. However, consistency in conclusions is still far-fetched. In light of this, we will carry out a study to evaluate the effectiveness and safety of complementary and alternative therapies for POIs. We therefore develop a study protocol for a proposed network meta-analysis (NMA) and systematic review on POI. METHODS: The following electronic bibliographic database will be searched: VIP database, Wanfang database, Chinese National Knowledge Infrastructure (CNKI), The Cochrane Library, PubMed, EMBASE and Web of Science from inception till 31 December 2019. A search at the World Health Organization (WHO) International Clinical Trials Registry Platform will also be done. Subsequently, the searched data will undergo independent screening, retrieving, and risk of bias assessment by 2 reviewers. Analysis will be performed on included studies using the NMA technique. Next, the primary outcomes will be compared using ADDIS 1.16.5 and Stata 15.0. RESULTS: The safety and effectiveness of alternative and complementary therapies used in the treatment of POI will be compared and evaluated. CONCLUSION: This work will provide high-quality evidence for clinicians in the field to build on for best practices in effective interventions (complementary and alternative therapies) for POI. ETHICS AND DISSEMINATION: This NMA is a secondary research which based on some previously published data. Therefore, the ethical approval was not necessary. PROSPERO REGISTRATION NUMBER: CRD42020163873.

7.
Med Phys ; 2020 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-32757298

RESUMEN

PURPOSE: Real-time tumor tracking through active correction by the multileaf collimator or treatment couch offers a promising strategy to mitigate delivery uncertainty due to intrafractional tumor motion. This study evaluated the performance of MLC and couch tracking using the prototype iTools Tracking system in TrueBeam Developer Mode and the application for abdominal cancer treatments. METHODS: Experiments were carried out using a phantom with embedded Calypso transponders and a motion simulation platform. Geometric evaluations were performed using a circular conformal field with sinusoidal traces and pancreatic tumor motion traces. Geometric tracking accuracy was retrospectively calculated by comparing the compensational MLC or couch motion extracted from machine log files to the target motion reconstructed from real-time MV and kV images. Dosimetric tracking accuracy was measured with radiochromic films using clinical abdominal VMAT plans and pancreatic tumor traces. RESULTS: Geometrically, the root-mean-square errors for MLC tracking were 0.5 mm and 1.8 mm parallel and perpendicular to leaf travel direction, respectively. Couch tracking on the other hand showed an average of 0.8 mm or less geometric error in all directions. Dosimetrically, both MLC and couch tracking reduced motion-induced local dose errors compared to no tracking. Evaluated with five pancreatic tumor motion traces, the average 2%/2mm global gamma pass rate of eight clinical abdominal VMAT plans was 67.4% (range: 26.4% - 92.7%) without tracking, which was improved to 86.0% (range: 67.9% - 95.6%) with MLC tracking, and 98.1% (range: 94.9% - 100.0%) with couch tracking. In sixteen out of forty deliveries with different plans and motion traces, MLC tracking did not achieve clinically acceptable dosimetric accuracy with 3%/3mm gamma pass rate below 95%. CONCLUSIONS: This study demonstrated the capability of MLC and couch tracking to reduce motion-induced dose errors in abdominal cases using a prototype tracking system. Clinically significant dose errors were observed with MLC tracking for certain plans which could be attributed to the inferior MLC tracking accuracy in the direction perpendicular to leaf travel, as well as the interplay between motion tracking and plan delivery for highly modulated plans. Couch tracking outperformed MLC tracking with consistently high dosimetric accuracy in all plans evaluated, indicating its clinical potential in the treatment of abdominal cancers.

8.
Infect Immun ; 2020 Aug 03.
Artículo en Inglés | MEDLINE | ID: mdl-32747599

RESUMEN

Mycoplasma hyopneumoniae is an important respiratory pathogen of pigs that causes persistent and secondary infections. However, the mechanisms by which this occurs are unclear. In this study, we established air-liquid interface culture systems for pig bronchial epithelial cells (Ali-PBECs) that were comparable to the conditions in the native bronchus in vivo We used this Ali-PBECs model to study the infection and migration characteristics of M. hyopneumoniae in vitro Based on the results, we confirmed that M. hyopneumoniae was able to adhere to Ali-PBECs and disrupt mucociliary function. Importantly, M. hyopneumoniae could migrate to the basolateral chamber through the paracellular route but not the transcellular pathway, and this was achieved by reversibly disrupting tight junctions (TJs) and increasing the permeability and damaging the integrity of the epithelial barrier. We examined the migration ability of M. hyopneumoniae using an Ali-PBECs model for the first time. The disruption of the epithelial barrier allowed M. hyopneumoniae to migrate to the basolateral chamber through the paracellular route, which may be related to the immune evasion, extrapulmonary dissemination and persistent infection of M. hyopneumoniae.

9.
Curr Microbiol ; 2020 Aug 03.
Artículo en Inglés | MEDLINE | ID: mdl-32748162

RESUMEN

A novel bacterial strain, designated HX-9-20T, was isolated from the sediment collected from the wastewater outlet of an agricultural chemical plant in Maanshan city, Anhui province, PR China. Cells of strain HX-9-20T were Gram-staining-negative, rod-shaped, translucent, non-motile, and strictly aerobic. Growth was observed between 15 and 35 °C (optimum 30 °C), at pH 6.0-8.0 (optimum pH 7.0), and in the presence of 0-0.4% (w/v) NaCl (optimum 0.2%). The predominant cellular fatty acids were summed feature 3 (C16:1 ω7c and/or C16:1 ω6c), C16:0 and summed feature 8 (C18:1 ω6c and/or C18:1 ω7c). The major quinone was ubiquinone Q-8. The major polar lipids were phosphatidylglycerol, phosphatidylethanolamine, and an aminophospholipid. Strain HX-9-20T contains 2-hydroxyputrescine and putrescine as the major polyamine. A phylogenetic analysis based on 16S rRNA gene sequences revealed that strain HX-9-20T was affiliated with the genus Caenimonas, exhibiting the highest sequence similarities with Caenimonas koreensis EMB320T (97.3% similarity) and Ramlibacter humi 18×22-1T (97.0%), and less than 97.0% similarity with other type strains. The average nucleotide identity (ANI) and digital DNA-DNA hybridization values (dDDH) between HX-9-20T and C. koreensis EMB320T were 76.9% and 23.5% respectively. The ANI and dDDH between HX-9-20T and R. humi 18×22-1T were 80.3% and 23.6%, respectively. The G + C content of the genomic DNA was 67.5 mol%. On the basis of the polyphasic taxonomic data, strain HX-9-20T represents a novel species of the genus Caenimonas, for which the name Caenimonas sedimenti sp. nov. is proposed. The type strain is HX-9-20T (=KCTC 72473T=CCTCC AB 2019266T).

10.
Scand J Gastroenterol ; : 1-8, 2020 Aug 04.
Artículo en Inglés | MEDLINE | ID: mdl-32749177

RESUMEN

BACKGROUND AND AIMS: Diarrhea was not uncommon in patients with coronavirus disease 2019 (COVID-19), but the significance remains undetermined. METHODS: This retrospective study included 157 diarrhea cases form 564 hospitalized COVID-19 patients who were admitted to Wuhan Union Hospital from January 20 to February 29, 2020. Clinical characteristics, the course and the outcome of patients with diarrhea were analyzed. The correlation between diarrhea and fecal presence of coronavirus was also determined. RESULTS: The overall morbidity of diarrhea was 27.8% (157/564) in COVID-19 patients. Among them, 38 cases presented only with diarrhea, and 119 cases in both diarrhea and respiratory symptoms. Patients with diarrhea and respiratory symptoms had higher levels of inflammatory activity, longer hospital stay (27.5 vs. 23.0 vs. 22.0 days, p = .029) and higher odds ratio of mortality (3.2 times and 2.2 times, respectively) than those with diarrhea only or respiratory symptoms only. However, patients with diarrhea had longer time from onset to admission (14.5 days vs. 11.0 days, p = .04), higher positive viral RNA in stool (80.0% vs. 52.4%, p = .016) than those with both diarrhea and respiratory symptoms. CONCLUSIONS: Diarrhea caused by high enteric viral burden may lead to long course and poor outcome in COVID-19 patients. The patients with diarrhea and respiratory symptoms were prone to serious condition, and had worse outcomes. However, the patients with diarrhea alone showed mild illness but delayed health-seeking.

11.
Artículo en Inglés | MEDLINE | ID: mdl-32758492

RESUMEN

Cryo-electron microscopy (cryoEM) has become one of the most important approach for structural biology. However, barriers are still there for an increased successful rate, a better resolution and improved efficiency from sample preparation, data collection to image processing. CryoEM sample preparation is one of the bottlenecks with many efforts made recently, including the optimization of supporting substrate (e.g. ultra-thin carbon, graphene, pure gold, 2d crystal of streptavidin, and affinity modification), which was aimed to solve air-water interface problem, or reduce beam induced motion (BIM), or change particle distribution in the grid hole. Here, we report another effort of developing a new supporting substrate, the amorphous nickel-titanium alloy (ANTA) film, for cryoEM sample preparation as a layer of holey supporting film covering on TEM grid. Our investigations showed advantages of ANTA film in comparison with conventional carbon film, including much better electron conductivity and trace non-specific interaction with protein. These advantages yield less BIM and significantly improved particle distribution during cryoEM experiment of human apo-ferritn, thus resulting an improved reconstruction resolution from a reduced number of micrographs and particles. Unlike the pure gold film, the usage of the ANTA film is just same with the carbon film, compatible to conventional automatic cryoEM data collection procedure.

13.
Int J Biol Sci ; 16(13): 2283-2295, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32760197

RESUMEN

Liver diseases are one of the leading causes of mortality in the world, mainly caused by different etiological agents, alcohol consumption, viruses, drug intoxication, and malnutrition. The maturation of gene therapy has heralded new avenues for developing effective interventions for these diseases. Derived from a remarkable microbial defense system, clustered regularly interspaced short palindromic repeats/CRISPR-associated proteins 9 system (CRISPR/Cas9 system) is driving innovative applications from basic biology to biotechnology and medicine. Recently, the mutagenic function of CRISPR/Cas9 system has been widely adopted for genome and disease research. In this review, we describe the development and applications of CRISPR/Cas9 system on liver diseases for research or translational applications, while highlighting challenges as well as future avenues for innovation.

14.
Clin Cardiol ; 2020 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-32761844

RESUMEN

BACKGROUND: Elevated tumor necrosis factor-α (TNF-α) is correlated with refractory Takayasu arteritis (TA), and resistance exercise have been shown to inhibit TNF-α. HYPOTHESIS: We aimed to explore the effect of resistance exercise in the clinical management of TA. METHODS: This clinical trial enrolled a total of 342 acute TA patients, who were subsequently randomized to undergo either resistance exercise or relaxation control twice per week for 12 weeks. The disease activity was defined using the primary outcome of Birmingham Vascular Activity Score (BVAS). Secondary outcomes included levels of plasma TNF-α and C-reactive protein (CRP), and the erythrocyte sedimentation rate (ESR). RESULTS: BVAS scores along with other laboratory parameters obtained from the patients in the resistance exercise group showed a gradual decline throughout the course of the trial. By contrast, outcomes appeared largely unaltered in the relaxation control group patients. Analyses also revealed that plasma TNF-α displayed strong linear correlations with ESR, BVAS scores, and plasma CRP levels. CONCLUSION: Resistance exercise could substantially improve treatment outcomes as well as laboratory parameters in patients with acute TA, probably through decreasing TNF-α.

15.
Zhongguo Yi Liao Qi Xie Za Zhi ; 44(4): 363-366, 2020 Apr 08.
Artículo en Chino | MEDLINE | ID: mdl-32762215

RESUMEN

Compared with normal medical consumables, the management of epidemic prevention consumables in response to COVID-19 is special. Based on the practical management experience of a hospital in Shanghai, this article expounds through various aspects such as classified protection requirements, interpretation of domestic and foreign standards for epidemic prevention consumables, targeted use countermeasures, material supply of Hubei medical teams, and the management of inbound and outbound of epidemic prevention consumables, covering the whole process of epidemic prevention consumables management. The purpose of this paper is to provide ideas and references for the management of epidemic prevention materials.

16.
Artículo en Inglés | MEDLINE | ID: mdl-32743789

RESUMEN

INTRODUCTION: Over the last few years, it has been demonstrated that a moist environment enhances the healing process and reduces scar formation of wounds. Such moist conditions can be created and maintained using hydrogels. The aim of this study was to evaluate wound healing, cooling efficacy, local tolerability, and cosmetic appearance of abrasive wounds treated with BepanGel wound care hydrogel. METHODS: This study was designed as a within-person, single-center, randomized, investigator-blind clinical investigation comparing a hydrogel-treated test field with an untreated test field in an abrasive wound model. In 33 subjects, two small superficial wounds were induced on the non-dominant forearms. Wounds were treated with BepanGel and covered with a standard semi-occlusive wound plaster or covered with a plaster alone for 11 consecutive days. Wound healing efficacy, cooling effect, and tolerability of the treatment were assessed over 12 investigational days. During follow-up at day 31, the cosmetic appearance of the wounds was evaluated. RESULTS: On day 12, the test field treated with BepanGel was completely healed in nearly all subjects (97.0%) in contrast with the test field treated with a plaster alone (18.2%, AUCdays 2-12p < 0.0001) as assessed by a blinded investigator. Two-thirds of the unblinded subjects indicated an immediate cooling effect of the hydrogel (p = 0.0555). At the end of the investigation, the cosmetic appearance of the BepanGel-treated test fields scored superior to the fields treated with a plaster alone as evaluated by a blinded investigator (p = 0.0005) and the unblinded subjects (p = 0.0078). The hydrogel was generally well tolerated and no signs of infection or adverse events (AEs) related to the treatment were observed. CONCLUSION: This evaluation shows that treatment of superficial cutaneous wounds with BepanGel results in improved wound healing as demonstrated by faster wound closure and a considerably better cosmetic appearance, while providing immediate cooling. TRIAL REGISTRATION NUMBER: EUDAMED-No.: CIV-19-09-029744.

17.
Chem Commun (Camb) ; 2020 Aug 03.
Artículo en Inglés | MEDLINE | ID: mdl-32744276

RESUMEN

The droplet-based microfluidic techniques have been applied widely in functional material synthesis and biomedical information measurements, wherein step emulsification as an integrated system combines the advantages of homogeneity and throughput in monodisperse droplet formation. This paper reviews the mechanisms and classical structures of step emulsification. In terms of droplet formation mechanisms, we describe the droplet size and detachment regimes related to the microchannel geometry. Distinguished by droplet formation, microfluidic step emulsification driven by interfacial tension and centrifugal step emulsification related to buoyancy are introduced respectively, including their improved structures for enhancing the droplet homogeneity and throughput. Finally, the perspectives about the developments of step emulsification in mechanisms, fabrications, and applications are discussed.

18.
J Mater Chem B ; 2020 Aug 03.
Artículo en Inglés | MEDLINE | ID: mdl-32744285

RESUMEN

Traditional techniques for the synthesis of nickel sulfide (NiS) nanoparticles (NPs) always present drawbacks of morphological irregularity, non-porous structure and poor long-term stability, which are extremely unfavorable for establishing effective therapeutic agents. Here, a category of hollow mesoporous NiS (hm-NiS) NPs with uniform spherical structure and good aqueous dispersity were innovatively developed based on a modified solvothermal reaction technique. Upon the successful synthesis of hm-NiS NPs, dopamine was seeded and in situ polymerized into polydopamine (PDA) on the NP surface, followed by functionalization with thiol-polyethylene glycol (SH-PEG) and encapsulation of the chemotherapeutic drug, doxorubicin (DOX), to form hm-NiS@PDA/PEG/DOX (NiPPD) NPs. The resultant NiPPD NPs exhibited a decent photothermal response and stability, attributed to the optical absorption of the hm-NiS nanocore and PDA layer in the near-infrared (NIR) region. Furthermore, stimulus-responsive drug release was achieved under both acidic pH conditions and NIR laser irradiation, owing to the protonation of -NH2 groups in the DOX molecules and local thermal shock, respectively. Lastly, a strong combinatorial photothermal-chemotherapeutic effect was demonstrated for tumor suppression with minimal systemic toxicity in vivo. Collectively, this state-of-the-art paradigm may provide useful insights to deepen the application of hm-NiS NPs for disease management and precision medicine.

19.
Acta Pharmacol Sin ; 2020 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-32737471

RESUMEN

Human infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19) and there is no cure currently. The 3CL protease (3CLpro) is a highly conserved protease which is indispensable for CoVs replication, and is a promising target for development of broad-spectrum antiviral drugs. In this study we investigated the anti-SARS-CoV-2 potential of Shuanghuanglian preparation, a Chinese traditional patent medicine with a long history for treating respiratory tract infection in China. We showed that either the oral liquid of Shuanghuanglian, the lyophilized powder of Shuanghuanglian for injection or their bioactive components dose-dependently inhibited SARS-CoV-2 3CLpro as well as the replication of SARS-CoV-2 in Vero E6 cells. Baicalin and baicalein, two ingredients of Shuanghuanglian, were characterized as the first noncovalent, nonpeptidomimetic inhibitors of SARS-CoV-2 3CLpro and exhibited potent antiviral activities in a cell-based system. Remarkably, the binding mode of baicalein with SARS-CoV-2 3CLpro determined by X-ray protein crystallography was distinctly different from those of known 3CLpro inhibitors. Baicalein was productively ensconced in the core of the substrate-binding pocket by interacting with two catalytic residues, the crucial S1/S2 subsites and the oxyanion loop, acting as a "shield" in front of the catalytic dyad to effectively prevent substrate access to the catalytic dyad within the active site. Overall, this study provides an example for exploring the in vitro potency of Chinese traditional patent medicines and effectively identifying bioactive ingredients toward a specific target, and gains evidence supporting the in vivo studies of Shuanghuanglian oral liquid as well as two natural products for COVID-19 treatment.

20.
Artículo en Inglés | MEDLINE | ID: mdl-32746246

RESUMEN

Existing hashing methods have yielded significant performance in image and multimedia retrieval, which can be categorized into two groups: shallow hashing and deep hashing. However, there still exist some intrinsic limitations among them. The former generally adopts a one-step strategy to learn the hashing codes for discovering the discriminative binary feature, but the latent discriminative information in the learned hashing codes is not well exploited. The latter, as deep neural network based hashing models, can learn highly discriminative and compact features, but relies on large-scale data and computation resources for numerous network parameters tuning with back-propagation optimization. Straightforward training of deep hashing models from scratch on small-scale data is almost impossible. Therefore, in order to develop efficient but effective learning to hash algorithm that depends only on small-scale data, we propose a novel non-neural network based deep-like learning framework, i.e. multi-level cascaded hashing (MCH) approach with hierarchical learning strategy, for image retrieval. The contributions are threefold. First, a hashing-in-hash architecture is designed in MCH, which inherits the excellent traits of traditional neural networks based deep learning, such that discriminative binary features that are beneficial to image retrieval can be effectively captured. Second, in each level the binary features of all preceding levels and the visual appearance feature are simultaneously cascaded as inputs of all subsequent levels to retrain, which fully exploits the implicated discriminative information. Third, a basic learning to hash (BLH) model with label constraint is proposed for hierarchical learning. Without loss of generality, the existing hashing models can be easily integrated into our MCH framework. We show experimentally on small- and large-scale visual retrieval tasks that our method outperforms several state-of-the-arts.

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