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1.
Methods Mol Biol ; 2183: 405-422, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32959256

RESUMO

A DNA vaccine is a plasmid encoding a vaccine antigen together with an efficient eukaryotic promoter to drive protein expression. The chief problem of DNA vaccines has been their suboptimal immunogenicity in humans. Many different flaviviruses infect and cause serious illness and even death in humans, but human vaccines are not available against most of the relevant flaviviruses with the exception of Japanese encephalitis virus. DNA vaccines are easy and fast to produce at relatively low cost, do not require handling of dangerous pathogens, are stable at room temperature allowing for low-cost storage and transportation, and are highly versatile, allowing for rapid changes in coding sequence design and synthesis. This makes a DNA vaccine approach ideally suited for development as a broad-based flavivirus vaccine platform. However, to be useful as a flavivirus prophylactic vaccine platform in humans, a method would need to be found to enhance DNA vaccine immunogenicity without the need for the cumbersome and expensive equipment involved with electroporation. We describe here a protocol used to test different adjuvants with flavivirus DNA vaccines to determine an optimal formulation. An optimal regimen involving a DNA adjuvanted vaccine prime followed by an adjuvanted protein vaccine boost is described and can be applied by readers to solve barriers to the development of other DNA vaccines where immunogenicity is a problem.

2.
Talanta ; 221: 121421, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33076058

RESUMO

Two-dimensional Cd-MOF/Tb3+ (Cd-MOF = [Cd (µ-2,3-pdc) (H2O)3]n (2,3-pdc = 2,3-pyridine dicarboxylic acid)) fluorescent nanosheets with the thickness of 1.4 nm were successfully synthesized by a simple solution route with subsequent ultrasonic exfoliation at room temperature. It was found that as-obtained Cd-MOF/Tb3+ ultrathin nanosheets could be homogeneously dispersed in aqueous system to form a sol with excellent stability. Also, the fluorescence intensity of nanosheets remarkably increased to almost 12 times higher than that of Cd-MOF/Tb3+ microsheets before exfoliation. Further investigations uncovered that the above strong fluorescence of Cd-MOF/Tb3+ nanosheets could be highly sensitively quenched by Cefixime antibiotic in aqueous solution without interference from other antibiotics, amino acids and pesticides. Hence, the as-obtained ultrathin Cd-MOF/Tb3+ nanosheets could be prepared as a highly selective and sensitive fluorescence probe for the detection of Cefixime in aqueous system. Compared with the bulk Cd-MOF/Tb3+ sensor, the Cd-MOF/Tb3+ ultrathin nanosheets sensor exhibited a far lower detection limit down to 26.7 nM for CFX. Also, the as-obtained nanosheets sensor presented satisfactory recovery ranging from 98.07% to 103.01% and acceptable repeatability (RSD < 6.29%, n = 6) for the detection of CFX in domestic water. Furthermore, the sensing mechanism studies revealed that the high selection of the present fluorescent probe for detection of CFX should be attributed to the cooperation of the photoinduced electron transfer and the inner filter effect.

4.
Nanotechnology ; 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33045697

RESUMO

Three isostructural pillared-layer frameworks with M-BDC-X layers supported by ditopic HL connectors, [M(HL)(BDC)0.5X]n (HL = 4'-(4-hydroxyphenyl)-4,2':6',4''-terpyridine, BDC = terephthalate, M = Cd, X = Cl for 1, M = Cd, X = formate for 2, and M = Co, X = formate for 3), were solvothermally synthesized, and used as photocatalysts for Pt-assisted visible-light-initiated hydrogen evolution from water splitting. These water-durable frameworks exhibit varied hydrogen production rates of 361.2, 271.3, and 327.5 µmol·g-1·h-1 in 12 hour due to their slightly different donor environments of the octahedral CdII and CoII ions. Further experimental and theoretical investigations reveal that the metal ions and the local coordination surroundings have essentially dominated the conduction band minimum and electric resistance of the charge transport, which play highly important roles for the improved catalytic hydrogen evolution ability. These findings demonstrate the electronic effect of the slightly ligand field modifications on the boosting hydrogen generation activity in the noble metal-assisted MOF photocatalytic systems.

5.
J Immunol Methods ; : 112871, 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-33007319

RESUMO

As a category A toxic, the botulinum toxin(BoNT) is responsible for human botulism with an estimated lethal dose of 1 ng/kg which greatly increases the potential risk of use as bioweapons. Therefore, the development of anti-BoNT antibodies is urgent. In this paper, the HC domain of BoNT/A was purified and immunized with Balb/c mice. Monoclonal antibodies were screened against BoNT/A from 55 stable positive hybridoma cell lines, and one with the strongest neutralizing activity, designated as ML06, was subcloned, sequenced, and classified as IgG1(κ) subclass. The mouse protection assays showed that ML06 can neutralize the toxin of BoNT/A effectively both in vitro and in vivo, in a dose-dependent manner. The therapeutic assays showed that only 20% of mice injected with 4 LD50 BoNT/A can survive another injection of ML06 after 4 h. The prophylaxis assays showed the residual ML06 from mice injected with ML06 two weeks ago can protect mice against 4 LD50 BoNT/A challenge completely. Collectively, our results indicated that ML06 served as a good candidate for further development of immune therapeutics for BoNT/A.

6.
Cell Death Differ ; 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33037394

RESUMO

Dysregulation of the balance between cell proliferation and cell death is a central feature of malignances. Death-associated protein kinase 3 (DAPK3) regulates programmed cell death including apoptosis and autophagy. Our previous study showed that DAPK3 downregulation was detected in more than half of gastric cancers (GCs), which was related to tumor invasion, metastasis, and poor prognosis. However, the precise molecular mechanism underlying DAPK3-mediated tumor suppression remains unclear. Here, we showed that the tumor suppressive function of DAPK3 was dependent on autophagy process. Mass spectrometry, in vitro kinase assay, and immunoprecipitation revealed that DAPK3 increased ULK1 activity by direct ULK1 phosphorylation at Ser556. ULK1 phosphorylation by DAPK3 facilitates the ULK1 complex formation, the VPS34 complex activation, and autophagy induction upon starvation. The kinase activity of DAPK3 and ULK1 Ser556 phosphorylation were required for DAPK3-modulated tumor suppression. The coordinate expression of DAPK3 with ULK1 Ser556 phosphorylation was confirmed in clinical GC samples, and this co-expression was correlated with favorable survival outcomes in patients. Collectively, these findings indicate that the tumor-suppressor roles of DAPK3 in GC are associated with autophagy and that DAPK3 is a novel autophagy regulator, which can directly phosphorylate ULK1 and activate ULK1. Thus, DAPK3 might be a promising prognostic autophagy-associated marker.

7.
Oncogene ; 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33051597

RESUMO

Oxidative stress-responsive kinase 1 (OSR1) plays a critical role in multiple carcinogenic signal pathways, and its overexpression has been found in various types of cancer; however, the pathophysiological role of OSR1 in breast cancer has not been evaluated. This study aims to elaborate on the role of OSR1 in breast cancer metastasis and the specific regulatory mechanism. Our results showed that OSR1 mRNA and protein were upregulated in both human breast cancer samples and cell lines. Moreover, phosphorylated OSR1 (p-OSR1) was an independent poor prognostic indicator in patients with breast cancer. OSR1 upregulation induced epithelial-to-mesenchymal transition (EMT) in normal and malignant mammary epithelial cells with the increasing metastatic capacity. In contrast, deleting OSR1 in aggressive breast cancer cells inhibited these phenotypes. OSR1 is the critical activator for transcription factors of EMT. Mechanistically, we found that OSR1 can directly interact and phosphorylate the linker region of Smad2 at Thr220 and Smad3 at Thr179. Phosphorylated Smad2/3 translocated into the nucleus to enhance transforming growth factor-ß1 (TGF-ß1) autocrine signalling and increase the transcription of EMT regulators. Importantly, interruption of the OSR1-Smad2/3-TGF-ß1 signalling axis elicited a robust anti-EMT and anti-metastatic effect in vitro and in vivo. Taken together, we conclude that OSR1-mediated Smad2/3-TGF-ß1 signalling promotes EMT and metastasis representing a promising therapeutic target in breast cancer treatment.

8.
Small ; : e2004619, 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33053256

RESUMO

Memristor, processing data storage and logic operation all-in-one, is an advanced configuration for next generation computer. In this work, a bismuth doped tin oxide (Bi:SnO2 ) memristor with ITO/Bi:SnO2 /TiN structure has been fabricated. Observing from transmission electron microscope (TEM) for the Bi:SnO2 device, it is found that the bismuth atoms surround the surface of SnO2 crystals to form the coaxial Bi conductive filament. The self-compliance current, switching voltage and operating current of Bi:SnO2 memristor are remarkably smaller than that of ITO/SnO2 /TiN device. With the content of 4.8% Bi doping, the SET operating power of doped device is 16 µW for ITO/Bi:SnO2 /TiN memory cell of 0.4 × 0.4 µm2 , which is cut down by two orders of magnitude. Hence, the findings in this study suggest that Bi:SnO2 memristors hold significant potential for application in low power memory and broadening the understanding of existing resistive switching (RS) mechanism.

9.
Phys Med Biol ; 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33053522

RESUMO

Compared with the conventional 1×1 acquisition mode of projection in computed tomography (CT) image reconstruction, the 2×2 acquisition mode improves the collection efficiency of the projection and reduces the X-ray exposure time. However, the collected projection based on the 2×2 acquisition mode has low resolution (LR) and the reconstructed image quality is poor, thus limiting the use of this mode in CT imaging systems. In this study, a novel sinogram-super-resolution generative adversarial network (SSR-GAN) model is proposed to obtain high-resolution (HR) sinograms from LR sinograms, thereby improving the reconstruction image quality under the 2×2 acquisition mode. The proposed generator is based on the residual network for LR sinogram feature extraction and super-resolution (SR) sinogram generation. A relativistic discriminator is designed to render the network capable of obtaining more realistic SR sinograms. Moreover, we combine the cycle consistency loss, sinogram domain loss, and reconstruction image domain loss in the total loss function to supervise SR sinogram generation. Then, a trained model can be obtained by inputting the paired LR/HR sinograms into the network. Finally, the classic FBP reconstruction algorithm is used for CT image reconstruction based on the generated SR sinogram. The qualitative and quantitative results of evaluations on digital and real data illustrate that the proposed model not only obtains clean SR sinograms from noisy LR sinograms but also outperforms its counterparts.

10.
Curr Med Res Opin ; : 1, 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33016133

RESUMO

Objective: The safety profile of traditional Chinese medicine injections has emerged as the greatest challenge to their clinical application. We aimed to perform a post-marketing surveillance study in a real-world setting to evaluate the safety of the Xuesaitong (XST) injection in China.Methods: This multicentre, post-marketing, observational study enrolled patients who received XST injections in 42 centres in China between March 2015 and November 2017. Adverse drug reactions (ADRs) and adverse drug events (ADEs) were collected and evaluated in a post-marketing database. Logistic regression analysis was performed to analyse the risk factors for ADRs.Results: A total of 30,008 consecutive patients with a mean age of 62.29 ± 14.58 years were included in this post-marketing study. The incidences of ADEs and ADRs were 0.5% and 0.33%, respectively. The most common clinical manifestations were damage to skin and appendages (47.66%). There were 4 new kinds of ADEs found in the present monitoring study. The majority of ADRs were type B (62.62%) and occurred within 24 hours after XST injection treatment. No severe ADRs were reported in this analysis. Multivariate logistic regression analysis showed that the hospital level (OR =0.607; 95% CI, 0.407-0.906; p = 0.0144), hypertension (OR =1.979; 95% CI, 1.323-2.959; p = 0.0009) and solvent type (OR =2.951; 95% CI, 1.608-5.417; p = 0.0005) were risk factors for ADR occurrence.Conclusion: XST injection is well tolerated and has a favourable safety profile for patients in a real-world setting. This post-marketing study provided further evidence of the safety of XST injections for clinical applications.

11.
Mol Med Rep ; 22(5): 4432-4441, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33000181

RESUMO

Cholangiocarcinoma (CCA) is the most common type of malignant tumor of the bile duct and is characterized by high morbidity and mortality; it is difficult to diagnose in the early stages and responds poorly to current conventional radiotherapy and chemotherapy. The present study investigated the role of GSK­3ß signaling on the anticancer effects of doxorubicin in human CCA cells. Blocking GSK­3ß enhanced the sensitivity of human CCA cells to doxorubicin (Dox)­induced apoptosis, which was accompanied by decreased AKT and focal adhesion kinase (FAK) activity. Moreover, inhibiting GSK­3ß using 6­bromoindirubin­3'­oxime, CHIR99021 or small interfering RNA decreased phosphorylation of FAK and AKT, and promoted apoptosis of Dox­induced human CCA cells. Moreover, FAK inhibition suppressed AKT activity independently of phosphoinositide 3­kinase activity. These results indicated that GSK­3ß protects human CCA cells against Dox­induced apoptosis via sustaining FAK/AKT activity.

12.
J Mater Chem B ; 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33001126

RESUMO

Aminated poly(glycidyl methacrylate)s-based polymers for gene delivery not only can reduce toxicity and improve solubility, but can improve gene transfection efficiency and reduce protein aggregation. In this study, we first prepared poly(glycidyl methacrylate) (PGMA) via reversible addition-fragmentation chain transfer (RAFT) polymerization, and then the obtained PGMA homopolymer was post-modified with ethanol amine (EA), 1-amino-2-propanol (AP), 3-(dibutylamino)propylamine (DA) and N-(2-hydroxyethyl)ethylenediamine (HA), respectively, to yield four kinds of PGMA-based gene vectors containing hydroxyl groups (abbreviated as PGEA, PGAP, PGDA and PGHA). The effects of the different side chains and hydroxyl groups on the biological properties of these four cationic polymers were investigated. We found that the transfection efficiency of the PGHA/p53 complex was higher than those of the other three polymer/gene complexes through MTT assay and laser scanning confocal microscopy. Hence, we chose HA for further post-modification to fabricate a cationic copolymer, PCL-ss-P(PEGMA-co-GHA) (abbreviated as PGHAP), via a combination of ring opening polymerization (ROP) and RAFT copolymerization. The PCL-ss-P(PEGMA-co-GHA) amphiphilic copolymer could self-assemble into nanoparticles, which could be used to encapsulate anticancer drug doxorubicin (DOX) and compress the p53 gene to form the DOX-loaded PCL-ss-P(PEGMA-co-GHA)/p53 complex (abbreviated as DPGHAP/p53). The gel retardation assay showed that p53 gene could be well immobilized and remained stable under the electronegative conditions. MTT assay showed that the DPGHAP/p53 complex had a significant antitumor effect on A549 cells and H1299 cells compared with free DOX or/and p53 gene therapy alone. Furthermore, the test results from live cell imaging systems revealed that the DPGHAP/p53 complexes could effectively deliver DOX and the p53 gene into A549 cells. Therefore, the constructed cationic polymer PCL-ss-P(PEGMA-co-GHA) has potential application prospects as a co-vector of anticancer drugs and genes.

13.
Respiration ; : 1-8, 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33032277

RESUMO

BACKGROUND: Most data about the trachea are collected during deep inspiration breath holding (DIBH) using multi-detector computed tomography (MDCT). Images of the physiological changes in the central airway are lacking. OBJECTIVE: The aim of this study was to explore the physiological changes in the central airway on MDCT during DIBH and deep expiration breath holding (DEBH). METHOD: The data from 62 patients (38 men and 24 women) who underwent enhanced computed tomography in our hospital were collected. Patients were grouped according to sex and age (18-45, 46-60, and >61 years). Anteroposterior diameter (APD) and transverse diameter (TD) at 3 levels (cricoid, intrathoracic inlet, and 2 cm above the carina), tracheal length, bronchial length, and subcarina angle (SCA) were measured. RESULTS: The average length of the trachea from the cricoid cartilage to the carina was 103.91 ± 10.37 mm at DEBH and 108.63 ± 11.31 mm at DIBH (p < 0.001). The APD of the trachea at the level of the cricoid, intrathoracic inlet, and 2 cm above the carina showed no differences between DEBH and DIBH. The TD of the trachea at the level of the cricoid, intrathoracic inlet, and 2 cm above the carina showed no differences between DEBH and DIBH. The average length of the right main bronchus during DEBH and DIBH was measured as 13.21 ± 3.60 and 13.24 ± 3.49 mm, respectively (p = 0.956). The average length of the left main bronchus at DEBH and DIBH was measured as 44.19 ± 5.50 and 44.27 ± 5.11 mm, respectively (p = 0.929). The average SCA was 81.74 ± 14.56 at DIBH, while it was 80.53 ± 14.38 at DEBH. The change in SCA between DIBH and DEBH showed no significant difference (p = 0.642). CONCLUSIONS: The APD at the level of the intrathoracic inlet is larger than that at the cricoid and 2 cm above the carina, while the TD is the opposite. These findings about the trachea and bronchus in our study may contribute to bronchoscopy examinations, tube applications, stent design, and stenting.

14.
J Orthop Surg Res ; 15(1): 453, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33008473

RESUMO

PURPOSE: Olecranon fracture is a common upper limb fracture, and several surgical approaches have been advocated for its fixation. To overcome the complications associated with common techniques, we present a novel shape-memory alloy concentrator, an alternative for tension band compression, to fix olecranon fracture. METHODS: Fifty-seven patients (26 men and 31 women) with olecranon fracture, with a mean age of 45 years, were included in this study. Each patient had undergone open reduction and internal fixation using the Nitinol (Ni-Ti) arched shape-memory connector (ASC). The clinical assessments were performed using the Disability of the Arm, Shoulder, and Hand (DASH) questionnaire and the Mayo Elbow Performance (MEP) score, which were both recorded at the final follow-up visit. RESULTS: The patients were followed up for 44 months on average (range, 31 to 56 months). No patients were lost to follow-up, and all of the olecranon fractures healed in an average of 15 weeks (range, 10 to 34 weeks). The mean DASH score was 8.6 (range, 0 to 32.4), and the mean MEP score was 92.5 (range, 74 to 100). Nine patients showed postoperative complications: prominent hardware (2), infection (1), loss of the range of functional motion (5), and heterotopic ossification (1). CONCLUSION: The ASC may serve as a favorable device for multi-fragmented and comminuted fractures with rare hardware irritation and may also provide continuous concentrative compression to accelerate osseous healing, thereby aiding the restoration and permitting an early rehabilitation with a low incidence of postoperative complications.

15.
Nat Genet ; 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33020667

RESUMO

Somatic mutations in driver genes may ultimately lead to the development of cancer. Understanding how somatic mutations accumulate in cancer genomes and the underlying factors that generate somatic mutations is therefore crucial for developing novel therapeutic strategies. To understand the interplay between spatial genome organization and specific mutational processes, we studied 3,000 tumor-normal-pair whole-genome datasets from 42 different human cancer types. Our analyses reveal that the change in somatic mutational load in cancer genomes is co-localized with topologically-associating-domain boundaries. Domain boundaries constitute a better proxy to track mutational load change than replication timing measurements. We show that different mutational processes lead to distinct somatic mutation distributions where certain processes generate mutations in active domains, and others generate mutations in inactive domains. Overall, the interplay between three-dimensional genome organization and active mutational processes has a substantial influence on the large-scale mutation-rate variations observed in human cancers.

16.
Arch Insect Biochem Physiol ; 105(3): e21741, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33002240

RESUMO

Apoptosis is a process of programmed cell death that is regulated by genes independently. The Bm30kc6 gene is a kind of small molecular lipoprotein about 30 kDa, expressed highly in the late stage of the silkworm hemolymph. Our study showed that overexpression of Bm30kc6 could decrease caspase-3 activation. Meanwhile, activation of caspase-3 increased when Bm30kc6 expression was disturbed by small interfering RNA (siRNA). Cell apoptosis was decreased when Bm30kc6 was overexpressed under UV treatment. The apoptosis rate induced by actinomycin D is similar to the trend by UV. It was inferred that Bm30kc6 has an inhibitory effect on the apoptosis of silkworm cells. The apoptosis-related genes, such as BmFadd, BmDredd, and BmDaxx were increased after overexpression of Bm30kc6 or decreased after interference of siRNA. It was speculated that there was an interactive relationship between Bm30kc6, BmDaxx, BmFadd, and BmDredd in the apoptosis signaling pathways. We investigated the transcription expression of the Bm30kc6 gene in different growth stages and tissues of the silkworm. The results showed that Bm30kc6 reached its peak in the hemolymph during the 6th to 7th days of the 5th instar, or in spinning post 24 h of the silk gland. In the silkworm BmN cells treated with caspase-3/7 inhibitor, the caspase-3 enzyme activity, and the expression levels of Bm30kc6, BmFadd, BmDredd, and BmDaxx were significantly reduced. The expression levels of Bm30kc6 increased sharply when silkworms were treated by molting hormone at Day 3 or 5 of the 5th instar. The results indicated that the expression of the Bm30kc6 gene was affected by the molting hormone and was likely to be its downstream target. In conclusion, the results suggest that the Bm30kc6 gene is involved in the regulation of the apoptotic signaling pathway and plays a role in the apoptotic process.

17.
J Clin Lab Anal ; : e23623, 2020 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-33067885

RESUMO

BACKGROUND: Thromboelastography (TEG) provides global assessment of hemostatic function and has been recommended to monitor potential coagulopathies during pregnancy in which hypercoagulable state is favored. In present study, we established the reference intervals (RIs) of the TEG parameters (R, K, MA, and α-angle) with Chinese pregnant women of third trimester. In addition, we examined the diagnostic efficacies of the TEG parameters in the patients diagnosed of gestational hypertension (GH), gestational diabetes mellitus (GDM), or preeclampsia (PE). METHODS: With specified including and excluding criteria, non-pregnant controls, healthy pregnant women, and pregnant women with GH, GDM, or PE had their venous blood drawn at Beijing Obstetrics and Gynecology Hospital, followed by TEG tests performed in the clinical laboratory. RESULTS: The RIs determined with the healthy pregnant women (in third trimester) for R, K, MA, and α-angle were 4.0-7.7, 1.2-3.2, 51.9-70.1, and 41.4-74.4, respectively. When compared with the healthy pregnancy group, the K value was significantly decreased in GH patients but increased in PE patients; MA was significantly lower in the PE group. In the receiver operating characteristic curve (ROC) analyses, K value was able to efficiently distinguish normal pregnancy from the GH patients, with an AUC of 0.86 which is far better than those of R (AUC = 0.57) and MA (AUC = 0.56). For the PE patients, the AUC of MA (0.69) was significantly greater than that of R (0.50). CONCLUSIONS: Thromboelastography may provide more accurate experimental basis for monitoring coagulation functions especially in pregnant women with complications of GH and PE.

18.
Artigo em Inglês | MEDLINE | ID: mdl-33097966

RESUMO

Lycopene is a dark red carotenoid belonging to C40 terpenoids and is widely found in a variety of plants, especially ripe red fruits and vegetables. Lycopene has been shown to reduce the risk of prostate cancer, other cancers, and cardiovascular disease. It is one of the most widely used carotenoids in the healthcare product market. Currently, commercially available lycopene is mainly extracted from tomatoes. However, production of lycopene from plants is costly and environmentally unfriendly. To date, there have been many reports on the biosynthesis of lycopene by microorganisms, providing another route for lycopene production. This review discusses the lycopene biosynthetic pathway and natural and engineered lycopene-accumulating microorganisms, as well as their production of lycopene. The effects of different metabolic engineering strategies on lycopene accumulation are also considered. Furthermore, this work presents perspectives concerning the microbial production of lycopene, especially trends to construct microbial cell factories for lycopene production. KEY POINTS: • Recent achievements in the lycopene biosynthesis in microorganisms. • Review of lycopene biosynthetic metabolism engineering strategy. • Discuss the current challenges and prospects of using microorganisms to produce lycopene.

19.
J Mater Chem B ; 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33043953

RESUMO

Gallium-based liquid metals have increasing applications in a wide variety of emerging areas and they are involved more in frontier studies, the energy industry and additive manufacturing production, and even in daily life. When exposed to open air, large amounts of microorganisms may interact with liquid metals. However, the research of the relationship between pure gallium-based liquid metals and bacterial cells is still limited. In this study, the antibacterial properties of eutectic gallium-indium (EGaIn) alloys were tested against the typical Gram-negative bacteria-Escherichia coli and the Gram-positive bacteria-Staphylococcus aureus and the experimental results displayed that the antibacterial rates reached 100%. We also explored the mechanism of the anti-bacterial properties of EGaIn alloys by measuring the surface composition of the EGaIn film and the concentration of dissolved metal ions. The morphology of the bacterial cells showed that the cell growth and division were influenced by exposure to EGaIn. We also found that the synergistic antibacterial effect came along with the production of reactive oxygen species (ROS). Moreover, the EGaIn film showed enhanced antibacterial activity compared to gallium nitrate at the same initial ion concentration in the solution. This study shows the enormous potential of the anti-bacterial effect of liquid metals.

20.
Proc Natl Acad Sci U S A ; 117(42): 26448-26459, 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-33020269

RESUMO

Wnt signaling plays a critical role in production and differentiation of neurons and undergoes a progressive reduction during cortical development. However, how Wnt signaling is regulated is not well understood. Here we provide evidence for an indispensable role of neddylation, a ubiquitylation-like protein modification, in inhibiting Wnt/ß-catenin signaling. We show that ß-catenin is neddylated; and inhibiting ß-catenin neddylation increases its nuclear accumulation and Wnt/ß-catenin signaling. To test this hypothesis in vivo, we mutated Nae1, an obligative subunit of the E1 for neddylation in cortical progenitors. The mutation leads to eventual reduction in radial glia progenitors (RGPs). Consequently, the production of intermediate progenitors (IPs) and neurons is reduced, and neuron migration is impaired, resulting in disorganization of the cerebral cortex. These phenotypes are similar to those of ß-catenin gain-of-function mice. Finally, suppressing ß-catenin expression is able to rescue deficits of Nae1 mutant mice. Together, these observations identified a mechanism to regulate Wnt/ß-catenin signaling in cortical development.

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