Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 3.569
Filtrar
1.
J Colloid Interface Sci ; 559: 197-205, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31627143

RESUMO

Mesoporous silica nanoparticle (MSN) demonstrates great potentials as a loading platform for bactericidal agents, but may be limited by its application form of bulk or powder. Herein, we developed MSN surface-enriched composite membranes with remarkable photodynamic antimicrobial activities via a facile electrospinning method. The mixture of zein and polycaprolactone (PCL) was served as the polymeric matrix, while the methylene blue (MB) loaded MSN was modified by trichloro (1H, 1H, 2H, 2H-heptadecafluorodecyl) silane (THFS) and acted as reactive oxygen species (ROS) generator to exert their antimicrobial performances. Owing to its low surface energy, the fluorinated MSN tended to be enriched on the surface of the nanofiber, hence significantly enhancing the ROS generation. Moreover, benefiting from the surface enrichment of the fluorinated nanoparticles, the composite membrane displayed obvious surface hydrophobicity and exhibited discernible bacterial repellency. Subsequently, upon visible light (660 nm) irradiation, the composite membrane demonstrated remarkable photodynamic antibacterial activities against Gram-positive Staphylococcus aureus (S. aureus) and Gram-negative Escherichia coli (E. coli) but without essential detrimental impacts on the mammalian cells. We envision that this self-enriched MSN composite membrane may find broad applications in bacterial infection-resistant areas.

2.
Bioresour Technol ; 295: 122274, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31670113

RESUMO

In this study, light exposure was applied to simultaneously enhance lipogenesis and ß-carotene biosynthesis of Rhodotorula glutinis with sodium acetate as the sole carbon source. The results showed that cell growth, intracellular lipogenesis and carotene biosynthesis were improved with an optimal exposure condition at 10 g/L and 20 g/L sodium acetate. Under high light exposure condition (8000 lx), cell growth and lipid production were inhibited while ß-carotene accumulation was promoted. The fatty acid compositions moreover revealed that more polyunsaturated fatty acids and linoleic acid were generated under light exposure, which demonstrated its crucial role in the oxidative stress resistance in R. glutinis. The expression levels of some genes in acetate consumption, lipogenesis and ß-carotene biosynthesis were found significantly upregulated under light exposure. The results proved that light exposure could be applied as an effective method to improve lipid and ß-carotene production with sodium acetate as the substrate in R. glutinis.


Assuntos
Rhodotorula , beta Caroteno , Ácidos Graxos , Lipogênese , Acetato de Sódio
3.
J Nanosci Nanotechnol ; 20(4): 2598-2602, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31492282

RESUMO

AlN nanowires macro-array were successfully fabricated on Si substrate by double template method and chemical vapour deposition. The research shows that AlN nanowires array with different diameter, length and coverage can be prepared by controlling the experimental conditions. The as-prepared AlN nanowires array were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Furthermore, the Ultraviolet absorption of AlN nanowires array as a sensors was investigated and calculated with the first principle.

4.
Insect Sci ; 27(1): 14-21, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31246335

RESUMO

Manipulating an exogenous or endogenous gene of interest at a defined level is critical for a wide variety of experiments. The Gal4/UAS system has been widely used to direct gene expression for studying complex genetic and biological problems in Drosophila melanogaster and other model organisms. Driven by a given tissue-specific Gal4, expressing UAS-transgene or UAS-RNAi (RNA interference) could be used to up- or down-regulate target gene expression, respectively. However, the efficiency of the Gal4/UAS system is roughly predefined by properties of transposon vector constructs and the insertion site in the transgenic stock. Here, we describe a simple way to modulate optomotor blind (omb) expression levels in its endogenous expression region of the wing disc. We co-expressed UAS-omb and UAS-omb-RNAi together under the control of dpp-Gal4 driver which is expressed in the omb expression region of the wing pouch. The repression effect is more sensitive to temperature than that of overexpression. At low temperature, overexpression plays a dominant role but the efficiency is attenuated by UAS-omb-RNAi. In contrast, at high temperature RNAi predominates in gene expression regulation. By this strategy, we could manipulate omb expression levels at a moderate level. It allows us to manipulate omb expression levels in the same tissue between overexpression and repression at different stages by temperature control.

5.
J Hazard Mater ; 383: 121198, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31541955

RESUMO

In this study, we discovered and isolated a new genus Brevibacillus strain from effluent of dyeing and finishing factory containing highly toxic p-chloroanilines (PCA). Based on the morphological, physiological and biochemical characteristics, as well as 16S rDNA sequence, the strain was identified and denominated as Brevibacillus S-618. Co-metabolism effect was found with extra carbon sources including sodium succinate, sodium citrate, ammonium chloride and glucose which can efficiently promote the biodegradation process of PCA. Under the optimal growth conditions at temperature of 30 °C, pH˜7 and air-water ratio of 0.3 m3/m3·min, the degradation rate of PCA in a 2 L pilot bioreactor with high concentration of 180 mg/L increased from 86.7% to 100% within 72 h after adding sodium succinate. The release of chloride ions during the growth process of the strain was equivalent to the degradation amount of PCA. Meanwhile, the cleavage pathway of PCA degradation by Brevibacillus S-618 was proposed by analysis of enzyme activities of microorganism and intermediate products in the reaction. Benefiting from excellent degradation ability and unique characters in high pollutant contents, high efficient bioreactor can easily be scale up for industrial application. Our study provides a facile route for cost-effectively and environmental-friendly degrading hazardous chemicals.

6.
J Nanosci Nanotechnol ; 20(6): 3361-3372, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-31748028

RESUMO

Gambogic acid (GA) is a natural compound with a polyprenylated xanthone structure that has antiinflammatory, antioxidant, and neuroprotective properties and acts as a chemopreventive agent. GA exhibits anti-tumor, antimicrobial, and anti-proliferative effects on cancer cells. In the current study, the effect of GA on phosphoinositide kinase-3 (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway was examined in human U251 glioma cells. Cell viability and apoptosis were evaluated by MTT and Annexin V/PI Double Staining. The expressions of P38, AKT, and mTOR were evaluated by western blot and qRT-PCR, respectively. MagBeads Total RNA Extraction Kit was used to isolate cell tissue RNA. GA decreased the phosphorylation of P38, AKT, and mTOR. Inhibitors of PI3K (LY294002) enhanced the phosphorylation of P38, AKT, and mTOR. GA reduced the phosphorylation of ribosomal protein precursors (Pre) and upstream binding factor (UBF), and insulin-like growth factor I (IGF-1) further enhanced the cell proliferation and expression of Pre and UBF. These results suggested that downregulation of PI3K/AKT/mTOR signaling pathway may be an important mediator in GA-affected ribosomal occurrence in glioma cells.

7.
Food Funct ; 10(11): 7588-7598, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31687714

RESUMO

Increasing evidence points to the effect of the gut microbiota on central nervous system functions. Supplementation of certain microbial strains has been demonstrated to alleviate depressive behaviors and neurological abnormalities. This study took the approach to screen for an anti-depressive Bifidobacterium longum strain from fourteen candidates and systematically verified its effect in a chronic stress-induced depression mice model. B. longum subsp. infantis strain CCFM687 could significantly enhance the biosynthesis of 5-hydroxytryptamine (5-HTP) in vitro in RIN14B cells through up-regulation of the Tph1 gene expression. Administration of CCFM687 in mice significantly improved the scores in behavioral tests and increased the level of 5-HTP and serotonin (5-HT) in the prefrontal cortex (PFC) of the brain. The brain-derived neurotrophic factor (BDNF) in the PFC was also increased, possibly through the 5-HT1A-CREB-BDNF pathway. In addition, CCFM687 alleviated the hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis response and accordingly reversed the peripheral inflammation status. Moreover, the stress-induced structural and functional dysbiosis of the gut microbiome was improved by CCFM687, through increased alpha diversity and abundance of butyrate-producing bacteria, in conjunction with inhibition of pathogenic gene expression. In summary, these results indicate that supplementation of B. longum subsp. infantis strain CCFM687 may prevent the onset of depression from chronic stress, and RIN14B could serve as an efficient cell model for rapid screening of anti-depressive probiotics.

8.
Int Immunopharmacol ; : 105972, 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31711938

RESUMO

Mastitis is a common veterinary clinical disease that restricts the development of dairy farming around the world. Morin, extracted from Mulberry Tree and other herbs, has been reported to possess the function of anti-bacteria, anti-oxidant, and anti-inflammatory. However, whether morin could protect lipopolysaccharide (LPS)-induced mouse mastitis in vivo has not well known. This study firstly aims to evaluate the effects of morin on LPS-induced mouse mastitis in vivo, and then try to illustrate the mechanism involved in the process. Before injected with LPS, mice were intraperitoneally pre-injected with different concentrations of morin, and mice of the control and LPS group were injected with the same amount of saline. Pathologic changes of mammary gland were determined by histopathological examination. Myeloperoxidase (MPO) activities of mammary gland were determined by the MPO kits. The mRNA expressions of inflammatory cytokines including TNF-α, IL-1ß and IL-6, and those of chemokine factors CCL2 and CXCL2, and those of tight junctions occludin claudin-3 were examined by qRT-PCR analysis. The activities of IκB, p65, ERK, P38, AKT, PI3K, NLPR3, claudin-1, claudin-3 and occludin were determined by western blotting. The results showed that morin alleviated LPS-induced edema, destructed structures and infiltrated inflammatory cells of mammary gland. Morin administration significantly decreased LPS-induced TNF-α, IL-1ß, IL-6, CCL2 and CXCL2 mRNA expressions. Furthermore, western blot analysis also showed that morin significantly reduced LPS-induced phosphorylation of p65, IκB, p38 and ERK, and enhanced LPS-induced phosphorylation of AKT and PI3K. It was also found that LPS-decreased claudin-3 and occludin expressions were also inhibited by morin treatment. In summary, above results suggest that morin indeed protect LPS-induced mouse mastitis in vivo, and the mechanism was through inhibiting the PI3K/AKT, MAPK, NF-κB and NLRP3 signaling pathways and protecting the integrity of blood-milk barrier by regulating the tight junction proteins expressions.

9.
Nucleic Acids Res ; 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31713614

RESUMO

SP_0782 from Streptococcus pneumoniae is a dimeric protein that potentially binds with single-stranded DNA (ssDNA) in a manner similar to human PC4, the prototype of PC4-like proteins, which plays roles in transcription and maintenance of genome stability. In a previous NMR study, SP_0782 exhibited an ssDNA-binding property different from YdbC, a prokaryotic PC4-like protein from Lactococcus lactis, but the underlying mechanism remains unclear. Here, we show that although SP_0782 adopts an overall fold similar to those of PC4 and YdbC, the ssDNA length occupied by SP_0782 is shorter than those occupied by PC4 and YdbC. SP_0782 exhibits varied binding patterns for different lengths of ssDNA, and tends to form large complexes with ssDNA in a potential high-density binding manner. The structures of SP_0782 complexed with different ssDNAs reveal that the varied binding patterns are associated with distinct capture of nucleotides in two major DNA-binding regions of SP_0782. Moreover, a comparison of known structures of PC4-like proteins complexed with ssDNA reveals a divergence in the binding interface between prokaryotic and eukaryotic PC4-like proteins. This study provides insights into the ssDNA-binding mechanism of PC4-like proteins, and benefits further study regarding the biological function of SP_0782, probably in DNA protection and natural transformation.

10.
Environ Sci Technol ; 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31682409

RESUMO

Cadmium (Cd) is one of the most prevalent toxic metal pollutants widely distributed in water and soil environments. Epidemiological studies have shown that exposure to Cd is implicated in the prevalence of nonalcoholic fatty liver disease (NAFLD) in middle-aged human population, but biological evidence is lacking and its toxicological mechanism remains unclear for the disease predisposition from environmental Cd exposure. In this study, we established a chronic Cd-exposure mouse model mimicking the liver Cd deposition in middle-aged human population to determine whether the environmental Cd exposure can induce NAFLD. Results showed that hepatic Cd burden at levels of 0.95 and 6.04 µg/g wet weight resulting from 20-week Cd exposure at different doses induced NAFLD and nonalcoholic steatohepatitis-like phenotypes in mice, respectively. The Cd exposure caused marked hepatic mitochondrial dysfunction and fatty acid oxidation deficiency, along with significant suppression of sirtuin 1 (SIRT1) signaling pathway in the liver. In vitro study confirmed that Cd evidently inhibited the mitochondrial fatty acid oxidation in hepatocytes and that SIRT1 signaling was potentially involved in the process. Our findings suggest that exposure to environmental Cd is a tangible risk factor for NAFLD, and the induced public health risks deserve greater attention.

11.
Chemistry ; 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31696587

RESUMO

Carbon nanofiber (CNF)-based supercapacitors have promising applications in the field of energy storage. It is desirable but remains challenging to develop CNF electrode materials with a large specific surface area (SSA), high specific capacitance (SC) and high power density, as well as excellent cycling stability and high reliability. In this study, we synthesize the acrylonitrile-acrylic acid copolymer P(AN- co -AA) for the preparation of nitrogen-doped microporous CNFs. The thermal degradation of the AA segment leads to the formation of micropores that are distributed not only on the CNF surface but also inside the material. The microporous structure and nitrogen content can be manipulated at the molecular level by adjusting the weight ratio between the AN and AA, and the SSA and SC could reach as high as 1099 m 2 g -1 and 156 F g -1 , respectively. After KOH activation, the Activated Carbon nanofiber (ACNF) possesses an extremely high SSA of 2117 m 2 g -1 and SC of 320 F g -1 , which are almost the highest values ever reported for electric double layer supercapacitors with an alkaline electrolyte. Furthermore, the capacitance retention can be maintained at 99% even after 16,000 cyclic tests, exhibiting outstanding durability and repeatability.

12.
Nat Commun ; 10(1): 5026, 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31690716

RESUMO

The majority of patients with neuroblastoma due to MYCN oncogene amplification and consequent N-Myc oncoprotein over-expression die of the disease. Here our analyses of RNA sequencing data identify the long noncoding RNA lncNB1 as one of the transcripts most over-expressed in MYCN-amplified, compared with MYCN-non-amplified, human neuroblastoma cells and also the most over-expressed in neuroblastoma compared with all other cancers. lncNB1 binds to the ribosomal protein RPL35 to enhance E2F1 protein synthesis, leading to DEPDC1B gene transcription. The GTPase-activating protein DEPDC1B induces ERK protein phosphorylation and N-Myc protein stabilization. Importantly, lncNB1 knockdown abolishes neuroblastoma cell clonogenic capacity in vitro and leads to neuroblastoma tumor regression in mice, while high levels of lncNB1 and RPL35 in human neuroblastoma tissues predict poor patient prognosis. This study therefore identifies lncNB1 and its binding protein RPL35 as key factors for promoting E2F1 protein synthesis, N-Myc protein stability and N-Myc-driven oncogenesis, and as therapeutic targets.

13.
Med Biol Eng Comput ; 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31754980

RESUMO

Taking advantage of motion sensing technology, a quantitative assessment method for lower limbs motor function of cerebral palsy (CP) based on the gross motor function measurement (GMFM)-24 scale was explored in this study. According to the motion analysis on GMFM-24 scale, we translated the assessment problem of GMFM-24 scale into a detection problem of different motion modes including static state, fall, step, turning, alternating gait, walking, running, lifting legs, kicking balls, and jumping. The surface electromyography (sEMG) electrodes and inertial sensors were adopted to capture motion data, and a framework integrating a series of detection algorithms was presented for the assessment of lower limbs gross motor function. Two groups of participants including 8 healthy adults and 14 CP children were recruited. A self-developed data acquisition equipment integrating 24 sEMG electrodes and 9 inertial units was adopted for data acquisition. A platform based on two laser beam sensors was used to perform cross-border detection. The parameters/thresholds of motion detection algorithms were determined by the data from healthy adults, and the lower limbs gross motor function evaluation was conducted on 14 CP children. The experimental results verified the feasibility and effectiveness of the proposed quantitative assessment method. Compared to the clinical assessment score based on GMFM-24 scale, 90.1% accuracy was obtained for evaluation of 303 tasks in 14 CP children. The objective motor function assessment method proposed has potential application value for the quantitative assessment of lower limbs motor function of CP children in clinical practice. Graphical abstract The algorithm framework for the assessment of lower limbs gross motor function. Using the GMFM-24 scale as the evaluation standard, a quantitative evaluation program for the lower limbs gross motor function of CP children based on motion sensing technology was proposed.

14.
Chin Med J (Engl) ; 132(22): 2647-2656, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31725459

RESUMO

BACKGROUND: Few data are available regarding the progression of liver disease and therapeutic efficacy in chronic hepatitis B virus (HBV) carriers infected by mother-to-child transmission (MTCT). This study aimed to investigate these two aspects by comparing the adult chronic HBV carriers in MTCT group with those in horizontal transmission group. METHODS: The 683 adult chronic HBV patients qualified for liver biopsy including 191 with MTCT and 492 with horizontal transmission entered the multi-center prospective study from October 2013 to May 2016. Biopsy results from 217 patients at baseline and 78 weeks post antiviral therapy were collected. RESULTS: Patients infected by MTCT were more likely to have e antigen positive (68.6% vs. 58.2%, χ = -2.491, P = 0.012) than those with horizontal transmission. However, in patients with MTCT, levels of alkaline phosphatase (ALP) (P = 0.031), Fibroscan (P = 0.013), N-terminal propeptide of Type III procollagen (PIIINP) (P = 0.014), and Laminin (LN) (P = 0.006) were high, in contrast to the patients with horizontal transmission for whom the levels of albumin (ALB) (P = 0.041), matrix metalloproteinase-3 (MMP-3) (P = 0.001) were high. The 47.2% of patients with MTCT and 36.8% of those with horizontal transmission had significant liver fibrosis (P = 0.013). Following antiviral therapy for 78 weeks, 21.2% and 38.0% patients with MTCT and horizontal transmission acquired hepatitis B e antigen (HBeAg) clearance, respectively (P = 0.043), and the virological response rates were 54.7% and 74.1% in the MTCT and horizontal groups, respectively (P = 0.005). MTCT was a risk factor for HBeAg clearance and virological response. CONCLUSION: Adult patients with MTCT were more prone to severe liver diseases, and the therapeutic efficacy was relatively poor, which underlined the importance of earlier, long-term treatment and interrupting perinatal transmission. TRIAL REGISTRATION: NCT01962155; https://clinicaltrials.gov.

15.
Mol Brain ; 12(1): 91, 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31699123

RESUMO

Autism spectrum disorder (ASD) is a heterogeneous group of complex neurodevelopmental disorders without a unique or definite underlying pathogenesis. Although savant syndrome is common in ASD, few models are available for studying the molecular and cellular mechanisms of this syndrome. In this study, we generated urinary induced pluripotent stem cells (UiPSCs) from a 13-year-old male autistic savant with exceptional memory. The UiPSC-derived neurons of the autistic savant exhibited upregulated expression levels of ASD genes/learning difficulty-related genes, namely PAX6, TBR1 and FOXP2, accompanied by hypertrophic neural somas, enlarged spines, reduced spine density, and an increased frequency of spontaneous excitatory postsynaptic currents. Although this study involved only a single patient and a single control because of the rarity of such cases, it provides the first autistic savant UiPSC model that elucidates the potential cellular mechanisms underlying the condition.

16.
Nat Prod Res ; : 1-7, 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31707857

RESUMO

A new indole alkaloid, namely naucleofficine H (1), was obtained from the aqueous extract of Nauclea officinalis, together with four known alkaloids, vincosamide (2), strictosamide (3), angustoline (4) and pumiloside (5). Their structures were characterized by analyzing their physicochemical data including NMR, and HRMS. In addition, five compounds were tested for their proliferation activities. The expression of vascular endothelial growth factor (VEGF), extra-cellular signal-regulated protein kinase 1 and 2 (ERK) and phosphorylation of ERK 1/2 (p-ERK) were also detected in HUVEC treated withbioactive compounds using western blotting. The result showed that these compounds could promote HUVEC cell proliferation. Compounds 3 and 5 could up-regulate VEGF and p-ERK in HUVEC.

17.
J Surg Oncol ; 120(8): 1302-1310, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31680243

RESUMO

BACKGROUND: The current study sought to investigate the impact of tumor size and total number of LN examined (TNLE) on the incidence of lymph node metastasis (LNM) among patients with duodenal neuroendocrine tumor (dNET). METHODS: Patients who underwent curative resection for dNETs between 1997-2016 were identified from 8 high-volume US centers. Risk factors associated with overall survival and LNM were identified and the optimal cut-off of TNLE relative to LNM was determined. RESULTS: Among 162 patients who underwent resection of dNETs, median patient age was 59 (interquartile range [IQR], 51-68) years and median tumor size was 1.2 cm (IQR, 0.7-2.0 cm); a total of 101 (62.3%) patients underwent a concomitant LND at the time of surgery. Utilization of lymphadenectomy (LND) increased relative to tumor size (≤1 cm:52.2% vs 1-2 cm:61.4% vs >2 cm:93.8%; P < .05). Similarly, the incidence of LNM increased with dNET size (≤1 cm: 40.0% vs 1-2 cm:65.7% vs >2 cm:80.0%; P < .05). TNLE ≥ 8 had the highest discriminatory power relative to the incidence of LNM (area under the curve = 0.676). On multivariable analysis, while LNM was not associated with prognosis (hazard ratio [HR] = 0.9; 95% confidence intervals [95%CI], 0.4-2.3), G2/G3 tumor grade was (HR = 1.5; 95%CI, 1.0-2.1). CONCLUSIONS: While the incidence of LNM directly correlated with tumor size, patients with dNETs ≤ 1 cm had a 40% incidence of LNM. Regional lymphadenectomy of a least 8 LN was needed to stage patients accurately.

18.
Zhongguo Zhen Jiu ; 39(11): 1187-90, 2019 Nov 12.
Artigo em Chinês | MEDLINE | ID: mdl-31724355

RESUMO

Four controversial types of simplex reinforcing-reducing manipulation of acupuncture and their possible meanings were summarized to explore several key elements of reinforcing-reducing manipulation of acupuncture, in addition, the simplex reinforcing-reducing manipulation of acupuncture was classified by single factor. It is concluded that the definition of simplex reinforcing-reducing manipulation of acupuncture should try not to include other non-manipulative elements. According to single factor, it can be divided into: needle-oriented reinforcing-reducing manipulation, twisting reinforcing-reducing manipulation, lifting and interpolating reinforcing-reducing manipulation, fast and slow reinforcing-reducing manipulation, breathing reinforcing-reducing manipulation, opening and closing reinforcing-reducing manipulation. In addition, after considering the effect and principle of number reinforcing-reducing manipulation, it can be considered.


Assuntos
Terapia por Acupuntura , Pontos de Acupuntura , Terapia por Acupuntura/instrumentação , Terapia por Acupuntura/métodos , Humanos , Meridianos , Agulhas
19.
Biochemistry ; 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31724401

RESUMO

The product of 1-deoxy-d-xyluose 5-phosphate (DXP) synthase, DXP, feeds into the bacterial biosynthesis of isoprenoids, thiamin diphosphate (ThDP), and pyridoxal phosphate. DXP is essential for human pathogens but not utilized by humans; thus, DXP synthase is an attractive anti-infective target. The unique ThDP-dependent mechanism and structure of DXP synthase offer ideal opportunities for selective targeting. Upon reaction with pyruvate, DXP synthase uniquely stabilizes the predecarboxylation intermediate, C2α-lactylThDP (LThDP), in a closed conformation. Subsequent binding of d-glyceraldehyde 3-phosphate induces an open conformation that is proposed to destabilize LThDP, triggering decarboxylation. Evidence for the closed and open conformations has been revealed by hydrogen-deuterium exchange mass spectrometry and X-ray crystallography, which indicate that H49 and H299 are involved in conformational dynamics and movement of the fork and spoon motifs away from the active site is important for the closed-to-open transition. Interestingly, H49 and H299 are critical for DXP formation and interact with the predecarboxylation intermediate in the closed conformation. H299 is removed from the active site in the open conformation of the postdecarboxylation state. In this study, we show that substitution at H49 and H299 negatively impacts LThDP formation by shifting the conformational equilibrium of DXP synthase toward an open conformation. We also present a method for monitoring the dynamics of the spoon motif that uncovered a previously undetected role for H49 in coordinating the closed conformation. Overall, our results suggest that H49 and H299 are critical for the closed, predecarboxylation state providing the first direct link between catalysis and conformational dynamics.

20.
J Inorg Biochem ; 202: 110887, 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31670257

RESUMO

Mn-doped mesoporous silica (MMS) nanocarriers were prepared by in situ doping Mn component for drug delivery. In the acidic or reductive microenvironment of tumor, the MnO bond can be broken up, and Mn components would be released from the silica framework, thus accelerating the degradation of the silica nanocarrier. Due to the mesoporous structure, MMS nanocarriers have a high specific surface area of 1125.56 m2/g, which is suitable for loading and controlled release of drug. And the encapsulation ratio of Dox and drug loading of MMS and MMS/PDA is 98.08%, 39.54% and 38.81% respectively. After loading Dox, polydopamine(PDA)was coated on the surface of MMS nanocarriers to reduce drug burst release and endow them pH-responsive release. The prepared Dox-MMS/PDA delivery system displays pH/redox dual-responsive degradation of carriers and drug release.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA