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1.
Int J Cancer ; 146(1): 103-114, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31199508

RESUMO

Next-generation sequencing of cell-free circulating DNA (cfDNA) has emerged as promising technique for identifying minimally invasive genomic profiling of tumor cells recently. However, it remains relatively unknown in LAM disease. In our study, paired cfDNA and genomic DNA (gDNA) in blood samples were obtained from 23 LAM patients and seven healthy controls to explore mutations profiles of targeted 70 cancer-related genes. As results, log2-based allele frequencies of mutations in cfDNA were significantly different from those of gDNA. By comparing the mutual mutations identified both in cfDNA and gDNA, a significant correlation was also observed. After removing mutations in gDNA, distinct somatic mutation profiles of cfDNA were observed in LAM patients. Forty of 70 targeted genes had recurrent mutations, of which ATM, BRCA2 and APC showed the highest frequency. Based on the mutation, correlation network constructed of 40 mutated genes, 11 hub genes bearing intensive interactions were highlighted, including BRCA1, BRCA2, RAD50, RB1, NF1, APC, MLH3, ATM, PDGFRA, PALB2 and BLM. Expression of the hub genes showed significant clusters between LAM patients and controls and that RAD50 and BRCA2 had the strongest associations with subject phenotypes. Myogenesis and estrogen response were confirmed to be positively regulated in LAM patients. Collectively, our study provided a landscape of genomic alterations in LAM and discovered several potential driver genes, that is, BRCA2 and RAD50, which shed a substantial light on the clinical application of key molecular markers and potential therapy targets for precision diagnosis and treatment in the future.

2.
Biomaterials ; 226: 119538, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31639541

RESUMO

Based on the ionizing radiation applied to the malignant tumor tissue, radiation therapy (RT) is the frequently-used non-surgical approach for cancer treatment. Hafnium Oxide (HfO2) based nanoagent has been used in clinical trials for radiosensitized tumor therapy. However, the current reported clinically used HfO2 nanoparticles are relay on intratumoral injectable, and the unmodified HfO2 nanoparticles tend to be aggregated in serum and cannot be injected by intravenous route, which significantly limited the types of treatable cancer. To overcome the limitation, in this work, we developed a large-scalable, intravenously injectable, and clearable HfO2 nanoassemblies (NAs) to enhance the radiotherapeutic effects. The HfO2 NAs exhibited meaningfully promoted free-radical generation upon X-ray radiation for cancer cell killing due to the improved the sensitiveness of the breast cancer cells. The PEGylated HfO2 NAs demonstrated efficient tumor-homing ability via intravenous injection and manifested by HfO2 NAs enhanced CT imaging in a 4T1 breast tumor model. Utilizing the radiation sensitization function of HfO2 NAs, excellent tumor killing efficacy was achieved via both intratumoral and intravenously injection administration. Importantly, our HfO2 NAs could be degraded and excreted efficiently in a reasonable period in living body and avoid long-term toxicity. Taken together, our work provides a new technique by an injectable CT imaging-guided radio-sensitivitiable nanosystem for the further potential clinic translation.

3.
J Hazard Mater ; 382: 121026, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31446355

RESUMO

In this work, 3D hierarchical Cu2SnS3@SnS2 flower assembled from nanopetals with sandwich-like Cu2SnS3-SnS2-Cu2SnS3 double interfacial heterojunction was successfully designed and synthesized on fluoride doped tin oxide (FTO) for photoelectrochemical (PEC) sensor by in situ electrodeposition p-type Cu2SnS3 nanoparticles on both inner and outer surfaces of n-type SnS2 nanopetals. The unique double interfacial heterojunction simultaneously combines 3D flower-like architectures to drastically increase the light trapping and absorption in visible-near infrared range (Vis-NIR), and dramatically inhibites the charge carrier recombination, which is crucial for boosting the PEC activity. Benefitting from the shape and compositional merits, the Cu2SnS3@SnS2 heterojunction possess dual-mode signal by controlling the electrodeposition time to manipulate the composition ratio of Cu2SnS3 and SnS2. The Cu2SnS3@SnS2/FTO electrode not only exhibits excellent photoeletro-reduction capacity for ultra-sensitive sensing trace persistent organic pollutant (nitrobenzene, NB), but also presents photoeletro-oxidization activity for high selective detection of L-cysteine (L-Cys) without any auxiliary enzyme under the light illumination. Dual mode sensor displayed superb performance for the detection of NB/L-Cys, showing a wide linear range from 100 pM to 300 µM/10 nM to 100 µM and a low detection limit (3S/N) of 68 pM/8.5 nM, respectively. Such a tunable double interfacial heterojunction design opened up new avenue for constructing multifunction PEC sensing platform.

4.
Front Biosci (Landmark Ed) ; 25: 699-709, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31585912

RESUMO

Diabetes causes diabetic nephropathy (DN) which is associated with increased morbidity and mortality in diabetic patients. We tested whether Resveratrol (Res) reverses the systemic effect of Streptozotocin (STZ) induced diabetes and DN. Res treatment opposed the effect of STZ on kidney weight, 24 h urinary albumin excretion, blood urea nitrogen (BUN) and serum creatinine (Scr). Res also decreased DN induced mTOR/ULK1-mediated autophagy and apoptosis and significantly reduced STZ mediated lipid deposition in nephrons, likely by decreasing the levels of lipogenic related proteins (SREBP-1c, ACS) and increased lipidolysis related proteins (PPARα, CPT-1). Together, these findings show the potential of Res in prevention of diabetic nephropathy.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31717718

RESUMO

People explosion and fast economic growth are bringing a more serious land resource shortage crisis. Rational land-use allocation can effectively reduce this burden. Existing land-use allocation models may deal with a lot of challenges of land-use planning. This study proposed a hybrid quantitative and spatial optimization land-use allocation model that could enrich the land-use allocation method system. This model has three advantages compared to former methods: (1) this model can simultaneously solve the quantitative land area optimization problem and spatial allocation problem, which are the two core aspects of land-use allocation; (2) the land suitability assessment method considers various geographical, economic and environmental factors which are essential to land-use allocation; (3) this model used an interval stochastic fuzzy programming land-use allocation model to solve the quantitative land area optimization problem. This model not only considers three uncertainties in the natural system but also involves various economic, social, ecological and environmental constraints-most of which are specifically put into the optimization process. The proposed model has been applied to a real case study in Liannan county, Guangdong province, China. The results could help land managers and decision makers to conduct sound land-use planning/policy and could help scientists understand the inner contradiction among economic development, environmental protection, and land use.

6.
Int J Mol Sci ; 20(21)2019 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-31717775

RESUMO

The joint toxicities of [BMIM]BF4, [BMIM]PF6, and [HMIM]BF4 on acetylcholinesterase (AChE) were systematically investigated by using a progressive approach from 1D single effect point, 2D concentration-response curve (CRC), to 3D equivalent-surface (ES) level. The equipartition equivalent-surface design (EESD) method was used to design 10 ternary mixtures, and the direct equipartition ray (EquRay) design was used to design 15 binary mixtures. The toxicities of ionic liquids (ILs) and their mixtures were determined using the microplate toxicity analysis (MTA) method. The concentration addition (CA), independent action (IA), and co-toxicity coefficient (CTC) were used as the additive reference model to analyze the toxic interaction of these mixtures. The results showed that the Weibull function fitted well the CRCs of the three ILs and their mixtures with the coefficient of determination (R2) greater than 0.99 and root-mean-square error (RMSE) less than 0.04. According to the CTC integrated with confidence interval (CI) method (CTCICI) developed in this study, the 25 mixtures were almost all additive action at 20% and 80% effect point levels. At 50% effect, at least half of the 25 mixtures were slightly synergistic action, and the remaining mixtures were additive action. Furthermore, the ESs and CRCs predicted by CA and IA were all within the CIs of mixture observed ESs and CRCs, respectively. Therefore, the toxic interactions of these 25 mixtures were actually additive action. The joint toxicity of the three ILs can be effectively evaluated by the ES method. We also studied the relationship between the mixture toxicities and component concentration proportions. This study can provide reference data for IL risk assessment of combined pollution.

7.
Small ; : e1905355, 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31714020

RESUMO

The unique feature of nacre-like 2D layered materials provides a facile, yet highly efficient way to modulate the transmembrane ion transport from two orthogonal transport directions, either vertical or horizontal. Recently, light-driven active transport of ionic species in synthetic nanofluidic systems attracts broad research interest. Herein, taking advantage of the photoelectric semiconducting properties of 2D transition metal dichalcogenides, the generation of a directional and greatly enhanced cationic flow through WS2 -based 2D nanofluidic membranes upon asymmetric visible light illumination is reported. Compared with graphene-based materials, the magnitude of the ionic photocurrent can be enhanced by tens of times, and its photo-responsiveness can be 2-3.5 times faster. This enhancement is explained by the coexistence of semiconducting and metallic WS2 nanosheets in the hybrid membrane that facilitates the asymmetric diffusion of photoexcited charge carriers on the channel wall, and the high ionic conductance due to the neat membrane structure. To further demonstrate its application, photonic ion switches, photonic ion diodes, and photonic ion transistors as the fundamental elements for light-controlled nanofluidic circuits are further developed. Exploring new possibilities in the family of liquid processable colloidal 2D materials provides a way toward high-performance light-harvesting nanofluidic systems for artificial photosynthesis and sunlight-driven desalination.

8.
J Cell Mol Med ; 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31724308

RESUMO

Proliferation and metastasis are significantly malignant characteristics of human lung cancer, but the underlying molecular mechanisms are poorly understood. Chromobox 4 (CBX4), a member of the Polycomb group (PcG) family of epigenetic regulatory factors, enhances cellular proliferation and promotes cancer cell migration. However, the effect of CBX4 in the progression of lung cancer is not fully understood. We found that CBX4 is highly expressed in lung tumours compared with adjacent normal tissues. Overexpression of CBX4 significantly promotes cell proliferation and migration in human lung cancer cell lines. The knockdown of CBX4 obviously suppresses the cell growth and migration of human lung cancer cells in vitro. Also, the proliferation and metastasis in vivo are blocked by CBX4 knockdown. Furthermore, CBX4 knockdown effectively arrests cell cycle at the G0/G1 phase through suppressing the expression of CDK2 and Cyclin E and decreases the formation of filopodia through suppressing MMP2, MMP9 and CXCR4. Additionally, CBX4 promotes proliferation and metastasis via regulating the expression of BMI-1 which is a significant regulator of proliferation and migration in lung cancer cells. Taken together, these data suggest that CBX4 is not only a novel prognostic marker but also may be a potential therapeutic target in lung cancer.

9.
Artigo em Inglês | MEDLINE | ID: mdl-31696238

RESUMO

Objectives Shift work is associated with metabolic disorders as it disturbs circadian rhythms. However, the potential association of shift work with knee osteoarthritis (KOA), a metabolic-related disease, has not been confirmed. The objective of this study was to quantify the association of shift work with the risk of KOA. Methods This retrospective cohort study comprising 13 741 retired workers from the Dongfeng Motor Corporation. KOA was defined by knee pain and clinical X-ray radiographs. Occupational history, including job description and shift work, was collected from face-to-face interviews using questionnaires. Cox proportional hazards regression models were used to estimate exposure-response relationships. Results During the 590 085 person-years of follow-up, a total of 847 cases of KOA (incidence of KOA was 143.5 per 100 000 person-years) were identified. After adjusting for potential confounders, shift work was independently associated with an elevated risk of KOA [hazard ratio (HR) 1.19, 95% confidence interval 1.03-1.36]. Compared with daytime workers, the risk of KOA increased with prolonged periods of shift work; the HR of KOA for participants with 1-9 years, 10-19 years, and ≥20 years shift work were 1.03 (95% CI 0.84-1.26), 1.19 (95% CI 0.98-1.46), and 1.42 (95% CI 1.15-1.76), respectively. The HR for KOA associated with shift work gradually decreased as the period after finishing shift work increased. Conclusion Our results indicated that shift work could be an independent risk factor for KOA.

10.
Cancer Imaging ; 19(1): 71, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31685015

RESUMO

OBJECTIVES: This study investigates the effectiveness of local application of doxorubicin(Dox)-loaded, polydopamine (PDA)- coated single crystal hematite (α- Fe2O3) nanocubes (Fe2O3-PDA-Dox) and combretastatin A-4 phosphate disodium(CA4P)in treating hepatocellular carcinoma (HCC) in rats. METHODS: The magnetic characteristics and photothermal effects of the nanoparticles were determined in vitro. Tumor-bearing Sprague-Dawley rats were divided into 3 groups of 8 according to treatment: controls, transarterial chemoembolization-photothermal ablation (pTACE) (Lipidol+Fe2O3-PDA-Dox + NIR), and CA4P + pTACE (CA4P+ Lipidol+Fe2O3-PDA-Dox + NIR). Drugs were administered through the hepatic artery, and the tumors exposed to 808-nm near-infrared radiation. The Fe content of tumors was assessed using neutron activation analysis. Treatment effectiveness was assessed using heating curves, magnetic resonance imaging, pathology results, and immunohistochemical analysis. RESULTS: The mean tumor Fe content was greater in rats treated with CA4P + pTACE (1 h, 23.72 ± 12.45 µg/g; 24 h, 14.61 ± 8.23 µg/g) than in those treated with pTACE alone (1 h, 5.66 ± 4.29 µg/g; 24 h, 2.76 ± 1.33 µg/g). The tumor T2 imaging signal was lower in rats treated with CA4P + pTACE. Following laser irradiation, the tumor temperature increased, with higher temperatures reached in the CA4P + pTACE group (62 °C vs 55 °C). Tumor cells exhibited necrosis, apoptosis, and proliferation inhibition, with greater effects in the CA4P + pTACE group. Transient liver and kidney toxicity were observed on day 3, with more severe effects after CA4P + pTACE. CONCLUSIONS: Fe2O3-PDA-Dox nanoparticles are effective for TACE-PTA. Pretreatment with CA4P increases nanoparticle uptake by tumors, increasing the treatment effectiveness without increasing hepatorenal toxicity.

11.
J Asian Nat Prod Res ; : 1-5, 2019 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-31755308

RESUMO

A new 23,24,25,26,27-five-nortriterpenoid (1), named resinacein T, was isolated from an ethanol extract of the fruiting bodies in Ganoderma resinaceum of family Ganodermataceae, together with two known lanostane triterpenoids, 3ß,7ß,15α,24-tetrahydroxy-11,23-dioxo-lanost-8-en-26-oic acid (2), and resinacein O (3). The structures of compounds (1-3) were elucidated using NMR and MS methods.

12.
Exp Neurol ; 323: 113084, 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31697945

RESUMO

OBJECTIVE: To establish an animal model for posttraumatic stress disorder in burn-injured patients. METHODS: Thermal-injured mice with 15% total body surface area were subjected to a series of neurobehavioral tests at 1 and 3 months postburn. Brains were collected for analysis of key molecules expression, spleens for T cell function analysis, and blood for biochemistry and hormones detection. RESULTS: Comparison with sham mice, burn mice showed extremely high locomotion in homecage, open field, and forced swimming tests, indicating a hyper-arousal state. Burn mice exhibited improved spatial memory in Morris Water Maze test and heightened context fear memory in context fear conditioning, suggesting re-experiencing behavior. Although burn mice showed pronounced passive avoidance in the step-through test, their active avoidance capability in response to the conditional stimulus in the shuttle box test was relatively deteriorated. Likewise, the retention of cue-feared memory was impaired in fear conditioning test. The above negative alterations in mood were recapitulated in open-field test, in which the burn mice displayed an anxiety-like behavior with less time spent in the center. However, no sign of depression was found in the forced swimming and sucrose preference tests. The negative mood of burn mice was reinforced by a deficit in sociality and preference for social novelty in social interaction test. These neurobehavioral alterations were associated with an increased expression of brain-derived neurotrophic factor along with a remarkable microgliosis and a moderate astrocytosis in the brain of burn vs. sham mice. Moreover, a prominent Th2 switch and consequent increased nuclear NF-κB translocation were seen in the splenic T cells from burn relative to sham mice. CONCLUSIONS: We conclude that even mild burn injury could lead to long-lasting cognitive and effective alterations in mice. These findings shed light on the interactions among neuropsychology, neurobiology, and immunology throughout the recovery period of burn injury.

13.
Acta Crystallogr F Struct Biol Commun ; 75(Pt 11): 697-706, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31702583

RESUMO

A high-affinity anti-cocaine monoclonal antibody, designated h2E2, is entering phase 1 clinical trials for cocaine abuse therapy. To gain insight into the molecular details of its structure that are important for binding cocaine and cocaine metabolites, the Fab fragment was generated and crystallized with and without ligand. Structures of the unliganded Fab and the Fab fragment bound to benzoylecgonine were determined, and were compared with each other and with other crystallized anti-cocaine antibodies. The affinity of the h2E2 antibody for cocaine is 4 nM, while that of the cocaine metabolite benzoylecgonine is 20 nM. Both are higher than the reported affinity for cocaine of the two previously crystallized anti-cocaine antibodies. Consistent with cocaine fluorescent quenching binding studies for the h2E2 mAb, four aromatic residues in the CDR regions of the Fab (TyrL32, TyrL96, TrpL91 and TrpH33) were found to be involved in ligand binding. The aromatic side chains surround and trap the tropane moiety of the ligand in the complex structure, forming significant van der Waals interactions which may account for the higher affinity observed for the h2E2 antibody. A water molecule mediates hydrogen bonding between the antibody and the carbonyl group of the benzoyl ester. The affinity of binding to h2E2 of benzoylecgonine differs only by a factor of five compared with that of cocaine; therefore, it is suggested that h2E2 would bind cocaine in the same way as observed in the Fab-benzoylecgonine complex, with minor rearrangements of some hypervariable segments of the antibody.

14.
Mol Neurobiol ; 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31728930

RESUMO

TREK-1, a two-pore-domain K+ channel, is highly expressed in the central nervous system. Although aberrant expression of TREK-1 is implicated in cognitive impairment, the cellular and functional mechanism underlying this channelopathy is poorly understood. Here we examined TREK-1 contribution to neuronal morphology, excitability, synaptic plasticity, and cognitive function in mice deficient in TREK-1 expression. TREK-1 immunostaining signal mainly appeared in hippocampal pyramidal neurons, but not in astrocytes. TREK-1 gene knockout (TREK-1 KO) increases dendritic sprouting and the number of immature spines in hippocampal CA1 pyramidal neurons. Functionally, TREK-1 KO increases neuronal excitability and enhances excitatory and inhibitory postsynaptic currents (EPSCs and IPSCs). The increased EPSCs appear to be attributed to an increased release probability of presynaptic glutamate and functional expression of postsynaptic AMPA receptors. TREK-1 KO decreased the paired-pulse ratio and severely occluded the long-term potentiation (LTP) in the CA1 region. These altered synaptic transmission and plasticity are associated with recognition memory deficit in TREK-1 KO mice. Although astrocytic expression of TREK-1 has been reported in previous studies, TREK-1 KO does not alter astrocyte membrane K+ conductance or the syncytial network function in terms of syncytial isopotentiality. Altogether, TREK-1 KO profoundly affects the cellular structure and function of hippocampal pyramidal neurons. Thus, the impaired cognitive function in diseases associated with aberrant expression of TREK-1 should be attributed to the failure of this K+ channel in regulating neuronal morphology, excitability, synaptic transmission, and plasticity.

15.
Hear Res ; 384: 107827, 2019 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-31683075

RESUMO

The association between shift work and hearing loss is unclear. We aimed to evaluate this association in a Chinese population independently and in combination with occupational noise. A total of 11,196 participants of the Dongfeng-Tongji cohort study were included. Shift work was self-reported and hearing loss was defined as a pure-tone mean of 25 dB or higher at 0.5, 1, 2, and 4 kHz in any ear. The Robust Poisson method were used to assess the relationship between shift work and hearing loss, and the prevalence ratios (PRs) were calculated. Compared to individuals who reported no shift work, the PRs of bilateral hearing loss were significantly higher for a shift work duration of fewer than 10 years in women, (PR = 1.024, 95% confidence interval [CI] = 1.002-1.053), but not in men (PR = 1.016, 95% confidence interval [CI] = 0.998-1.035). The association between short duration of shift work and bilateral hearing loss was just statistically significant in women when those with occupational noise exposure were excluded (PR = 1.067, 95%CI = 1.015-1.122). When shift work and occupational noise exposure were combined, the PRs for hearing loss were highest among individuals with the longest shift work (≥10 years) and longest noise exposure (≥20 years) durations, whether for bilateral (PR = 1.114, 95%CI = 1.068-1.162) or any ear (PR = 1.065, 95%CI = 1.034-1.096). A short duration of shift work may be a risk factor for hearing loss in women and could increase the prevalence of hearing loss when combined with occupational noise.

16.
EBioMedicine ; 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31727599

RESUMO

BACKGROUND: Prostate cancer (PCa) is a leading cause of cancer-related death in males. Aberrant expression of long noncoding RNAs (lncRNAs) is frequently reported in human malignancies. This study was performed to explore the role of LSAMP-AS1 in epithelial-mesenchymal transition (EMT), proliferation, migration and invasion of PCa cells. METHODS: Initially, the differentially expressed lncRNAs in PCa were screened out by microarray analysis. The clinicopathological and prognostic significance of LSAMP-AS1 was evaluated. LSAMP-AS1 was over-expressed or silenced to investigate the roles in EMT, proliferation, migration and invasion of PCa cells. Moreover, the relationships between LSAMP-AS1 and miR-183-5p, as well as miR-183-5p and decorin (DCN) were characterized. The tumorigenicity of PCa cells was verified in nude mice. RESULTS: LSAMP-AS1 was poorly expressed in PCa tissues and cells. Low expression of LSAMP-AS1 was indicative of poor overall survival and disease-free survival, and related to Gleason score, TNM stage, and risk stratification. Over-expressed LSAMP-AS1 inhibited EMT, proliferation, migration and invasion of PCa cells, as well as tumor growth in nude mice. Meanwhile, over-expression of LSAMP-AS1 resulted in up-regulation of E-cadherin and down-regulation of Vimentin, N-cadherin, Ki67, PCNA, MMP-2, MMP-9, Ezrin and Fascin. Notably, LSAMP-AS1 competitively bound to miR-183-5p which directly targets DCN. It was confirmed that the inhibitory effect of LSAMP-AS1 on PCa cells was achieved by binding to miR-183-5p, thus promoting the expression of DCN. CONCLUSION: LSAMP-AS1 up-regulates the DCN gene by competitively binding to miR-183-5p, thus inhibiting EMT, proliferation, migration and invasion of PCa cells.

17.
FEBS Open Bio ; 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31729835

RESUMO

The SOX6 transcription factor has been implicated in the development of cancer, but its role in lung cancer is incompletely understood. Here, we report that SOX6 expression is frequently downregulated in lung adenocarcinoma tissues. Moreover, SOX6 can inhibit the proliferation and invasion of lung adenocarcinoma cells, which may occur through cell cycle arrest at G1/S due to upregulation of p53 and p21CIPI and downregulation of cyclin D1 and beta-catenin. Univariate and multivariate analysis revealed that the expression of SOX6 is significantly associated with patient disease-related survival and is an independent prognostic factor for lung adenocarcinoma. These data suggest that SOX6 may act as a suppressor of lung adenocarcinoma.

18.
Protein Sci ; 2019 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-31762145

RESUMO

Chloramphenicol acetyltransferases (CATs) were among the first antibiotic resistance enzymes identified and have long been studied as model enzymes for examining plasmid-mediated antibiotic resistance. These enzymes acetylate the antibiotic chloramphenicol, which renders it incapable of inhibiting bacterial protein synthesis. CATs can be classified into different types: Type A are known to be important for antibiotic resistance to chloramphenicol and fusidic acid. Type B are often called xenobiotic acetyltransferases and adopt a similar structural fold to streptogramin acetyltransferases (SATs), which are known to be critical for streptogramin antibiotic resistance. Type C have recently been identified and can also acetylate chloramphenicol but their roles in antibiotic resistance are largely unknown. Here, we structurally and kinetically characterized three Vibrio CAT proteins from a non-pathogenic species (Allivibrio fisheri) and two important human pathogens (Vibrio cholerae, Vibrio vulnificus). We found all three proteins, including one in a superintegron (V. cholerae), acetylated chloramphenicol but did not acetylate aminoglycosides or dalfopristin. We also determined the 3D crystal structures of these CATs alone and in complex with crystal violet and taurocholate. These compounds are known inhibitors of Type A CATs, but have not been explored in Type B and Type C CATs. Based on sequence, structure, and kinetic analysis, we concluded the V. cholerae and V. vulnificus CATs belong to the Type B class and the A. fisheri CAT belongs to the Type C class. Ultimately, our results provide a framework for studying the evolution of antibiotic resistance gene acquisition and chloramphenicol acetylation in Vibrio and other species. This article is protected by copyright. All rights reserved.

19.
Org Biomol Chem ; 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31774099

RESUMO

An efficient protocol to synthesize 3-alkylated quinoxalin-2(1H)-ones through photocatalytic decarboxylation coupling reactions of quinoxalin-2(1H)-ones with N-hydroxyphthalimide ester was developed. The control experiment showed that a radical was involved in this transformation. This approach provides an alternative way to obtain various valuable corresponding products in moderate-to-good yields.

20.
Cell Death Dis ; 10(12): 883, 2019 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-31767833

RESUMO

Dysfunction in long noncoding RNAs (lncRNAs) is reported to participate in the initiation and progression of human cancer; however, the biological functions and molecular mechanisms through which lncRNAs affect pancreatic cancer (PC) are largely unknown. Here, we report a novel lncRNA, LINC01111, that is clearly downregulated in PC tissues and plasma of PC patients and acts as a tumor suppressor. We found that the LINC01111 level was negatively correlated with the TNM stage but positively correlated with the survival of PC patients. The overexpression of LINC01111 significantly inhibited cell proliferation, the cell cycle, and cell invasion and migration in vitro, as well as tumorigenesis and metastasis in vivo. Conversely, the knockdown of LINC01111 enhanced cell proliferation, the cell cycle, and cell invasion and migration in vitro, as well as tumorigenesis and metastasis in vivo. Furthermore, we found that high expression levels of LINC01111 upregulated DUSP1 levels by sequestering miR-3924, resulting in the blockage of SAPK phosphorylation and the inactivation of the SAPK/JNK signaling pathway in PC cells and thus inhibiting PC aggressiveness. Overall, these data reveal that LINC01111 is a potential diagnostic biomarker for PC patients, and the newly identified LINC01111/miR-3924/DUSP1 axis can modulate PC initiation and development.

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