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1.
Int J Hyg Environ Health ; 223(1): 106-115, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31606406

RESUMO

The application of Water Safety Plans (WSPs) in China varies throughout the country. Although pilot WSP projects in China were initiated shortly after WSP was introduced by the World Health Organization (WHO) in 2004, they have yet to be used for water supply facilities at a large scale. To better understand the evolution of WSP application in China, a systematic review was conducted to identify all published WSP related studies in China. Eighteen studies, which included 311 water systems, were included in the final analysis. Risk matrix, water supply risk factors, and other data were extracted and analyzed. Text mining methods were also used to better understand risks that can be addressed by WSPs (both potential and actual risks). This study revealed a number of noteworthy differences between and among urban and rural water systems in China. The primary risks associated with most urban water supply systems tended to be related to mechanical failure/s in the water treatment process. Rural water supply systems appear to suffer from similar problems, but insufficient overall management capacity was more prevalent in rural systems. Overall, the evidence suggests that, to date, the use of WSPs in China has been primarily limited to pilot studies, and full implementation of WSPs in China appears to still be in the early stages. The paper closes with a summary of the key obstacles identified as well as a discussion of policies and technical options which could increase the use of WSPs in both urban and rural China. Among other recommendations, the data indicate that there is strong need for the development and implementation of a simplified WSP approach designed specifically for small rural systems in China.

2.
J Nanosci Nanotechnol ; 20(3): 1417-1424, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31492302

RESUMO

As a bone implant material, porous tantalum (Ta) has better corrosion resistance and more suitable elastic modulus than titanium. Surface nanomodification can accelerate the integration of Ta implants with bone tissue, which has broad application prospects in the field of dental implantology. Due to mechanical stress and load wear, nanoscale Ta fragments are inevitably exfoliated from the implant surface and brought into direct contact with osteoblasts surrounding the implant. These wear fragments may affect the biological characteristics of osteoblasts and thus the stability of implants. To date, the interaction of nanoscale Ta fragments with osteoblasts has not been clearly investigated. In the current study, we used the mouse osteoblast cell line MC3T3-E1 to explore the effects of Ta nanoparticles (Ta-NPs) on the cytotoxicity, oxidative stress and autophagy of osteoblasts. We found that a low concentration (12.5 µg/mL) of Ta-NPs can promote the proliferation of osteoblasts, while the Ta-NPs began to induce a decrease in cell viability at concentrations ≥25 µg/mL. Increased cell mortality, reactive oxygen species (ROS) production and decreased mitochondrial membrane potential (MMP) occurred in a dose-dependent manner after Ta-NP treatment. Moreover, with Ta-NP stimulation, the ratio of LC3-II/LC3-I increased, and the level of p62 protein was reduced. However, the degradation of p62 was not continuously increased when the concentration of Ta-NPs was ≥25 µg/mL. These results indicate that Ta-NPs induced osteoblast damage via oxidative stress. Autophagy activation may be a key factor in the cellular response to Ta-NP toxicity and could have an important impact on determining the survival or death of osteoblasts.

3.
Methods Mol Biol ; 2043: 237-250, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31463916

RESUMO

ADAMTS (a disintegrin-like and metalloprotease domain with thrombospondin type 1 motifs) proteins regulate tissue homeostasis and extracellular matrix (ECM)-related pathogenesis. Some ADAMTS proteins interact with or process multiple ECM proteins, including fibrillins, fibronectin, and collagens. Therefore, characterization and quantification of these ECM fiber systems is essential to understand their functional relationship with ADAMTS proteins. Here we describe unbiased methods to quantify various aspects of ADAMTS-related ECM fiber systems in cell culture and in tissues. We focus on cell counting, overall fiber intensity, fiber length, and focal adhesion analysis in cell culture, and on the quantification of immunohistochemical and immunofluorescent tissue sections. We use ImageJ/Fiji, a widely used Java-based open source software which provides efficient and customizable quantification methods for microscopy images.

4.
Sci Total Environ ; 698: 134122, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31505349

RESUMO

Carbon black nanoparticles (CBNPs) are core component of fine particulate matter (PM2.5) in the atmosphere. It was reported that the particle in the atmosphere with smaller size and the larger the specific surface area are easier to reach the deep respiratory tract or even the alveoli through the respiratory barrier and cause lung injury. Therefore, it has been believed that ultrafine or nanometer particles with more toxic than those with larger particle sizes. Moreover, it was confirmed that CBNPs could induce inflammation, oxidative stress and changes in cell signaling and gene expression in mammalian cells and organs. However, the cytotoxicity mechanism of them has been uncertain so far. The aim of the present study was to explore the underlying mechanism of cytotoxicity induced by CBNPs on A549 cells. In the current research, the viabilities of A549 cells were detected by Cell Counting Kit-8 (CCK-8) assay. The further metabolomics studies were conducted to detect the cytotoxic effect of CBNPs on A549 cells with an IC50 value of 70 µg/mL for 48 h. Potential differential compounds were identified and quantified using a novel on-line acquisition method based on ultra-liquid chromatography quadrupole time-of-flight mass spectrometry(UHPLC-Q-TOF/MS). The cytotoxicity mechanism of CBNPs on A549 cells was evaluated by multivariate data analysis and statistics. As a result, a total of 32 differential compounds were identified between CBNPs exposure and control groups. In addition, pathway analysis showed the metabolic changes were involved in the tricarboxylic acid (TCA) cycle, alanine, aspartate and glutamate metabolism, histidine metabolism and so on. It is also suggested that CBNPs may induce cytotoxicity by affecting the normal process of energy metabolism and disturbing several vital signaling pathways and finally induce cell apoptosis.

5.
Nanotechnology ; 31(4): 045604, 2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-31578003

RESUMO

Gallium nitride (GaN)-based nanowires (NWs) have attracted much attention for the fabrication of novel nanostructured devices. In this paper, the influence of an AlN seeding layer on the nucleation of self-assembled GaN NWs grown by plasma-assisted molecular beam epitaxy (MBE) on Si (111) substrates has been investigated. Not only is the formation of a two-dimensional compact GaN layer at the bottom of the NWs suppressed, but also a high density of vertically aligned well-separated GaN NWs originating from GaN islands are successfully obtained after introducing annealing and nitridation processes. Scanning electronic microscope and transmission electron microscope measurements show that the NWs have a high crystalline wurtzite structure nearly free of dislocations and stacking faults and the NW diameter remains constant over almost the entire length. Due to the temperature-dependent diffusion length of Ga adatoms during the nucleation process, the formation of well-separated NWs relies on the distribution and morphology of the underlying AlN seeding layer. Moreover, the SiNx layer served as mask to inhibit coalescence at the nucleation sites. The developed growth processes and the obtained results provide a viable path facilitating the use of MBE growth techniques to fabricate III-nitride NW-based materials and related devices on Si substrates.

6.
Chemosphere ; 241: 125075, 2019 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-31683435

RESUMO

Carbon black nanoparticle (CBNP) is a core constituent of air pollutants like fine particulate matter (PM2.5) as well as a common manufactural material. It was proved to pose adverse effects on lung function and even provoke pulmonary fibrosis. However, the underlying mechanisms of CBNPs-induced pulmonary fibrosis remain unclear. The present study aimed to investigate the mechanism of fibrotic effects caused by CBNPs in rat lung and human bronchial epithelial (16HBE) cells. Forty-nine male rats were randomly subjected to 7 groups, means the 14-day exposure group (30 mg/m3), the 28-day exposure groups (5 mg/m3 and 30 mg/m3), the 90-day exposure group (30 mg/m3) and their respective controls. Rats were nose-only-inhaled CBNPs. 16HBE cells were treated with 0, 50, 100 and 200 µg/mL CBNPs respectively for 24 h. Besides, Forkhead transcription factor class O (FOXO)3a and miR-96 overexpression or suppression 16HBE cells were established to reveal relative mechanisms. Our results suggested CBNPs induced pulmonary fibrosis in time- and dose-dependent manners. CBNPs induced persisting inflammation in rat lung as observed by histopathology and cytology analyses in whole lung lavage fluid (WLL). Both in vivo and in vitro, CBNPs exposure significantly increased the expression of NLRP3 inflammasome, accompanied by the increased reactive oxygen species (ROS), decreased miR-96 and increased FOXO3a expressions dose -and time-dependently. MiR-96 overexpression or FOXO3a suppression could partially rescue the fibrotic effects through inhibiting NLRP3 inflammasome. Conclusively, our research show that CBNPs-induced pulmonary fibrosis was at least partially depended on activation of NLRP3 inflammasome which modulated by miR-96 targeting FOXO3a.

7.
Neuropsychologia ; : 107255, 2019 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-31715196

RESUMO

Episodic future thinking (EFT), the mental ability of projecting oneself into the future to pre-experience an event, has strong adaptive value for allowing people to consider potential consequences before taking actions. EFT includes two important components: the ability to construct detailed and vivid scenes of future events to achieve a goal (measured here by the EFT-sensory perceptual qualities scale) and the ability to subjectively experience "mental time travel" in which the person feels oneself to be in the future (measured here by the EFT-Autonoetic consciousness scale). However, little is known about the neuroanatomical structures of EFT. To shed light on this question, we employed voxel-based morphometry (VBM) to investigate the neural substrates underlying EFT. In Sample 1 (135 participants), EFT-sensory perceptual qualities was positively correlated with the gray matter (GM) volume of the hippocampus and putamen. EFT-Autonoetic consciousness was positively correlated with GM volume of the insula and amygdala, and negatively correlated with GM volumes of the medial frontal gyrus. The verification results from Sample 2 (59 participants) found that EFT-sensory perceptual qualities can be predicted by the GM volumes of the hippocampus and putamen, and EFT-Autonoetic consciousness can be predicted by the GM volumes of insula and amygdala. The present findings suggest that the hippocampus, putamen, and amygdala and insula are key regions for scene construction, goal-directed processing, and emotion respectively, and play important roles in the underlying structural neural substrates of EFT.

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-31704682

RESUMO

Staphylococcus aureus infection poses a serious threat to public health, and antibiotic resistance has complicated the clinical treatment and limited the solutions available to solve this problem. Cold atmospheric plasma (CAP) is a promising strategy for microorganism inactivation. However, the mechanisms of microbial inactivation or resistance remain unclear. In this study, we treated S. aureus strains with a self-assembled CAP device and found that CAP can kill S. aureus in an exposure time-dependent manner. In addition, liquid environment can influence the survival rate of S. aureus post CAP treatment. The S. aureus cells can be completely inactivated in normal saline and phosphate buffered saline but not in tryptic soy broth culture medium. Scanning and transmission electron microscopy revealed that the CAP-treated S. aureus cells maintained integrated morphological structures, similar to the wild-type strain. Importantly, the CAP-treated S. aureus cells exhibited reduced pigment phenotype. Deletion of staphyloxanthin biosynthetic genes crtM and crtN deprived the pigmentation ability of S. aureus Newman. Both Newman-ΔcrtM and Newman-ΔcrtN mutants presented high sensitivity to CAP treatment, whereas Newman-ΔcrtO exhibited comparable survival rate to wild-type Newman after CAP treatment. Our data demonstrated that the yellow pigment intermediates of the staphyloxanthin biosynthetic pathway are responsible for the protection of S. aureus from CAP inactivation. The key enzymes, such as CrtM and CrtN, of the golden staphyloxanthin biosynthetic pathway could be important targets for the design of novel sterilization strategies against S. aureus infections.Importance Staphylococcus aureus is an important pathogen that can widely distribute in the community and clinical settings. The emergence of S. aureus with multiple antibiotics resistance has complicated the staphylococcal infection control. The development of alternative strategies with powerful bactericidal effects is urgently needed. Cold atmospheric plasma (CAP) is a promising strategy for microorganism inactivation. Nevertheless, the underlying mechanisms of microbial inactivation or resistance are not completely illustrated. In this study, we validated the bactericidal effects of CAP on S. aureus, including antibiotics-resistant strains. We also found that the golden staphyloxanthin, as well as its yellow pigment intermediates, protected S. aureus against CAP, and blocking staphyloxanthin synthesis pathway at the early steps could strengthen the sensitivity of S. aureus to CAP treatment. These data provide insights into the germicidal mechanism of CAP from the aspect of bacteria, and suggest new targets against S. aureus infections.

10.
Bioorg Med Chem Lett ; 29(24): 126638, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31685340

RESUMO

Viral infectivity factor (Vif) is one of the accessory protein of human immunodeficiency virus type I (HIV-1) that inhibits host defense factor, APOBEC3G (A3G), mediated viral cDNA hypermutations. Previous work developed a novel Vif inhibitor 2-amino-N-(2-methoxyphenyl)-6-((4-nitrophenyl)thio)benzamide (1) with strong antiviral activity. Through optimizations on the two side branches, a series of compound 1 derivatives (2-18) were designed, synthesized and tested in vitro for their antiviral activities. The biological results showed that compound 5 and 16 inhibited the virus replication efficiently with EC50 values of 9.81 and 4.62 µM. Meanwhile, low cytotoxicities on H9 cells were observed for the generated compounds by the MTT assay. The structure-activity relationship of compound 1 was preliminarily clarified, which gave rise to the development of more potent Vif inhibitors.

12.
ACS Infect Dis ; 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31709791

RESUMO

The smart design of ß-lactamase inhibitors allowed us to combat extended-spectrum ß-lactamase (ESBL)-producing organisms for many years without developing resistance to these inhibitors. However, novel resistant variants have emerged recently, and notable examples are the CTX-M-190 and CTX-M-199 variants, which carried a S130T amino acid substitution and exhibited resistance to inhibitors such as sulbactam and tazobactam. Using mass spectrometric and crystallographic approaches, this study depicted the mechanisms of inhibitor resistance. Our data showed that CTX-M-64 (S130T) did not cause any conformational change or exert any effect on its ability to hydrolyze ß-lactam substrates. However, binding of sulbactam, but not clavulanic acid, to the active site of CTX-M-64 (S130T) led to the conformational changes in such active site, which comprised the key residues involved in substrate catalysis, namely, Thr130, Lys73, Lys234, Asn104, and Asn132. This conformational change weakened the binding of the sulbactam trans-enamine intermediate (TSL) to the active site and rendered the formation of the inhibitor-enzyme complex, which features a covalent acrylic acid (AKR)-T130 bond, inefficient, thereby resulting in inhibitor resistance in CTX-M-64 (S130T). Understanding the mechanisms of inhibitor resistance provided structural insight for the future development of new inhibitors against inhibitor-resistant ß-lactamases.

13.
Sci Rep ; 9(1): 16493, 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31712742

RESUMO

The North Pacific Ocean is a significant carbon sink region, but little is known about the dynamics of particulate organic carbon (POC) and the influences of physical and biological processes in this region at the basin scale. Here, we analysed high-resolution surface POC data derived from MODIS-Aqua during 2003-2017, together with satellite-derived sea surface chlorophyll and temperature (SST). There are large spatial and temporal variations in surface POC in the North Pacific. Surface POC is much lower in the subtropical region (<50 mg m-3) than in the subarctic region (>100 mg m-3), primarily resulting from the south-to-north variability in biological production. Our analyses show significant seasonal and interannual variability in surface POC. In particular, there is one peak in winter-spring in the western subtropical region and two peaks in late spring and fall in the western subarctic region. Surface POC is positively correlated with chlorophyll (r = ~1) and negatively correlated with SST (r = ~-0.45, P < 0.001) south of 45°N, indicating the strong influence of physically driven biological activity on the temporal variability of POC in the subtropical region. There is a significantly positive but relatively lower correlation coefficient (0.6-0.8) between POC and chlorophyll and an overall non-significantly positive correlation between POC and SST north of 45°N, reflecting the reduction in the POC standing stock due to the fast sinking of large particles. The climate modes of the Pacific Decadal Oscillation, El Niño-Southern Oscillation and North Pacific Gyre Oscillation have large impacts on POC in various seasons in the subtropical region and weak influences in the subarctic region. Surface POC was anomalously high after 2013 (increased by ~15%) across the basin, which might be the result of complex interactions of physical and biological processes associated with an anomalous warming event (the Blob).

14.
Comput Biol Med ; 115: 103508, 2019 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-31698237

RESUMO

The effect of untreated Obstructive Sleep Apnoea (OSA) on cerebral haemodynamics and CA impairment is an active field of research interest. A breath-hold challenge is usually used in clinical and research settings to simulate cardiovascular and cerebrovascular changes that mimic OSA events. This work utilises temporal arterial oxygen saturation (SpO2) and photoplethysmography (PPG) signals to estimate the temporal cerebral blood flow velocity (CBFv) waveform. Measurements of CBFv, SpO2, and PPG, were acquired concurrently from volunteers performing two different protocols of breath-hold challenge in the supine position. Past values of the SpO2 and PPG signals were used to estimate the current values of CBFv using different permutations and topologies of supervised learning with shallow artificial neural networks (ANNs). The measurements from one protocol were used to train the ANNs and find the optimum topologies, which in turn were tested using the other protocol. Data collected from 10 normotensive, healthy subjects (four females, age 28.5 ±â€¯6.1 years, Body Mass Index (BMI) 24.0 ±â€¯4.7 kg/m2) were used in this study. The results show that different subjects have different optimum topologies for ANNs, thus indicating the effects of inter-subject variability on ANNs. Successfully reconstructed blind waveforms for the same subject group in the second protocol showed a reasonable accuracy of 60-80% estimation compared to the measured waveforms. HYPOTHESIS: Temporal waveforms for SpO2 and PPG contain adequate information to estimate the temporal CBFv waveform using ANNs. METHODOLOGY: Concurrent measurements of SpO2 and PPG using pulse oximetry from the forehead and CBFv from the middle cerebral artery (MCA) using transcranial Doppler (TCD) were recorded from healthy, normotensive subjects performing a breath-hold challenge. The breath-hold challenge mimicked the cerebrovascular response to apnoea, and was recorded by measuring CBFv in MCA. Two protocols were used, each consisting of five breath-holding manoeuvres and differing in terms of the time between the five successive breath-holds. Using data from one protocol, several permutations of the temporal values of SpO2 and PPG signals were used as inputs to different ANN topologies, in order to train and find the optimum model. The optimum model was evaluated using the data from the other protocol as a blind dataset. RESULTS: Using the first protocol for training, optimum ANN configurations were found to be different for each subject, and accuracy of 75-87% was achieved. When these optimum ANN models were tested using the second protocol as a blind dataset, the accuracy achieved was around 60-80%. CONCLUSIONS: A novel approach employing temporal records of SpO2 and PPG can be used to estimate the CBFv waveform using ANNs with acceptable accuracy. Increases in the size and diversity of the population dataset and the use of features extracted from SpO2 and PPG signals are needed for generalisation of the method and potential future clinical applications.

15.
Artigo em Inglês | MEDLINE | ID: mdl-31747750

RESUMO

Boron nitride (BN) has attracted great attention with unexpected ability in aerobic catalysis. Still, its related probe reactions are relatively rare, and the effect of BN supported metal catalyst on O2 activation is still ambiguous and opinions are varied. In this work, porous BN (pBN) supported Au catalyst with porous structure and exposed edges exhibits high activity in the oxidative cross-esterification reactions between aromatic and C1-C3 aliphatic alcohols at ambient temperature. The turnover frequency value for methyl benzoate is 118 h-1 at 30 °C and the calculated apparent activation energy (Ea, 58 kJ/mol) is comparable to that of AuPd/TiO2, Ru/Al2O3 and PdBiTe catalysts. Combined with TPD results, the loading of Au enhances desorption of O2 and the interaction with alcohols, thus a synergistic effect between the O-rich pBN and Au is considered. The free-radical scavenger can dramatically suppress the conversion (~6%) suggesting that the reaction proceeds via the O2* radicals. According to the vibration of νO-O, δOO-H and vB-O-O-B detected by ATR-IR, we prone to consider the oxygen activation route by the edge B atoms. Then a possible L-H reaction mechanism was proposed: benzyl alcohol and O2 adsorb on the Au/pBN initially; then O2 is converted to O2*, and the α-H elimination proceeds; as the semi-acetal formed, another α-H termination proceeds and methyl benzoate is finally formed.

16.
Bone ; 131: 115151, 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31751752

RESUMO

Dentin matrix protein 1 (DMP1) is primarily expressed in osteocytes, although a low level of DMP1 is also detected in chondrocytes. Removing Dmp1 in mice or a mutation in humans leads to hypophosphatemic rickets (identical to X-linked hypophosphatemia). The deformed skeletons were currently thought to be a consequence of an inhibition of chondrogenesis (leading to an accumulation of hypertrophic chondrocytes and a failure in the replacement of cartilage by bone). To precisely study the mechanisms by which DMP1 and phosphorus control temporomandibular condyle formation, we first showed severe malformed condylar phenotypes in Dmp1-null mice (great expansions of deformed cartilage layers and subchondral bone), which worst as aging. Next, we excluded the direct role of DMP1 in condylar hypertrophic-chondrogenesis by conditionally deleting Dmp1 in hypertrophic chondrocytes using Col10a1-Cre and Dmp1 loxP mice (displaying no apparent phosphorous changes and condylar phenotype). To address the mechanism by which the onset of endochondral phenotypes takes place, we generated two sets of tracing lines in the Dmp1 KO background: AggrecanCreERT2-ROSA-tdTomato and Col 10a1-Cre-ROSA-tdTomato, respectively. Both tracing lines displayed an acceleration of chondrogenesis and cell trans-differentiation from chondrocytes into bone cells in the Dmp1 KO. Next, we showed that administrations of neutralizing fibroblast growth factor 23 (FGF23) antibodies in Dmp1-null mice restored hypophosphatemic condylar cartilage phenotypes. In further addressing the rescue mechanism, we generated compound mice containing Col10a1-Cre with ROSA-tdTomato and Dmp1 KO lines with and without a high Pi diet starting at day 10 for 39 days. We demonstrated that hypophosphatemia leads to an acceleration of chondrogenesis and trans-differentiation of chondrocytes to bone cells, which were largely restored under a high Pi diet. Finally, we identified the causative molecule (ß-catenin). Together, this study demonstrates that the Dmp1-null caused hypophosphatemia, leading to acceleration (instead of inhibition) of chondrogenesis and bone trans-differentiation from chondrocytes but inhibition of bone cell maturation due to a sharp increase in ß-catenin. These findings will aid in the future treatment of hypophosphatemic rickets with FGF23 neutralizing antibodies.

17.
Artigo em Inglês | MEDLINE | ID: mdl-31778164

RESUMO

OBJECTIVES: To investigate the genomic and phenotypic characteristics of an MDR Empedobacter falsenii strain isolated from a Chinese patient, which was phenotypically resistant to all last-line antibiotics (carbapenems, colistin and tigecycline). METHODS: Species identity was determined by MALDI-TOF MS analysis. The complete genome sequence of the isolate was determined by WGS and the genetic elements conferring antimicrobial resistance were determined. The origin of this strain was tracked by phylogenetic analysis. RESULTS: The E. falsenii strain was genetically most closely related to an Empedobacter sp. strain isolated from the USA. Members of E. falsenii are speculated to be intrinsically resistant to colistin. The carbapenem resistance of this strain was conferred by a chromosomal blaEBR-2 variant gene. Phylogenetic analysis indicated that the gene encoding the EBR ß-lactamase was widely distributed in Empedobacter spp. Tigecycline resistance was mediated by a tet(X) variant gene encoded by a non-conjugative and non-typeable plasmid. CONCLUSIONS: The MDR phenotype of the E. falsenii isolate was conferred by different mechanisms. Findings from us and others indicate that E. falsenii may serve as a reservoir for carbapenem and tigecycline resistance determinants.

18.
Environ Pollut ; 255(Pt 2): 113320, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31610505

RESUMO

Smoky coal burning is a predominant manner for heating and cooking in most rural areas, China. Air pollution is associated with the risk of atherosclerosis, however, the link between indoor air pollution induced by smoky coal burning and atherosclerosis is not very clear. Therefore, we designed a cross-sectional study to evaluate the association of long-term exposure to smoky coal burning pollutants with the risk of atherosclerosis. 426 and 326 participants were recruited from Nangong, China and assigned as the coal exposure and control group according to their heating and cooking way, respectively. The indoor air quality (PM2.5, CO, SO2) was monitored. The association between coal burning exposure and the prevalence of atherosclerosis was evaluated by unconditional logistic regression analysis, adjusted for confounding factors. The inflammatory cytokines mRNAs (IL-8, SAA1, TNF-α, CRP) expression in whole blood were examined by qPCR. People in the coal exposure group had a higher risk of carotid atherosclerosis compared with the control (risk ratio [RR], 1.434; 95% confidence interval [95%CI], 1.063 to 1.934; P = 0.018). The association was stronger in smokers, drinkers and younger (<45 years old) individuals. The elevation of IL-8 (0.24, 95%CI, 0.06-0.58; P < 0.05), CRP (0.37, 95%CI, 0.05-0.70; P < 0.05), TNF-α (0.41, 95%CI, 0.14-0.67; P < 0.01) mRNAs expression in whole blood were positively related to coal exposure. Our results suggested long-term exposure to smoky coal burning emissions could increase the risk of carotid atherosclerosis. The potential mechanism might relate that coal burning emissions exposure induced inflammatory cytokines elevation which had adverse effects on atherosclerotic plaque, and then promoted the development of atherosclerosis.

19.
Pediatr Surg Int ; 35(12): 1363-1368, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31576466

RESUMO

AIM OF THE STUDY: Human breast milk reduces the risk and severity of necrotizing enterocolitis (NEC). Exosomes are extracellular vesicles (EVs) found in high concentrations in milk, and they mediate intercellular communication and immune responses. The aim of this study is to compare the protective effects of exosomes that are derived from different time periods of breast milk production against intestinal injury using an ex vivo intestinal organoid model. METHODS: Colostrum, transitional and mature breast milk samples from healthy lactating mothers were collected. Exosomes were isolated using serial ultracentrifugation and filtration. Exosomes' presence was confirmed using transmission electron microscopy (TEM) and western blot. To form the intestinal organoids, terminal ileum was harvested from neonatal mice pups at postnatal day 9, crypts were isolated and organoids were cultured in matrigel. Organoids were either cultured with exposure to lipopolysaccharide (LPS), or in treatment groups where both LPS and exosomes were added in the culturing medium. Inflammatory markers and organoids viability were evaluated. MAIN RESULTS: Human milk-derived exosomes were successfully isolated and characterized. LPS administration reduced the size of intestinal organoids, induced inflammation through increasing TNFα and TLR4 expression, and stimulated intestinal regeneration. Colostrum, transitional and mature human milk-derived exosome treatment all prevented inflammatory injury, while exosomes derived from colostrum were most effective at reducing inflammatory cytokine. CONCLUSIONS: Human breast milk-derived exosomes were able to protect intestine organoids against epithelial injury induced by LPS. Colostrum exosomes offer the best protective effect among the breast-milk derived exosomes. Human milk exosomes can be protective against the development of intestinal injury such as that seen in NEC.

20.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(5): 1387-1394, 2019 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-31607288

RESUMO

OBJECTIVE: To investigate the effect of metformin on the proliferation, apoptosis and energy metabolism of acute myeloid leukemia (AML) K562 cells and the possible mechanism. METHODS: Different doses (0, 5, 10, 20 and 30 mmol/L) of metformin was added into the K562 cells, which were cultivated for 24 h, 48 h and 72 h. The inverted optical microscope was used to observe the cell growth, CCK 8 was used to detect the cell vitality. The appropriate metformin doses (0, 10, 20 and 30 mmol/L) and the best time (48 h) were selected for subsequent experiments. The flow cytometer with Annexin V-FITC /PI doulde staining was used to detect apoptosis; the glucose detection kit and lactate detection kit were used to detect glucose consumption and lactate production; fluorescence quantitative PCR was used to detect glycolysis-related gene expression, and Western blot was used to detect protein expression. RESULTS: Metformin inhibited the proliferation of K562 cells in a dose-dependent manner (r=0.92), and the relative survival in the 30 mmol/L group was as low as 19.84% at 72 h. When treated with metformin for 48 h, the apoptosis rates of 0, 10, 20 and 30 mmol/L groups were 5.14%, 12.19%, 26.29% and 35.5%, respectively. Compared with the control group, the glucose consumption and lactate secretion of K562 cells treated with metformin were significantly reduced (P<0.05), and showed a dose-dependent effect(r=0.94,r=0.93,respectively). Metformin inhibited the expression of GLUT1, LDHA, ALDOA, PDK1, and PGK1 genes of K562 cells (P<0.05) showing a dose-dependent manner(r=0.83,r=0.80,r=0.72,r=0.76,r=0.73,respectively). Metformin inhibited the expression of P-Akt, P-S6, GLUT1, LDHA proteins of K562 cells(P<0.05), showing a dose-dependent relationship(r=0.80,r=0.92,r=0.83,r=0.92,respectively). CONCLUSION: Metformin can inhibit the growth and proliferation of K562 cells and promote the apoptosis of K562 cells by inhibiting glycolysis energy metabolism. PI3K/Akt/mTOR signaling pathway may be one of the molecular mechanisms of metformin on k562 cells.


Assuntos
Metformina/farmacologia , Apoptose , Proliferação de Células , Glicólise , Humanos , Células K562 , Fosfatidilinositol 3-Quinases
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