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1.
Food Chem ; 339: 127813, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-32916401

RESUMO

Bisphenol S (BPS), a structural analog of Bisphenol A (BPA), has been widely used as a substitute for epoxy resin, food packaging materials, and other products due to the limited application of BPA. Studies in vivo and in vitro have indicated that BPA could induce fat accumulation like an obesogen. The main goal of this study was to investigate the role and mechanism of BPS in lipid metabolism using Caenorhabditis elegans (C. elegans) as a model. Results showed that both the overall fat deposition and the triglyceride level were significantly increased in a non-monotonically increasing trend, and the low dose of BPS (0.01 µM) exhibited a stronger influence. Additionally, BPS enhanced fat synthesis depending on daf-16, fat-5, fat-6 and fat-7, and inhibited fatty acid oxidation via nhr-49 and acs-2. This study further indicate that fat accumulation induced by BPS requires nhr-49, which also mediated the nuclear hormone signaling pathway.

2.
Carbohydr Polym ; 252: 117158, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33183609

RESUMO

Magnetic NiFe2O4 nanoparticles and multi-walled carbon nanotubes functionalized cellulose composite (m-NiFe2O4/MWCNTs@cellulose) as a magnetic bioadsorbent was prepared and used for effectively removing Congo Red (CR) from aqueous solution. The chemical and physical properties of the prepared m-NiFe2O4/MWCNTs@cellulose were characterized by XRD, TGA, FT-IR, VSM, SEM and TEM. Batch experiments were carried out to investigate the adsorption capacity and mechanisms. Effects of different adsorption parameters such as initial CR concentration, adsorbent dosage and temperature were studied. Results demonstrated that m-NiFe2O4/MWCNTs@cellulose had high adsorption capacity for CR from aqueous solution. The obtained experimental data fitted well with the pseudo-second-order equation and followed the Langmuir isotherm model with a maximum adsorption capacity of 95.70 mg g-1 for CR. The m-NiFe2O4/MWCNTs@cellulose with rapid magnetic separation and high adsorption capacity can be a promising and recyclable engineering biomaterials for purification and treatment of practical wastewater.

3.
Methods Mol Biol ; 2185: 159-179, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33165848

RESUMO

Leukemic stem cells are highly dynamic and heterogeneous. Analysis of leukemic stem cells at the single-cell level should provide a wealth of insights that would not be possible using bulk measurements. Mass spectrometry (MS)-based proteomic workflows can quantify hundreds or thousands of proteins from a biological sample and has proven invaluable for biomedical research, but samples comprising large numbers of cells are typically required due to limited sensitivity. Recent developments in sample processing, chromatographic separations, and MS instrumentation are now extending in-depth proteome profiling to single mammalian cells. Here, we describe specific techniques that increase the sensitivity of single-cell proteomics by orders of magnitude, enabling the promise of single-cell proteomics to become a reality. We anticipate such techniques can significantly advance the understanding of leukemic stem cells.

4.
Cancer Lett ; 2020 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-33129957

RESUMO

Hepatocellular carcinoma (HCC) is a prevalent human malignancy with high morbidity worldwide. Hepatocarcinogenesis is a complex multistep process, and its underlying molecular mechanisms remain largely unknown. Recently, long non-coding RNAs (lncRNAs), a class of newly discovered molecules, have been revealed as essential regulators in the development of HCC. HCC-associated lncRNAs affect multiple malignant phenotypes by modulating gene expression or protein activity. Moreover, the dysregulation of lncRNAs in the liver is also associated with diseases predisposing to HCC, such as chronic viral infection, nonalcoholic steatohepatitis, and liver fibrosis/cirrhosis. A deeper understanding of the lncRNA regulatory network in the multistep processes of HCC development will provide new insights into the diagnosis and treatment of HCC. In this review, we introduce the biogenesis and function of lncRNAs and summarize recent knowledge on how lncRNAs regulate the malignant hallmarks of HCC, such as uncontrolled cell proliferation, resistance to cell death, metabolic reprogramming, immune escape, angiogenesis, and metastasis. We also review emerging insights into the role of lncRNAs in HCC-associated liver diseases. Finally, we discuss the potential applications of lncRNAs as early diagnostic biomarkers and therapeutic targets.

5.
J Biomed Nanotechnol ; 16(6): 842-852, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33187580

RESUMO

Self-assembling peptide hydrogels have a high water content, good biocompatibility and have become a competitive research object in the fields of tissue engineering, cancer treatment and drug delivery. In our research, a hexapeptide with high pH sensitivity was designed and synthesized by utilizing a solid-phase synthesis method. Under physiological conditions, the peptide could self-assemble into a hydrogel. When it reached the tumor acidic microenvironment, the peptide was degraded and doxorubicin was released to exert its antitumor effect. A series of physicochemical properties were investigated, including gelling ability, secondary structure, micromorphology, rheological properties and drug release studies. The results illustrated that PIDO peptide hydrogel has good pH responsiveness and injectability. In vitro cytotoxicity experiments and in vivo antitumor experiments showed that PIDO peptide hydrogel has a highly effective therapeutic effect on tumor cells and is less toxic to normal tissues. Our research provides a promising option for targeted drug delivery and sustainable release.


Assuntos
Neoplasias da Mama , Hidrogéis , Neoplasias da Mama/tratamento farmacológico , Doxorrubicina/farmacologia , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Humanos , Microambiente Tumoral
6.
Medicine (Baltimore) ; 99(46): e23130, 2020 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-33181684

RESUMO

BACKGROUND: Polycystic ovary syndrome (PCOS) is one of the common gynecological endocrine system diseases. It is characterized by excessive androgen, rare or anovulation, and polycystic ovary morphology. Coenzyme Q10 (CoQ10) is a fat-soluble natural vitamin, which has a continuous oxidation-reduction cycle and is an effective antioxidant that can protect ovaries from oxidative damage. This study aims to systematically summarize and analyze the scientific literatures on glucose metabolism index, lipid profiles, inflammatory factor, and sex hormone level of PCOS patients treated with CoQ10 to provide a reference basis for clinical treatment. METHODS: We will retrieve the following electronic databases from the built-in until March 2021: Cochrane Library, PubMed, EMBASE, Web of Science, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), Clinical Trials. gov, Chinese Scientific Journal Database (VIP), and Wang-fang database. Two reviewers will independently scan the articles searched, de-duplication, filtering, quality assessment. Differences will be resolved by discussion between the 2 reviewers or by a third reviewers. All analyses were systematic to evaluate interventions based on the Cochrane handbook. Meta-analysis and/or subgroup analysis will be performed on the basis of the included studies. DISCUSSION: This review will be to investigate the efficacy of CoQ10 supplementation on glucose metabolism, lipid profiles, and biomarkers of inflammation in women with PCOS and provide a high-quality synthesis to assess whether CoQ10 is an effective and safe intervention for PCOS. The results of the analysis will be published in a scientific journal after peer-review. SYSTEMATIC REVIEW REGISTRATION: INPLASY 2020100013.


Assuntos
Glicemia/metabolismo , Inflamação/sangue , Lipídeos , Síndrome do Ovário Policístico , Ubiquinona/análogos & derivados , Biomarcadores/sangue , Feminino , Humanos , Lipídeos/sangue , Lipídeos/classificação , Metanálise como Assunto , Síndrome do Ovário Policístico/tratamento farmacológico , Síndrome do Ovário Policístico/metabolismo , Projetos de Pesquisa , Revisões Sistemáticas como Assunto , Resultado do Tratamento , Ubiquinona/farmacologia , Vitaminas/farmacologia
7.
Artigo em Inglês | MEDLINE | ID: mdl-33236880

RESUMO

Graphene has attracted extensive attention for the supply of electrically conductive, optically transparent, and mechanical robust electrodes for flexible optoelectrical devices, as an alternative to commercial indium tin oxide, due to its superior mechanical, electrical, and optical properties. However, conventional chemical vapor deposition is impeded by harsh conditions and complicated processes, and it is still a challenge to fabricate high-performance graphene transparent electrode in a facile and scalable solution-processable route. Herein, a wetting-induced scalable solution-processable approach to fabricate graphene hybrid with conductive ionogel and poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS), i.e., graphene/ionogel@PEDOT:PSS (G/Ionogel@PEDOT:PSS), for high-performance flexible transparent electrode (FTE) is reported, achieving a low sheet resistance of 30 Ω sq-1 and a high transmittance of 88% at 550 nm. The as-fabricated trinary hybrid FTE as both transparent electrode and electrochromic layer is applied to a compact indium tin oxide (ITO)-free three-layered flexible electrochromic device, showing fast switching response, good electrochromic contrast, and reliable stability. Our work enables a scalable solution-processable approach for the generation of graphene-based FTE and functional devices.

8.
Front Immunol ; 11: 589997, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33193421

RESUMO

Background and Aims: Pyruvate kinase M2 (PKM2) is an essential regulator of the Warburg effect, but its biological function promoting immune escape of hepatocellular carcinoma (HCC) is unclear. Methods: GEPIA web tool and immunohistochemistry (IHC) analysis were employed to evaluate the clinical relevance of PKM2 in HCC patients. Both in vitro CCK-8, colony formation, and transwell assays, and in vivo xenografts were performed to evaluate the malignancy of HCC cells. PKM2 and PD-L1 levels were examined by Western blot, qRT-PCR, and IHC. The role of PKM2 on in vivo immune response was also investigated. Results: PKM2 was significantly upregulated in HCC and associated with a poor prognosis of HCC patients. Knockdown of PKM2 inhibited in vitro proliferation, migration, and invasion of HCC cells, as well as in vivo tumor growth. Strikingly, PKM2 showed a strong correlation with the expression of immune inhibitory cytokines and lymphocyte infiltration in HCC. The overexpression of PKM2 sensitized HCC to immune checkpoint blockade, which enhanced IFN-γ positive CD8 T cells in HCC mice models. Conclusion: PKM2 might be a predictor and a potential therapeutic target for immune checkpoint inhibitors in HCC.

9.
Int J Biol Macromol ; 2020 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-33172614

RESUMO

Bitter melon polysaccharides (BPS) have been reported to have hypolipidemic effects. However, the precise mechanism of BPS regulating lipid metabolism remains elusive. Water-soluble (WBPS) and alkali-soluble bitter melon polysaccharides (ABPS) were extracted to evaluate the fat-lowering bioactivities in HepG2 cells and Caenorhabditis elegans. WBPS and ABPS were slightly different in the uronic acid contents (22.23% and 5.69%), monosaccharide composition, molecular weight (Mw: 332 kDa and 1552 kDa, respectively) and IR spectra. In palmitic acid-treated HepG2 cell, the ABPS exhibited better effects on accelerating glucose consumption and decreasing the triglyceride content than WBPS via stimulating glucose consumption (GLUT4) and gluconeogenesis (PEPCK). In the model of glucose-treated C. elegans, we observed that both WBPS and ABPS obviously suppressed the fat accumulation, more significantly by ABPS, along with no toxicity towards some physical activities. Fat-5, fat-6 and fat-7 mediated fatty acid desaturases pathways were further confirmed to be involved in the lipid-lowering effects of BPSs. Our studies demonstrated that both WBPS and ABPS can exhibit effects on fat- lowering in HepG2 cells and C. elegans.

10.
Integr Cancer Ther ; 19: 1534735420972486, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33238770

RESUMO

BACKGROUND: Jiedu Sangen Decoction (JSD), a traditional Chinese medicine formula, has been widely applied in the treatment of gastrointestinal cancer, especially in colorectal cancer. Our study mainly aimed to assess the combined efficacy of Jiedu Sangen aqueous extract (JSAE) and a PD-L1 inhibitor (PI) in colon cancer cells migration and invasion, along with epithelial-mesenchymal transition, and then provide deep insights into the potential mechanism. METHODS: We explored the inhibitory effects on invasion and metastasis and the reverse effect on EMT process in CT-26 colon cancer cell via Transwell migration assay, Matrigel invasion assay and confocal laser scanning microscopy. Furthermore, regulation in expression of EMT-related proteins and molecular biomarkers and underlying signal pathway proteins were detected through Western blotting and IHC. RESULTS: The combination of JSD and PD-L1 inhibitor could inhibit migration, invasive ability and EMT of CT-26 cells in a concentration-dependent manner. Meanwhile, JSD combined with PD-L1 inhibitor could also remarkably reverse EMT and metastasis in vivo. In addition, the protein expression of N-cadherin, Slug, Snail, Vimentin was down-regulated along with E-cadherin s up-regulation with the combination of JSD and PD-L1 inhibitor, while that of PI3K/AKT was notably down-regulated. CONCLUSIONS: These findings indicated that JSAE and a PD-L1 inhibitor could drastically inhibit the migration and invasion of colorectal cancer by reversing EMT through the PI3K/AKT signaling pathway.

11.
Int J Chron Obstruct Pulmon Dis ; 15: 2857-2867, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33192059

RESUMO

Purpose: Tobacco smoking, biomass smoke, and occupational exposure are the main risk factors for chronic obstructive pulmonary disease (COPD). The present study analyzes data on exposure to these factors in a cohort of patients with COPD and assesses their differences in demographic and clinical characteristics. Patients and Methods: The cross-sectional observational study was conducted from November 2016 to December 2019. Inclusion criteria were patients aged over 40 years old with post-bronchodilator forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) <0.7. At baseline, demographic features and exposure history were recorded. Moreover, respiratory symptoms were assessed by the COPD Assessment Test (CAT) and modified Medical Research Council scale (mMRC). A generalized linear mixed model was used to adjust for potential confounders. Results: A total of 5183 patients with COPD were included in the final analysis. The results demonstrate that exposure to tobacco combined with other risk factors resulted in significantly higher CAT scores (16.0 ± 6.7 vs 15.3 ± 6.3, P = 0.003) and more severe dyspnea (patients with mMRC ≥ 2, 71.5% vs 61.6%, P < 0.001) than exposure to tobacco alone. In addition, COPD patients with biomass smoke exposure alone had higher CAT scores than patients with only tobacco or occupational exposure (17.5 ± 6.3 vs 15.3 ± 6.3, and 15.2 ± 6.3, respectively, P < 0.05 for each comparison) and were more likely to be female and older. In addition, COPD patients who suffered from occupational exposure developed more severe dyspnea than those exposed to tobacco alone (70.8% vs 61.6%, P < 0.05), as did those exposed to biomass smoke alone (74.2% vs 61.6%, P < 0.05). This difference remained strong even after adjustment for potential confounders. Conclusion: There are significant demographic and clinical differences among COPD patients with tobacco smoking, biomass smoke, and occupational exposures.

12.
Environ Int ; 146: 106252, 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33242729

RESUMO

OBJECTIVE: Globally, developed countries such as the United States, Canada, Germany, Korea, have carried out long-term and systematic biomonitoring programs for environmental chemicals in their populations. The China National Human Biomonitoring (CNHBM) was to document the extent of human exposure to a wide array of environmental chemicals, to understand exposure profiles, magnitude and ongoing trends in exposure in the general Chinese population, and to establish a national biorepository. METHODS: CNHBM adopted three-stage sampling method to obtain a nationally representative sample of the population. A total of 21,888 participants who were permanent residents in 31 provinces were designed to interviewed in this national biomonitoring (152 monitoring sites × 3 survey units × 2 sexes × 6 age groups × 4 persons = 21,888 persons) in 2017-2018. Unlike the US National Health and Nutrition Examination Survey, the CNHBM will follow the same participants in subsequent cycles allowing for dynamic, longitudinal data sets for epidemiologic follow-up. Each survey cycle of CNHBM will last 2 years and each subsequent cycle will occur 3 years after the prior cycle's completion. RESULTS: In 2017-2018, the CNHBM created a large cohort of Chinese citizens that included districts/counties questionnaire, community questionnaire collecting information on villages/communities, individual questionnaire, household questionnaire, comprehensive medical examination, and collection of blood and urine samples for measurement of clinical and exposure biomarkers. A total of 21,746 participants were finally included in CNHBM, accounting for 99.4% of the designed sample size; and 152 PSUs questionnaires, 454 community questionnaires, 21,619 family questionnaires, 21,712 cases of medical examinations, 21,700 individual questionnaires, 21,701 blood samples and 21,704 urine samples were collected, respectively. Planned analyses of blood and urine samples were to measure both inorganic and organic chemicals, including 13 heavy metals and metalloids, 18 poly- and per-fluorinated alkyl substances, 12 phthalate metabolites, 9 polycyclic aromatic hydrocarbons metabolites, 4 environmental alkylated phenols, and 2 benzene metabolites. CONCLUSIONS: CNHBM established the first nationally representative, prospective cohort in the Chinese population to understand the baseline and trend of internal exposure of environmental chemicals in general population, and to understand environmental toxicity.

13.
Environ Sci Technol ; 2020 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-33190472

RESUMO

Arctic and Antarctic marine ecosystems, which are important components of global biodiversity, have been severely threatened by environmental pollutants in recent decades. In this study, polybrominated diphenyl ethers (PBDEs) and their hydroxylated and methoxylated analogues (OH-PBDEs and MeO-PBDEs) were analyzed in seawater, sediment, and marine organisms (algae, invertebrates, and fishes) collected surrounding the Arctic Yellow River Station (n = 83) and the Antarctic Great Wall Station (n = 72). PBDEs and the analogues were detectable in all polar marine matrices, except MeO-PBDEs in seawater. The concentrations of ∑PBDEs, ∑MeO-PBDEs, and ∑OH-PBDEs in the marine organisms were in the range of 0.33-16 ng/g lipid weight (lw), n.d.-2.6 ng/g lw, and 0.12-2.3 ng/g lw in the Arctic and 0.06-31 ng/g lw, n.d.-5.8 ng/g lw, and 0.17-35 ng/g lw in Antarctica, respectively. Biota-sediment bioaccumulation factor (BSAF, g TOC/g lipid) values of MeO-PBDEs (0.002-0.14) and OH-PBDEs (0.004-0.18) were lower than the BSAF values of PBDEs (0.85-12). Trophic magnification was found for ∑MeO-PBDEs, whereas trophic dilution was observed for ∑OH-PBDEs in both regions. This is one of very few investigations on trophic transfer of PBDE metabolites in the Antarctic and Arctic regions and will further strengthen concerns about the ecological risk of PBDE metabolites in remote areas.

14.
Front Immunol ; 11: 558143, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33178187

RESUMO

Disease relapse and graft-versus-host disease (GVHD) are the major complications affecting the outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT). While the functions of αßT cells are extensively studied, the role of donor γδT cells in allo-HSCT is less well defined. Using TCRδ-/- donors lacking γδT cells, we demonstrated that donor γδT cells were critical in mediating graft-versus-leukemia (GVL) effect during allo-HSCT. In the absence of donor γδT cells, IFN-γ production by CD8+ T cells was severely impaired. Vγ4 subset was the major γδT cell subset mediating the GVL effect in vivo, which was partially dependent on IL-17A. Meanwhile, donor γδT cells could mitigate acute GVHD in a murine allo-HSCT model by suppressing CD4+ T cell activation and the major γδT cell subset that exerted this protective function was also Vγ4 γδT cells. Therefore, our findings provide evidence that donor γδT cells, especially Vγ4 subset, can enhance GVL effect and mitigate aGVHD during allo-HSCT.

15.
Int Immunopharmacol ; 88: 106981, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33182030

RESUMO

BACKGROUND: Spontaneous abortion is a common disease in human pregnancy. Increasing evidence suggests that proper function of trophoblasts and immune balance of the maternal-fetal interface are crucial for successful pregnancy. Macrophages are involved in the maternal-fetal immune microenvironment. However, mechanisms associated with how macrophages impair trophoblasts' function in spontaneous abortion remain to be explored. METHODS: Firstly, the characteristics of the isolated macrophage-derived exosomes were verified by TEM and Western blot. Then, we established the co-culture of macrophage-derived exosomes with trophoblasts, and explored the role of the exosomes in trophoblasts. Moreover, expression of miR-153-3p in the macrophage-derived exosomes was detected. A miR-153-3p mimic was transfected into trophoblasts to investigate its function in the biological functions of trophoblast cells. MRNA and protein expressions were detected by qRT-PCR and Western blot. CCK8 assay was performed to measure cell proliferation and Transwell assay was utilized to examine migration of trophoblasts. RESULTS: Compared with those in normal pregnant women, decidual macrophage-derived exosomes from unexplained recurrent spontaneous abortion (URSA) patients suppressed the proliferation and migration of trophoblast cells through the IDO/STAT3 pathway. MiR-153-3p was highly expressed in exosomes released from decidual macrophages of URSA patients. Transfecting miR-153-3p mimics into trophoblast cells directly inhibited IDO genes, which suppressed STAT3 pathway activation, regulating the biological behavior of trophoblast cells. CONCLUSIONS: This study outlines the role of decidual macrophage-derived exosomal miR-153-3p in successful pregnancy maintenance, paving a new approach for the development of novel treatments for URSA.

16.
SLAS Technol ; : 2472630320973591, 2020 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-33213279

RESUMO

Low-volume liquid handling capabilities in bioanalytical workflows can dramatically improve sample processing efficiency and reduce reagent costs, yet many commercial nanoliter liquid handlers cost tens of thousands of dollars or more. We have successfully adapted a low-cost and open-source commercial pipetting robot, the Opentrons OT-1, to accurately aspirate and dispense nanoliter volumes. Based on fluorescence measurements, the modified OT-1 was able to reproducibly transfer 50 nL of water with less than 3% measurement error and 5% coefficient of variation (CV). For 15 nL transfers, the volume measurements indicated less than 4% error and 4% CV. We applied this platform to the preparation of low-nanogram proteomic samples for liquid chromatography-mass spectrometry analysis, demonstrating that the modified OT-1 is an effective platform for nanoliter liquid handling. At a total materials cost of less than $6000, including the commercial liquid handler and all modifications, this system is also far less expensive than other platforms with similar capabilities, placing automated nanoliter handling within reach of a far broader scientific community.

17.
Nanoscale ; 2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33216101

RESUMO

Lithium sulfur batteries are expected to be one of the most promising energy storage systems due to their high energy density, low cost and environmental friendliness. However, the shuttle effect of lithium polysulfides severely hampers their practical application. The design of the sulfur cathode is one of the most important approaches to overcome the problem. In this work, MoS2 nanosheets have been successfully grown on the surface of hollow carbon spheres (HCS) to obtain MoS2@HCS nanocomposites with uniform morphology. The growth behavior of MoS2 nanosheets was also proved by adjusting the pore structure of HCS. With a sulfur loading of 74%, the MoS2@HCS/S cathode exhibits a high initial reversible capacity of 1419 mA h g-1 at a current density of 0.1 C and remains at 1010 mA h g-1 after 100 cycles. Even at 0.5 C, a capacity of 795 mA h g-1 can be retained after 600 cycles, corresponding to a capacity retention rate of 63.1%. By adjusting the concentration of the sulfur source, the relationship between different growth quantities of MoS2 and the cycling performance of the battery was also investigated. The excellent electrochemical performance of the MoS2@HCS/S cathode can be fully attributed to its physical and chemical double adsorption effect on lithium polysulfides, which has been confirmed through the visible adsorption and X-ray Photoelectron Spectroscopy (XPS) experiments. This work provides a simple design concept and method to synthesize a nanocomposite-based sulfur host for high performance lithium sulfur batteries.

18.
Diabetes ; 2020 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-33154070

RESUMO

Toll-like receptor 9 (TLR9) is highly expressed in B cells and B cells are important in the pathogenesis of type 1 diabetes (T1D) development. However, the intrinsic effect of TLR9 in B cells on beta cell autoimmunity is not known. To fill this knowledge gap, we generated non-obese diabetic (NOD) mice with a B cell-specific deficiency of TLR9 (TLR9fl/fl/CD19-Cre+ NOD). The B cell-specific deletion of TLR9 resulted in near complete protection from T1D development. Diabetes protection was accompanied by an increased proportion of IL-10-producing B cells. We also found that TLR9-deficient B cells were hyporesponsive to both innate and adaptive immune-stimuli. This suggested that TLR9 in B cells modulates T1D susceptibility in NOD mice by changing the frequency and function of IL-10-producing B cells. Molecular analysis revealed a network of TLR9 with MMPs, TIMP1 and CD40, all of which are inter-connected with IL-10. Our study has highlighted an important connection of an innate immune molecule in B cells to the immuno-pathogenesis of T1D. Thus, targeting the TLR9 pathway, specifically in B cells, may provide a novel therapeutic strategy for T1D treatment.

19.
Antimicrob Resist Infect Control ; 9(1): 166, 2020 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-33109242

RESUMO

BACKGROUND: This study reports the global trends of antimicrobial susceptibility to ceftaroline and ceftazidime-avibactam using data from the Antimicrobial Testing Leadership and Surveillance (ATLAS) program between 2012 and 2016. METHODS: For the 2012-2016 ATLAS program, 205 medical centers located in Africa-Middle East (n = 12), Asia-Pacific (n = 32), Europe (n = 94), Latin America (n = 26), North America (n = 31), and Oceania (n = 10) consecutively collected the clinical isolates. The minimum inhibitory concentrations (MICs) and in vitro susceptibilities to ceftaroline and ceftazidime-avibactam were assessed using the Clinical and Laboratory Standards Institute (CLSI) 2019and European Committee on Antimicrobial Susceptibility Testing (EUCAST) 2019 guidelines. RESULTS: Between 2012 and 2016, 176,345 isolates were collected from around the globe and included in the analysis. Regarding Gram-negative bacteria, ceftazidime-avibactam demonstrated high susceptibility (> 90%) against Enterobacteriaceae and Pseudomonas aeruginosa, with increased antimicrobial activity observed from the addition of avibactam (4 mg/L) to ceftazidime. Regarding Gram-positive bacteria, ceftaroline showed > 90% susceptibility against Staphylococcus aureus, Streptococcus pneumoniae, α-and ß-hemolytic Streptococcus. The antimicrobial susceptibilities to ceftaroline and ceftazidime-avibactam were mostly stable from 2012 to 2016, but the susceptibilities to ceftazidime-avibactam to carbapenem-resistant (CR) Klebsiella pneumonia (88.4-81.6%) and to CR-P. aeruginosa (89.6-72.7%) decreased over time. In terms of regional difference, the susceptibilities of methicillin-resistant S. aureus to ceftaroline in Asia and of CR-K. pneumonia to ceftazidime-avibactam in Asia/Africa-Middle East were lower compared with other regions, while the susceptibility of CR-P. aeruginosa to ceftazidime-avibactam in North America was higher. CONCLUSION: The addition of avibactam improves the activity of ceftazidime against Enterobacteriaceae and P. aeruginosa. The global antimicrobial susceptibilities to ceftaroline and ceftazidime-avibactam were, in general, stable from 2012 to 2016, but a marked reduction in the susceptibilities of specific species and CR-P. aeruginosa to ceftazidime-avibactam was observed.

20.
Sci Total Environ ; 755(Pt 2): 142658, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33045597

RESUMO

Drinking water treatment plants (DWTPs) are thought to be able to remove many micropollutants including nanoplastics (NPs) and microplastics (MPs). However, few studies have focused on the water treatment process itself producing NPs and/or MPs. This paper discussed the possibility of releasing NPs and MPs from organic membranes in drinking water treatment plants. The effects of physical cleaning, chemical agents, mechanical stress, aging, and wear on the possibility of membrane breach during long-term use were analyzed. Further analysis based on membrane aging mechanisms and material properties revealed that the membrane filtration systems could release NPs/MPs to drinking water supply networks. Although the toxicity of membrane materials to human body needs further study, the action that should be taken to treat the release of NPs/MPs in DWTPs cannot be ignored: (1) in-depth study of the generation and release mechanisms of NPs/MPs; (2) reconsideration of membrane life cycle design; (3) determination of NPs/MPs concentration limits in drinking water through toxicity assessment; (4) accelerating development of biomembrane and inorganic membrane materials; and (5) unification of NPs/MPs sampling and testing standard. Accordingly, more research needs to be conducted to investigate the release of NPs and/or MPs from DWTPs.

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