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1.
Environ Pollut ; 259: 113918, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-32023794

RESUMO

Natural sources, such as soil and wind-erosion dust (SWD), biomass open burning (BOB), sea salt spray (SSAS) and biogenic source (BIO), are major contributors to atmospheric emissions of trace elements (TEs) globally. In this study, we used a comprehensive approach to account for area-, production- and biofuel consumption-based emission factor calculation methods, and thus developed an integrated high-resolution emission inventory for 15 types of TEs (As, B, Cd, Co, Cr, Cu, Hg, Mn, Mo, Ni, Pb, Sb, Se, V and Zn) originated from natural sources in China for the year 2015. The results show that national emissions of TEs in 2015 range from 7.45 tons (Hg) to 1, 400 tons (Zn) except for the extremely high emissions of Mn (10, 677 tons). SWD and BIO are identified as the top two source contributors, accounting for approximately 67.7% and 26.1% of the total emissions, respectively. Absolute emissions of TEs from natural sources are high in the Xinjiang, Inner Mongolia and Tibet autonomous regions with large areas of bare soil and desert. However, emission intensity of TEs per unit area in the Southern provinces of China is higher than those in Northern China and Southwestern China, with the Yunnan and Sichuan provinces displaying the highest emission intensity. Our results suggest that controlling SWD can play a significant role in reducing fugitive particulate matter and the associated emissions of TEs from natural sources in China; and desertification control is particularly critical in the Northwest provinces where the majority of deserts are located.

2.
Mol Microbiol ; 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32039533

RESUMO

The Lyme disease bacterium Borrelia burgdorferi has 7~11 periplasmic flagella (PF) that arise from the cell poles and extend towards the midcell as a flat-ribbon, which is distinct from other bacteria. FlhF, a signal-recognition-particle (SRP)-like GTPase, has been found to regulate flagellar number and polarity; however, its role in B. burgdorferi remains unknown. B. burgdorferi has an FlhF homolog (BB0270). Structural and biochemical analyses show that BB0270 has a similar structure and enzymatic activity as its counterparts from other bacteria. Genetics and cryo-electron tomography studies reveal that deletion of BB0270 leads to mutant cells that have less PF (4 ± 2 PF per cell tip) and fail to form a flat-ribbon, indicative of a role of BB0270 in the control of PF number and configuration. Mechanistically, we demonstrate that BB0270 localizes at the cell poles and controls the number and position of PF via regulating flagellar protein stability and the polar localization of the MS-ring protein FliF. Our study not only provides detailed characterizations of BB0270 and its profound impacts on flagellar assembly, morphology, and motility in B. burgdorferi, but also unveils mechanistic insights into how spirochetes control their unique flagellar patterns.

3.
Dig Liver Dis ; 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-32061504

RESUMO

BACKGROUND: The sensitivity of endoscopy in diagnosing chronic atrophic gastritis is only 42%, and multipoint biopsy, despite being more accurate, is not always available. AIMS: This study aimed to construct a convolutional neural network to improve the diagnostic rate of chronic atrophic gastritis. METHODS: We collected 5470 images of the gastric antrums of 1699 patients and labeled them with their pathological findings. Of these, 3042 images depicted atrophic gastritis and 2428 did not. We designed and trained a convolutional neural network-chronic atrophic gastritis model to diagnose atrophic gastritis accurately, verified by five-fold cross-validation. Moreover, the diagnoses of the deep learning model were compared with those of three experts. RESULTS: The diagnostic accuracy, sensitivity, and specificity of the convolutional neural network-chronic atrophic gastritis model in diagnosing atrophic gastritis were 0.942, 0.945, and 0.940, respectively, which were higher than those of the experts. The detection rates of mild, moderate, and severe atrophic gastritis were 93%, 95%, and 99%, respectively. CONCLUSION: Chronic atrophic gastritis could be diagnosed by gastroscopic images using the convolutional neural network-chronic atrophic gastritis model. This may greatly reduce the burden on endoscopy physicians, simplify diagnostic routines, and reduce costs for doctors and patients.

4.
Am J Emerg Med ; 2020 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-32063428
5.
Nucleic Acids Res ; 2020 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-32064513

RESUMO

REV3L, the catalytic subunit of DNA polymerase ζ (Pol ζ), is indispensable for translesion DNA synthesis, which protects cells from deleterious DNA lesions resulting from various intrinsic and environmental sources. However, REV3L lacks a proofreading exonuclease activity and consequently bypasses DNA lesions at the expense of increased mutations, which poses a severe threat to genome stability. Here we report a site-specific proteolytic event of human REV3L. We show that REV3L is cleaved by a threonine aspartase, Taspase1 (TASP1), to generate an N-terminal 70-kDa fragment (N70) and a polypeptide carrying the C-terminal polymerase catalytic domain in human cells. Strikingly, such a post-translational cleavage event plays a vital role in controlling REV3L stability by preventing ubiquitination and proteasome-mediated degradation of REV3L. Indicative of the biological importance of the above REV3L post-translational processing, cellular responses to UV and cisplatin-induced DNA lesions are markedly impaired in human HCT116 cell derivatives bearing defined point mutations in the endogenous REV3L gene that compromise REV3L cleavage. These findings establish a new paradigm in modulating the abundance of REV3L through site-specific proteolysis in human cells.

6.
Oncologist ; 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32058619

RESUMO

LESSONS LEARNED: Administration of lapatinib with food significantly increased its plasma concentration in Chinese patients with metastatic breast cancer. There were no serious adverse events during the study and no significant differences in lapatinib-related adverse events between the fasted and fed states. BACKGROUND: Lapatinib, a small molecular reversible dual tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR) and human epidermal growth receptor 2 (HER2), was approved for use in combination with capecitabine to treat metastatic HER2-positive breast cancer. Administration of lapatinib in the fasted state was recommended; however, our preliminary phase II trial data showed that administration of lapatinib with food increased its concentration. METHODS: This study was a single-center, open-label, and prospective self-controlled clinical study. Ten Chinese patients with metastatic breast cancer were enrolled from June 2017 to April 2018. They were required to receive lapatinib plus physician's choice of chemotherapy. Patients were required to take lapatinib orally on an empty stomach continually for 10 days, and then take lapatinib with food continually for the next 10 days. Plasma concentration was measured by liquid chromatography on the 9th and 10th day of each state. RESULTS: Area under the concentration-time curve (AUC) of the fasted state and the fed state was 21.23 ± 8.91 mg*h/L (Coefficient of variation (CV)% 42%) and 60.60 ± 16.64 mg*h/L (CV% 27%), respectively. The mean plasma concentration in the fasted state was 0.88 ± 0.39 mg/L (CV% 45%), and that in the fed state was 2.53 ± 0.77 mg/L (CV% 30%). Compared with taking lapatinib on an empty stomach, receiving lapatinib with food significantly increased the plasma concentration of lapatinib (Wilcoxon match-paired test, p = .005). In addition, there were no serious adverse events during the study or significant difference in lapatinib-related adverse events between the two states. CONCLUSION: Our study shows that receiving lapatinib with food can increase its plasma concentration with no significantly increased drug-related toxicity. We suggest that a larger-sample-size clinical trial is needed to fully understand the effect of administration of lapatinib with food.

7.
Carbohydr Polym ; 233: 115840, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32059892

RESUMO

Cellulose nanocrystals (CNC) were prepared using acid hydrolysis of cellulose fiber. The CNC modified topo-chemically by grafting of bulky cholesterol moieties which changed subsequent morphology, thermal behavior, lyotropic crystalline properties, and host-guest release behavior. Bond formation between the cellulose nanocrystals surfaces and cholesterol was confirmed by FT-IR and solid-state NMR. The product indicated strong hydrophobic characteristics with an ordered chiral nematic self-assembly. This novel biomaterials were exploited through uptake of folic acid as part of a preliminary host-guest system. The guest molecule released as a function of physiologically relevant pHs was examined.

8.
Acta Pharmacol Sin ; 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32060412

RESUMO

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

9.
J Nutr ; 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32060554

RESUMO

BACKGROUND: The association between high selenium (Se) intake and metabolic disorders such as type 2 diabetes has raised great concern, but the underlying mechanism remains unclear. OBJECTIVE: Through targeted metabolomics analysis, we examined the liver sugar and acylcarnitine metabolism responses to supranutritional selenomethionine (SeMet) supplementation in pigs. METHODS: Thirty-six castrated male pigs (Duroc-Landrace-Yorkshire, 62.0 ± 3.3 kg) were fed SeMet adequate (Se-A, 0.25 mg Se/kg) or SeMet supranutritional (Se-S, 2.5 mg Se/kg) diets for 60 d. The Se concentration, biochemical, gene expression, enzyme activity, and energy-targeted metabolite profiles were analyzed. RESULTS: The Se-S group had greater fasting serum concentrations of glucose (1.9-fold), insulin (1.4-fold), and free fatty acids (FFAs,1.3-fold) relative to the Se-A group (P < 0.05). The liver total Se concentration was 4.2-fold that of the Se-A group in the Se-S group (P < 0.05), but expression of most selenoprotein genes and selenoenzyme activity did not differ between the 2 groups. Seven of 27 targeted sugar metabolites and 4 of 21 acylcarnitine metabolites significantly changed in response to high SeMet (P < 0.05). High SeMet supplementation significantly upregulated phosphoenolpyruvate carboxy kinase (PEPCK) activity by 64.4% and decreased hexokinase and succinate dehydrogenase (SDH) activity by 46.5-56.7% (P < 0.05). The relative contents of glucose, dihydroxyacetone phosphate, α-ketoglutarate, fumarate, malate, erythrose-4-phosphate, and sedoheptulose-7-phosphate in the Se-S group were 21.1-360% greater than those in the Se-A group (P < 0.05). The expression of fatty acid synthase (FASN) and the relative contents of carnitine, hexanoyl-carnitine, decanoyl-carnitine, and tetradecanoyl-carnitine in the Se-S group were 35-97% higher than those in the Se-A group (P < 0.05). CONCLUSIONS: Dietary high SeMet-induced hyperglycemia and hyperinsulinemia were associated with suppression of sugar metabolism and elevation of lipid synthesis in pig livers. Our research provides novel insights into high SeMet intake-induced type 2 diabetes.

10.
Food Chem Toxicol ; 137: 111179, 2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-32035215

RESUMO

Methamphetamine (METH) is a highly addictive stimulant that results in serious and persistent neurotoxic effects. Studies have indicated that luteolin, a flavonoid, may confer neuroprotection against neurotoxicity. Nevertheless, the effects of luteolin on METH-induced neurotoxicity have not been sufficiently verified. In the present study, Sprague Dawley rats were pretreated with luteolin (100 mg/kg) or sodium dodecyl sulfate water, followed by administration of METH (15 mg/kg) or saline. Rat striata were then collected for RNA-sequencing and subsequent analyses. A total of 347 differentially expressed genes (DEGs) were identified in the METH group with 20 pathways, including the phosphoinositol 3 kinase (PI3K)/protein kinase B (Akt), found to be enriched by the KEGG analysis. Seventy-five of the 347 DEGs were modulated in luteolin-pretreated rats, which were enriched into 12 pathways, containing the PI3K/Akt. Results further showed that luteolin pretreatment significantly repressed the METH-induced increases of PI3K, Akt, p-Akt, p53, Bax, caspase 3, normalized the ratio of p-Akt/Akt, and autophagy-related proteins (Beclin1, Atg5 and LC3-II) expression. Taken together, these findings indicate that luteolin attenuates METH-induced apoptosis and autophagy by suppressing the PI3K/Akt pathway. In this case, it exerts protection against METH-induced neurotoxicity. This provides a platform for development of potential therapies for METH treatment.

11.
Transl Psychiatry ; 10(1): 32, 2020 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-32066676

RESUMO

In rodent models of depression, (R)-ketamine has greater potency and longer-lasting antidepressant effects than (S)-ketamine; however, the precise molecular mechanisms underlying the antidepressant actions of (R)-ketamine remain unknown. Using RNA-sequencing analysis, we identified novel molecular targets that contribute to the different antidepressant effects of the two enantiomers. Either (R)-ketamine (10 mg/kg) or (S)-ketamine (10 mg/kg) was administered to susceptible mice after chronic social defeat stress (CSDS). RNA-sequencing analysis of prefrontal cortex (PFC) and subsequent GSEA (gene set enrichment analysis) revealed that transforming growth factor (TGF)-ß signaling might contribute to the different antidepressant effects of the two enantiomers. (R)-ketamine, but not (S)-ketamine, ameliorated the reduced expressions of Tgfb1 and its receptors (Tgfbr1 and Tgfbr2) in the PFC and hippocampus of CSDS susceptible mice. Either pharmacological inhibitors (i.e., RepSox and SB431542) or neutralizing antibody of TGF-ß1 blocked the antidepressant effects of (R)-ketamine in CSDS susceptible mice. Moreover, depletion of microglia by the colony-stimulating factor 1 receptor (CSF1R) inhibitor PLX3397 blocked the antidepressant effects of (R)-ketamine in CSDS susceptible mice. Similar to (R)-ketamine, the recombinant TGF-ß1 elicited rapid and long-lasting antidepressant effects in animal models of depression. Our data implicate a novel microglial TGF-ß1-dependent mechanism underlying the antidepressant effects of (R)-ketamine in rodents with depression-like phenotype. Moreover, TGF-ß1 and its receptor agonists would likely constitute a novel rapid-acting and sustained antidepressant in humans.

12.
Artigo em Inglês | MEDLINE | ID: mdl-32067445

RESUMO

Here, we have fabricated a dual-wavelength electrochemiluminescence ratiometric biosensor based on electrochemiluminescent resonance energy transfer (ECL-RET). In this biosensor, Au nanoparticle-loaded graphitic phase carbon nitride (Au-g-C3N4) as donor, and Au-modified dimethylthiodiaminoterephthalate (TAT) analogue (Au@TAT) as acceptor are investigated for the first time. Besides, tetrahedron DNA probe is immobilized onto Au-g-C3N4 to improve the binding efficiency of transcription factor and ECL ratiometric changes on the basis of the ratio of ECL intensity of 595 nm and 460 nm are obtained through the formation of sandwich structure of DNA probe-antigen-antibody. Our biosensor achieves the assay of NF-κB p50 with a detection limit of 5.8 pM as well as high stability and specificity.

14.
Dalton Trans ; 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32031193

RESUMO

Three new phenylphosphonate (PhPO3) and salicylate (Sal) substituted heterometallic titanium-oxo clusters (ST-M), namely [Ti6Mn2O4(OEt)4(PhPO3)2(Sal)6(EtOH)2] (ST-Mn), [Ti6Zn2O4(OEt)4(PhPO3)2(Sal)6(EtOH)2(H2O)2] (ST-Zn) and [Ti6Tb2O4(OiPr)4(PhPO3)2(Sal)6Cl2(iPrOH)2]·iPrOH (ST-Tb), were synthesized. The most impressive structural feature of these compounds is the calixarene-type carboxylate endpoint in the Ti6-oxo core, which can readily capture metal ions with different radii and coordination geometries, for example, Mn2+, Zn2+ and Tb3+ ions in this case, to generate neutral mixed-metal Ti6M2-oxo clusters. Flower-like ST-Mn (denoted as FST-Mn) nanocrystals formed by nanosheets can be facilely obtained in gram-scale quantities from a simple solution reaction using Triton X-100 as a conditioning agent. The catalytic activity of these materials was evaluated by photocatalytic degradation of rhodamine B (RhB), among which FST-Mn showed the highest catalytic activity. Under visible light, 93.0% of RhB (50 ppm, 100 mL) was decomposed within 30 min catalyzed by FST-Mn without adding hydrogen peroxide, which is quite preeminent among Ti based catalysts. The catalytic decomposition efficiency under the same experimental conditions was 80.0% for ST-Mn, 24.6% for ST-Zn and 17.6% for ST-Tb. Investigation of the degradation mechanism showed that h+ and ·OH were the dominant active species in the decomposition of RhB. Moreover, the reusability and stability of FST-Mn were also verified.

15.
Artigo em Inglês | MEDLINE | ID: mdl-32032012

RESUMO

Exploring two dimensional (2D) magnetic materials is important for both fundamental research and practical applications in nanoscale spintronics. Although dispersive doping of atoms in 2D nonmagnetic transition-metal dichalcogenides (TMD) has been broadly studied in recent years, the regular linear substitution inside 2D nonmagnetic TMD is rarely explored. Herein, based on first-principles calculations, we report a series of hybrid magnetic structures formed by linear atomic doping in MoS2 monolayer. We demonstrate that F and Fe atoms linear-doped MoS2 are ferromagnetic semi-metals while Mn and Co atoms linear-doped MoS2 are ferromagnetic semiconductors in their ground states. Except for F dopant, the magnetic ground states of Mn, Fe, or Co atom linear-doped MoS2 are independent of the width of linear defect. The thermal and lattice dynamical stabilities of linear-doped MoS2 monolayer are confirmed with the molecular dynamics simulations and phonon spectra. A ferromagnetic semi-metal or semiconductor to half-metallic ferromagnet transition in doped MoS2 monolayer is revealed with applying strain. Further, atomically thin magnetic zone with different shapes can also be achieved by arranging the dopants. The induced magnetic properties render linear-doped MoS2 a promising material for spintronics in the nanoscale.

16.
Hip Int ; : 1120700019900638, 2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-32026726
17.
Sci Total Environ ; 711: 135155, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32000348

RESUMO

The increasing production and use of silver nanoparticles (AgNPs) have attracted more and more attention due to their environmental and health risks. Municipal sewage biological treatment unit has been playing an important role in the removal of AgNPs. This study investigated the mechanism and characteristics of AgNPs and their removal from aqueous solution by activated sludge. Results from Scanning Electron Microscope and Energy Dispersive Spectrometer (SEM/EDS) showed that mixed AgNPs were immobilized by activated sludge. It was shown by X-ray photoelectron spectroscopy (XPS) that the fixed AgNPs had an oxidation state of +1. It was inferred by fourier transform infra-red (FTIR) spectra that AgNPs were adsorbed by activated sludge via binding with its primary amino (R-NH2) radical groups on the surface. These results revealed that the major mechanism for the removal of AgNPs by activated sludge was adsorption. The experiment data were in agreement with the Langmuir and Redlich-Peterson isotherms. The maximum adsorption capacity ranged from 12-32 mg g-1 at temperatures of 10-30 °C. Thermodynamic experiment showed that the adsorption of AgNPs by activated sludge was a spontaneous and endothermic reaction. The adsorption kinetics data were in good agreement with the pseudo-second-order model. The factor results indicated that the adsorption of AgNPs onto activated sludge was influenced by electrostatic repulsion, agglomeration, and the process of oxidation and sulfurization.

18.
Artigo em Inglês | MEDLINE | ID: mdl-32049410

RESUMO

Supramolecular assemblies are promising building blocks for the fabrication of functional soft devices for high-tech applications. However, the lack of effective methods for large-scale manipulation and integration of nano-sized supramolecular structures on soft substrate has greatly hindered the access to such goals. Here, we show how functional soft devices composed of micellar filaments and hydrogels can be created through a versatile approach involving guided dewetting, transfer-printing and laser-assisted patterning strategies. Such an approach enables unprecedented control over the location and alignment of the micellar filaments on hydrogel substrates. As examples, freely suspended micellar "fishnet" immobilized on hydrogels are formed, showing the capability of trapping and releasing micro-objects and the piconewton force sensitivity. Additionally, by incorporating responsive moieties into hydrogels, shape-morphing actuators with micelle-controlled rolling directionality are successfully constructed. We believe that this strategy paves the way towards functional soft devices for, for instance, the fundamental studies on supramolecular assemblies.

19.
Artigo em Inglês | MEDLINE | ID: mdl-32052078

RESUMO

Dendritic cells are crucial for the initiation and regulation of immune responses against cancer and pathogens. DCs are heterogeneous and highly specialized antigen-presenting cells. Human DCs comprise several subsets with different phenotypes and functional properties. In the steady state, human DC subsets have been well studied. However, the components of DC subsets and their immune functions during the inflamed setting are poorly understood. We identified and characterized DC subsets in the malignant pleural effusions of NSCLC patients. We analyzed the capacity of these DC subsets to induce T-cell differentiation. We observed the presence of inflammatory DCs (infDCs) and macrophages in the malignant pleural effusions of NSCLC patients, as identified by the CD11C+HLA-DR+CD16-BDCA1+ and CD11C+HLA-DR+CD16+BDCA1- phenotypes, respectively. InfDCs represented approximately 1% of the total light-density cells in the pleural effusion and were characterized by the expression of CD206, CD14, CD11b, and CD1α, which were absent on blood DCs. InfDCs also expressed CD80, although at a low level. As infDCs did not express CD40, CD83 and CD275, they remained functionally immature. We found that TLR agonists promoted the maturation of infDCs. Compared with macrophages, infDCs had a weaker capacity to phagocytose necrotic tumor cell lysates. However, only infDCs induced autologous memory CD4+ T-cell differentiation into Th1 cells. For the first time, we found that infDCs were present in the malignant pleural effusions of NSCLC patients. We conclude that infDCs represent a distinct human DC subset and induce Th1 cell differentiation in the presence of TLR agonists.

20.
Artigo em Inglês | MEDLINE | ID: mdl-32019305

RESUMO

The heterogeneous Fenton-like process is regarded as a promising approach to produce reactive oxygen species for water purification and environmental remediation. Here, we report a simple and rational strategy for the design of an efficient catalyst by reducing the dimensionality instead of changing the composition or structure. Based on theoretical and experimental evidence, considerable active sites were exposed on the low-dimensional Ti3C2Tx monolayer surface and showed outstanding reactivity toward peroxymonosulfate activation, which was mainly because of the superior compatibility between the highest occupied molecular orbital of catalysts and lowest unoccupied molecular orbital of Oxone. Stimulated emission depletion super-resolution microscopy innovatively provided visual insights into the spatiotemporal heterogeneous activation process and revealed that the unilaminar Ti3C2Tx nanosheet exhibited preferable reaction dynamics relative to its inert bulk counterpart, with an aqueous 2,4-dichlorophenoxyacetic acid degradation rate ∼376 times higher than that when using bulk Ti3C2Tx as the activator.

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