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1.
Sci Total Environ ; 715: 136943, 2020 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-32007896

RESUMO

In this study, to assess the immunotoxicity of deltamethrin on fish, adult Chinese rare minnows (Gobiocypris rarus) were exposed to 0.1, 0.3, and 1 µg/L deltamethrin for 28 d. Many immunological parameters and histopathological alterations were determined. The results showed that lymphocyte number was markedly decreased at 0.3 and 1 µg/L treatments, whereas the neutrophil number was strongly increased at 1 µg/L treatments (p < 0.05). Furthermore, lysozyme (LYS), immunoglobulin M (IgM), and complement component 3 (C3) levels at 0.3 and 1 µg/L treatments were markedly reduced, whereas alkaline phosphatase (ALP) activity were marked increased at 1 µg/L treatments (p < 0.05). The transcripts of almost all TLR (Toll-like receptor) signaling pathway-related genes were up-regulated. Histological lesions in the livers, intestines, and gills were observed at all treatments. Then, all remaining fish from controls and deltamethrin-exposed groups were injected with Pseudomonas fluorescens (P. fluorescens) for 48 h. At 24 and 48 h post-injection with P. fluorescens (hpi), the lymphocyte numbers were strongly reduced at 0.3 and 1 µg/L deltamethrin-exposed groups, whereas LYS and C3 levels were strongly reduced at 0.3 and 1 µg/L deltamethrin-exposed groups (p < 0.05). Obvious reduces in IgM levels were also detected at 0.3 and 1 µg/L deltamethrin-exposed groups at 48 hpi (p < 0.05). The transcripts of almost all TLR signaling pathway-related genes were significantly down-regulated, whereas the levels of related microRNAs (miRNAs) were markedly increased at all deltamethrin-exposed groups at 24 and 48 hpi. Moreover, the bacterial load in the liver and the mortality of fish were significantly increased at 1 µg/L deltamethrin-exposed groups at 24 and 48 hpi (p < 0.05). Furthermore, obvious histological damage in the livers, intestines, and gills were observed at all deltamethrin-exposed fish at 48 hpi. Overall, our results demonstrated that environmentally relevant concentration deltamethrin suppressed immunity and rendered the fish vulnerable to P. fluorescens infection, subsequently inducing mortality.

2.
Acta Pharmacol Sin ; 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32047261

RESUMO

Norditerpenoids and dinorditerpenoids represent diterpenoids widely distributed in the genus Podocarpus with notable chemical structures and biological activities. We previously reported that nagilactone E (NLE), a dinorditerpenoid isolated from Podocarpus nagi, possessed anticancer effects against lung cancer cells in vitro. In this study we investigated the in vivo effect of NLE against lung cancer as well as the underlying mechanisms. We administered NLE (10 mg·kg-1·d-1, ip) to CB-17/SCID mice bearing human lung cancer cell line A549 xenograft for 3 weeks. We found that NLE administration significantly suppressed the tumor growth without obvious adverse effects. Thereafter, RNA sequencing (RNA-seq) analysis was performed to study the mechanisms of NLE. The effects of NLE on A549 cells have been illustrated by GO and pathway enrichment analyses. CMap dataset analysis supported NLE to be a potential protein synthesis inhibitor. The inhibitory effect of NLE on synthesis of total de novo protein was confirmed in Click-iT assay. Using the pcDNA3-RLUC-POLIRES-FLUC luciferase assay we further demonstrated that NLE inhibited both cap-dependent and cap-independent translation. Finally, molecular docking revealed the low-energy binding conformations of NLE and its potential target RIOK2. In conclusion, NLE is a protein synthesis inhibitor with anticancer activity.

3.
Chem Commun (Camb) ; 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-32022002

RESUMO

A litchi-like MoSx-Fe@UiO-66-(OH)2 nanocomposite with amorphous MoSx-Fe nanoparticles uniformly anchored on the surface of UiO-66-(OH)2 is synthesized through sequential room-temperature redox and coordination reaction. The composite exhibits high catalytic activity and durability for hydrogen evolution in an acidic electrolyte, delivering 1000 mA cm-2 at -297 mV and outperforming Pt/C under high current densities.

4.
Sensors (Basel) ; 20(3)2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-32024015

RESUMO

This paper studies three-dimensional (3D) straight line path following and obstacle avoidance control for an underactuated autonomous underwater vehicle (AUV) without lateral and vertical driving forces. Firstly, the expected angular velocities are designed by using two different methods in the kinematic controller. The first one is a traditional method based on Line-of-sight (LOS) guidance law, and the second one is an improved method based on model predictive control (MPC). At the same time, a penalty item is designed by using the obstacle information detected by onboard sensors, which can realize the real-time obstacle avoidance of the unknown obstacle. Then, in order to overcome the uncertainty of the dynamics model and the saturation of actual control input, the dynamic controller is designed by using sliding mode control (SMC) technology. Finally, in the simulation experiment, the performance of the improved control method is verified by comparison with two traditional control methods based on LOS guidance law. Since the constraint of an AUV's angular velocities are considered in MPC, simulation results show that the improved control method uses MPC, and SMC not only improves the tracking quality of the AUV when switching paths near the waypoints and realizes real-time obstacle avoidance but also effectively reduces the mean square error (MSE) and saturation rate of the rudder angle. Therefore, this control method is more conducive to the system stability and saves energy.

5.
Bioresour Technol ; 302: 122892, 2020 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-32028149

RESUMO

The impact of algal biochar addition on mesophilic and thermophilic anaerobic co-digestion of algal biomass and food waste was investigated with a focus on semi-continuous operations and functional microbial communities. Under batch co-digestion, the highest co-digestion synergy was observed for a mixture of 25% food waste and 75% algal biomass. During semi-continuous co-digestion of 25% food waste-75% algal biomass mixture, biochar amended digesters exhibited a 12-54% increase in average methane yield (275.8-394.6 mL/gVS) compared to the controls. Elevated temperature induced narrow distributions of volatile fatty acids (VFAs) by inhibiting the production of branched VFAs. Genus Proteiniphilum was selectively enriched by 3.2 folds in mesophilic digesters with biochar amendment while genus Defluviitoga was selectively enriched in thermophilic digesters due to elevated temperature. Methanogenic communities were significantly different in mesophilic and thermophilic digesters. Biochar amendment contributed to shifts in the predominant methanogens leading to a more balanced state of two methanogenic pathways.

6.
Pharmacol Res ; 152: 104618, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31891789

RESUMO

Several decades have passed since resveratrol (RSV) was first identified in red wine. Researchers have reported the pleiotropic anti-oxidant, anti-inflammatory, anti-cancer, anti-aging, and neuronal protective effects of resveratrol and its glycosylated derivative. However, few studies have distinguished the minute differences in the properties between resveratrol and its glycosylated derivative in terms of synaptic plasticity. As an abundant natural product of glycosylated resveratrol, the derivative 2,3,4',5-tetrahydroxystilbene-2-O-ß-d-glucoside (TSG) has been determined to be a better option for long-term potentiation (LTP) in the hippocampus under physiological and pathological conditions than resveratrol. TSG, as well as its parent molecule RSV, could elicit early-LTP and recover fast excitatory postsynaptic potentials (EPSPs) in the hippocampus. Using various modalities, including pre- and post-whole-cell patch clamping techniques in the calyx of Held, pharmacological inhibition of the N-methyl-d-aspartic acid receptor (NMDAr) and the α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor (AMPAr) as well as protein kinase C (PKC) activation, we demonstrated that TSG, unlike RSV, could merely promote NMDA-mediated EPSC via PKCß cascade. Our results provide new knowledge that glycosylation of resveratrol could significantly improve its specificity in promoting sole NMDAr mediation of EPSPs, in addition to improving solubility and resistance against oxidation in vivo. These observations could contribute to further exploration of pharmaceutical evaluation of glycosylated stilbene in the future.

7.
Anal Biochem ; 592: 113576, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31917958

RESUMO

To develop a precise and convenient method to evaluate the virus transmission risk of biologically sourced materials, an integrated cell culture-qPCR (ICC-qPCR) method for Pseudorabies virus (PRV) was established and revised for applications to this new field. The optimized post-infection period was found at 12-hr to achieve a reasonable detection limit (-0.25 Log10TCID50/100 µL, Logs) and a quantitative range (0.75-3.75 Logs). The results of mimic samples suggested that three 10-fold dilutions at the time of virus inoculation combined with three washes after virus absorption, and the sets of non-amplified samples as controls could efficiently eliminate the false positive signals caused by high levels of noninfectious viruses. The virus inactivation validation studies of acellular porcine corneas suggested that the logs inactivation of PRV at 12 kGy irradiation dose obtained by general ICC-qPCR, revised ICC-qPCR and cell culture were 2.49, 4.85 and 5.08, respectively. At 25 kGy, those were 2.31, 4.85 and 5.08, respectively. The results obtained by the revised ICC-qPCR were consistent with cell culture and more precise than general ICC-qPCR. Therefore, the revised ICC-qPCR proposed in this study has an application prospect in the PRV inactivation validation studies of biologically sourced materials.

8.
Anat Rec (Hoboken) ; 2020 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-31930691

RESUMO

Tooth developmental stage evaluation is important in dental and chronological age estimation, and it is important for accurate diagnoses and appropriate treatment in dental practice. It is routinely assessed by clinical observations and radiographic techniques. This study aimed at ascertaining tooth developmental stage judgments made by examiners and Mimics software according to the Nolla method with radiographs. Meanwhile, the true tooth developmental stages would be explored with histological analysis. Twenty freshly slaughtered porcine heads were collected and hemisected, and both the left and right mandibular samples were numbered. The developmental stages of the second and third permanent molars (M2 and M3) were evaluated by examiners and Mimics software analysis. The ratio of the radiopaque calcified area to the dental follicle (RCA/DF) at different stages was calculated. Both non-decalcified and decalcified samples were processed for histologic observation. The results showed significant differences between RCA/DF ratios from different developmental stages. There was a high positive correlation between the examiners' evaluation results and Mimics analysis results. Radiograph judgments and histology observation results were consistent from Stages 2-6. However, radiograph images of Stage 1 samples showed only crypts present, while under a surgical operating microscope, a bell-shaped tooth germ was observed. This was also confirmed by normal and hard tissue histology. In conclusion, radiograph judgments made by either examiners or Mimics software were both reliable. Mimics analysis can be a useful tool in evaluating tooth developmental stages. However, judgments need to be made cautiously in early developmental stages.

9.
Biosens Bioelectron ; 153: 112045, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31989940

RESUMO

Ionic liquid composite electrodes have been widely utilized for the fabrication of electrochemical biosensors. However, the biosensing electrode modified with ionic conducting solids remains unexplored. Herein, we prepared a superionic conducting potassium ferrite (K2Fe4O7) under hydrothermal conditions for modifying glassy carbon electrode (GCE). The modified electrode (K2Fe4O7/GCE) showed an excellent electrocatalytic activity towards the oxidation of dopamine (DA). The oxidation peak currents increased linearly with increasing DA concentrations in the range of 1 µM-140 µM, and the detection limit is 0.22 µM (S/N = 3). The developed DA sensor exhibited not only good selectivity for the determination of DA without interfering from ascorbic acid (AA), uric acid (UA), glucose and inorganic ions, but also good reproducibility and stability. Furthermore, the sensor was applied to determine DA concentration in bovine serum and obtained a satisfied result. This study provides a new approach for developing electrochemical biosensors based on ionic conducting solid materials.

10.
Mol Immunol ; 119: 8-17, 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31927202

RESUMO

Motile sperm domain containing 2 (MOSPD2) is a single-pass membrane protein to which until recently little function had been ascribed. Although its mammalian homologs have been identified, the status of the mospd2 gene in lower vertebrates is still unknown. In the present study, cDNA of the mospd2 gene of barbel steed (Hemibarbus labeo) was cloned and sequenced to characterize its potential involvement in the innate immune system of this fish. Sequence analysis revealed that the predicted barbel steed MOSPD2 protein contained an N-terminal extracellular portion composed of a CRAL-TRIO domain, a motile sperm domain, and a transmembrane domain, as well as a short C-terminal intracellular domain. Phylogenetic tree analysis indicated that barbel steed MOSPD2 is closely related to that of zebrafish. Barbel steed mospd2 transcripts were detected in a wide range of tissues, with the highest level being found in the gill. In response to lipopolysaccharide (LPS) treatment or Aeromonas hydrophila infection, mospd2 gene expression was significantly altered in the head kidney, spleen, and mid-intestine. The expression of mospd2 gene was detected in monocytes/macrophages (MO/MФ), neutrophils, and lymphocytes, and was found to be mainly expressed in MO/MФ. At the same time, using flow cytometry, we also confirmed that MOSPD2 protein is located on MO/MФ, neutrophil, and lymphocyte membranes. Following treatment with LPS or A. hydrophila, MOSPD2 protein expression was induced in these immune cells. The migration of MO/MФ and neutrophils decreased significantly upon MOSPD2 blockade with anti-MOSPD2 IgG in a dose-dependent manner, whereas this treatment had no significant effect on lymphocytes migration. To the best of our knowledge, our study, for the first time, provides evidence that MOSPD2 mediates the migration of MO/MФ and neutrophils in a fish species.

11.
Inflammation ; 43(1): 32-43, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31894450

RESUMO

Air pollution events frequently occur in China during the winter. Most investigations of pollution studies have focused on the physical and chemical properties of PM2.5. Many of these studies have indicated that PM2.5 exacerbates asthma or eosinophil inflammation. However, few studies have evaluated the relationship between bacterial loads in PM2.5, and especially pathogenic bacteria and childhood asthma. Airborne PM2.5 samples from heavily polluted air were collected in Hangzhou, China between December 2014 and January 2015. PM2.5 and ovalbumin (OVA) were intratracheally administered twice in 4-week intervals to induce the allergic pulmonary inflammation in adolescent C57/BL6 mice. PM2.5 exposure caused neutrophilic alveolitis and bronchitis. In the presence of OVA, the levels of the Th2 cytokines IL-4, IL-12, and IL-17 were significantly increased in bronchoalveolar lavage fluids (BALF) after PM2.5 exposure, while eosinophil infiltration and mucin secretion were also induced. In addition to adjuvant effects on OVA-induced allergic inflammation, PM2.5 exposure also led to the maturation of dendritic cells. These results suggest that PM2.5 exposure may aggravate lung eosinophilia and that PM2.5-bound microbial can exacerbate allergic and inflammatory lung diseases.

12.
Toxicol Appl Pharmacol ; 389: 114882, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31953203

RESUMO

Pulmonary fibrosis is a prototypic chronic progressive lung disease with high morbidity and mortality worldwide. Novel effective therapeutic agents are urgently needed owing to the limited treatment options in clinic. Herein, nagilactone D (NLD), a natural dinorditerpenoid obtained from Podocarpus nagi, was found to suppress transforming growth factor-ß1 (TGF-ß1)-mediated fibrotic process in vitro and bleomycin (BLM)-induced pulmonary fibrosis in vivo. NLD attenuated TGF-ß1-induced expression of fibrotic markers including type I and III collagen, fibronectin, α-SMA, and CTGF in human pulmonary fibroblasts (WI-38 VA-13 and HLF-1 cells). Mechanism study indicated that NLD suppressed TGF-ß1-induced up-regulation of TßR I, and Smad2 phosphorylation, nuclear translocation, and transcriptional activation. Moreover, NLD ameliorated BLM-induced histopathological abnormalities in the lungs of experimental fibrotic mice, suppressed synthesis of relative fibrotic markers and fibroblast-to-myofibroblast transition, as well as BLM-induced up-regulation of TßR I expression and Smad signaling in mouse lungs. These data collectively support NLD to be a potential therapeutic agent for pulmonary fibrosis.

13.
Zhongguo Dang Dai Er Ke Za Zhi ; 22(1): 47-52, 2020 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-31948524

RESUMO

OBJECTIVE: To study the influence of dasatinib treatment on body height in children with acute myeloid leukemia (AML). METHODS: A retrospective analysis was performed for the clinical data of 86 AML children aged <17 years. According to the treatment regimen, these children were divided into a conventional chemotherapy group and a dasatinib chemotherapy group. The 57 children in the conventional chemotherapy group were given conventional chemotherapy drugs without tyrosine kinase inhibitor, and the 29 children in the dasatinib chemotherapy group were given conventional chemotherapy drugs and dasatinib. The two groups were compared in terms of height standard deviation score (HtSDS) at the beginning of treatment and after treatment, as well as the change in HtSDS after 1 and 2 years of treatment. RESULTS: There was no significant difference in HtSDS between the conventional and dasatinib chemotherapy groups before treatment. Within the first two years of treatment, the dasatinib chemotherapy group had a similar change trend of HtSDS as the conventional chemotherapy group. Four children in the dasatinib chemotherapy group reached the final adult height during follow-up, which was significantly lower than the target height (P=0.044). In the conventional chemotherapy group, there was no significant difference between final adult height and target height. In the dasatinib chemotherapy group, the children in adolescence had a significant change in HtSDS after treatment (P=0.032). CONCLUSIONS: Dasatinib treatment may affect the final height of children with AML, and the use of dasatinib after the beginning of adolescence may lead to growth disorder, but dasatinib treatment has little effect on body height in the short-term treatment.


Assuntos
Estatura , Dasatinibe/uso terapêutico , Leucemia Mieloide Aguda , Adolescente , Criança , Transtornos do Crescimento , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Estudos Retrospectivos
14.
Brief Bioinform ; 2020 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-31982909

RESUMO

By reviewing previous CpG-related studies, we consider that the transcription regulation of about half of the human genes, mostly housekeeping (HK) genes, involves CpG islands (CGIs), their methylation states, CpG spacing and other chromosomal parameters. However, the precise CGI definition and positioning of CGIs within gene structures, as well as specific CGI-associated regulatory mechanisms, all remain to be explained at individual gene and gene-family levels, together with consideration of species and lineage specificity. Although previous studies have already classified CGIs into high-CpG (HCGI), intermediate-CpG (ICGI) and low-CpG (LCGI) densities based on CpG density variation, the correlation between CGI density and gene expression regulation, such as co-regulation of CGIs and TATA box on HK genes, remains to be elucidated. First, this study introduces such a problem-solving protocol for human-genome annotation, which is based on a combination of GTEx, JBLA and Gene Ontology (GO) analysis. Next, we discuss why CGI-associated genes are most likely regulated by HCGI and tend to be HK genes; the HCGI/TATA± and LCGI/TATA± combinations show different GO enrichment, whereas the ICGI/TATA± combination is less characteristic based on GO enrichment analysis. Finally, we demonstrate that Hadoop MapReduce-based MR-JBLA algorithm is more efficient than the original JBLA in k-mer counting and CGI-associated gene analysis.

15.
Sci Total Environ ; 703: 135655, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-31767324

RESUMO

Marine copepods play an important role in transferring mercury to higher trophic levels in aquatic ecosystems. Exposure time is an important environmental parameter that potentially influences the bioaccumulation and biomagnification of Hg in copepods, which increases the uncertainty in risk assessments of Hg in food chains. In the present study, we employed the radiotracer technique to evaluate the efflux behavior of inorganic mercury [Hg(II)] and methylmercury (MeHg), and the effects of exposure time in a population of Tigriopus japonicus copepods. Exposure treatments were compared to understand the effects of exposure time (1 d, 3 d, and 7 d) on the release routes and efflux rate constants (ke) of Hg in copepods. During a depuration period of 5 d, the ke value of Hg(II) in the three exposure treatments ranged from 0.190-0.330 d-1, while the ke of MeHg was generally slower and ranged from 0.031-0.051 d-1. The exposure time significantly affected the efflux rates of Hg(II), i.e., a longer exposure time caused a higher retained Hg(II) burden in copepods, while no significant changes were observed in the MeHg treatments. The release routes of Hg in T. japonicus included excretion, feces production, and reproduction. In all the treatments, the excretion of Hg was the most important release route. The relative contribution of reproduction significantly increased in the MeHg exposure treatments, while the contribution of water excretion decreased with exposure time. Our study demonstrated that the retention of Hg(II) and the maternal transfer of MeHg were time-dependent and significantly affected by exposure time. Long-term exposure caused a decrease in the ke of Hg(II) and increase in the contribution of MeHg transfer to nauplii, thereby indicating an increasing risk of biological transmission of Hg under long-term exposure.

16.
Eur J Clin Microbiol Infect Dis ; 39(1): 93-101, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31807989

RESUMO

Previously treated TB patients still pose a serious threat to global control of TB, yet new re-treatment therapies were little studied. This study aimed to examine the therapeutic effects of new re-treatment regimens, and explore risk factors associated with recurrence after successful treatment. We conducted a cohort study in nine regions of China and enrolled previously treated TB patients from October, 2008 to December, 2010. Patients were randomly divided into four treatment regimen groups including standard, high-dose, long-course, and individualized treatment. After treatment, those with successful treatment outcomes were followed up to 7 years. The effects of different regimens and the information of recurrence were recorded. Risk factors to poor treatment outcomes were calculated using logistic regression model, while risk factors to recurrence or death were calculated using Cox model. Four hundred ninety-two participants were enrolled during the study time and 419 patients were included in our analysis of treatment effects. Overall, the treatment success rate is 75.9%, and the recurrence and death rate is 6.9% and 3.8%, respectively. Reduced risks of poor outcomes were observed in patients who were treated with high-dose and individualized regimen compared with standard regimen, and the adjusted ORs were 0.3 (0.1-0.6), 0.2 (0.1-0.5), respectively. In our analysis of factors associated with recurrence, all documented variables were not significant. Revised re-treatment regimen has better therapeutic effects compared to standard regimen, but it was not associated with lower risk of TB recurrence. Further studies are warranted to evaluate the role of other revised re-treatment regimens in recurrence risk. Trial registration: chictr.org Identifier: ChiCTR1800017441.

17.
Cell Signal ; 66: 109441, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31644943

RESUMO

Myocardial ischemia/reperfusion (IR) injury is one of the most prevalent cardiovascular diseases, known for its high mortality and morbidity worldwide. Based on pre-existing evidence, LGALS3 has been found to be closely associated with cardiac diseases. Hence, the objective of our study is to explore the potential function of KCNQ1OT1/microRNA-204-5p (miR-204-5p)/ LGALS3 axis on myocardial IR injury and the underlying mechanism. A myocardial IR injury mouse model was established in vivo and an in vitro cardiomyocyte model was induced by hypoxia/Reoxygenation exposure. Next, gain- and loss-of-function experiments were employed in order to measure the viability and apoptosis of cardiomyocytes and the area of ischemic infarct by CCK-8, TUNEL staining and Evans blue/TTC double staining. LGALS3 was found to be highly expressed in myocardial IR injury. The downregulation of LGALS3 resulted in the alleviation of myocardial IR injury in mouse models. In addition, KCNQ1OT1 could promote the LGALS3 expression by binding to miR-204-5p, which led to aggravated myocardial IR injury. In conclusion, KCNQ1OT1 binds to miR-204-5p to exacerbate myocardial IR injury in mice through the up-regulation of LGALS3, providing a novel insight for myocardial IR injury treatment.

18.
Arch Toxicol ; 94(1): 245-256, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31630224

RESUMO

Idiosyncratic drug-induced liver injury (IDILI) is a rare but potentially severe adverse drug reaction. To date, identifying individuals at risk for IDILI remains challenging. This is a prospective study, where a nested case-control (1:5) design was adopted. For six patients who had abnormalities in liver function test after Polygonum multiflorum Thunb. (PM) ingestion (susceptible group), 30 patients with normal liver function were matched (tolerant group). Based on liquid chromatography-mass spectrometry, metabolomics analysis was done on serum samples prior to PM ingestion, to screen the differential metabolites and characterize metabolomic profiles of patient serum in the two groups. Multivariate analysis showed that there were remarkable separations between susceptible and tolerant groups. A total of 25 major differential metabolites were screened out, involving glycerophospholipid metabolism, sphingolipid metabolism, fatty acid metabolism, histidine metabolism and aromatic amino acid metabolism. Wherein, the area under the curve of the receiver operating characteristic curves of metabolites PE 22:6, crotonoyl-CoA, 2E-tetradecenoyl-CoA, phenyllactic acid, indole-5,6-quinone, phosphoribosyl-ATP were all greater than 0.9. The overall serum metabolic profile comprising of 25 metabolites could clearly distinguish susceptible and tolerant groups. This proof-of-concept study used metabolomics to characterize the metabolic profile of IDILI risk individuals before drug ingestion for the first time. The metabolome characteristics in patient serum before PM ingestion may predict the risk of liver injury after PM ingestion.

19.
Nano Lett ; 20(2): 1262-1271, 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-31877053

RESUMO

Conventional refrigeration methods based on compression-expansion cycles of greenhouse gases are environmentally threatening and cannot be miniaturized. Electrocaloric effects driven by electric fields are especially well suited for implementation of built-in cooling in portable electronic devices. However, most known electrocaloric materials present poor cooling performances near room temperature, contain toxic substances, and require high electric fields. Here, we show that lead-free ferroelectric thin-film bilayers composed of (Bi0.5Na0.5)TiO3-BaTiO3 (BNBT) and Ba(Zr0.2Ti0.8)O3-(Ba0.7Ca0.3)TiO3 (BCZT) display unprecedentedly large electrocaloric effects of ∼23 K near room temperature under moderate electric bias. The giant electrocaloric effect observed in BNBT/BCZT bilayers, which largely surpasses the sum of the individual caloric responses measured in BNBT and BCZT, is originated from the presence of compositional bound charges at their interface. Our discovery of interface charge-induced giant electrocaloric effects indicates that multilayered oxide heterostructures hold tremendous promise for developing highly efficient and scalable solid-state cooling applications.

20.
J Exp Med ; 217(1)2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31636135

RESUMO

Follicular helper T (Tfh) cells provide essential help for humoral immune response. Transcriptional factor Bcl6 is the master regulator for Tfh generation and is induced very early after T cell activation in a CD28-dependent manner, but how CD28 signal promotes Bcl6 early expression remains unknown. Here we found that CD28 signal quickly induces expression of the H3K36me2 methytransferase Nsd2, which is required for Bcl6 expression as early as the first cell division after T cell activation. Nsd2 deficiency in T cells leads to decreased Bcl6 expression, impaired Tfh generation, compromised germinal center response, and delayed virus clearance. Ectopic Bcl6 expression rescues the Tfh defect of Nsd2 KO cells. ICOS signal is dispensable for early Nsd2 induction but required for sustained Nsd2 expression, which is critical for Tfh maintenance. Overexpression of Nsd2 increases Bcl6 expression and enhances Tfh generation; 4-mo-old mice even develop spontaneous Tfh. Overall, our study reveals Nsd2 as a critical epigenetic regulator for Tfh differentiation.

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