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1.
J Environ Sci (China) ; 105: 64-70, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34130840

RESUMO

Simulation of fine particulate matter (PM2.5) exposure is essential for evaluating adverse health effects. In this work, an ambient exposure system that mimicked real atmospheric conditions was installed in Taiyuan, China to study impacts of chronic PM2.5 exposure on adult and aged mice as well as Sirtuin3 knockout (Sirt3 KO) mice and wild-type (WT) mice. The real-ambient exposure system eliminated the possible artificial effects caused from exposure experiments and maintained the physiochemical characteristics of PM2.5. The case studies indicated that aged mice exhibited apparent heart dysfunction involving increased heart rate and decreased blood pressure after 17-week of real-ambient PM2.5 exposure. Meanwhile, 15-week of real-ambient PM2.5 exposure decreased the heart rate and amounts of associated catecholamines to induce heart failure in Sirt3 KO mice. Additionally, the increased pro-inflammatory cytokines and decreased platelet related indices suggested that inflammation occurred. The changes of biomarkers detected by targeted metabolomics confirmed metabolic disorder in WT and Sirt3 KO mice after exposed to real-ambient PM2.5. These results indicated that the real-ambient PM2.5 exposure system could evaluate the risks of certain diseases associated with air pollution and have great potential for supporting the investigations of PM2.5 effects on other types of rodent models.

2.
Environ Int ; 155: 106665, 2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-34098336

RESUMO

Dioxins, environmentally stable and ubiquitous, have been found to induce metabolic changes especially in lipids and be related to multiple diseases. However, limited study is available on lipid alternations related to human exposure to dioxins. This study aims to explore the serum lipidomic characterization and to understand the underlying mechanisms of adverse health risks associated with dioxin exposure. A lipidomic study integrating nontargeted lipidomics, and targeted free fatty acid (FFA) and acyl-coenzyme A (acyl-CoA) analyses were conducted to investigate the 94 serum samples from two groups of male workers with remarkably different dioxin concentrations. The obtained results exhibited distinct lipidomic signatures between the high and low exposed groups. A total of 37 lipids were identified with the significant changes. The results revealed that dioxin exposure caused accumulations of triglyceride (TG), ceramide (Cer) and sphingoid (So), remodeling of glycerophospholipid (GP), imbalanced FFA metabolism, as well as upregulation of platelet-activating factor (PAF). These findings implied the associations between dioxin exposure and potential adverse health risks including inflammation, apoptosis, cardiovascular diseases (CVDs), and liver diseases. This study is the first to explain the associations between dioxin exposure and health effects at the level of lipid metabolism.

3.
Anal Chem ; 93(23): 8178-8187, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-34061502

RESUMO

Imaging of lipids of whole-body specimens in two-dimensional (2D) analysis provides a global picture of the lipid changes in lipid-disturbed diseases, enabling a better understanding of lipid functions and lipid-modulation processes in different organs. However, 2D imaging of a single cross section can hardly characterize the whole-body lipid alterations. In this work, a three-dimensional matrix-assisted laser desorption/ionization mass spectrometry imaging (3D MALDI-MSI) approach was developed for analysis of whole-body zebrafish, for the first time, and applied to identify altered lipids and map their spatial distributions by using a zebrafish model of Niemann-Pick disease type C1 (NPC1), a neurovisceral lipid storage disorder causing both neurodegenerative disorder and visceral organ damage. The constructed 3D fish model provided comprehensive information on the 3D distribution of lipids of interest and allowed direct correlations between these lipids and organs of the fish. Obtained results revealed that several sphingolipids and phospholipids showed significant alterations and exhibited different localization patterns in various organs such as the brain, spinal cord, intestines, and liver-spleen region in the npc1 gene mutant fish compared to those of the wild type. The whole-body 3D MALDI-MSI approach revealed unique lipid signatures for different NPC1-affected organs, which might offer insights into the link between the impaired lipid storage and subsequent clinical symptoms, such as neurodegeneration and hepatosplenomegaly.

4.
Sci Total Environ ; 790: 148077, 2021 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-34090159

RESUMO

Pollutant-attached microplastics have received increasing attention in recent years. However, information regarding the influence of hydroxyl group content of pollutants on the adsorption and desorption behavior is unclear, which affects their fate and risks in the aquatic environment. In this study, we investigated the adsorption and desorption behavior of anthracene (ANT) and its hydroxy derivatives (OHAs), including 2-hydroxyanthracene (MOHA), 2,6-dihydroxyanthracene (DOHA), and 1,8,9-trihydroxyanthracene (TOHA) on polyvinyl chloride (PVC) microplastics, and their interaction mechanism through the batch, characterization, and computational experiments. The results showed that the adsorption of ANT and OHAs on PVC microplastics conformed to the pseudo-second-order kinetic model and was exothermic spontaneously. The adsorption efficiency on PVC followed the order of ANT > MOHA > DOHA > TOHA, indicating that increase in hydroxyl group substitution degree will inhibit pollutant adsorption on PVC microplastics. Conversely, the release amounts of MOHA from PVC into simulated gastric fluids were higher than those of ANT. Experimental and computational results suggested that the affinity of ANT/OHAs to PVC microplastics was the most likely outcome in hydrophobic effect, electrostatic repulsion, and CH-π interaction forces. These findings help elucidate the mechanisms of pollutant adsorption on microplastics and evaluate the risk of pollutant-attached microplastics in the aquatic environment.

5.
J Hazard Mater ; 414: 125582, 2021 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-34030421

RESUMO

With the potential biomedical applications of nanomaterials such as silver nanoparticles (SNPs), nanotoxicity concerns are growing, and the importance of NP and protein interactions is far from being addressed enough. Here, we identified the major binding protein on SNPs in blood as human serum albumin (HSA) using polyacrylamide gel electrophoresis and liquid chromatography-mass spectrometry/mass spectrometry. By comparing with the previous methods, we emphasized surface area concentration as a new dose metric to address the importance of NP curvature. SNPs interacted with cysteine and cystine, disrupting the secondary structure and conformation of HSA, and this tendency became stronger on small SNPs than large ones. The protein corona significantly alleviated the toxicity and decreased SNPs' internalization in a particle size-dependent manner, where more significant inhibition effects occurred on larger particles at the same area concentration. These findings may shed light on nanotoxicity and also the design of safe nanomaterials by a comprehensive preconsideration of the metrological method.


Assuntos
Nanopartículas Metálicas , Nanopartículas , Coroa de Proteína , Humanos , Nanopartículas Metálicas/toxicidade , Tamanho da Partícula , Prata/toxicidade
6.
Analyst ; 146(9): 2991-2997, 2021 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-33949450

RESUMO

A spherical thiol-functionalized covalent organic framework (COF-SH) was designed via a facile thiol-yne click reaction of a alkynyl-terminated COF and pentaerythritol tetra(3-mercaptopropionate). The COF-SH was explored as a new adsorbent for the selective enrichment of Hg2+. The as-prepared COF-SH exhibited a uniform mesoporous structure, a high abundance of binding sites, and good chemical stability, which endow it with great performance for the adsorption of Hg2+ and its corresponding maximum adsorption capacity was up to 617.3 mg g-1. Furthermore, the adsorption behavior of Hg2+ on the COF-SH wasin good agreement with the Langmuir and pseudo-second-order models. The influences of adsorbent dosage, pH, selectivity, and reusability of the COF-SH on Hg2+ adsorption were also investigated. Besides this, the COF-SH showed high selectivity towards Hg2+ even in the presence of a high concentration of K+, Na+, Ca2+, Mg2+ and Zn2+ metal ions. Using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS), the corresponding limit of detection (LOD) of Hg2+ was determined at very low concentrations of 80 pg mL-1 (equal to 396 amoL µL-1). In addition, the COF-SH was successfully applied to rapidly enrich and sensitively detect Hg2+ in industrial sewage, with recoveries in the range of 101.8-103.4%, demonstrating the promising potential of COF-SH as an effective adsorbent for use in environmental sample pretreatment.

7.
J Hazard Mater ; 417: 126002, 2021 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-33992918

RESUMO

Hexachlorobutadiene, pentachloroanisole, and chlorobenzenes are regulated to control their release into the environment. There is little information regarding the distribution and risks of these pollutants in Chinese rivers. Therefore, we selected a prosperous agricultural and industrial region in South China as our study area and investigated the contamination profiles and risks of these pollutants in sediment and fish tissue samples. The results showed that, when compared with their levels in sediment, these lipophilic pollutants tended to accumulate in fish tissues in the following order: liver > brain > muscle. Some trichlorobenzene was found to be the result of reductive dechlorination of higher chlorinated benzenes. Hexachlorobutadiene and hexachlorobenzene could pose medium risks at certain sampling sites, but in general, almost no risk was found to the ecosystem. When the estimated daily human intakes of analytes through fish consumption were calculated for different age groups, the results suggested the analytes were unlikely to be a serious health concern for human. Our results could be used to update the existing data on the occurrence of these pollutants in the aquatic environment and to provide information for further pollution control by the local government.

8.
J Chromatogr A ; 1649: 462236, 2021 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-34038777

RESUMO

The widespread presence of lipid hydroperoxides in foodstuffs and biological samples has aroused great attentions in recent years, while it remains challenging for analysis of the fragility of O - O bond linkage of peroxides. In this present study, we explored the utility of electrospray ionization mass spectrometry (ESI-MS) for characterization of two fatty acid hydroperoxides from oxidation of linoleic acid and α-linolenic acid, which are the essential fatty acids abundant in many seeds and vegetable oils. The results indicated that in-source fragmentation occurred in the detection of the two fatty acid hydroperoxides in both positive and negative ion modes, which yielded characteristic fragments for ESI-MS analysis. In addition, the genotoxicity of fatty acid hydroperoxides for generation of nucleoside adducts was investigated. It was found that a variety of nucleoside adducts were formed from the reactions of fatty acid hydroperoxides and nucleosides. Furthermore, the decomposition products of the fatty acid hydroperoxides were determined, which provided evidence to elucidate the reaction mechanism for formation of nucleoside adducts.

9.
Sci Total Environ ; 787: 147677, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34004538

RESUMO

Metabolic transformations play critical roles in the bioavailability and toxicities of environmental pollutants and toxicants. However, most previous research has focused on the metabolic reactions in host tissues, the gut microbiota-mediated biotransformation of environmental compounds is understudied. Using triclocarban (TCC) as a model environmental compound, here we study the metabolic fate of TCC in gut tissues and determine the roles of gut microbiota involved. We find that compared with other tissues, the colon tissue has a unique metabolic profile of TCC, with high abundance of the parent compound TCC and its free-form metabolites. Using a variety of approaches including antibiotic-mediated suppression of gut bacteria in vivo, germ-free mice, and in vitro culture of fecal bacteria, we found that the unique metabolic profile of TCC in the colon is mediated by the actions of gut microbiota. Overall, our findings support that gut microbiota plays important roles in colonic metabolism of TCC, highlighting the importance to consider the contributions of gut microbiota in toxicology evaluation of environmental compounds.

10.
Environ Int ; 154: 106646, 2021 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-34049269

RESUMO

Cadmium is a well-known hazardous pollutant that mainly comes from dietary, tobacco and occupational exposure, posing threat to kidney. However, there is still a lack of systematic study on metabolic pathways and urinary biomarkers related to its nephrotoxicity under cadmium exposure for both females and males. In this study, a mass spectrometry-based metabolomics investigation of a cohort of 144 volunteers was conducted to explore sex-specific metabolic alteration and to screen biomarkers related to cadmium-induced nephrotoxicity. When the concentration of urinary cadmium increased, creatine pathway, amino acid metabolism especially the tryptophan metabolism, aminoacyl-tRNA biosynthesis, and purine metabolism were primarily influenced regardless of the gender. Also, the most specific biomarkers linked with nephrotoxicity based on the statistical analysis were detected including creatine, creatinine, l-tryptophan, adenine and uric acid. The study outcome might provide information to reflect the body burden and help improve health policy for risk assessment.

11.
Sci Total Environ ; 782: 146866, 2021 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-33848856

RESUMO

Ambient PM2.5 has been proved to be an independent risk factor for cardiovascular diseases; however, little information is available on the age-dependent effects of PM2.5 on the cardiovascular system and the underlying mechanisms following chronic exposure. In this study, multi-aged mice were exposed to PM2.5 via the newly developed real-ambient PM2.5 exposure system to investigate age-related effects on the heart after long-term exposure. First, the chemical and physical properties of PM2.5 used in the exposure system were analyzed. The heart rate of conscious mice was recorded, and results showed that exposure of aged mice to PM2.5 for 26 weeks significantly increased heart rate. Histological analysis and ELISA assays indicated that aged mice were more sensitive to PM2.5 exposure in terms of inducing cardiac oxidative stress and inflammation. Furthermore, untargeted metabolomics revealed that taurine was involved with the PM2.5-induced cardiac dysfunction. The reduced taurine concentration in the heart was examined by LC-MS and imaging mass spectrometry; it may be due to the increased p53 expression level, ROS and inflammatory cytokines. These results emphasize the age-dependent effects of PM2.5 on the cardiovascular system and suggest that taurine may be the novel cardiac effect target for PM2.5-induced heart dysfunction in the aged.


Assuntos
Poluentes Atmosféricos , Cardiopatias , Poluentes Atmosféricos/análise , Poluentes Atmosféricos/toxicidade , Animais , Coração , Cardiopatias/induzido quimicamente , Camundongos , Camundongos Endogâmicos C57BL , Estresse Oxidativo , Material Particulado/análise , Material Particulado/toxicidade , Taurina
12.
Environ Toxicol Pharmacol ; 85: 103653, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33812011

RESUMO

Ambient air fine particulate matter (PM2.5) may increase cardiovascular disease risks. In this study, we investigated the miR-208/GATA4/myosin heavy chain (MHC) regulation mechanisms on cardiac injury in rats after PM2.5 exposure via an animal inhalation device. The results showed that PM2.5 exposure for 2 months caused pathological heart injury, reduced nucleus-cytoplasm ratio, and increased the levels of CK-MB and cTnI, showing cardiac hypertrophy. Oxidative stress and inflammatory responses were also observed in rats' hearts exposed to PM2.5. Of note, PM2.5 exposure for 2-month significantly elevated GATA4 and ß-MHC mRNA and protein expression compared with the corresponding controls, along with the high-expression of miR-208b. The ratios of ß-MHC/α-MHC expression induced by PM2.5 were remarkably raised in comparison to their controls. It suggested that the up-regulation of miR-208b/ß-MHC and GATA4 and the conversion from α-MHC to ß-MHC may be the important causes of cardiac hypertrophy in rats incurred by PM2.5.

13.
J Hazard Mater ; 416: 125795, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33836324

RESUMO

We reported the discovery and identification of emerging sulfur-containing polycyclic aromatic hydrocarbons, namely polycyclic aromatic sulfur heterocycles (PASHs), in PM2.5 collected from two typical regions of China, Taiyuan and Guangzhou. Until now, there is no research on contamination status, sources and potential health risks of this unexpected group of organic contaminants in PM2.5. High atmospheric concentrations (ngm-3) and significant time-dependent variations were determined in PM2.5 of Taiyuan from 2017 to 2018. Coal combustion/secondary formation and traffic emission/secondary formation were apportioned as possible pollution sources for the PM2.5-bound PASHs in Taiyuan and Guangzhou, respectively. Dithiothreitol and cell viability assays were applied for evaluations of PASH-induced reactive oxygen species (ROS) production and cell toxicity based on the determined real exposure levels for adults. The results illustrated that PASHs in PM2.5 possibly caused oxidative stress and inhibition of human bronchial epithelial cells in seriously polluted regions such as Taiyuan, suggesting that the pollutant-induced health concerns may need more investigations. This study provides new insights into PM2.5 pollution, and is beneficial for the development of effective contamination control strategies and reduction of risks on public health.

14.
Rapid Commun Mass Spectrom ; 35(14): e9117, 2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-33928686

RESUMO

RATIONALE: Triclosan (TCS) and triclocarban (TCC) are ubiquitous antimicrobial agents incorporated in consumer and personal care products. Due to their human health risks, it is essential to develop a sensitive and accurate analytical method to simultaneously quantify TCS, TCC, as well as their metabolites and byproducts in urine and serum samples. METHODS: The quantitative parameters of TCS, TCC, TCC metabolites and byproducts (2'-OH-TCC, 3'-OH-TCC, 6-OH-TCC, DHC, DCC, NCC) were optimized by using ultra-high-performance liquid chromatography/electrospray ionization tandem mass spectrometry (UHPLC/ESI-MS/MS). Enzymatic hydrolysis of the samples was optimized based on enzyme dosage and incubation time. The efficiencies of solid-phase extraction (SPE) and liquid-liquid extraction (LLE) were compared. The effectiveness of the established method was evaluated, and method application was validated using real urine and serum samples. RESULTS: The conjugates were sufficiently hydrolyzed under 500 U/mL ß-glucuronidase and 80 U/mL sulfatase at 37°C for 4 h. Compared with the LLE method, SPE achieved higher extraction efficiency in both urine and serum samples. The optimized SPE-UHPLC/ESI-MS/MS method showed low limits of detection (LODs) in the range 0.001-0.3 ng/mL and good linearity (R2 > 0.99) at 0.01-150 ng/mL in both matrices. Excellent recoveries of 82.0%-120.7% (urine) and 76.7%-113.9% (serum) were obtained with low relative standard deviation (RSD, <7.6%) for inter-day and intra-day injections. This method was applicable to quantify target compounds in multiple biological urine and serum samples. Notably, TCS and TCC were detected with average concentrations of 8.37 and 10.46 ng/mL, respectively, in 15 Chinese female urine samples, with the simultaneous detection of TCC metabolites and byproducts. CONCLUSIONS: A reliable method was established to simultaneously determine TCS, TCC, TCC metabolites and byproducts in urine and serum samples by using UHPLC/ESI-MS/MS. This sensitive methodology provides the basis for the evaluation of TCS and TCC exposure at the metabolic level.

15.
Gastroenterology ; 160(7): 2467-2482.e3, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33647280

RESUMO

BACKGROUNDS & AIMS: Squalene epoxidase (SQLE) is the rate-limiting enzyme for cholesterol biosynthesis. We elucidated the functional significance, molecular mechanisms, and clinical impact of SQLE in nonalcoholic steatohepatitis (NASH). METHODS: We performed studies with hepatocyte-specific Sqle overexpression transgenic (Sqle tg) mice and mice given high-fat high-cholesterol (HFHC) or methionine- and choline-deficient (MCD) diet to induce NASH. SQLE downstream target carbonic anhydrase III (CA3) was identified using co-immunoprecipitation and Western Blot. Some mice were given SQLE inhibitor (terbinafine) and CA3 inhibitor (acetazolamide) to study the therapeutic effects in NASH. Human samples (N = 217) including 65 steatoses, 80 NASH, and 72 healthy controls were analyzed for SQLE levels in liver tissue and in serum. RESULTS: SQLE is highly up-regulated in human NASH and mouse models of NASH. Sqle tg mice triggered spontaneous insulin resistance, hepatic steatosis, liver injury, and accelerated HFHC or MCD diet-induced NASH development. Mechanistically, SQLE tg mice caused hepatic cholesterol accumulation, thereby triggering proinflammatory nuclear factor-κB signaling and steatohepatitis. SQLE directly bound to CA3, which induced sterol regulatory element-binding protein 1C activation, acetyl-CoA carboxylase, fatty acid synthase, and stearoyl-CoA desaturase1 expression and de novo hepatic lipogenesis. Combined targeting SQLE (terbinafine) and CA3 (acetazolamide) synergistically ameliorated NASH in mice with superior efficacy to either drug alone. Serum SQLE with CA3 could distinguish patients with NASH from steatosis and healthy controls (area under the receiver operating characteristic curve, 0.815; 95% confidence interval, 0.758-0.871). CONCLUSIONS: SQLE drives the initiation and progression of NASH through inducing cholesterol biosynthesis, and SQLE/CA3 axis-mediated lipogenesis. Combined targeting of SQLE and CA3 confers therapeutic benefit in NASH. Serum SQLE and CA3 are novel biomarkers for the noninvasive diagnosis of patients with NASH.

16.
Cell ; 184(8): 2212-2228.e12, 2021 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-33713620

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can cause acute respiratory disease and multiorgan failure. Finding human host factors that are essential for SARS-CoV-2 infection could facilitate the formulation of treatment strategies. Using a human kidney cell line-HK-2-that is highly susceptible to SARS-CoV-2, we performed a genome-wide RNAi screen and identified virus dependency factors (VDFs), which play regulatory roles in biological pathways linked to clinical manifestations of SARS-CoV-2 infection. We found a role for a secretory form of SARS-CoV-2 receptor, soluble angiotensin converting enzyme 2 (sACE2), in SARS-CoV-2 infection. Further investigation revealed that SARS-CoV-2 exploits receptor-mediated endocytosis through interaction between its spike with sACE2 or sACE2-vasopressin via AT1 or AVPR1B, respectively. Our identification of VDFs and the regulatory effect of sACE2 on SARS-CoV-2 infection shed insight into pathogenesis and cell entry mechanisms of SARS-CoV-2 as well as potential treatment strategies for COVID-19.


Assuntos
/imunologia , Interações entre Hospedeiro e Microrganismos/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Vasopressinas/imunologia , Internalização do Vírus , /imunologia , Linhagem Celular , Humanos , Ligação Proteica
17.
Ecotoxicol Environ Saf ; 215: 112128, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33773150

RESUMO

Perfluorooctanoic acid (PFOA) is one of the most commonly used perfluorinated chemicals in industry. Wide concerns of PFOA toxicity are increased in recent years. However, report on immunotoxicity of PFOA was quite limited. This study aimed to investigate the immunotoxicity of PFOA exposure on macrophage RAW264.7. We assessed the effects of PFOA exposure on macrophage cell viability, cell apoptosis and cellular ROS level, and detected prominent cytokines release by RAW264.7. The results indicated that the cell viability of macrophage RAW264.7 was decreased by PFOA in dose- and time-dependent manners. Specifically, the exposure of 200 µM PFOA significantly increased apoptosis and ROS generation in macrophage, and thus caused cell damage. The ELISA results displayed that 100 µM PFOA exposure induced macrophage activation and enhanced cytokines secretion, including TNF-α, IL-1, IL-6, and IL-12. We also conducted nontargeted metabolomics based on LC-MS/MS and unveiled the perturbed metabolic pathways in macrophages induced by sublethal doses of PFOA (10 µM and 100 µM). Remarkably, global metabolomics results displayed that 10 µM PFOA exposure affected glutamine related pathways and the exposure at 100 µM conspicuously changed glutathione and fatty acid oxidation metabolism. These findings showed that 10 µM PFOA exposure could impel metabolic reprogramming of macrophage to trigger inflammatory response, although such dose displayed no obvious effect on cell viability, cellular ROS or apoptosis events of macrophage RAW264.7.


Assuntos
Caprilatos/toxicidade , Fluorcarbonetos/toxicidade , Animais , Apoptose/efeitos dos fármacos , Cromatografia Líquida , Citocinas , Metabolismo dos Lipídeos , Macrófagos/fisiologia , Metabolômica , Transdução de Sinais , Espectrometria de Massas em Tandem , Fator de Necrose Tumoral alfa
18.
Proc Natl Acad Sci U S A ; 118(14)2021 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-33782135

RESUMO

Recent findings regarding nicotinamide adenine dinucleotide (NAD+)-capped RNAs (NAD-RNAs) indicate that prokaryotes and eukaryotes employ noncanonical RNA capping to regulate gene expression. Two methods for transcriptome-wide analysis of NAD-RNAs, NAD captureSeq and NAD tagSeq, are based on copper-catalyzed azide-alkyne cycloaddition (CuAAC) click chemistry to label NAD-RNAs. However, copper ions can fragment/degrade RNA, interfering with the analyses. Here we report development of NAD tagSeq II, which uses copper-free, strain-promoted azide-alkyne cycloaddition (SPAAC) for labeling NAD-RNAs, followed by identification of tagged RNA by single-molecule direct RNA sequencing. We used this method to compare NAD-RNA and total transcript profiles of Escherichia coli cells in the exponential and stationary phases. We identified hundreds of NAD-RNA species in E. coli and revealed genome-wide alterations of NAD-RNA profiles in the different growth phases. Although no or few NAD-RNAs were detected from some of the most highly expressed genes, the transcripts of some genes were found to be primarily NAD-RNAs. Our study suggests that NAD-RNAs play roles in linking nutrient cues with gene regulation in E. coli.

19.
Environ Sci Technol ; 55(8): 5117-5127, 2021 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-33691405

RESUMO

Humans are constantly exposed to antimicrobial triclocarban (TCC) via direct skin contact with personal care and consumer products, but the safety of long-term dermal exposure to TCC remains largely unknown. Herein, we used a mouse model to evaluate the potential health risks from the continuous dermal application of TCC at human-relevant concentrations. After percutaneous absorption, TCC circulated in the bloodstream and largely entered the liver-gut axis for metabolic disposition. Nontargeted metabolomics approach revealed that TCC exposure perturbed mouse liver homeostasis, as evidenced by the increased oxidative stress and impaired methylation capacity, leading to oxidative damage and enhancement of upstream glycolysis and folate-dependent one-carbon metabolism. Meanwhile, TCC was transformed in the liver through hydroxylation, dechlorination, methylation, glucuronidation, sulfation, and glutathione conjugation. TCC-derived xenobiotics were subsequently excreted into the gut, and glucuronide and sulfate metabolites could be further deconjugated by the gut microbiota into their active free forms. In addition, microbial community analysis showed that the composition of gut microbiome was altered in response to TCC exposure, indicating the perturbation of gut homeostasis. Together, through tracking the xenobiotic-biological interactions in vivo, this study provides novel insights into the underlying impacts of dermally absorbed TCC on the liver and gut microenvironments.


Assuntos
Carbanilidas , Microbioma Gastrointestinal , Microbiota , Animais , Carbanilidas/toxicidade , Homeostase , Fígado , Camundongos
20.
Anal Chem ; 93(11): 4788-4793, 2021 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-33683863

RESUMO

Mass spectrometry imaging (MSI) could provide vast amounts of data at the temporal-spatial scale in heterogeneous biological specimens, which challenges us to segment accurately suborgans/microregions from complex MSI data. Several pipelines had been proposed for MSI spatial segmentation in the past decade. More importantly, data filtering was found to be an efficient procedure to improve the outcomes of MSI segmentation pipelines. It is not clear, however, how the filtering procedure affects the MSI segmentation. An improved pipeline was established by elaborating the filtering prioritization and filtering algorithm. Lipidomic-characteristic-based MSI data of a whole-body mouse fetus was used to evaluate the established pipeline on localization of the physiological position of suborgans by comparing with three commonly used pipelines and commercial SCiLS Lab software. Two structural measurements were used to quantify the performances of the pipelines including the percentage of abnormal edge pixel (PAEP) and CHAOS. Our results demonstrated that the established pipeline outperformed the other pipelines in visual inspection, spatial consistence, time-cost, and robustness analysis. For example, the dorsal pallium (isocortex) and hippocampal formation (Hpf) regions, midbrain, cerebellum, and brainstem on the mouse brain were annotated and located by the established pipeline. As a generic pipeline, the established pipeline could help with the accurate assessment and screening of drug/chemical-induced targeted organs and exploration of the progression and molecular mechanisms of diseases. The filter-based strategy is expected to become a critical component in the standard operating procedure of MSI data sets.

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