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1.
Phys Chem Chem Phys ; 2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35506927

RESUMO

CL-20 (2,4,6,8,10,12-hexanitro-2,4,6,8,10,12-hexaazaisowurtzitane, also known as HNIW) is one of the most powerful energetic materials. However, its high sensitivity to environmental stimuli greatly reduces its safety and severely limits its application. In this work, ab initio based neural network potential (NNP) energy surfaces for both ß-CL-20 and CL-20/TNT co-crystals were constructed. To accurately simulate the thermal decomposition processes of these two crystal systems, reactive molecular dynamics simulations based on the NNPs were performed. Many important intermediate species and their associated reaction paths during the decomposition had been identified in the simulations and the direct results on detonation temperatures of both systems were provided. The simulations also showed clearly that 2,4,6-trinitrotoluene (TNT) molecules in the co-crystal act as a buffer to slow down the chain reactions triggered by nitrogen dioxide and this effect is more significant at lower temperatures. Specifically, the addition of TNT molecules in the CL-20/TNT co-crystal introduces intermolecular hydrogen bonds between CL-20 and TNT molecules in the system, thereby increasing the thermal stability of the co-crystal. The current reactive molecular dynamics simulation is performed based on the NNP which helps in accelerating the speed of ab initio molecular dynamics (AIMD) simulation by more than 3 orders of magnitude while preserving the accuracy of density functional theory (DFT) calculations. This enabled us to perform longer-time simulations at more realistic temperatures that traditional AIMD methods cannot achieve. With the advantage of the NNP in its powerful fitting ability and transferability, the NNP-based MD simulation can be widely applied to energetic material systems.

2.
Natl Sci Rev ; 9(4): nwac055, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35548380

RESUMO

The World Health Organization has issued new air quality guidelines (AQG). Based on 2020 data, achieving the new AQG for PM2.5 could prevent an additional 285,000 chronic deaths and 13,000 acute deaths, across China, compared with the previous AQG. The new AQG can better protect health but cannot be achieved without coordinated air-pollution-control and climate-mitigation efforts.

3.
Radiother Oncol ; 2022 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-35537605

RESUMO

PURPOSE: To assess the impact of prospectively sparing the parotid ducts via MRI sialography on patient reported xerostomia for those receiving definitive radiotherapy (RT) for oropharyngeal squamous cell carcinoma. METHODS AND MATERIALS: Thirty-eight patients with oropharynx cancer to be treated with definitive RT underwent pre-treatment MRI sialograms to localize their parotid ducts. The parotid ducts were maximally spared during treatment planning. Patients reported symptoms (PRO-CTCAE and QLQ-H&N35) were collected at 6 and 12 months post-RT and compared to a historical cohort who underwent conventional parotid gland mean dose sparing. Regression models were generated using parotid and submandibular gland doses with and without incorporating the dose to the parotid ducts to determine the impact of parotid duct dose on patient reported xerostomia. RESULTS: At 6 months post-RT, 12/26 (46%) patients reported ≥moderate xerostomia when undergoing parotid ductal sparing compared to 43/61 (70%) in the historical cohort (p = 0.03). At 12 months post-RT, 8/22 (36%) patients reported ≥moderate xerostomia when undergoing parotid ductal sparing compared to 34/68(50%) in the historical cohort (p = 0.08). Using nested logistic regression models, the mean parotid duct dose was found to significantly relate to patient reported xerostomia severity at 6 months post-RT (p = 0.04) and trended towards statistical significance at 12 months post-RT (p = 0.09). At both 6 and 12 months post-RT, the addition of mean parotid duct dose significantly improved model fit (p <0.05). CONCLUSIONS: MRI sialography guided parotid duct sparing appears to reduce the rates of patient-reported xerostomia. Further, logistic regression analysis found parotid duct dose to be significantly associated with patient reported xerostomia. A significant improvement in model fit was observed when adding mean parotid duct dose compared to models that only contain mean parotid gland dose and mean contralateral submandibular gland dose.

4.
J Environ Manage ; 313: 114855, 2022 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-35390662

RESUMO

A magnetic FeCo2O4/Co3O4 nanocomposite was successfully synthesized by a facile hydrothermal method as an efficient activator for persulfate (PS) activation to degrade tetracycline (TC) in an aqueous solution. TC removal and mineralization efficiencies reached up to 91.63% and 43.57% in 120 min in the FCC-3/PS system, respectively. The mixed-valence of Fe/Co in the nanocomposite catalyst was beneficial for electrons transfer between Co and Fe elements and enhanced the redox circulation of Fe and Co in between divalent and trivalent. Surficial analysis and phosphate adsorption test confirmed the existence of -OH groups on the surfaces of FeCo2O4/Co3O4 nanocomposite. Fe/Co redox and surficial hydroxyl in the catalyst played significant roles in the TC potentiation degradation, which was contributed by the plenty of adsorbed -OH groups and excellent dispersity of FeCo2O4 in the FeCo2O4/Co3O4 composite. The sulfate radicals were major species followed by the hydroxyl radicals, and the surficial adsorbed hydroxyl made great contributions to radical generation. The cycling test and intermediate toxicity analysis indicated that the nanocomposite was considered stable and practicable in water treatment. This work demonstrated that the FeCo2O4/Co3O4 nanocomposite was an effective and environ-friendly catalyst towards PS activation for removing organic pollutants from water.


Assuntos
Tetraciclina , Poluentes Químicos da Água , Antibacterianos , Cobalto , Radical Hidroxila , Oxirredução , Óxidos , Poluentes Químicos da Água/análise
5.
Sci Total Environ ; 834: 155361, 2022 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-35460793

RESUMO

Organophosphate esters (OPEs) in the environment have been the focus of increasing attention due to their ubiquity and potential toxicity. However, there is little information on the occurrence and characteristics of OPEs in rural areas, especially those with cold year-round temperatures and frozen soil in winter. In this study, environmental samples were collected, in summer and winter, from villages and towns in Northeast China differing in the types and intensities of their anthropogenic activities. The samples were analyzed for 12 OPEs. The results showed the widespread presence of alkyl-OPEs, Cl-OPEs, and aryl-OPEs in the water, soil, snow, and ice of the study sites. In summer, tris(1-chloro-2-propyl) phosphate (TCPP) and tris(2-chloroethyl) phosphate (TCEP) were the primary compounds in water and soil, respectively. The ∑12OPE concentration in three villages varied from 46.26 to 257.37 ng/L in water, and from 6.62 to 19.46 ng/g in soils. The ∑12OPE concentrations in water were lower in winter than summer, but conversely, ∑12OPE concentrations in frozen soils in winter were higher than those in soils in summer. In winter, there was a shift in the predominant OPEs in water and frozen soils, with dominance of TCEP and complex compounds, respectively. Obvious seasonal characteristics of the potential sources and ecological risks of OPEs in these areas were also determined, with more complex sources of OPEs seen in summer than winter. In summer, only 2-ethylhexyl diphenyl phosphate (EHDPP) in water posed a potential risk, while in summer and, especially, in winter, EHDPP and tris(2-ethylhexyl) phosphate posed potential risks in soils. The high ∑12OPE concentration in snow (56.77 ng/L) implied that wet deposition can amplify OPEs in other environmental compartments. This is the first systematic report on OPEs in a cold rural area. Our findings highlight the need for seasonal monitoring of OPEs in similar areas.

6.
Inorg Chem ; 61(18): 7026-7031, 2022 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-35466674

RESUMO

A layered oxytelluride, Ba2ZnO2Ag2Te2, which consists of alternating stacks of ZnO2 and Ag2Te2 layers with Ba ions in between, has been synthesized via high-pressure reaction. At ambient temperature, it contains discrete [ZnO2]2- linear units similar to Ba2ZnO2Ag2Se2 (Cmca), meaning that the unusual linear coordination around zinc center is stable even when a greater tensile strain is applied by the sandwiched Ag2Te2 layers in addition to barium ions. Upon heating, this compound undergoes an order-disorder phase transition from orthorhombic (Cmca) to tetragonal (I4/mmm) system at 350 K, transforming the ZnO2 lattice in linear coordination into a lattice with disordered oxide ions, suggesting the presence of cis/trans coordination coexistence as well as correlated disorder.

7.
Ann Transl Med ; 10(5): 242, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35402583

RESUMO

Background: Ultrafiltration (UF) volume and peritoneal solute transport rate (PSTR) are common parameters used to evaluate the efficacy of peritoneal dialysis (PD) on individual patients. It is unclear whether the level of exosomal microRNA (miRNA) in peritoneal dialysis effluent (PDE) can predict UF or PSTR. This study was designed to investigate if there is a correlation between PDE exosomal miRNA (miR-432-5p) levels and various UF volumes and PSTRs in PD patients. It also aimed to explore the underlying mechanism of water and dialytic sodium removal (DSR). Methods: The PSTR was quantified using the 4-hour (4 h) 3.86% dialysate to plasma creatinine ratio. The PDE exosomes (PDE-exo) were isolated by ultracentrifugation. An miRNA assay was used to identify the different miRNA in the PDE-exo of patients in a high (H; PSTR >0.65, n=5) and low (L; PSTR <0.65, n=5) group. We focused on miR-432-5p as bioinformatic analysis had shown that it could be involved in sodium transport. We used mimic/inhibitor transfection and dual luciferase reporter assay to verify the target genes of miR-432-5p. We used PKH-67 stained PDE-exo to observe their interaction with human MeT-5A mesothelial cells. Results: Our results showed that the PDE-exo-miR-432-5p level was higher in group H than in group L. The levels of PDE-exo-miR-432-5p were positively correlated with PSTR (r=0.391; P<0.05; n=40) and negatively correlated with the 4 h UF volume (r=-0.376; P<0.05; n=40) and 4 h DSR (r=-0.535; P<0.01; n=24). Epithelial sodium channel α subunit (α-ENaC) was revealed as a direct target gene of miR-432-5p and expressed on both human peritoneum and MeT-5A cells. Furthermore, we found the PKH67 labeled-PDE-exo could be internalized into MeT-5A cells. Conclusions: A high PDE-exo-miR-432-5p level was associated with poor UF volume and DSR. It may be that PDE-exo-miR-432-5p affects DSR through downregulating α-ENaC expression.

8.
Foods ; 11(8)2022 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-35454706

RESUMO

Globally, obesity and its metabolic complications, which are intimately linked to diet, are major public health problems. Cyclodextrins (CDs) are cyclic oligosaccharides consisting of (α-1,4)-linked D-glucopyranose units that can reduce fat bioavailability and affect metabolism by improving intestinal flora as prebiotics. We compared the effects of three CDs on preventing fat accumulation and remodeling gut microbiota in a high-fat diet-fed C57BL/6J mouse model. α-CD maximized energy expenditure by 12.53%, caused the RER value to drop from 0.814 to 0.788, and increased the proportion of fatty acid oxidation for energy supply. ß-CD supplementation resulted in a marked 24.53% reduction in weight gain and a decrease in epididymal-fat-relative weight from 3.76% to 2.09%. It also minimized ectopic fat deposition and improved blood lipid parameters. γ-CD maximized the concentration of SCFAs in the cecum from 6.29 to 15.31 µmol/g. All three CDs reduced the abundance ratio of Firmicutes and Bacteroidetes to a low-fat diet level, increased the abundance of Lactobacillus and Akkermansia, and reduced the abundance of Allobaculum and Ruminococcus. These findings imply that a combination of multiple CDs may exert superior effects as a potential strategy for obesity prevention.

9.
PLoS One ; 17(4): e0266126, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35363815

RESUMO

The drivers' hazard perception plays an important role in preventing and reducing the occurrence of traffic accidents. In order to explore the drivers' hazard perception and their behavioral characteristics in overt and covert hazards, hazardous events of three traffic conflict types (vehicle to vehicle, vehicle to cyclist and vehicle to pedestrian) were designed for overt and covert hazards based on the UC-win/Road driving simulation software, respectively. 35 drivers were organized to conduct the driving simulation tests. The data of driving behavior was collected when they were driving. A comparative analysis of drivers' hazard perception ability and driving behavior characteristics was carried out for hazardous scenarios and traffic conflict types. The result has shown that drivers are more likely to take slowing measures or brake earlier in overt hazard scenarios to ensure safe driving. And drivers are more likely to be involved in collisions in covert hazard scenarios. The types of traffic conflict have a significant effect on the hazard perception ability of drivers (F = 5.92, p < 0.01). Drivers have the strongest hazard perception for cyclists and the weakest hazard perception for pedestrians. Traffic conflict types has a significant effect on drivers' average braking depth (F = 32.31, p < 0.01), average speed (F = 13.78, p < 0.01), and average acceleration (F = 9.26, p < 0.01).


Assuntos
Condução de Veículo , Acidentes de Trânsito/prevenção & controle , Percepção
10.
J Cancer ; 13(6): 1882-1894, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35399723

RESUMO

To investigate the important roles of the cancer-promoting long non-coding RNAs (lncRNAs) in cervical cancer, the up-regulated lncRNAs and prognostic analysis were identified through Lnc2Cancer and Lncar. LncRNA-regulated miRNA and miRNA-target mRNA were analyzed based on starBase v2.0 and miTarbase to predict the lncRNA-miRNA-mRNA ceRNA network. Based on the above findings, the abnormally expressed histocompatibility leukocyte antigen complex P5 (HCP5) was identified in 31 cervical cancer patients through RT-qPCR. The stable cell lines were constructed to explore the effect of HCP5 on the promotion of cervical cancer and the regulatory role on the expression of miR-216a-5p and CDC42. Cell Counting Kit-8 (CCK8) assay, cell clone formation, and transwell assay were used to examine proliferation and migration ability of cervical cancer cells. The results displayed that the overexpression of HCP5 promoted cervical cancer cell proliferation and migration in vitro, and the elevated HCP5 can also promote tumor growth in vivo. Besides, RT-qPCR and western blot assay revealed that elevated HCP5 suppressed miR-216a-5p expression and then up-regulated the expression of CDC42. In contrast, knocking down HCP5 resulted in increased expression of miR-216a-5p and then downregulated the expression of CDC42. Rescue experiments also demonstrated that miR-216a-5p could in part intercept in promotion impact caused by HCP5 on cervical cancer cells. Above all, HCP5, as an oncogene, can promote proliferation and migration ability of cervical cancer via the regulation of the miR-216a-5p/CDC42 axis.

11.
J Hazard Mater ; 432: 128559, 2022 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-35299109

RESUMO

Atmospheric oxidation can produce electrophilic compounds, altering the health effects induced by fine particulate matter (PM2.5); however, little is known about these electrophilic compounds or their health effects. Using electron capture negative ionization, we systematically detected 301 electrophilic compounds from personal PM2.5 samples in a panel study in urban Beijing. Most were oxygen-containing compounds with 3-17 double bond equivalents (DBE), suggesting the dominance of oxidized aromatic structures. Over 64% of the species, mostly outdoor-originated, were associated with inflammatory cytokines in both exhaled breath condensate and serum. Primary components of polycyclic aromatic hydrocarbons (PAHs) and high-DBE oxygenated PAHs, mainly from fossil fuel combustion, were positively associated with interleukin (IL)- 6, a cytokine related to oxidative homeostasis. Oxidized secondary species, particularly maleic and phthalic anhydrides, were negatively associated with IL-2/IL-8, which changed by - 3.8% to - 16.4% per one-fold increase in the abundance of the secondary source, indicating the immune disorders in response to the oxidized aerosols. Mediation analysis demonstrated the necessity of transformation products between atmospheric oxidation capacity and IL-2/IL-8 inhibition. This study provides new information on particulate electrophilic compounds and highlights the role of atmospheric chemistry in specific immune disorders.


Assuntos
Poluentes Atmosféricos , Hidrocarbonetos Policíclicos Aromáticos , Poluentes Atmosféricos/análise , Poluentes Atmosféricos/toxicidade , Monitoramento Ambiental , Interleucina-2/análise , Interleucina-8 , Material Particulado/análise , Material Particulado/toxicidade , Hidrocarbonetos Policíclicos Aromáticos/análise , Hidrocarbonetos Policíclicos Aromáticos/toxicidade
12.
Adv Mater ; 34(17): e2200321, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35230725

RESUMO

Colloidal quantum dots (CQD) have emerged as attractive materials for infrared (IR) photodetector (PD) applications because of their tunable bandgaps and facile processing. Presently, zinc oxide is the electron-transport layer (ETL) of choice in CQD PDs; however, ZnO relies on continuous ultraviolet (UV) illumination to remove adsorbed oxygen and maintain high external quantum efficiency (EQE), speed, and photocurrent. Here, it is shown that ZnO is dominated by electropositive crystal planes which favor excessive oxygen adsorption, and that this leads to a high density of trap states, an undesired shift in band alignment, and consequent poor performance. Over prolonged operation without UV exposure, oxygen accumulates at the electropositive planes, trapping holes and degrading performance. This problem is addressed by developing an electroneutral plane composition at the ZnO surface, aided by atomic layer deposition (ALD) as the means of materials processing. It is found that ALD ZnO has 10× lower binding energy for oxygen than does conventionally deposited ZnO. IR CQD PDs made with this ETL do not require UV activation to maintain low dark current and high EQE.

13.
Front Immunol ; 13: 850998, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35309354

RESUMO

CXCL13 is a B-cell chemokine produced mainly by mesenchymal lymphoid tissue organizer cells, follicular dendritic cells, and human T follicular helper cells. By binding to its receptor, CXCR5, CXCL13 plays an important role in lymphoid neogenesis, lymphoid organization, and immune responses. Recent studies have found that CXCL13 and its receptor CXCR5 are implicated in the pathogenesis of several autoimmune diseases, such as rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosus, primary Sjögren's syndrome, myasthenia gravis, and inflammatory bowel disease. In this review, we discuss the biological features of CXCL13 and CXCR5 and the recent findings on the pathogenic roles of the CXCL13/CXCR5 axis in autoimmune diseases. Furthermore, we discuss the potential role of CXCL13 as a disease biomarker and therapeutic target in autoimmune diseases.


Assuntos
Artrite Reumatoide , Doenças Autoimunes , Quimiocina CXCL13 , Células Dendríticas Foliculares/metabolismo , Humanos , Tecido Linfoide/metabolismo , Receptores CXCR5/metabolismo
14.
Anal Chem ; 94(10): 4335-4342, 2022 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-35235305

RESUMO

In this work, a series of multiphoton terpyridine agents (ZA, ZA-Mex, and ZA-Hex) for fluorescence lifetime imaging microscopy (FLIM) are designed and synthesized. The results from photophysical property research reveal that ZA-Hex, as an N-hexylated terpyridine salt, has stronger three-photon aggregation-induced emission (AIE) properties compared to ZA-Mex due to enhanced intramolecular charge transfer (ICT) performance. All three terpyridine derivatives possess suitable fluorescence intensities and stable fluorescence lifetimes under different pH conditions (pH = 4.0-8.0), thereby performing multiphoton fluorescence lifetime imaging. For biological imaging applications, it is found that ZA shows good lipid droplet (LD) turn-on fluorescence performance, and ZA-Hex could easily accumulate in mitochondria with high specificity. This is the first report of terpyridine salts as three-photon AIE probes used for multiphoton FLIM imaging.


Assuntos
Corantes Fluorescentes , Imagem Óptica , Corantes Fluorescentes/química , Microscopia de Fluorescência/métodos , Microscopia de Fluorescência por Excitação Multifotônica , Mitocôndrias , Organelas
15.
Redox Biol ; 52: 102292, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35325805

RESUMO

Diabetic retinopathy (DR) is one of the leading causes of blindness in the world, and timely prevention and treatment are very important. Previously, we found that a neurodegenerative factor, Glia maturation factor-ß (GMFB), was upregulated in the vitreous at a very early stage of diabetes, which may play an important role in pathogenesis. Here, we found that in a high glucose environment, large amounts of GMFB protein can be secreted in the vitreous, which translocates the ATPase ATP6V1A from the lysosome, preventing its assembly and alkalinizing the lysosome in the retinal pigment epithelial (RPE) cells. ACSL4 protein can be recognized by HSC70, the receptor for chaperone-mediated autophagy, and finally digested in the lysosome. Abnormalities in the autophagy-lysosome degradation process lead to its accumulation, which catalyzes the production of lethal lipid species and finally induces ferroptosis in RPE cells. GMFB antibody, lysosome activator NKH477, CMA activator QX77, and ferroptosis inhibitor Liproxstatin-1 were all effective in preventing early diabetic retinopathy and maintaining normal visual function, which has powerful clinical application value. Our research broadens the understanding of the relationship between autophagy and ferroptosis and provides a new therapeutic target for the treatment of DR.


Assuntos
Autofagia Mediada por Chaperonas , Diabetes Mellitus , Retinopatia Diabética , Ferroptose , Autofagia , Diabetes Mellitus/metabolismo , Retinopatia Diabética/tratamento farmacológico , Retinopatia Diabética/metabolismo , Fator de Maturação da Glia/metabolismo , Fator de Maturação da Glia/farmacologia , Humanos , Lisossomos/metabolismo
16.
Clin Nutr ; 41(4): 838-846, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35263693

RESUMO

BACKGROUND AND AIMS: Neural tube defects (NTDs) are severe congenital malformations and have a complex etiology. This study aimed to explore the association between selected essential trace elements (ETEs) and metabolic pathway markers in the serum of women and the likelihood of NTDs. METHODS: The study included 99 mothers of offspring with and 114 mothers of offspring without NTDs. Five ETEs (iron, zinc, selenium [Se], cobalt, and molybdenum) and 106 metabolic pathway markers in maternal serum were quantified. The associations between ETEs and metabolic pathway markers and the chance of NTDs were examined. Mediating effects of the metabolic pathway markers on the association between Se and the likelihood of NTDs were evaluated. RESULTS: Compared to a Se concentration below the median, a concentration above the median was associated with a decreased chance of NTDs with an odds ratio of 0.29 (95% confidence interval: 0.11-0.66). The concentrations of 32 metabolic pathway markers differed between mothers of offspring with and without NTDs; five of these (asymmetric dimethylarginine, ornithine, glutamate, proline, and phenylalanine) were associated with increased chances of NTDs, with adjusted odds ratios of 3.01 (1.31-7.31), 2.79 (1.18-6.86), 2.38 (1.03-5.75), 2.41 (1.05-5.75), and 2.27 (1.09-5.40), respectively, for the higher interquartile of concentration compared to the lower one. Three arginine pathway metabolic markers (i.e., dimethylarginine, ornithine, and proline) mediated the association between Se and the occurrence of NTDs. CONCLUSION: This study suggests an association between Se and a reduced chance of NTDs. The arginine pathway may play a role in mediating this association.


Assuntos
Defeitos do Tubo Neural , Selênio , Arginina , Estudos de Casos e Controles , Feminino , Humanos , Redes e Vias Metabólicas , Defeitos do Tubo Neural/epidemiologia , Defeitos do Tubo Neural/prevenção & controle
17.
Nat Biotechnol ; 2022 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-35347328

RESUMO

Whole-genome sequencing (WGS) can identify variants that cause genetic disease, but the time required for sequencing and analysis has been a barrier to its use in acutely ill patients. In the present study, we develop an approach for ultra-rapid nanopore WGS that combines an optimized sample preparation protocol, distributing sequencing over 48 flow cells, near real-time base calling and alignment, accelerated variant calling and fast variant filtration for efficient manual review. Application to two example clinical cases identified a candidate variant in <8 h from sample preparation to variant identification. We show that this framework provides accurate variant calls and efficient prioritization, and accelerates diagnostic clinical genome sequencing twofold compared with previous approaches.

18.
Sci Total Environ ; 829: 154657, 2022 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-35314239

RESUMO

BACKGROUND: Ambient particulate matter (PM), especially its carbonaceous composition black carbon (BC) increases cardiometabolic risks, yet the underlying mechanisms are incompletely understood. Ceramides (Cer; a class of sphingolipids) are biological intermediates in glucose metabolism. OBJECTIVES: To explore whether Cer metabolism mediates impaired glucose homeostasis following short-term PM exposure. METHODS: In a panel study in Beijing, China, 112 participants were followed-up between 2016 and 2017. Targeted lipidomic analyses quantified 26 sphingolipids in 387 plasma samples. Ambient BC and PM with aerodynamic diameter ≤ 2.5 µm (PM2.5) were continuously monitored in a station. We examined the associations of sphingolipid levels with average BC and PM2.5 concentrations 1-14 days before clinical visits using linear mixed-effects models, and explored the mediation effects of sphingolipids on PM-associated fasting blood glucose (FBG) difference using mediation analyses. RESULTS: Increased levels of FBG and multiple sphingolipids in Cer metabolic pathways were associated with BC exposure in 1-14-day time window, but not with PM2.5 exposure. For each 10 µg/m3 increase in the average BC concentration 1-14 days before the clinical visits, species in the Cer C24:1 pathway (Cer, dihydroceramide, hexosylceramide, lactosylceramide, and sphingomyelin C24:1) increased in levels ranging from 11.8% (95% confidence interval [CI]: -6.2-33.2) to 48.7% (95% CI: 8.8-103.4), as did the Cer C16:0, C18:0, and C20:0 metabolic pathway species, ranging from 3.2% (95% CI: -5.6-12.9) to 32.4% (95% CI: 7.0-63.8), respectively. The Cer C24:1 metabolic pathway species mediated 6.5-25.5% of the FBG increase associated with BC exposure in 9-day time window. The Cer C16:0, C18:0, and C20:0 metabolic pathway species mediated 5.4-26.2% of the BC-associated FBG difference. CONCLUSIONS: In conclusion, Cer metabolism may mediate impaired glucose homeostasis following short-term BC exposure. The current findings are preliminary, which need to be corroborated by further studies.

19.
Neurosci Bull ; 2022 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-35279808

RESUMO

In mammals, the piezoelectric protein, Prestin, endows the outer hair cells (OHCs) with electromotility (eM), which confers the capacity to change cellular length in response to alterations in membrane potential. Together with basilar membrane resonance and possible stereociliary motility, Prestin-based OHC eM lays the foundation for enhancing cochlear sensitivity and frequency selectivity. However, it remains debatable whether Prestin contributes to ultrahigh-frequency hearing due to the intrinsic nature of the cell's low-pass features. The low-pass property of mouse OHC eM is based on the finding that eM magnitude dissipates within the frequency bandwidth of human speech. In this study, we examined the role of Prestin in sensing broad-range frequencies (4-80 kHz) in mice that use ultrasonic hearing and vocalization (to >100 kHz) for social communication. The audiometric measurements in mice showed that ablation of Prestin did not abolish hearing at frequencies >40 kHz. Acoustic associative behavior tests confirmed that Prestin-knockout mice can learn ultrahigh-frequency sound-coupled tasks, similar to control mice. Ex vivo cochlear Ca2+ imaging experiments demonstrated that without Prestin, the OHCs still exhibit ultrahigh-frequency transduction, which in contrast, can be abolished by a universal cation channel blocker, Gadolinium. In vivo salicylate treatment disrupts hearing at frequencies <40 kHz but not ultrahigh-frequency hearing. By pharmacogenetic manipulation, we showed that specific ablation of the OHCs largely abolished hearing at frequencies >40 kHz. These findings demonstrate that cochlear OHCs are the target cells that support ultrahigh-frequency transduction, which does not require Prestin.

20.
Zhongguo Zhong Yao Za Zhi ; 47(4): 980-987, 2022 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-35285198

RESUMO

The ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS~E) technology was employed to compare the chemical components between the aerial and underground parts of Coptis chinensis samples from different batches. According to the retention time, molecular ion peak, and LC-MS~E fragment information of the reference substances and available literature, we identified a total of 40 components. Thirty-three and 31 compounds were respectively identified in the underground part(taproots) and the aerial part(stems and leaves) of C. chinensis. Among them, 24 compounds, including alkaloids(e.g., berberine and jatrorrhizine) and phenolic acids(e.g., chlorogenic acid, quinic acid, and tanshinol), were common in the two parts. In addition, differential components were also identified, such as magnoline glucoside in the underground part and(±) lariciresionol-4-ß-D-glucopyranoside in the aerial part. The analysis of fragmentation pathways based on spectra of reference substances indicated the differences among samples of different batches. Furthermore, we performed the principal component analysis(PCA) for the peak areas of C. chinensis in different batches. The results showed that the underground part and the aerial part were clearly clustered into two groups, indicating that the chemical components contained in the two parts were different. Furthermore, the results of partial least squares discriminant analysis(PLS-DA) identified 31 differential compounds(VIP value>1) between the underground part and the aerial part, mainly including alkaloids, phenolic acids, lignans, and flavonoids. This study proves that C. chinensis possesses great development potential with multiple available compounds in stems and leaves. Moreover, it sheds light on for the development and utilization of non-medicinal organs of C. chinensis and other Chinese medicinal herbs.


Assuntos
Espectrometria de Massas por Ionização por Electrospray , Espectrometria de Massas em Tandem , Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massas por Ionização por Electrospray/métodos , Espectrometria de Massas em Tandem/métodos , Tecnologia
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