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1.
Environ Pollut ; 282: 117031, 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33831629

RESUMO

In this study, 24 surface water samples were collected from Dongting Lake, China, in the wet and dry seasons, then the concentrations, composition profiles and spatio-seasonal variations of nine organophosphate triesters (OPEs) and five organophosphate diesters (Di-OPs) were determined. Significantly higher total OPE concentrations (∑OPEs) were observed in the wet season (49.5-148 ng L-1) than in the dry season (5.00-45.7 ng L-1) suggesting higher input via tributaries discharge as well as wet deposition in the studied region. Whereas lower levels of TnBP and (triphenyl phosphate (TPHP) in wet season reflected their possible degradation under solar irradiation. Comparable levels of total Di-OPs (∑Di-OPs) were found in the wet season (3.41-13.9 ng L-1) and dry season (1.01-12.3 ng L-1). Tri(2-chloroethyl) phosphate and tris(2-chloroisopropyl) phosphate were the main OPE components, while diphenyl phosphate, di-n-butyl phosphate and bis(1,3-dichloro-2-propyl) phosphate were the main Di-OP components. High levels of OPEs and Di-OPs were found in Datong Lake suggesting possible local emissions potentially related to fishery activity in the land-locked lake. Samples at river mouths to the lake also have higher levels of target OPEs and Di-OPs, the results disclosed obvious discharges from tributaries in Hunan Province. Negligible non-carcinogenic and carcinogenic risks were determined based on the measured concentrations in source waters. A limited ecological risk aquatic organisms in the Dongting Lake was identified, with most risk from TPHP.

2.
ACS Nano ; 15(3): 5428-5438, 2021 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-33689300

RESUMO

NIR-II (1000-1700 nm) fluorescence imaging is continually attracting strong research interest. However, current NIR-II imaging materials are limited to small molecules with fast blood clearance and inorganic nanomaterials and organic conjugated polymers of poor biodegradability and low biocompatibility. Here, we report a highly biodegradable polyester carrying tandem NIR-II fluorophores as a promising alternative. The polymer encapsulated a platinum intercalator (56MESS, (5,6-dimethyl-1,10-phenanthroline) (1S,2S-diaminocyclohexane) platinum(II)) and was conjugated with both a cell-targeting RGD peptide and a caspase-3 cleavable peptide probe to form nanoparticles for simultaneous NIR-II and apoptosis imaging. In vitro, the nanoparticles were approximately 4-1000- and 1.5-10-fold more potent than cisplatin and 56MESS, respectively. Moreover, in vivo, they significantly inhibited tumor growth on a multidrug-resistant patient-derived mouse model (PDXMDR). Finally, through label-free laser desorption-ionization mass spectrometry imaging (MALDI-MSI), in situ 56MESS release in the deeper tumors was observed. This work highlighted the use of biodegradable NIR-II polymers for monitoring drugs in vivo and therapeutic effect feedback in real-time.

3.
Artigo em Inglês | MEDLINE | ID: mdl-33645210

RESUMO

Flexible sensors with wide sensing ranges require responsiveness under tiny and large strains. However, the development of strain sensors with wide detection ranges is still a great challenge due to the conflict between the tiny strain requirements of sparse conductive networks and the large strain requirement of dense conductive networks. Herein, we present a facile method for fabricating a gradient conductive network composed of sparse and dense conductive networks. The surface penetration technology in which carbon black (CB) penetrated from the natural rubber latex (NRL) glove surface to the interior was used to fabricate a gradient conductive network. The prolonged immersion time from 1 to 30 min caused the penetration depth of CB to increase from 2 to 80 µm. Moreover, CB formed hierarchical rough micro- and nanoscale structures, creating a superhydrophobic surface. The gradient conductive network of sensors produced an ultrawide detection range of strain (0.05-300%) and excellent reliability and reproducibility. The sensors can detect a wide range of human motions, from tiny (wrist pulse) to large (joint movements) motion monitoring. The flexible sensors attached to a flexible basement can be used to detect pressure in a wide detection range (1.7-2900 kPa). Pressure responsiveness was used to detect the weight, sound pressure, and dripping of tiny droplets. The sensor showed an excellent response to organic solvents, and the response intensity increased with the increasing swelling degree of the solvent for NRL.

4.
Chem Commun (Camb) ; 57(21): 2629-2632, 2021 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-33587067

RESUMO

In this work, we have developed a simple and reliable platform for simultaneous analysis of telomerase and miRNA. A three-dimensional bipedal DNA walking strategy is designed utilizing gold nanoparticles and MnO2 nanosheets. Given the merits of fast, sensitive and selective analysis, the developed method has great potential application in early clinical diagnosis.

5.
Curr Med Chem ; 2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33634752

RESUMO

Cancer is composed of a serious of uncontrollably c ells, which finally form tumors to negatively impact the functions of the body and induce other serious diseases, even lead people to death. During the last decades, scientists devote great effort to study cancer, however there are no effective diagnosis and treatments. Nanomaterials have attracted great attention in biomedical field in recent years, which have been widely used as optical imaging probes and delivery systems for cancer therapy. Among the numerous nanomaterials, polymeric nanoparticles occupy a prominent position because of their tunable micro-size, multifunctional surface, prominent biocompatibility and high drug-carrying capacity. These significant advantages endow them over the traditional nanomaterials and become a potential therapy for cancer. In this review, we focus on the applications of polymeric nanoparticles in cancer theranostics, especially as the drug delivery systems for cancer treatment. This review provides an overview of the advancement of synthesis, application of polymeric nanoparticles-based drug delivery systems and highlights the evaluation for cancer therapy.

6.
Ophthalmol Ther ; 2021 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-33548046

RESUMO

INTRODUCTION: The aim of this study was to compare the functional optical zone (FOZ) after correction of high myopic astigmatism and low myopic astigmatism by small-incision lenticule extraction (SMILE). METHODS: In this prospective study, 30 patients who received SMILE for high myopic astigmatism correction (cylinderical diopters ≤ - 2.0D) were enrolled in the high astigmatism group (HA). The control group comprised 40 patients who underwent SMILE for low myopic astigmatism correction (LA; cylinderical diopters ≥ - 0.5D). FOZ was delineated as the area outlined by a change of 0.5D relative to the power at the corneal vertex on the total corneal refractive power map. An ellipse-fitting program (MatLab) was used to calculate some parameters of the FOZ. Visual quality evaluations were also conducted, including evaluations of wavefront aberrations, optical quality, and intraocular scattering, and completion of a quality of life questionnaire. All of the right eyes were analyzed in the study. RESULTS: The preoperative average treatment spherical equivalent (- 5.77 ± 1.86D vs. - 6.49 ± 1.49D; P = 0.074), lenticule thickness (120.87 ± 23.27 µm vs. 118.53 ± 21.66 µm; P = 0.666), and programmed optical zone (6.58 ± 0.17 mm vs. 6.65 ± 0.18 mm; P = 0.104) were comparable between the HA and LA groups. The long axes (6.99 ± 1.14 mm vs. 5.32 ± 0.61 mm; P < 0.001), short axes (4.66 ± 0.96 mm vs. 4.23 ± 0.64 mm; P = 0.047), and area (25.90 ± 8.03 mm2 vs. 17.92 ± 4.36 mm2; P < 0.001) of the FOZ were significantly larger in the HA group than in the LA group. The centration of the FOZ were comparable between the two groups (0.62 ± 0.25 mm vs. 0.70 ± 0.25 mm; P = 0.194). Postoperative spherical aberration was lower in the HA group than in the LA group (0.07 ± 0.05 µm vs. 0.14 ± 0.10 µm; P = 0.001). There was no significant difference in the ocular scatter index (0.80 ± 0.46 vs. 0.73 ± 0.46; P = 0.447), modulated transfer function (MTF)cutoff (37.89 ± 9.79 cpd vs. 39.78 ± 7.45 cpd; P = 0.363), and Strehl in two dimensions (Strehl2D) ratio (0.20 ± 0.04 vs. 0.20 ± 0.04; P = 0.363) between the HA group and the LA group. There were no significant differences in the scores on quality of life between the HA and LA groups (45.88 ± 2.15 vs. 45.64 ± 1.84; P = 0.423). Correlation analysis revealed that increase in the spherical aberration was significantly correlated with the long axes, short axes and area in the FOZ in both groups. CONCLUSION: With a comparable optical design and attempted correction in SMILE, the eyes with higher myopic astigmatism correction achieved larger FOZ than the eyes with lower myopic astigmatism correction. Consequently, less spherical aberration induction was created after higher myopic astigmatism correction. This result may be associated with less corneal volume sculpted by laser for the higher astigmatism treatment, leading to fewer biochemical responses and les change in corneal aspherity. Good retinal image quality and satisfied quality of life were achieved at a comparable level in both study groups.

7.
Environ Pollut ; 275: 116601, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33549891

RESUMO

DNA methylation (DNAm) plays a significant role in deleterious health effects inflicted by fine particulate matter (PM2.5) on the human body. Recent studies have reported that DNAm of imprinted control regions (ICRs) in imprinted genes may be a sensitive biomarker of environmental exposure. Less is known about specific biomarkers of imprinted genes after PM2.5 exposure. The relationship between PM2.5 and its chemical constituents and DNAm of ICRs in imprinted genes after short-term exposure was investigated to determine specific human biomarkers of its adverse health effects. A panel study was carried out in healthy young people in Guangzhou, China. Mixed-effects models were used to evaluate the influence of PM2.5 and its constituent exposure on DNAm while controlling for potential confounders. There was no significant correlation between DNAm and personal PM2.5 exposure mass. DNAm changes in eight ICRs (L3MBTL1, NNAT, PEG10, GNAS Ex1A, MCTS2, SNURF/SNRPN, IGF2R, and RB1) and a non-imprinted gene (CYP1B1) were significantly associated with PM2.5 constituents. Compared to non-imprinted genes, imprinted gene methylation was more susceptible to interference with PM2.5 constituent exposure. Among those genes, L3MBTL1 was the most sensitive to personal PM2.5 constituent exposure. Moreover, transition metals derived from traffic sources (Cd, Fe, Mn, and Ni) significantly influenced DNAm of the imprinted genes, suggesting the importance of more targeted measures to reduce toxic constituents. Bioinformatics analysis indicated that imprinted genes (RB1) may be correlated with pathways and diseases (non-small cell lung cancer, glioma, and bladder cancer). The present study suggests that screening the imprinted gene for DNAm can be used as a sensitive biomarker of PM2.5 exposure. The results will provide data for prevention of PM2.5 exposure and a novel perspective on potential mechanisms on an epigenetic level.


Assuntos
Poluentes Atmosféricos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Adolescente , Poluentes Atmosféricos/análise , China , Metilação de DNA , Exposição Ambiental/análise , Humanos , Material Particulado/análise , Adulto Jovem
8.
Chem Res Toxicol ; 34(1): 47-53, 2021 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-33397103

RESUMO

Particulate matter (PM2.5) exposure is reported to have deleterious effects on health. Maternal PM2.5 exposure has been confirmed to damage the growth of somatic cells and enhance the incidence of chronic respiratory diseases in children. Here we aim to investigate the impact of in utero PM2.5 exposure on early birth weight and postnatal lung development. Pregnant Sprague-Dawley rats were administered PM2.5 (0.1, 0.5, 2.5, or 7.5 mg/kg) intraperitoneally every 3 days until birth. Maternal and birth outcomes and somatic growth were monitored. Lungs were collected on PND1 (where PND = postnatal day) and PND28; the lung wet-to-dry weight ratio (W/D) was analyzed, and reactive oxygen species (ROS) levels were measured. Expression of Toll-like receptor 4 (TLR4) and NF-κB were evaluated by Western blotting and quantitative RT-PCR. There were no significant intergroup differences for maternal outcomes; however, offspring exposed in utero to 2.5 and 7.5 mg/kg PM2.5 were significantly smaller in litter weight than the controls. In utero exposure to 2.5 and 7.5 mg/kg PM2.5 led to lower body weight after birth and disrupted lung development during infancy. ROS levels were significantly increased in the 7.5 mg/kg PM2.5 group. PM2.5-treated rats showed upregulated pulmonary expression of TLR4 and NF-κB. Maternal PM2.5 exposure enhances the risk of low birth weight and affects lung alveolar development. The underlying molecular mechanisms may involve TLR4/NF-κB signaling.

9.
Ecotoxicol Environ Saf ; 208: 111633, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33396153

RESUMO

Exposure to phthalates poses potential to damage multiple organs and system in the body. However, limited data are available regarding effects of seasonal exposure levels of phthalates and indicators reflecting inflammatory response. We designed a pilot study with repeated measures. We recruited 106 eligible habitants from Wuhan city, China. They completed questionnaires, physical examinations and provided urine specimens in winter and summer seasons. We found that urinary levels of low-molecular-weight phthalate metabolites were higher in summer than in winter (all P < 0.01). In winter, an interquartile range increase (1.264 µg/L) in 3-day moving average of high-molecular-weight phthalate metabolites corresponded to a 13.634% (95% CI: -22.331, -3.941) decrease in mean platelet volume, 25.879% (95% CI: -37.424, -12.204) for lymphocyte count or 10.862% (95% CI: -18.716, -2.125) for platelet count (P < 0.05 or P < 0.01). However, in summer, an interquartile range increase (1.215 µg/L) in urinary levels of high-molecular-weight phthalate metabolites corresponded to an 8.743% (95% CI: 4.217, 13.467) increase in platelet distribution width value or a 4.597% (95% CI: 2.335, 6.780) for mean platelet volume value at 3-day lag (both P < 0.01). In conclusion, phthalate exposure exhibited the potential for the activation of platelet function, particularly in winter. Seasonal variations of phthalate exposure should be considered when assessing health risk.


Assuntos
Exposição Ambiental/efeitos adversos , Poluentes Ambientais/efeitos adversos , Inflamação/etiologia , Ácidos Ftálicos/efeitos adversos , China , Exposição Ambiental/análise , Poluentes Ambientais/metabolismo , Poluentes Ambientais/urina , Feminino , Humanos , Inflamação/sangue , Masculino , Ácidos Ftálicos/metabolismo , Ácidos Ftálicos/urina , Projetos Piloto , Projetos de Pesquisa , Medição de Risco , Estações do Ano
10.
Environ Int ; 147: 106298, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33387880

RESUMO

BACKGROUND: Bisphenol A (BPA) is a widespread endocrine-disrupting chemical with estrogen like effects, which could interfere with the human reproductive system by disrupting the normal function of granulosa cells (GCs) leading to abnormal ovarian function. However, the mechanism of its toxicity on human GCs has not been clearly described thus far. METHODS: 106 normogonadotropic infertile women undergoing their first in-vitro fertilization-embryo transfer (IVF-ET) cycle were recruited. Urinary BPA level and the early outcomes of IVF-ET were analysed. Patients were divided to low and high BPA exposure groups using the median urinary BPA concentration as the cut-off value. In-vivo and in-vitro studies were conducted using mice and human granulosa cell line (KGN cells). Female Kunming mice approximately 6-8 weeks of age were poisoned with BPA at different dosages (1, 10 or 100 µg/kg) by oral gavage once daily for 2 weeks, while KGN cells were exposed to BPA at the concentration of 1, 10 or 100 nM for 24 h, 48 h or 72 h. BPA-induced ovarian morphologic changes were analysed by histopathology investigation. Cell viability and apoptosis were evaluated using CCK-8, TUNEL and flowcytometric, respectively. Hormone levels were determined using ELISA and the molecular mechanism studies were conducted using immunofluorescence, RT-PCR and western blots. RESULTS: The oocyte retrieval rate, maturation rate and embryo implantation rate significantly decreased with the higher level of urinary BPA concentration. Peak E2 level was lower in high BPA group, but no statistical significance could be observed. In BPA treated mice, cystic dilation of the follicles with a decreased number of GCs could be observed histopathologically. Decreased E2, P4 and AMH level and GCs autophagy could be detected both in-vivo and in-vitro with the activation of AMPK/mTOR/ULK1 signalling pathway. As being confirmed in KGN cells, phosphorylated AMPK and ULK1 increased while phosphorylated mTOR decreased, and by inhibition autophagy using knockdown of AMPK or 3-MA, adverse effects of BPA exposure in-vitro could be reversed. CONCLUSION: BPA exposure might abnormally influence human ovarian functions leading to abnormal folliculogenesis by activation of autophagy in GCs through AMPK/mTOR/ULK1 pathway.

11.
Biomaterials ; 265: 120456, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33099066

RESUMO

External stimuli-responsive nanomedicine with desirable repetitive on-demand drug release character is postulated to greatly accommodate patients' flexible medication regime. To this object, light-activatable liposomes (Pt/Ce6-LP) integrated with both a Ce6 photodynamic component and a tetravalent platinum prodrug (Pt(IV)) chemotherapeutic component are engineered. This multifunctional system was rationally designed using unsaturated phospholipid to achieve repetitive on-demand drug release under discontinuous light irradiation, thus performing chemo-photodynamic therapy effect and immunopotentiation in hypoxic tumor. Furthermore, glutathione (GSH) consumption during transformation from Pt(IV) prodrug to Pt(II) can avoid depletion of reactive oxygen species (ROS) in photodynamic therapy (PDT). Note this positive feedback loop appears to remodel the redox balance of H2O2 and GSH in tumors, alleviating the hypoxic tumor microenvironment. The alleviated hypoxia is found to be critical to the enhancement of PDT efficacy, reversal of cisplatin resistance in tumors, and polarization of tumor-associated macrophages (TAMs) to the immunocompetent M1-phynotype. Pt/Ce6-LP with light radiation demonstrates significant antitumor effect and persistent post-medication inhibition in patient-derived tumor xenograft model of hepatocellular carcinoma.

12.
Cytokine ; 137: 155308, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33128924

RESUMO

PURPOSE: To determine the concentrations of vitreous proinflammatory cytokines and angiogenesis-related growth cytokines in highly myopic (HM) patients and controls. METHODS: Vitreous humor (VH) was obtained from patients during vitrectomy for rhegmatogenous retinal detachment (RRD), myopic retinoschisis (MRS), idiopathic epiretinal membrane (ERM), or macular hole (MH). High myopia was defined as an axial length (AL) of ≥26.0 mm and a spherical equivalent refractive error more negative than -6.0 D. A multiplex fluorescent-bead-based immunoassay was employed to measure the levels of 29 designated cytokines. The results were compared across groups. RESULTS: Seventy-eight VH samples were collected from 78 patients (36 HM versus 42 controls). Vascular endothelial growth factor (VEGF) was significantly higher in the VH samples from HM patients than in those from the controls. Five inflammation-related factors, interferon γ (IFN-γ), interleukin 6 (IL6), IFN-γ-induced protein 10 (IP-10), eotaxin, and macrophage inflammatory protein 1α (MIP-1α), were significantly higher in the HM group than in the control group. The vitreous concentrations of well-known angiogenic growth factors monocyte chemoattractant protein 1 (MCP1) and IL5 were significantly elevated in the VH samples from HM patients. CONCLUSIONS: Proinflammatory cytokines and angiogenic growth factors were elevated in the VH of HM patients, suggesting that an elevated inflammatory status and higher levels of angiogenic factors are present in eyes with HM.

13.
Environ Sci Technol ; 2020 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-33289392

RESUMO

Although lead associated with intelligence decline in children has long been reported, studies combining intelligence determination, molecular mechanisms exploration, and biomarker screen are quite rare. In this study, based on 333 children aged 9-11, we determined the role of DNA methylation (DNAm) in the relationship of lead exposure with children's intelligence. DNAm was measured from children's blood DNA specimens, and mediation analysis was performed to identify DNAm biomarkers mediating the lead-intelligence relationship. We identified forty-three differentially methylated regions (DMRs), and two fragments (FAM50B1 and PTCHD3) significantly mediated the lead-intelligence relationship, with contribution rates of 30.36% (p = 0.010) and 60.36% (p < 0.001), respectively. In addition, blood lead levels (BLLs) lower than 100 µg/L still adversely affected children's IQs and DNAm of the two fragments. Our data suggests that DNAm mediates lead-associated cognitive delay in children and blood lead reference value for school-aged children (100 µg/L) should be revised, and the candidate biomarkers can be used in related neurological diseases in future.

14.
Environ Monit Assess ; 192(12): 804, 2020 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-33263891

RESUMO

We investigated the occurrence and distribution of 18 antibiotics in surface water from Dongting Lake, as well as in influents and effluents from a municipal wastewater treatment plant (WWTP) and a swine farm. The total concentrations of target antibiotics in surface water ranged from limit of quantification to 3107 and 5.32-107 ng L-1 in the dry season and wet season, respectively. Among these studied antibiotics, ciprofloxacin (CIP) and lomefloxacin were as the main components in the dry season, while CIP, oxytetracycline, and chlortetracycline were the main components in the wet season. The concentrations of target compounds exhibited obvious temporal-spatial variation characteristic in the studied region, suggesting their different emission sources related to pig breeding, aquaculture, and human activities, as well as possible degradation in the aquatic system. We estimated that the daily total input and output masses of antibiotics in the influent and effluent from the swine farm were 12.1 mg d-1 pig-1 and 7.49 µg d-1 pig-1, while they were 103 µg d-1 inhabitant-1 and 22.9 µg d-1 inhabitant-1 in the WWTP. The risk assessment results indicated that CIP posed a moderate or high risk to algae in most locations in Dongting Lake.

15.
Eur J Med Chem ; : 113050, 2020 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-33280896

RESUMO

To ameliorate the deficiencies (e.g. solubility, membrane permeability and non-selective cytotoxicity) of paclitaxel (PTX), we synthesized a "smart" PDC (peptide-drug conjugate), by linking PTX with a multifunctional peptide consisting of a tumor targeting peptide (TTP) and a cell penetrating peptide (CPP), to construct the TTP-CPP-PTX conjugate, LTP-1. LTP-1 could intelligently deliver PTX into LHRH receptor-overexpressed MCF-7 cells, showing 2 times higher cellular uptake than PTX, and enhanced cytotoxicity with IC50 of 3.8 nM (vs 6.6 nM for PTX). LTP-1 exhibited less cytotoxicity to normal cells and the ability to overcome PTX-resistance. Furthermore, LTP-1 had higher in vivo antitumor efficacy than PTX (TGI of 83.4% and 65.7% for LTP-1 and PTX, respectively, at 12 mmol/kg) without apparent toxicities. In summary, we proposed and testified the concept of constructing a novel PDC molecule, which can potentially conquer the drawbacks of PTX. LTP-1 represents a new class of antitumor PDC deserving further investigation.

16.
Nano Lett ; 20(11): 8141-8150, 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33172280

RESUMO

The ferroptosis effect has been illuminated with a clear Fenton reaction mechanism that converts endogenous hydrogen peroxide (H2O2) into highly oxidative hydroxyl radicals (·OH) in ROS-amplified tumor therapy. This ferroptosis-related oxidation effect was then further enhanced by the enzyme-like roles of cisplatin (CDDP). This CDDP-induced apoptosis was promoted in reverse by ferroptosis via the depletion of glutathione (GSH) and prevention of DNA damage repair. Here, we have developed degradable metallic complexes (PtH@FeP) containing an Fe(III)-polydopamine (FeP) core and HA-cross-linked CDDP (PtH) shell, exaggerating in situ toxic ROS production via the synergistic effect of CDDP and Fe(III). Taken together, the rationally designed PtH@FeP provided a new strategy for self-amplified synergistic chemotherapy/ferroptosis/photothermal therapy (PTT) antitumor effects with a reduced dosage that facilitates clinical safety.

17.
Environ Sci Technol ; 2020 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-33211967

RESUMO

The hadal trenches are the most remote and inaccessible habitats on earth and were once believed to be pristine. A recent study has reported the detection of high levels of persistent organic pollutants (POPs), including polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs), in endemic amphipods from two hadal trenches (Mariana and Kermadec) in the Western Pacific, implicating that the trenches are indeed polluted. However, a fundamental question remains unanswered, if and to what extent such the physical environment of the trenches is polluted by POPs. In this study, we sampled Mariana, Mussau, and New Britain trenches and analyzed samples of amphipods, sediment, and suspended particulate matter (SPM). Our results show that the amphipods contained elevated levels of PCBs and PBDEs, comparable to those reported in the earlier study. We also detected significantly high concentrations (up to 1343 ng g-1 lw) of chlorinated pesticides, such as dichlorodiphenyltrichloroethanes and chlordanes. Furthermore, four brominated natural products (BNPs), which structurally resembled methoxylated brominated diphenyl ethers or polybrominated biphenyls, were identified in the endemic amphipods. However, neither POPs nor BNPs were detected in sediments or SPM. Taken together, we propose that the POPs detected in endemic amphipods likely resulted from bioaccumulation by feeding on polluted large detritus (e.g., carrion) falling to the trench bottoms from the surface ocean.

18.
Transl Vis Sci Technol ; 9(11): 5, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33101782

RESUMO

Purpose: To explore the agreement between the wavefront supported custom ablation (WASCA) aberrometer and manifest refraction (MR) and cycloplegic refraction (CR) in hyperopia testing. Methods: Ninety eyes of 90 hyperopic patients (spherical equivalent ≥ +0.5 D) were evaluated; MR, CR, and WASCA refraction (WR) were performed consecutively. Analysis pupil size was 6.0 mm in WASCA measurement using the Seidel method. The conventional notation was transferred into vector components for analysis, i.e., spherical equivalent (M) and two cross-cylinders at axis 0° (J0) and axis 45° (J45). Bland-Altman plots were used to test the agreement between the two measurements. Results: The mean Ms obtained with MR and CR were 3.23 ± 1.74 D and 4.04 ± 2.04 D, respectively (P < 0.001), and the correlation was high (r = 0.90, P < 0.001). The WR was highly correlated with MR and CR in terms of M (r = 0.89, 0.87), but not significantly correlated in J0 and J45. The total dioptric power vector error was 0.18 ± 1.00 D between WR and MR and -0.64 ± 1.03 D between WR and CR. The limits of agreement of all vector components were beyond ± 1.0 D. With hyperopia level increase, WR tended to overestimate MR (P = 0.04), whereas WR always underestimated CR. Conclusions: WASCA could act as a reference of subjective refraction in hyperopia measurement, the exchangeability is not fully applicable. Translational Relevance: WASCA can provide an alternative for objective refraction in hyperopia measurement.

19.
Nanoscale ; 12(38): 19939-19952, 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-32991664

RESUMO

Tumor vaccines are a promising form of cancer immunotherapy, but difficulties such as neo-antigen identification, activation of immune cells, and tumor infiltration prevent their clinical breakthrough. Interestingly, nanotechnology-based photothermal therapy (PTT) has great potential to overcome these barriers. Previous studies have shown that serum exosomes (hEX) from hyperthermia-treated tumor-bearing mice displayed an array of patient-specific tumor-associated antigens (TAAs), and strong immunoregulatory abilities in promoting dendritic cell (DC) differentiation and maturation. Here, we developed a tumor vaccine (hEX@BP) by encapsulating black phosphorus quantum dots (BPQDs) with exosomes (hEX) against a murine subcutaneous lung cancer model. In comparison with BPQDs alone (BP), hEX@BP demonstrated better long-term PTT performance, greater elevation of tumor temperature and tumor targeting efficacy in vivo. Vaccination with hEX@BP in combination with PTT further demonstrated an outstanding therapeutic efficacy against established lung cancer, and promoted the infiltration of T lymphocytes into the tumor tissue. Our findings demonstrated that hEX@BP might be an innovative cancer photo-nanovaccine that offers effective immuno-PTT against cancers.

20.
J Med Chem ; 63(19): 10816-10828, 2020 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-32882127

RESUMO

Floxuridine (FUdR, 5-fluoro-2-deoxyuridine) was widely used in patients with tumor. But the poor activity and severe side effects have been observed in the clinic, which resulted from increased degradation cleavage of FUdR to 5-FU by thymidine phosphorylase and reduced transporter-mediated entry into cells. In this study, we have synthesized a series of l-aspartic acid ß-esters and l-glutamic acid γ-esters of FUdR to improve the metabolic stability of FUdR and target FUdR to cancer cells via amino acid transporter ATB0,+ which was exclusively up-regulated in some cancerous tissue. The uptake mechanism, stability, in vitro/in vivo antiproliferation action, pharmacokinetics, and tissue distribution were studied. The combined results showed the unusual 5'-ß-l-Asp-FUdR possessed a better tumor inhibition rate and a better metabolic stability than FUdR through a ATB0,+-mediated prodrug approach. The present study provided the first proof-of-concept of exploiting ATB0,+ for tumor-selective delivery of nucleoside analogues in the form of prodrug.

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