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1.
Proc Natl Acad Sci U S A ; 121(14): e2317574121, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38530899

RESUMO

Fine particulate matter (PM2.5) is globally recognized for its adverse implications on human health. Yet, remain limited the individual contribution of particular PM2.5 components to its toxicity, especially considering regional disparities. Moreover, prevention solutions for PM2.5-associated health effects are scarce. In the present study, we comprehensively characterized and compared the primary PM2.5 constituents and their altered metabolites from two locations: Taiyuan and Guangzhou. Analysis of year-long PM2.5 samples revealed 84 major components, encompassing organic carbon, elemental carbon, ions, metals, and organic chemicals. PM2.5 from Taiyuan exhibited higher contamination, associated health risks, dithiothreitol activity, and cytotoxicities than Guangzhou's counterpart. Applying metabolomics, BEAS-2B lung cells exposed to PM2.5 from both cities were screened for significant alterations. A correlation analysis revealed the metabolites altered by PM2.5 and the critical toxic PM2.5 components in both regions. Among the PM2.5-down-regulated metabolites, phosphocholine emerged as a promising intervention for PM2.5 cytotoxicities. Its supplementation effectively attenuated PM2.5-induced energy metabolism disorder and cell death via activating fatty acid oxidation and inhibiting Phospho1 expression. The highlighted toxic chemicals displayed combined toxicities, potentially counteracted by phosphocholine. Our study offered a promising functional metabolite to alleviate PM2.5-induced cellular disorder and provided insights into the geo-based variability in toxic PM2.5 components.


Assuntos
Poluentes Atmosféricos , Doenças Mitocondriais , Humanos , Poluentes Atmosféricos/análise , Fosforilcolina , Material Particulado/análise , Pulmão , Carbono/análise , Monitoramento Ambiental
2.
Environ Res ; 247: 118214, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38246302

RESUMO

The contaminant status, spatial distribution, partitioning behavior, and ecological risks of 26 legacy and emerging perfluoroalkyl and polyfluoroalkyl substances (PFASs) in Laizhou Bay, China were investigated. The concentrations of ∑PFASs in surface and bottom seawater ranged from 37.2 to 222 ng/L and from 34.2 to 305 ng/L with an average of 116 ± 62.7 and 138 ± 93.8 ng/L, respectively. There were no significant differences in the average concentrations between the surface and bottom seawater (P > 0.05). Perfluorooctanoic acid (PFOA) and short-chain PFASs dominated the composition of PFASs in seawater. The concentrations of ∑PFASs in sediments ranged from 0.997 to 7.21 ng/g dry weight (dw), dominated by perfluorobutane sulfonate (PFBS), perfluorobutanoic acid (PFBA), and long-chain PFASs. The emerging alternatives of perfluoro-1-butane-sulfonamide (FBSA) and 6:2 fluorotelomer sulfonic acid (6:2 FTSA) were detected for the first time in Laizhou Bay. The ∑PFASs in seawater in the southwest of the bay were higher than those in the northeast of the bay. The ∑PFASs in sediments in the northeast sea area were higher than those in the inner area of the bay. Log Kd and log Koc values increased with increasing carbon chain length for PFASs compounds. Ecological risk assessments indicated a low ecological risk associated with HFPO-DA but a moderate risk associated with PFOA contamination in Laizhou Bay. Positive matrix factorization (PMF) analysis revealed that fluoropolymer manufacturing, metal plating plants, and textile treatments were identified as major sources contributing to PFASs contamination.


Assuntos
Ácidos Alcanossulfônicos , Caprilatos , Fluorocarbonos , Poluentes Químicos da Água , Baías , Poluentes Químicos da Água/análise , Monitoramento Ambiental , Fluorocarbonos/análise , China , Medição de Risco , Ácidos Alcanossulfônicos/análise
3.
Ecotoxicol Environ Saf ; 281: 116668, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38964058

RESUMO

The study of the fractions and distribution characteristics of organic phosphorus in the sediment of the water level fluctuating zone of Nansi Lake is conducive to revealing the transformation of phosphorus in the lake, and has important scientific significance for controlling the eutrophication of Nansi Lake. Based on the sediment of the water level fluctuation zone of Nansi Lake. The improved Hedley continuous grading extraction, ultraviolet-visible spectroscopy and three-dimensional fluorescence spectroscope were used to characterize the structural characteristics and stability of organic molecules in the sediment, and to reflect the differences in the structure and stability of organophosphate in the water level fluctuating zone. Principal component analysis (PCA), Redundancy analysis (RDA) and correlation heat map analysis were used to analyze the correlation between phosphorus and physicochemical index. The results showed that the alternation between wet-dry conditions was more favorable for the release of phosphorus from sediment, compared to continuous inundation conditions. Moreover, the higher the frequency of wet-dry alternations, the greater the release of phosphorus in different forms from the sediment. Wet-dry alternation resulted in a reduction of substituent on the aromatic rings of sediment DOM (dissolved organic matter), and the continuous drying would increase the molecular weight and humidification degree of DOM in the sediment. Correlation analysis showed that NaOH-Po content in sediment was significantly negatively correlated with TP, IP, OP and various organophosphorus forms, indicating a close transformation relationship between phosphorus forms in sediment. The results can provide a scientific basis for controlling the release of endogenous phosphorus and the risk of eutrophication in Nansi Lake.

4.
BMC Med Educ ; 24(1): 624, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38840091

RESUMO

BACKGROUND: The incidence of mental health problems among medical graduate students is much higher than among students of other disciplines. This can have adverse consequences for the medical students themselves as well as their future patients. This study aims to understand the pressures faced by Chinese medical students and the current status of mental health education. It also propose recommendations for the current situation and prospects for the future. METHOD: The authors conducted in-depth semi-structured interviews with 22 master's students from five medical schools during November 2023. All interview sessions were recorded and transcribed verbatim. The transcriptions were analyzed using the Colaizzi's seven-step method. RESULT: Three main themes were extracted from the students' statements: sources of psychological stress, ways to cope with stress, and perspectives on mental health education. The study showed that current mental health education in China is mostly in the form of printed mental health education manuals and mental health lectures, and there is no active tiered intervention for students at different levels. It is suggested that reforms should be made to shift to a model where the school proactively identifies problems and intervenes based on feedback. CONCLUSION: This study reveals the widespread psychological stress and shortcomings in current education methods. To address these challenges, institutions should develop tailored interventions, including tiered support systems, open dialogue promotion, and resilience training. Future research should focus on evaluating innovative interventions' effectiveness, ultimately fostering a supportive environment that enhances students' success and contributes to a healthier healthcare workforce.


Assuntos
Adaptação Psicológica , Pesquisa Qualitativa , Estresse Psicológico , Estudantes de Medicina , Humanos , China , Estudantes de Medicina/psicologia , Masculino , Feminino , Adulto , Entrevistas como Assunto , Saúde Mental , Educação de Pós-Graduação em Medicina , Capacidades de Enfrentamento , População do Leste Asiático
5.
Int J Mol Sci ; 25(5)2024 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-38473897

RESUMO

The H9N2 avian influenza virus causes reduced production performance and immunosuppression in chickens. The chicken yolk sac immunoglobulins (IgY) receptor (FcRY) transports from the yolk into the embryo, providing offspring with passive immunity to infection against common poultry pathogens. FcRY is expressed in many tissues/organs of the chicken; however, there are no reports investigating FcRY expression in chicken macrophage cells, and how H9N2-infected HD11 cells (a chicken macrophage-like cell line) regulate FcRY expression remains uninvestigated. This study used the H9N2 virus as a model pathogen to explore the regulation of FcRY expression in avian macrophages. FcRY was highly expressed in HD11 cells, as shown by reverse transcription polymerase chain reactions, and indirect immunofluorescence indicated that FcRY was widely expressed in HD11 cells. HD11 cells infected with live H9N2 virus exhibited downregulated FcRY expression. Transfection of eukaryotic expression plasmids encoding each viral protein of H9N2 into HD11 cells revealed that nonstructural protein (NS1) and matrix protein (M1) downregulated FcRY expression. In addition, the use of a c-jun N-terminal kinase (JNK) activator inhibited the expression of FcRY, while a JNK inhibitor antagonized the downregulation of FcRY expression by live H9N2 virus, NS1 and M1 proteins. Finally, a dual luciferase reporter system showed that both the M1 protein and the transcription factor c-jun inhibited FcRY expression at the transcriptional level. Taken together, the transcription factor c-jun was a negative regulator of FcRY, while the live H9N2 virus, NS1, and M1 proteins downregulated the FcRY expression through activating the JNK signaling pathway. This provides an experimental basis for a novel mechanism of immunosuppression in the H9N2 avian influenza virus.


Assuntos
Vírus da Influenza A Subtipo H9N2 , Influenza Aviária , Animais , Galinhas/metabolismo , Vírus da Influenza A Subtipo H9N2/fisiologia , Sistema de Sinalização das MAP Quinases , Linhagem Celular , Macrófagos/metabolismo , Fatores de Transcrição/metabolismo
6.
Clin Immunol ; 255: 109747, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37634854

RESUMO

Staphylococcus aureus (S. aureus) contamination commonly occurs in orthopedic internal fixation operations, leading to a delayed healing of the defected bone tissue. However, antibiotic treatments are ineffective in dealing with S. aureus bone infections due to the rise in multiple antimicrobial resistances. Here, we reported the protective effects of a recombinant five-antigen S. aureus vaccine (rFSAV) in an S. aureus infected bone defect model. In this study, we found the number of M2 macrophages markedly increased in the defect site and played a critical role in the healing of defected bone mediated by rFSAV. Mechanistically, rFSAV mediated increased level of IL-13 in bone defect site predominant M2 macrophage polarization. In summary, our study reveals a key role of M2 macrophage polarization in the bone regeneration process in S. aureus infection induced bone defect, which provide a promising application of rFSAV for the treatment of bone infection for orthopedic applications.

7.
Anal Chem ; 95(7): 3556-3562, 2023 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-36757384

RESUMO

The broad application of plastic products has resulted in a considerable release of microplastics (MPs) into the ecosystem. While MPs in other environmental matrices (e.g., soil and water) have been studied for a long time, the atmospheric fine particulate matter (PM2.5)-bound MPs are rarely investigated due to the lack of an appropriate analytical approach. The prevalently used visual and spectroscopic means (e.g., optical microscopy, Fourier-transform infrared spectroscopy, and Raman spectroscopy) suffer from obvious drawbacks that cannot precisely detect MPs of tiny sizes and provide quantitative information. In the present study, a novel strategy that does not require sample pretreatment was developed to first effectuate accurate quantification of polyethylene MP (PE-MP) in PM2.5 based on pyrolysis-gas chromatography-tandem mass spectrometry (Pyr-GC-MS/MS). It featured acceptable recoveries (97%-110%), high sensitivity (LOD = 1 pg), and qualified precisions (RSD of 3%-13%). Employing this approach, for the first time, exact atmospheric concentrations of PE-MPs in PM2.5 from megacities in North (Zhengzhou and Taiyuan) and South (Guangzhou) China were obtained, and relatively serious pollution was found in Taiyuan. The 100% sample detection rates also suggested the widespread occurrence and possible human exposure risks of PM2.5-bound PE-MPs. In brief, the new strategy could conduct direct, sensitive, and accurate quantification of PE-MP in PM2.5, favoring further studies of environmental fates, distributions, and toxicities of atmospheric MPs.

8.
Mol Pharm ; 20(5): 2513-2526, 2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-37071030

RESUMO

Docetaxel (DTX), a semisynthetic analogue of paclitaxel, is often used to treat cancers. Owing to its poor aqueous solubility, the current formulation of DTX for clinical applications involves using high surfactant and ethanol concentrations, causing hypersensitivity reactions. To overcome this issue, we developed a reduction-responsive DTX prodrug encapsulated within human serum albumin (HSA) nanoparticles (DTX-SS-COOH/HSA NPs). First, the DTX prodrug was conjugated to undecanoic acid through a disulfide bond (DTX-SS-COOH) via a four-step reaction. Subsequently, DTX-SS-COOH/HSA NPs were prepared via the desolvation method. The NPs exhibited a spherical structure with a diameter range of 140-220 nm, as revealed by dynamic light scattering and transmission electron microscopy. Fluorescence quenching analysis confirmed the formation of DTX-SS-COOH/HSA, which was ascribed to electrostatic interactions and hydrophobic forces. Notably, NPs with a feed mole ratio corresponding to DTX-SS-COOH/HSA = 9:1 demonstrated high drug-loading and encapsulation efficiency of 12.84 and 93.11%, respectively, alongside good stability. Moreover, the reduced responsiveness experiment revealed an accelerated DTX release in the presence of glutathione. An in vivo pharmacokinetic study indicated that DTX-SS-COOH/HSA NPs demonstrated considerably a prolonged circulation time (6.2-fold) compared to that of free DTX. Ultimately, the antitumor test of MDA-MB-231 tumor-bearing mice revealed that DTX-SS-COOH/HSA NPs were superior to DTX/HSA NPs for tumor growth inhibition. Thus, DTX-SS-COOH/HSA NPs represent a promising DTX nanoformulation for clinical application.


Assuntos
Antineoplásicos , Nanopartículas , Neoplasias , Pró-Fármacos , Humanos , Camundongos , Animais , Docetaxel , Albumina Sérica Humana , Paclitaxel , Portadores de Fármacos/química , Nanopartículas/química , Linhagem Celular Tumoral , Antineoplásicos/uso terapêutico , Antineoplásicos/química , Neoplasias/tratamento farmacológico
9.
Mol Pharm ; 20(10): 4971-4983, 2023 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-37699256

RESUMO

mRNA vaccines encoding a single spike protein effectively prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, the emergence of SARS-CoV-2 variants leads to a wide range of immune evasion. Herein, a unique trivalent mRNA vaccine based on ancestral SARS-CoV-2, Delta, and Omicron variant spike receptor-binding domain (RBD) mRNAs was developed to tackle the immune evasion of the variants. First, three RBD mRNAs of SARS-CoV-2, Delta, and Omicron were coencapsulated into lipid nanoparticles (LNPs) by using microfluidic technology. After that, the physicochemical properties and time-dependent storage stability of the trivalent mRNA vaccine nanoformulation were tested by using dynamic light scattering (DLS). In vitro, the trivalent mRNA vaccine exhibited better lysosomal escape ability, transfection efficiency, and biocompatibility than did the commercial transfection reagent Lipo3000. In addition, Western blot analyses confirmed that the three RBD proteins can be detected in cells transfected with the trivalent mRNA vaccine. Furthermore, ex vivo imaging analysis indicated that the livers of BALB/c mice had the strongest protein expression levels after intramuscular (IM) injection. Using a prime-boost strategy, this trivalent vaccine elicited robust humoral and T-cell immune responses in both the high-dose and low-dose groups and showed no toxicity in BALB/c mice. Three specific IgG antibodies in the high-dose group against SARS-CoV-2, Delta, and Omicron variants approached ∼1/1,833,333, ∼1/1,866,667, and ∼1/925,000, respectively. Taken together, two doses of inoculation with the trivalent mRNA vaccine may provide broad and effective immunization responses against SARS-CoV-2 and variants.


Assuntos
COVID-19 , SARS-CoV-2 , Animais , Camundongos , Humanos , SARS-CoV-2/genética , Vacinas contra COVID-19 , COVID-19/prevenção & controle , Imunização , Vacinas de mRNA , Anticorpos Neutralizantes
10.
Bioorg Med Chem ; 78: 117135, 2023 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-36577327

RESUMO

Vascular endothelial growth factor A (VEGFA) plays an important role in the healing of skin wound. However, the application of VEGFA protein in clinic is limited because of its high cost manufacturing, complicated purification and poor pharmacokinetic profile. Herein, we developed nucleoside-modified mRNA encoding VEGFA encapsulated ionizable lipid nanoparticles (LNP) to improve angiogenesis and increase wound healing rate. First, VEGFA mRNA was synthesized by an in vitro transcription (IVT) method. After that, VEGFA mRNA-LNP was prepared by encapsulating mRNA in ionizable lipid based nanoparticles via a microfluidic mixer. The physicochemical properties of VEGFA mRNA-LNP were investigated via dynamic light scattering (DLS) and transmission electron microscopy (TEM). The results showed that the VEGFA mRNA-LNP possessed regular spherical morphology with an average size of 112.67 nm and a negative Zeta potential of -3.43 mV. The LNP delivery system had excellent lysosome escape capability and high transfection efficiency. ELISA and Western Blot analysis indicated that the mRNA-LNP could express VEGFA protein in Human umbilical vein endothelial cells (HUVECs). Besides, endothelial tube formation, cell proliferation and scratch assays were performed. The results revealed VEGFA mRNA-LNP boosted angiogenesis, cell proliferation and cell migration by expressing VEGFA protein. Finally, C57BL/6 mouse model of skin wound was established and intradermally treated with VEGFA mRNA-LNP. The VEGFA mRNA-LNP treated wounds were almost healed with an average wound size of 1.56 mm2 compared with the blank of 18.66 mm2 after 9 days. The results indicated that the VEGFA mRNA-LNP was able to significantly expedite wound healing. Histological analysis further demonstrated tissue epithelialization, collagen deposition and enhancement of vascular density after treatment. Taken together, VEGFA mRNA-LNP can be uptaken by cells to express protein effectively and promote wound healing, which may provide a promising strategy for clinical remedy.


Assuntos
Nanopartículas , Fator A de Crescimento do Endotélio Vascular , Camundongos , Animais , Humanos , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , RNA Mensageiro/genética , Camundongos Endogâmicos C57BL , Cicatrização , Nanopartículas/química , Células Endoteliais da Veia Umbilical Humana/metabolismo
11.
Ecotoxicol Environ Saf ; 264: 115437, 2023 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-37696081

RESUMO

As one of the most important transportation hubs and industrial bases in China, Zhengzhou has suffered from serious PM2.5 pollution for a long time. However, the investigation of contamination status and possible exposure risks of environmentally persistent free radicals (EPFRs) in PM2.5 from Zhengzhou is rare. In this work, a comprehensive study of pollution levels, seasonal variations, sources, and potential health risks of PM2.5-bound EPFRs in Zhengzhou was conducted for the first time. The atmospheric concentrations of EPFRs in PM2.5 from Zhengzhou ranged from 1.732 × 1012 spin m-3 to 7.182 × 1014 spin m-3 between 2019 and 2020. Relatively serious contamination was noticed in winter and spring. Primary fossil fuel combustion and Fe-mediated secondary formation were apportioned as possible sources of PM2.5-bound EPFRs in Zhengzhou. Moreover, to avert the bias of the toxicity assessment induced by utilization of incompletely extracted EPFRs from sample filter, simulatively generated EPFRs were applied to toxicological evaluations (cell viability and reactive oxygen species assays). Corresponding experimental dosages were based on the estimated adults' annual exposure amounts of EPFRs in real PM2.5 samples. The results elucidated that EPFRs might cause growth inhibition and oxidative stress of human lung cells, suggesting the possible exposure-induced health concerns for local people in Zhengzhou. This study provides practical information of real contamination status of PM2.5-bound EPFRs in Zhengzhou, which is favorable to local air pollution control and reduction of exposure risks on public health in central China.


Assuntos
Estresse Oxidativo , Adulto , Humanos , Radicais Livres , Material Particulado/toxicidade , Espécies Reativas de Oxigênio , China , Cidades
12.
Anal Chem ; 94(35): 12136-12143, 2022 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-35993787

RESUMO

Matrix deposition plays an important role in obtaining high-quality and reliable molecular spatial location information for matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI). To control the matrix film formation, an automatic matrix spraying apparatus was developed with the introduction of a noncontact heating lamp. Compared with the unheated condition, the noncontact heating lamp suppressed the coffee-ring effect and the diffusion phenomenon of the analyte effectively by controllable matrix film formation. Meanwhile, the signal intensity was increased by 2-5 fold. To prove the ability of the matrix deposition apparatus, the apparatus combined with metabolomics analysis was used to show the spatial distribution of the substance in sprouted potato tubers. The potential biomarkers at m/z 868.5049 and m/z 852.5101 were identified as α-solanine and α-chaconine, and the synthesis pathways were further searched. To further demonstrate the quality of MALDI images including localization and spatial resolution, lipid distribution in rat brain tissue was investigated by the developed noncontact heating matrix spraying apparatus. An excellent match with distinguishable compartments of lipids in the rat brain was obtained between the H&E-stained sections and MALDI-MSI images. These results indicate that the developed noncontact heating matrix spraying apparatus is reliable and provides a low-cost, high-quality, rapid approach for MALDI-MSI.


Assuntos
Calefação , Metabolômica , Animais , Encéfalo/metabolismo , Diagnóstico por Imagem , Metabolômica/métodos , Ratos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos
13.
Mol Pharm ; 19(12): 4588-4600, 2022 12 05.
Artigo em Inglês | MEDLINE | ID: mdl-35731922

RESUMO

Protein kinase N3 (PKN3), by virtue of its abnormal expression in prostate cells, has been widely used as a target of RNAi (shRNA, siRNA, miRNA) therapy. The major challenges of PKN3 RNAi therapy lie in how to design effective interference sequences and delivery systems. Herein, new PKN3 shRNA sequences (shPKN3-2459 and shPKN3-3357) were designed, and bioreducible, biodegradable, ionizable lipid-based nanoparticles were developed for shPKN3 delivery. First, an ionizable lipid (DDA-SS-DMA) bridged with disulfide bond and ester bonds was synthesized by a three-step reaction and confirmed by MS, 1H NMR, and 13C NMR. The ionizable lipid was mixed with cholesterol, DSPC, PEG-lipid, and shPKN3 by a microfluidic mixer to prepare lipid nanoparticles (LNP-shPKN3) which were characterized by DLS and TEM. Afterward, the pH and glutathione (GSH)-responsiveness of the DDA-SS-DMA based LNP delivery system were investigated by lysosome escape and gel electrophoresis assays. Compared with the commercial transfection reagent Lipo2000, the DDA-SS-DMA based delivery system showed higher transfection efficiency and lower toxicity. Western blot analysis, invasion tests, and migration assays were performed to evaluate the silencing effect of shPKN3 in vitro. In in vivo studies, high tumor suppression (65.8%) and treatment safety were evident in the LNP-shPKN3-2459 treatment group. Taken together, the DDA-SS-DMA based delivery system encapsulating shPKN3-2459 showed significant antitumor efficacy and might be a promising formulation for the treatment of prostate cancer.


Assuntos
Nanopartículas , Neoplasias da Próstata , Humanos , Masculino , Lipídeos/química , Nanopartículas/química , Próstata , Neoplasias da Próstata/genética , Neoplasias da Próstata/terapia , RNA Interferente Pequeno
14.
Environ Sci Technol ; 56(11): 6914-6921, 2022 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-34551519

RESUMO

The wide use and continuous abrasion of rubber-related products appears to be leading to an incredible release of p-phenylenediamine (PPD) antioxidants in the environment. However, no related research has been conducted on the pollution characteristics and potential health risks of PM2.5-bound PPDs. We report for the first time the ubiquitous distributions of six emerging PPDs and a quinone derivative, N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine quinone (6PPDQ), in PM2.5 from urban areas of China. Atmospheric contamination levels of PM2.5-bound PPDs were found to be mostly in pg m-3 amounts between 2018 and 2019. Urban vehicle rubber tire abrasion was found to probably contribute to the PPDs in PM2.5 and accounted for their significant spatiotemporal-dependent concentration variations. Furthermore, 6PPDQ, an emerging oxidation product of 6PPD in the environment, was first quantified (pg m-3) with a total detection rate of 81% in the urban PM2.5, demonstrating its broad existence. On the basis of the determined ambient concentrations, the annual intakes of PPDs and 6PPDQ for adults were not low, indicating their possible human health risks induced by long-term exposure. This study confirms the widespread occurrence of PPDs and 6PPDQ in PM2.5, showing that the pollution of such compounds in urban air should not be underestimated.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Adulto , Poluentes Atmosféricos/análise , Antioxidantes , China , Monitoramento Ambiental , Humanos , Material Particulado/análise , Fenilenodiaminas , Quinonas , Borracha
15.
Bioorg Med Chem ; 69: 116884, 2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-35752145

RESUMO

Protein kinase N3 (PKN3), an AGC-family member, is often overexpressed in breast tumor cells. RNAi therapy is a promising approach to inhibit tumor growth by reducing the expression of PKN3. In this report, lipid nanoparticles encapsulated with new shRNA PKN3 (SS-LNP/shPKN3) with redox-responsiveness were developed in order to specifically down-regulate the expression of PKN3 for breast cancer treatment. The SS-LNP/shPKN3 was prepared by microfluidic method using disulfide bonds based ionizable lipid as main component. The as-prepared SS-LNP/shPKN3 lipid nanoparticles were characterized via using dynamic light scattering (DLS) and transmission electron microscopy (TEM). The results indicated that the obtained SS-LNP/shPKN3 exhibited uniform particle size and regular spherical morphology. Moreover, glutathione (GSH) triggered release of shPKN3 confirmed the redox-responsiveness of the SS-LNP/shPKN3. Finally, the anti-tumor effect of SS-LNP/shPKN3 was evaluated against MDA-MB-231 cells and derived xenograft tumor bearing mice. It was found that the SS-LNP/shPKN3-2 had the highest PKN3 protein inhibition rate of 60.8% and tumor inhibition rate of 62.3%. Taken together, the SS-LNP/shPKN3 might be a potential therapeutic strategy for breast cancer.


Assuntos
Neoplasias da Mama , Nanopartículas , Animais , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Feminino , Humanos , Lipossomos , Camundongos , Nanopartículas/química , Proteína Quinase C , RNA Interferente Pequeno/química
16.
Environ Res ; 206: 112597, 2022 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-34954148

RESUMO

To prevent the transmission of the novel coronavirus disease 2019 (COVID-19), China adopted nationwide lockdown measures on January 25, 2020, leading to an evident diminution in the observed air pollutants. To investigate the influence of the lockdown on atmospheric chemistry, the specific molecular composition, oxidative potential of organic aerosols (OAs) in PM2.5 were studied using a high-resolution orbitrap mass spectrometry at a typical coal-combustion city, Linfen, in the North China Plain (NCP). The major air pollutants including PM2.5, PM10, SO2, NO2, and CO were observed to be diminished by 28.6-45.4%, while O3 was augmented by 52.5% during the lockdown compared to those before the lockdown. A significant decrease of oxygen-containing (CHO) compounds (24.7%) associated with anthropogenic acids was observed during the lockdown, implying a reduction in fossil fuel combustion. The coal-burning related sulfur-containing organosulfates (CHOS-) and nitrooxy-sulfates (CHONS-) have also shown attenuated in both their relative abundances and anthropogenic/biogenic ratios. Amine/amide-like CHON + components have decreased by 27.6%, while nitro/nitrooxy-containing CHON- compounds have only decreased by 7.1%. Multi-source nitrogen-containing (CHN) compounds have shown a moderate elimination of 24.0%, while the identified high-condensed azaarenes have fallen from 17.7% to 14.7%, implying a potential reduction in the health risk of OAs during quarantine. The measurement of OAs' oxidative potential through dithiothreitol (DTT) assay has confirmed that as it had dropped from 0.88 nmol min-1 m-3 to 0.80 nmol min-1 m-3. High correlations were observed between the abundance of OA subgroups with the concentration of PM2.5 after the execution of the lockdown, suggesting a potential elevation in the contribution of organic components to the total PM2.5 level. Our study provides insightful compositional and health-related information in the variation of OAs during the lockdown period and attests to the validity of joint-control strategy in controlling the level and health risks of numerous atmospheric pollutants.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , COVID-19 , Aerossóis/análise , Poluentes Atmosféricos/análise , Poluição do Ar/análise , China , Controle de Doenças Transmissíveis , Monitoramento Ambiental , Humanos , Estresse Oxidativo , Material Particulado/análise , SARS-CoV-2
17.
J Environ Sci (China) ; 115: 443-452, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-34969472

RESUMO

The COVID-19 pandemic has raised awareness about various environmental issues, including PM2.5 pollution. Here, PM2.5 pollution during the COVID-19 lockdown was traced and analyzed to clarify the sources and factors influencing PM2.5 in Guangzhou, with an emphasis on heavy pollution. The lockdown led to large reductions in industrial and traffic emissions, which significantly reduced PM2.5 concentrations in Guangzhou. Interestingly, the trend of PM2.5 concentrations was not consistent with traffic and industrial emissions, as minimum concentrations were observed in the fourth period (3/01-3/31, 22.45 µg/m3) of the lockdown. However, the concentrations of other gaseous pollutants, e.g., SO2, NO2 and CO, were correlated with industrial and traffic emissions, and the lowest values were noticed in the second period (1/24-2/03) of the lockdown. Meteorological correlation analysis revealed that the decreased PM2.5 concentrations during COVID-19 can be mainly attributed to decreased industrial and traffic emissions rather than meteorological conditions. When meteorological factors were included in the PM2.5 composition and backward trajectory analyses, we found that long-distance transportation and secondary pollution offset the reduction of primary emissions in the second and third stages of the pandemic. Notably, industrial PM2.5 emissions from western, southern and southeastern Guangzhou play an important role in the formation of heavy pollution events. Our results not only verify the importance of controlling traffic and industrial emissions, but also provide targets for further improvements in PM2.5 pollution.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , COVID-19 , Poluentes Atmosféricos/análise , Poluição do Ar/análise , China/epidemiologia , Controle de Doenças Transmissíveis , Monitoramento Ambiental , Humanos , Pandemias , Material Particulado/análise , SARS-CoV-2
18.
Analyst ; 145(24): 7985-7992, 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33048074

RESUMO

Developing suitable molecular tools for monitoring SO2 and its derivatives in living organisms is attractive due to their importance for human health. Herein, the first near-infrared fluorescent probe Mito-HN with aggregation-induced emission enhancement (AIEE) characteristics for ratiometric sensing of SO2 derivatives in vitro, in cells, and in zebrafish was designed and synthesized. By connecting the electron-donating naphthopyran and electron-withdrawing hemicyanine via the alkenyl group, this probe displays a near-infrared fluorescence emission and notable solid-state luminescence with AIEE features. Based on the specific 1,4-addition reaction of HSO3-/SO32- with the C[double bond, length as m-dash]C double bond of Mito-HN, this probe can specifically sense HSO3- in real time with an excellent near-infrared ratiometric fluorescence effect, a low detection limit of 0.17 µM, and a fast response time of less than 30 s. Cell imaging and zebrafish imaging results demonstrate that Mito-HN can ratiometrically not only sense endogenous SO2 derivatives in mitochondria but also monitor SO2 in living organisms. We anticipate that Mito-HN could be applied for the diagnosis of SO2-related diseases in the future.


Assuntos
Corantes Fluorescentes , Peixe-Zebra , Animais , Células HeLa , Humanos , Microscopia de Fluorescência , Mitocôndrias , Dióxido de Enxofre
19.
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.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Poluentes Atmosféricos/análise , Poluentes Atmosféricos/toxicidade , Poluição do Ar/análise , Animais , China , Camundongos , Modelos Animais , Material Particulado/análise , Material Particulado/toxicidade
20.
Ecotoxicol Environ Saf ; 191: 110225, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-32001423

RESUMO

Numerous studies have demonstrated adverse effects on human health after exposure to fine particulate matter (PM2.5). However, it is still not clear how the toxicological effects and the health risks vary among PM samples of different compositions and concentrations. In this study, we examined effects of region- and season-dependent differences of PM2.5 on cytotoxicity, and the contributions of PAHs, nitro-PAHs (N-PAHs) and hydroxy-PAHs (OH-PAHs) to PM2.5 toxicity by determining different toxicological indicators in three lung cell lines. The results illustrated significant differences in components concentrations and biological responses elicited by PM2.5 collected in different cities and seasons. The concentrations of most PAHs, N-PAHs and OH-PAHs were much higher in Taiyuan than in Guangzhou. PM2.5 from Taiyuan exhibited lower cell viability and higher reactive oxygen species (ROS) and interleukin-6 (IL-6) release on lung cells than those from Guangzhou. Specifically, PM2.5 collected in summer from Taiyuan caused higher levels of pro-inflammatory responses and oxidative potential than those collected in winter. The correlation analysis between 19 PAHs, 17 N-PAHs and 12 OH-PAHs and the measured indicators demonstrated that PAHs were more related to PM2.5-induced CCK-8 cytotoxicity and IL-6 release in Taiyuan while N-PAHs and OH-PAHs were more related to PM2.5-induced CCK-8 cytotoxicity and dithiothreitol (DTT)-based redox activity in Guangzhou, suggesting that the toxicity of PM2.5 from Taiyuan was mostly correlated with PAHs while the toxicity of PM2.5 from Guangzhou was closely associated with N-PAHs and OH-PAHs. These results revealed that composition differences in PM2.5 from different regions and seasons significantly accounted for the differences of their toxicological effects.


Assuntos
Poluentes Atmosféricos/toxicidade , Material Particulado/toxicidade , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , Poluentes Atmosféricos/química , Linhagem Celular , China , Cidades , Humanos , Interleucina-6/metabolismo , Material Particulado/química , Hidrocarbonetos Policíclicos Aromáticos/química , Espécies Reativas de Oxigênio/metabolismo , Estações do Ano
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