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1.
Ann Surg ; 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33605586

RESUMO

OBJECTIVE: To clarify whether systemic lymph node dissection (LND) influences the safety of surgery and the survival of patients with locally advanced esophageal squamous cell carcinoma (ESCC) after neoadjuvant chemoradiotherapy (nCRT). SUMMARY BACKGROUND DATA: Prognostic impact of systemic lymphadenectomy during surgery after nCRT for ESCC is still uncertain and requires clarification. METHODS: This is a secondary analysis of NEOCRTEC5010 trial which compared nCRT followed by surgery versus surgery alone for locally advanced ESCC. Relationship between number of LND and perioperative, recurrence and survival outcomes were analyzed in the nCRT group. RESULTS: Three-year overall survival was significantly better in the nCRT group than the S group (75.2% vs 61.5%; P=0.011). In the nCRT group, greater number of LND was associated with significantly better overall survival (HR, 0.358; P < 0.001) and disease-free survival (HR, 0.415; P=0.001), but without any negative impact on postoperative complications. Less LND (< 20 vs ≥ 20) was significantly associated with increased local recurrence (18.8% vs 5.2%, P=0.004) and total recurrence rates (41.2% vs 25.8%, P=0.027). Compared to patients with persistent nodal disease, significantly better survival was seen in patients with complete response and with LND ≥ 20, but not in those with LND < 20. CONCLUSIONS: Systemic lymph node dissection does not increase surgical risks after nCRT in ESCC patients. And it is associated with better survival and local disease control. Therefore, systemic lymphadenectomy should still be considered as an integrated part of surgery after nCRT for ESCC.

2.
Sci Adv ; 7(6)2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33547084

RESUMO

The ongoing unprecedented severe acute respiratory syndrome caused by the SARS-CoV-2 outbreak worldwide has highlighted the need for understanding viral-host interactions involved in mechanisms of virulence. Here, we show that the virulence factor Nsp1 protein of SARS-CoV-2 interacts with the host messenger RNA (mRNA) export receptor heterodimer NXF1-NXT1, which is responsible for nuclear export of cellular mRNAs. Nsp1 prevents proper binding of NXF1 to mRNA export adaptors and NXF1 docking at the nuclear pore complex. As a result, a significant number of cellular mRNAs are retained in the nucleus during infection. Increased levels of NXF1 rescues the Nsp1-mediated mRNA export block and inhibits SARS-CoV-2 infection. Thus, antagonizing the Nsp1 inhibitory function on mRNA export may represent a strategy to restoring proper antiviral host gene expression in infected cells.


Assuntos
/metabolismo , Expressão Gênica , Interações entre Hospedeiro e Microrganismos/genética , RNA Mensageiro/metabolismo , Proteínas não Estruturais Virais/metabolismo , Fatores de Virulência/metabolismo , Transporte Ativo do Núcleo Celular/genética , Animais , Chlorocebus aethiops , Células HEK293 , Humanos , Poro Nuclear/metabolismo , Proteínas de Transporte Nucleocitoplasmático/genética , Proteínas de Transporte Nucleocitoplasmático/metabolismo , RNA Mensageiro/genética , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Transfecção , Células Vero , Proteínas não Estruturais Virais/genética
3.
J Electrocardiol ; 65: 96-101, 2021 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-33588259

RESUMO

BACKGROUND: Coronavirus disease 2019 (COVID-19) continues to impact populations around the globe. Information regarding the incidences and implications of arrhythmias in COVID-19 is limited. METHODS: A total of 463 patients with COVID-19 and who had at least one electrocardiogram recording from February 1 to March 19, 2020, in Wuhan Union Hospital were enrolled in the study. RESULTS: Arrhythmias occurred in 85 of 463 (18.4%) patients: atrial arrhythmias in 10.2%, junctional arrhythmias in 0.2%, ventricular arrhythmias in 3.5%, and conduction block in 7.3%. Compared with patients without arrhythmias, those with arrhythmias had higher mortality, both during the time from symptom onset (p < 0.001) and from admission to follow-up (p < 0.001). The frequencies of severe COVID-19 (44.7% vs. 21.2%; p < 0.001) and death (25.9% vs. 10.1%; p < 0.001) were higher in patients with arrhythmias than in those without arrhythmias. Atrial arrhythmias and ventricular arrhythmias could predict severity and mortality, their odds ratios (OR) were 4.45 (95% confidence interval [CI] 2.35 to 8.40), 5.80 (95% CI 1.89 to 17.76) respectively for severity, and were 3.51 (95% CI 1.74 to 7.08), 3.41 (95% CI 1.13 to 10.24) respectively for mortality. High levels of interleukin-6 (IL-6) and IL-10 were associated with the occurrence of arrhythmias (all p < 0.05). CONCLUSION: Arrhythmias were significantly associated with COVID-19 severity and mortality. Atrial arrhythmia was the most frequent arrhythmia type. IL-6 and IL-10 levels can predict the risk of arrhythmias in COVID-19 patients.

4.
Science ; 2021 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-33542149

RESUMO

The cyclic GMP-AMP synthase (cGAS) detects microbial and self-DNA in the cytosol to activate immune and inflammatory programs. cGAS also associates with chromatin especially after nuclear envelope breakdown when cells enter mitosis. How cGAS is regulated during cell cycle transition is not clear. Here we found direct biochemical evidence that cGAS activity was selectively suppressed during mitosis, and uncovered two parallel mechanisms underlying this suppression. First, cGAS was hyperphosphorylated at the N terminus by mitotic kinases, including Aurora kinase B. The N terminus of cGAS was critical for sensing nuclear chromatin, but not mitochondrial DNA. Chromatin sensing was blocked by hyperphosphorylation. Secondly, oligomerization of chromatin-bound cGAS, which is required for its activation,was prevented. Together, these mechanisms ensure that cGAS is inactive when associated with chromatin during mitosis, which may help to prevent autoimmune reaction.

5.
Artigo em Inglês | MEDLINE | ID: mdl-33430594

RESUMO

Although the power conversion efficiency of perovskite solar cells has reached 25.5%, their long-term stability is still a barrier to commercialization. In this work, 1-methyl-3-(3',3',4',4',4'-pentafluorobutyl)imidazolium tetrafluoroborate (MFIM-2) ionic liquid and another two analogues were used as additives to study their interaction mechanism with the FAPbI3 perovskite layer. The results reveal that MFIM-2 suppressed the formation of PbI2 crystals during crystallization, enlarged the grain size, and reduced the defect density, which led to an increased photovoltage of 1.12 V and efficiency of 19.4%. Furthermore, the moisture stability of the solar cell devices was also improved. Devices with MFIM-2 retained above 83% of the original value after 35 days in an atmosphere with about 25% relative humidity, and the perovskite film with MFIM-2 showed no phase transition in a 10 month aging process. These results demonstrate that the additive strategy of the polyfluoroalkylated imidazolium salt is a promising way for simultaneously extending the lifetime and improving the device performance of the perovskite solar cells.

6.
Cancer Cell ; 39(1): 109-121.e5, 2021 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-33338427

RESUMO

Tumors with defective mismatch repair (dMMR) are responsive to immunotherapy because of dMMR-induced neoantigens and activation of the cGAS-STING pathway. While neoantigens result from the hypermutable nature of dMMR, it is unknown how dMMR activates the cGAS-STING pathway. We show here that loss of the MutLα subunit MLH1, whose defect is responsible for ~50% of dMMR cancers, results in loss of MutLα-specific regulation of exonuclease 1 (Exo1) during DNA repair. This leads to unrestrained DNA excision by Exo1, which causes increased single-strand DNA formation, RPA exhaustion, DNA breaks, and aberrant DNA repair intermediates. Ultimately, this generates chromosomal abnormalities and the release of nuclear DNA into the cytoplasm, activating the cGAS-STING pathway. In this study, we discovered a hitherto unknown MMR mechanism that modulates genome stability and has implications for cancer therapy.

7.
BMC Genomics ; 21(1): 861, 2020 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-33272205

RESUMO

BACKGROUND: As a heavy metal, manganese (Mn) can be toxic to plants. Stylo (Stylosanthes) is an important tropical legume that exhibits tolerance to high levels of Mn. However, little is known about the adaptive responses of stylo to Mn toxicity. Thus, this study integrated both physiological and transcriptomic analyses of stylo subjected to Mn toxicity. RESULTS: Results showed that excess Mn treatments increased malondialdehyde (MDA) levels in leaves of stylo, resulting in the reduction of leaf chlorophyll concentrations and plant dry weight. In contrast, the activities of enzymes, such as peroxidase (POD), phenylalanine ammonia-lyase (PAL) and polyphenol oxidase (PPO), were significantly increased in stylo leaves upon treatment with increasing Mn levels, particularly Mn levels greater than 400 µM. Transcriptome analysis revealed 2471 up-regulated and 1623 down-regulated genes in stylo leaves subjected to Mn toxicity. Among them, a set of excess Mn up-regulated genes, such as genes encoding PAL, cinnamyl-alcohol dehydrogenases (CADs), chalcone isomerase (CHI), chalcone synthase (CHS) and flavonol synthase (FLS), were enriched in secondary metabolic processes based on gene ontology (GO) analysis. Numerous genes associated with transcription factors (TFs), such as genes belonging to the C2H2 zinc finger transcription factor, WRKY and MYB families, were also regulated by Mn in stylo leaves. Furthermore, the C2H2 and MYB transcription factors were predicted to be involved in the transcriptional regulation of genes that participate in secondary metabolism in stylo during Mn exposure. Interestingly, the activation of secondary metabolism-related genes probably resulted in increased levels of secondary metabolites, including total phenols, flavonoids, tannins and anthocyanidins. CONCLUSIONS: Taken together, this study reveals the roles of secondary metabolism in the adaptive responses of stylo to Mn toxicity, which is probably regulated by specific transcription factors.

8.
Med Hypotheses ; 144: 110261, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33254560

RESUMO

The contribution of various modes of transmission of SARS-CoV-2 has been the subject of recent intensive debate. The predominant route of the viral transmission is via exhaled droplets of different sizes which can be inhaled by nearby exposed individuals or deposited on peoples and surfaces. Touching contaminated surfaces followed by hand to facial transfer has been identified as a potential infection route. As humans involuntarily touch their faces over 20 times per hour a hand washing with soap and water is recommended to avoid hands to face transmission. To date however, there is no clear explanation how the viruses arrive form the face into the nose and the lung. Our hypothesis is that during the physiological nasal air inspiration the virion particles attached on the face close to the nose are resuspended in the air and then are inhaled into the nose. Our preliminary fluid dynamics simulations confirm our hypothesis. Further experimental and computational studies are warranted.

9.
Sci Adv ; 6(42)2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33055160

RESUMO

The cyclic GMP-AMP synthase (cGAS), a sensor of cytosolic DNA, is critical for the innate immune response. Here, we show that loss of cGAS in untransformed and cancer cells results in uncontrolled DNA replication, hyperproliferation, and genomic instability. While the majority of cGAS is cytoplasmic, a fraction of cGAS associates with chromatin. cGAS interacts with replication fork proteins in a DNA binding-dependent manner, suggesting that cGAS encounters replication forks in DNA. Independent of cGAMP and STING, cGAS slows replication forks by binding to DNA in the nucleus. In the absence of cGAS, replication forks are accelerated, but fork stability is compromised. Consequently, cGAS-deficient cells are exposed to replication stress and become increasingly sensitive to radiation and chemotherapy. Thus, by acting as a decelerator of DNA replication forks, cGAS controls replication dynamics and suppresses replication-associated DNA damage, suggesting that cGAS is an attractive target for exploiting the genomic instability of cancer cells.

10.
Artigo em Inglês | MEDLINE | ID: mdl-33009612

RESUMO

To better understand the cardiopulmonary alterations associated with personal exposed PM2.5-bound heavy meals, we conducted a cross-sectional study in 2018 on 54 general residents. For each subject, PM2.5 exposure filter was collected by a low-volume sampler for 24 h; blood and urine samples were collected subsequently. Heavy metals in PM2.5, blood, and urine samples were determined by inductively coupled plasma mass spectrometry method. PM2.5-bound Mn, Cd, Sb, Pb, and Ni levels were 20.5, 9.27, 9.59, 28.3, and 16.9 ng/m3, respectively. The distribution of these metals followed the order: Pb (33.47%) > Mn (24.24%) > Ni (19.99%) > Sb (11.34%) > Cd (10.96%). The distribution of heavy meals in PM2.5, blood, and urine differed from each other. PM2.5-bound Cd, Pb levels were positively correlated with blood Cd, Pb levels (r = 0.323, r = 0.334, p < 0.05), respectively. PM2.5-bound Cd level was significantly higher in smoking group than non-smoking group (28.8 vs. 7.27 ng/m3, p < 0.01), same as Sb level (12.0 vs. 9.34 ng/m3, p < 0.01). Cd and Pb exposure might interact with cardiovascular function through autonomic regulation. No significant correlation was observed between metal exposure and pulmonary function. In conclusion, our data suggested that personal exposure to specific PM2.5-bound heavy metals might interact with profound cardiovascular alterations.

11.
Artigo em Inglês | MEDLINE | ID: mdl-33029779

RESUMO

How to promote the carbon productivity embodied in trade and regional balanced development has become the focus of attention to combat climate change and improve regional management. Taking the Pan-Yangtze River Delta region for example and based on the input-output model, this paper explored the relationship between inter-industry economic spillover and embodied carbon productivity in trade from 2007 to 2012. Results indicated that the intra-regional multiplier effect presented a slow downward trend during the studied period, while the trend in the inter-regional integration was intensifying. Moreover, the multiplier effect of the lower reaches of the Yangtze River was relatively lower than that of the middle reaches. Owing to the geographical location and industrial structure, the industries in the middle reaches of the Yangtze River were strongly correlated. In addition, the regional multiplier effect was mostly concentrated in industries with high carbon emission intensity. The economic spillovers between regions showed a growing trend from 2007 to 2012, indicating that regional economic integration was further strengthened, and the economic spillovers in the Yangtze River Delta region were significantly higher than those in the middle reaches. Furthermore, from the perspective of embodied carbon productivity in trade, most of Shanghai's carbon productivity to other regions was mostly less than 10,000 Yuan per ton, which means Shanghai had little demand for intermediate products of other regions, and inter-regional trade between Shanghai and other regions brought less total output and more environmental pollution to other regions, while Shanghai obtained more total output through trade. As embodied carbon productivity in trade in Jiangsu and Zhejiang was more than 10,000 Yuan per ton, Jiangsu and Zhejiang had played an important role in realizing the coordinated development of low carbon in the Pan-Yangtze River Delta. In particular, for Anhui and Jiangxi, embodied carbon productivity in the Yangtze River Delta region was relatively low. Therefore, in order to achieve green, coordinated, and high-quality economic development in the Pan-Yangtze River Delta region, Anhui and Jiangxi should not only strengthen regional cooperation with Shanghai, Zhejiang, and Jiangsu, but also they should avoid regional zero-sum game competition in regional climate policy. In other words, for policy-makers in the Pan-Yangtze River Delta, promoting the deep integration of industrial chain and regional coordinated development, and thus, improving carbon productivity during the regional development process, should receive more attention.

12.
Nature ; 586(7829): 363-364, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32989308
14.
Cancer Manag Res ; 12: 7331-7339, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32884347

RESUMO

Background: This study aimed to assess the predictive value of tumor volume changes of esophagus evaluated by serial computed tomography (CT) scans before, during, and after radical chemoradiotherapy (CRT) for treatment outcomes in patients with esophageal cancer (EC). Methods: Fifty-three patients with histologically confirmed EC were included for analysis. Gross tumor volume of esophagus (GTVe) was manually contoured on the CT images before treatment, at a twentieth fraction of radiotherapy, at completion of CRT and three months after treatment. GTVe reduction ratio (RR) was calculated to reveal changes of tumor volume by time. The Kaplan-Meier method was used to estimate survival and for univariate analysis. The Cox regression model was performed for multivariate analysis. Results: Predominant reduction of GTVe was observed during the first 20 fractions of radiotherapy. Age, pretreatment GTVe, GTVe three months after treatment and GTVe RR at twentieth fraction of radiotherapy were all significantly associated with overall survival (OS) in a univariate analysis. Gender was correlated with locoregional recurrence-free survival (LRRFS) in univariate analysis. Multivariate analysis showed that GTVe ≤20 cc, GTVe RR at twentieth fraction of radiotherapy ≥35% were positive predictive factors of OS and pretreatment GTVe ≤20 cc was prognostic for a favorable LRRFS. Conclusion: Pretreatment tumor volume and intratreatment volume reduction ratio are reliable prognostic factors for esophageal cancer treated with definitive CRT.

15.
Int J Endocrinol ; 2020: 3760375, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32908502

RESUMO

Objective: The aim of this study was to explore whether iodine nutrition is associated with the risk of thyroid nodules among adult population in Zhejiang Province, China. Methods: A cross-sectional study was conducted in the general population aged 18 years or older. A total of 2,710 subjects received physical examination, questionnaires, and thyroid ultrasonography. Urinary iodine concentration (UIC) and thyroid hormone levels were measured and documented for each subject. 4 multiple logistic regression models adjusted for other risk factors were applied to analyze the association between iodine nutrition and thyroid nodules. Results: The prevalence of thyroid nodules was 15.5% among all adults. As indicated by all 4 models, subjects with UIC varying from 200 µg l-1 to 399 µg l-1 had lower risk of thyroid nodules compared with those with relatively low UIC (<100 µg l-1), with approximately 37-57 percent reduction in risk. Moreover, subjects with UIC between 100 and 199 µg l-1 had a decreased risk of thyroid nodules in model 1 and 2 (OR = 0.75, 95% CI, 0.58-0.97; OR = 0.75, 95% CI, 0.58-0.97, respectively). However, there was no significant difference of risk in thyroid nodules between subjects with high UIC (≥400 µg l-1) and low UIC (<100 µg l-1). Furthermore, intake of iodized salt was inversely associated with risk of thyroid nodules, with approximately 69-77 percent reduction in risk. Conclusion: The relationship between UIC and the risk of thyroid nodules is U-shaped. Consumption of noniodized salt is an independent risk factor of thyroid nodules.

16.
Chem Commun (Camb) ; 56(80): 12069-12072, 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-32909019

RESUMO

A BODIPY dye functionalized with uracil-ethynyl groups at the 2,6-positions supramolecularly polymerized into J-aggregates directed by intermolecular H-bonds and featured intense absorption and resonant fluorescence. The alignment of J-aggregated chromophores in a thin film was achieved by a rubbing method and polarized photoluminescence with a dichroic ratio up to 14.3 was obtained.

17.
Toxicol In Vitro ; 68: 104933, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32652171

RESUMO

Indoor pollution with cooking oil fumes (COF) as one of the main components is closely related to ocular surface disorders. However, as the most abundant aldehyde in COF, the toxicity of trans, trans-2,4-decadienal (tt-DDE) on human cornea has not been explored before. In the present study, we observed a time- and dose-dependent cytotoxicity induced by tt-DDE in human corneal epithelial (HCE) cells, as evidenced by decreased cell viability, altered cell morphology, and increased proportion of apoptotic cells. Exposure to tt-DDE also led to an increase in reactive oxygen species (ROS) production, MMP loss, and a decrease in intracellular ATP levels. In addition, after exposure to tt-DDE, the expression of endoplasmic reticulum (ER) stress-related proteins (Bip, pIRE1, XBP1, pPERK, peIF2α, ATF4, and CHOP) increased, indicating that ER stress was activated. Moreover, pretreatment of HCE cells with two ER stress inhibitors (200 nM ISRIB or 1 mM 4-PBA) effectively attenuated oxidative stress induced by tt-DDE. These results suggested that tt-DDE could cause damage to HCE cells by triggering oxidative stress and ER stress. Furthermore, regulation of ER stress can be considered as a potential protective method for tt-DDE-induced ocular surface disorders.

18.
Immunity ; 53(1): 43-53, 2020 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-32668227

RESUMO

Besides its role as the blueprint of life, DNA can also alert the cell to the presence of microbial pathogens as well as damaged or malignant cells. A major sensor of DNA that triggers the innate immune response is cyclic guanosine monophosphate (GMP)-adenosine monophosphate (AMP) (cGAMP) synthase (cGAS), which produces the second messenger cGAMP. cGAMP activates stimulator of interferon genes (STING), which activates a signaling cascade leading to the production of type I interferons and other immune mediators. Recent research has demonstrated an expanding role of the cGAS-cGAMP-STING pathway in many physiological and pathological processes, including host defense against microbial infections, anti-tumor immunity, cellular senescence, autophagy, and autoimmune and inflammatory diseases. Biochemical and structural studies have elucidated the mechanism of signal transduction in the cGAS pathway at the atomic resolution. This review focuses on the structural and mechanistic insights into the roles of cGAS and STING in immunity and diseases revealed by these recent studies.

19.
Nat Immunol ; 21(8): 868-879, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32690950

RESUMO

STING is essential for control of infections and for tumor immunosurveillance, but it can also drive pathological inflammation. STING resides on the endoplasmic reticulum (ER) and traffics following stimulation to the ERGIC/Golgi, where signaling occurs. Although STING ER exit is the rate-limiting step in STING signaling, the mechanism that drives this process is not understood. Here we identify STEEP as a positive regulator of STING signaling. STEEP was associated with STING and promoted trafficking from the ER. This was mediated through stimulation of phosphatidylinositol-3-phosphate (PtdIns(3)P) production and ER membrane curvature formation, thus inducing COPII-mediated ER-to-Golgi trafficking of STING. Depletion of STEEP impaired STING-driven gene expression in response to virus infection in brain tissue and in cells from patients with STING-associated diseases. Interestingly, STING gain-of-function mutants from patients interacted strongly with STEEP, leading to increased ER PtdIns(3)P levels and membrane curvature. Thus, STEEP enables STING signaling by promoting ER exit.


Assuntos
Retículo Endoplasmático/metabolismo , Regulação da Expressão Gênica/fisiologia , Proteínas de Membrana/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Transdução de Sinais/fisiologia , Animais , Retículo Endoplasmático/imunologia , Humanos , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/metabolismo , Proteínas de Membrana/imunologia , Camundongos , Proteínas do Tecido Nervoso/imunologia , Transporte Proteico/fisiologia
20.
Ocul Surf ; 18(4): 554-564, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32565256

RESUMO

PURPOSE: To explore the molecular mechanisms of PM2.5-induced dysfunction in human corneal epithelial cells (HCECs) and the potential role of the plasminogen activator inhibitor type-2 (PAI-2) in PM2.5-induced autophagy in vitro and in vivo. METHODS: RNA-Seq was performed to identify the differentially expressed genes (DEGs) in PM2.5-exposed HCECs compared to unexposed condition, followed by validation via real-time PCR (qRT-PCR). Corneal fluorescein staining and tear secretion were assessed in the PM2.5-exposed rat model. The expression of PAI-2 and autophagy-related markers were examined via immunoblotting, immunofluorescence staining and/or qRT-PCR in PM2.5-exposed or unexposed HCECs and rat corneas. PAI-2-knockdown HCECs were generated to study PAI-2's role in the PM2.5-induced autophagy in HCECs. RESULTS: A total of 434 DEGs-240 up-regulated and 194 down-regulated-were identified in PM2.5-exposed HCECs rather than unexposed HCECs. The expression of a few genes related to proliferation, inflammation, and aryl hydrocarbon stimulation were significantly altered by PM2.5 exposure. PAI-2 expression was up-regulated in PM2.5-exposed HCECs, sharing a similar fluctuation trend with autophagy-related markers LC3B II and BECN1 according to various exposure periods. Moreover, PAI-2 knockdown significantly suppressed the expression of LC3B and BECN1 in PM2.5-exposed HCECs. The corneal fluorescein staining was enhanced and tear secretion was significantly reduced in PM2.5-exposed rat eyes. PAI-2 expression was also increased in PM2.5-exposed rat corneas, together with the up-regulation of several autophagy-related markers. CONCLUSION: The present study identified the altered expression of hundreds of genes in PM2.5-exposed HCECs, which suggests the importance of PM2.5 for cornea health. The involvement of PAI-2 was discovered in the PM2.5-induced autophagy in HCECs as well as likely in rat corneas, which implied that PAI-2 may become a potential target of clinical treatment of PM2.5-associated ocular surface diseases.

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