Effects of occupational exposure to dust, gas, vapor and fumes on chronic bronchitis and lung function.

Background: Chronic obstructive pulmonary disease (COPD) is one of the leading causes of mortality worldwide, and therefore the identification of the modifiable risk factors [such as exposure to vapors, gases, dust and fumes (VGDF)] for accelerate disease progression has important significance. Methods: We conducted COPD surveillance in six cities of southern China between 2014 and 2019. We recorded the diagnosis of chronic bronchitis, respiratory symptoms, occupational exposure to VGDF and other covariates by using a structured questionnaire. Logistic regression and multivariate linear regression model were adopted for analysis. We performed sensitivity analyses based on two methods of propensity score (PS) methods to evaluate the robustness of our results. Results: A total of 7,418 participants were included. Cough [odds ratios (ORs): 1.60, 95% confidence interval (CI): 1.22 to 2.08] and phlegm (OR: 1.49, 95% CI: 1.19 to 1.85) correlated significantly with exposure to dust. There was an increased risk of cough (OR: 1.53, 95% CI: 1.11 to 2.07) for occupational exposure to gas/vapor/fume. Dual exposure to dust and gas/vapor/fume was associated with a significantly increased risk of chronic bronchitis (OR: 1.74, 95% CI: 1.20 to 2.52), cough (OR: 1.43, 95% CI: 1.15 to 1.79) and phlegm (OR: 1.49, 95% CI: 1.24 to 1.79). In 5,249 participants with complete data of spirometry, gas/vapor/fume was associated with a decreased ratio of forced expiratory volume in one second and forced vital capacity (FEV1/FVC) (ß: -1.05, 95% CI: -1.85 to -0.26) and maximal mid-expiratory flow (MMEF) (ß: -0.15, 95% CI: -0.23 to -0.07). Dual exposure to dust and gas/vapor/fume was significantly associated with decreased FEV1/FVC (ß: -0.74, 95% CI: -1.28 to -0.20) and MMEF (ß: -0.06, 95% CI: -0.12 to -0.01). Results of sensitivity analysis were not materially changed. Conclusions: VGDF exposure is associated with chronic bronchitis, respiratory symptoms and decreased lung function, suggesting that VGDF contributes to the pathogenesis and progression of COPD.

The dynamic role of nucleoprotein SHCBP1 in the cancer cell cycle and its potential as a synergistic target for DNA-damaging agents in cancer therapy.

BACKGROUND: Malignant tumours seriously threaten human life and health, and effective treatments for cancer are still being explored. The ability of SHC SH2 domain-binding protein 1 (SHCBP1) to induce cell cycle disturbance and inhibit tumour growth has been increasingly studied, but its dynamic role in the tumour cell cycle and corresponding effects leading to mitotic catastrophe and DNA damage have rarely been studied. RESULTS: In this paper, we found that the nucleoprotein SHCBP1 exhibits dynamic spatiotemporal expression during the tumour cell cycle, and SHCBP1 knockdown slowed cell cycle progression by inducing spindle disorder, as reflected by premature mitotic entry and multipolar spindle formation. This dysfunction was caused by G2/M checkpoint impairment mediated by downregulated WEE1 kinase and NEK7 (a member of the mammalian NIMA-related kinase family) expression and upregulated centromere/kinetochore protein Zeste White 10 (ZW10) expression. Moreover, both in vivo and in vitro experiments confirmed the significant inhibitory effects of SHCBP1 knockdown on tumour growth. Based on these findings, SHCBP1 knockdown in combination with low-dose DNA-damaging agents had synergistic tumouricidal effects on tumour cells. In response to this treatment, tumour cells were forced into the mitotic phase with considerable unrepaired DNA lesions, inducing mitotic catastrophe. These synergistic effects were attributed not only to the abrogation of the G2/M checkpoint and disrupted spindle function but also to the impairment of the DNA damage repair system, as demonstrated by mass spectrometry-based proteomic and western blotting analyses. Consistently, patients with low SHCBP1 expression in tumour tissue were more sensitive to radiotherapy. However, SHCBP1 knockdown combined with tubulin-toxic drugs weakened the killing effect of the drugs on tumour cells, which may guide the choice of chemotherapeutic agents in clinical practice. CONCLUSION: In summary, we elucidated the role of the nucleoprotein SHCBP1 in tumour cell cycle progression and described a novel mechanism by which SHCBP1 regulates tumour progression and through which targeting SHCBP1 increases sensitivity to DNA-damaging agent therapy, indicating its potential as a cancer treatment.

Extracellular polysaccharides from Sporidiobolus pararoseus alleviates rheumatoid through ameliorating gut barrier function and gut microbiota.

Rheumatoid arthritis (RA) is becoming a prevalent autoimmune disease affecting people worldwide, necessitating the exploration of novel therapeutic approaches due to the associated adverse effects of conventional therapeutic drugs. Sporidiobolus pararoseus polysaccharide (SPP) has been shown to exhibit significant immune stimulation and antioxidant activities. In this study, we constructed a mouse model of type II collagen-induced arthritis (CIA) to investigate the effects and potential mechanisms of SPP intervention on RA. Results showed that SPP intervention alleviated the degree of ankle swelling, joint histopathologic changes, joint pathological score and the expression of serum-associated inflammatory mediators (such as IL-1ß and IL-6). 16S rRNA sequencing results indicated that SPP intervention significantly remodeled the intestinal microbiota composition. In particular, SPP intervention significantly increased the relative abundance of beneficial bacteria (Parabacteroides, Bacteroides and Rikenellaceae_RC9_gut_group) with the potential to degrade fungal polysaccharides or produce short-chain fatty acids (SCFAs). The production of SCFAs (especially acetic acid, propionic acid and butyric acid) indeed increased significantly. These SCFAs played an important role in maintaining intestinal barrier function and regulating immune homeostasis, which helped reduce inflammatory responses and alleviate the symptoms of RA.

Clinical application of convolutional neural network for mass analysis on mammograms.

Background: The detection of masses on mammogram represents one of the earliest signs of a malignant breast cancer. However, masses may be hard to detect due to dense breast tissue, leading to false negative results. In this study, we aimed to explore the clinical application of the convolutional neural network (CNN)-based deep learning (DL) system constructed in our previous work as an objective and accurate tool for breast cancer screening and diagnosis in Asian women. Methods: This retrospective analysis included 324 patients with masses detected on mammograms at Shenzhen People's Hospital between April and December 2019. (I) Detection: images were independently analyzed by two junior radiologists who were blinded to relative results. Then, a senior radiologist analyzed the images after reviewing all the relevant information as the reference. (II) Classification: masses were classified by the same two junior radiologists and in consensus by two other seniors. Images were also input into the DL system. The sensitivity of detection by junior radiologists and the DL system, effects of different factors [breast density; patient age; morphology, margin, size, breast imaging reporting and data system (BI-RADS) category of the mass] on detection, the accuracy, sensitivity, and specificity of classification, and the area under the receiver operating characteristic (ROC) curve (AUC), were evaluated. Results: A total of 618 masses were detected. The detection sensitivity of the two junior radiologists [78.0% (482/618) and 84.0% (519/618), respectively] was lower than that of the DL system [86.2% (533/618)]. Breast density significantly affected the detection by two junior radiologists (both P=0.030), but not by the DL system (P=0.385). The AUC for classifying masses as negative (BI-RADS 1, 2, 3) or positive (BI-RADS 4A, 4B, 4C, 5) for the DL system was significantly higher compared to those of the two junior radiologists, but not significantly different compared to seniors [DL system, 0.697; junior, 0.612 and 0.620 (P=0.021, 0.019); senior in consensus, 0.748 (P=0.071)]. Conclusions: The CNN-based DL system could assist junior radiologists in improving mass detection and is not affected by breast density. This DL system may have clinical utility in women with dense breasts, including reducing the impact caused by inexperienced radiologists and the potential for missed diagnoses.

Immunosenescence and macrophages: From basics to therapeutics.

Ageing decreases the function of the immune system and increases susceptibility to some chronic, infectious, and autoimmune diseases. Senescence cells, which produce senescence-associated secretory phenotypes (SASPs), can activate the innate and adaptive immune responses. Macrophages are among the most abundant innate immune cell types in senescent microenvironments. Senescence-associated macrophages, recruited by SASPs, play a vital role in establishing the essential microenvironments for maintaining tissue homeostasis. However, it's important to note that these senescence-associated macrophages can also influence senescent processes, either by enhancing or impeding the functions of tissue-resident senescent cells. In this discussion, we describe the potential targets of immunosenescence and shed light on the probable mechanisms by which macrophages influence cellular senescence. Furthermore, we analyze their dual function in both clearing senescent cells and modulating age-related diseases. This multifaceted influence operates through processes including heightened inflammation, phagocytosis, efferocytosis, and autophagy. Given the potential off-target effects and immune evasion mechanisms associated with traditional anti-ageing strategies (senolytics and senomorphics), 'resetting' immune system tolerance or targeting senescence-related macrophage functions (i.e., phagocytotic capacity and immunosurveillance) will inform treatment of age-related diseases. Therefore, we review recent advances in the use of macrophage therapeutics to treat ageing and age-associated disorders, and outline the key gaps in this field.

Progress in the development of TRPV1 small-molecule antagonists: Novel Strategies for pain management.

Transient receptor potential vanilloid 1 (TRPV1) channels are widely distributed in sensory nerve endings, the central nervous system, and other tissues, functioning as ion channel proteins responsive to thermal pain and chemical stimuli. In recent years, the TRPV1 receptor has garnered significant interest as a potential therapeutic approach for various pain-related disorders, particularly TRPV1 antagonists. The present review offers a comprehensive, systematic exploration of both first- and second-generation TRPV1 antagonists in the context of pain management. Antagonists are categorized and explicated according to their structural characteristics. Detailed examination of binding modes, structural features, and pharmacological activities, alongside a critical appraisal of the advantages and limitations inherent to typical compounds within each structural category, are undertaken. Detailed discussions of the binding modes, structural features, pharmacological activities, advantages, and limitations of typical compounds within each structural category offer valuable insights and guidance for the future research and development of safer, more effective, and more targeted TRPV1 antagonists.

Increased expression levels of DLX5 inhibit the development of the nervous system.

INTRODUCTION: Preeclampsia is a hypertensive disorder of pregnancy. DLX5 plays an important role in the migration and differentiation of subglobus pallidus precursor cells. METHODS: We established a zebrafish line expressing high levels of DLX5 and investigated changes in behavior and development of the nervous system. RESULTS: The ratios of brain volume area to whole body area at 96 hpf zebrafish in the experimental group (gRNA + CasRx) were significantly lower than the WT group and the negative control group (casRx) (P < 0.01). Behavioral trajectory distances and movement speeds exhibited by the 6th day of development in zebrafish in the experimental group (gRNA + CasRx) were significantly shorter (P < 0.01) and lower (P < 0.05) than the negative control group (gRNA + CasRx), respectively. CONCLUSIONS: Data suggested that the increased expression levels of DLX5 can inhibit brain volume development and behavioral activities in zebrafish. Maybe the high expression levels of DLX5 in the pathological state of preeclampsia can inhibit the development of the nervous system in offspring.

Microstructural Evolution and Micro-Corrosion Behaviour of Flash-Welded U71Mn Joints as a Function of Post-Weld Heat Treatment.

The microstructural evolution and corrosion behaviour of railroad flash-butt-welded U71Mn joints and the effect of heat treatment were investigated via scanning electron microscopy and electrochemical measurements. The joint structures were found to mainly comprise pearlite and a few ferrites. The grains became finer and more homogeneous after heat treatment. Additionally, there was a decrease in the corrosion current density (1.71 × 10-5 A cm-2) and increases in the absolute corrosion potential (0.86 mV) and corrosion resistance (1088.83 Ω-1cm2). This was primarily attributed to the fewer Cl- ions at the homogeneous grain boundaries and fewer oxidation reactions on the joints after heat treatment. The findings of this study explain corrosion failure and will guide the development of corrosion-resistant joints for improved railroad quality.

Classification of asymmetry in mammography via the DenseNet convolutional neural network.

Purpose: To investigate the effectiveness of a deep learning system based on the DenseNet convolutional neural network in diagnosing benign and malignant asymmetric lesions in mammography. Methods: Clinical and image data from 460 women aged 23-82 years (47.57 ± 8.73 years) with asymmetric lesions who underwent mammography at Shenzhen People's Hospital, Shenzhen Luohu District People's Hospital, and Shenzhen Hospital of Peking University from December 2019 to December 2020 were retrospectively analyzed. Two senior radiologists, two junior radiologists, and the DL system read the mammographic images of 460 patients, respectively, and finally recorded the BI-RADS classification of asymmetric lesions. We then used the area under the curve (AUC) of the receiver operating characteristic (ROC) to evaluate the diagnostic efficacy and the difference between AUCs by the Delong method. Results: Specificity (0.909 vs. 0.835, 0.790, χ2=8.21 and 17.22, p＜0.05) and precision (0.872 vs. 0.763, 0.726, χ2=9.23 and 5.22, p＜0.05) of the DL system in the diagnosis of benign and malignant asymmetric lesions were higher than those of junior radiologist A and B, and there was a statistically significant difference between AUCs (0.778 vs. 0.579, 0.564, Z = 4.033 and 4.460, p＜0.05). Furthermore, the AUC (0.778 vs. 0.904, 0.862, Z = 3.191, and 2.167, p＜0.05) of benign and malignant asymmetric lesions diagnosed by the DL system was lower than that of senior radiologist A and senior radiologist B. Conclusions: The DL system based on the DenseNet convolution neural network has high diagnostic efficiency, which can help junior radiologists evaluate benign and malignant asymmetric lesions more accurately. It can also improve diagnostic accuracy and reduce missed diagnoses caused by inexperienced junior radiologists.

Ca-EDTA restores the activity of ceftazidime-avibactam or aztreonam against carbapenemase-producing Klebsiellapneumoniae infections.

Developing an effective therapy to overcome carbapenemase-positive Klebsiella pneumoniae (CPKp) is an important therapeutic challenge that must be addressed urgently. Here, we explored a Ca-EDTA combination with aztreonam or ceftazidime-avibactam in vitro and in vivo against diverse CPKp clinical isolates. The synergy testing of this study demonstrated that novel aztreonam-Ca-EDTA or ceftazidime-avibactam-Ca-EDTA combination was significantly effective in eliminating planktonic and mature biofilms in vitro, as well as eradicating CPKp infections in vivo. Both combinations revealed significant therapeutic efficacies in reducing bacterial load in internal organs and protecting treated mice from mortality. Conclusively, this is the first in vitro and in vivo study to demonstrate that novel aztreonam-Ca-EDTA or ceftazidime-avibactam-Ca-EDTA combinations provide favorable efficacy and safety for successful eradication of carbapenemase-producing Klebsiella pneumoniae planktonic and biofilm infections.

Recent progress on tyrosine kinase 2 JH2 inhibitors.

Tyrosine kinase 2 (TYK2) is a member of the Janus kinase (JAK) family, which can regulate the signaling of multiple pro-inflammatory cytokines, including IL12, IL23 and type I interferon (IFNα/ß), and its inhibitors can treat autoimmune diseases caused by the abnormal expression of IL12 and IL23. Interest in TYK2 JH2 inhibitors has increased as a result of safety concerns with JAK inhibitors. This overview introduces TYK2 JH2 inhibitors that are already on the market, including Deucravactinib (BMS-986165), as well as those currently in clinical trials, such as BMS-986202, NDI-034858, and ESK-001.

Interactive effects of gestational diabetes mellitus and maximum level of total bile acid in maternal serum on adverse pregnancy outcomes in women with intrahepatic cholestasis of pregnancy.

OBJECTIVE: To study the combined effect of gestational diabetes mellitus (GDM) and maximum level of maternal serum total bile acid (TBA) on the incidence of adverse pregnancy outcomes in women with intrahepatic cholestasis of pregnancy (ICP). METHODS: This was an observational study with 724 women with ICP. Perinatal outcomes were compared by the presence of GDM. Logistic regression was used to assess the independent and multiplicative interactions of GDM and maximum maternal serum TBA on adverse pregnancy outcomes. Additive interactions were calculated using an Excel sheet developed by Andersson to calculate relative excess risks. RESULTS: The incidence of GDM in patients with ICP was 21.55%. Maternal age, pre-pregnancy weight, parity, and gravidity were positively correlated with GDM. Hypertensive disorders of pregnancy (HDP) and fetal distress rates were higher in the GDM vs. non-GDM group. There were no significant differences in biochemical outcomes (i.e., Triglyceride (TG), low density lipoprotein (LDL), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bile acid (TBA)) between the two groups. In terms of adverse pregnancy outcomes, GDM was only associated with maximum TBA concentration for cesarean section. No additive or pairwise interactions were detected between GDM and maximum TBA concentration and HDP, PPH, preterm delivery, LGA, SGA, and cesarean section. CONCLUSION: GDM independently contributes to adverse pregnancy outcomes among women with ICP. However, the combined effects of GDM and maximum TBA concentration on adverse pregnancy outcomes do not appear to be multiplicative or additive.

Topical combined Phyllanthus emblica Linn. and simvastatin improves wound healing in diabetic mice by enhancing angiogenesis and reducing neutrophil infiltration.

The present study aimed to investigate the effects of combined Phyllanthus emblica Linn. (PE) and simvastatin (SIM) on diabetic wounds in male BALB/C mice. Bilateral full thickness wound excisions were performed in the control and diabetic groups (45 mg/kg streptozotocin, intraperitoneally injected daily for 5 days). The diabetic mice received daily treatment with four different types of cream: Vehicle [diabetes mellitus (DM) + Vehicle group], 100% PE (DM + PE group), 5% SIM (DM + SIM group) and combined 100% PE + 5% SIM (DM + Combination group) for 4, 7 and 14 days. The tissue malondialdehyde (MDA) and IL-6 protein levels, the number of infiltrated neutrophils, and the percentages of wound closure (%WC), capillary vascularity (%CV) and re-epithelialization (%RE) were subsequently measured. The results indicated that in the DM + Combination group, %CV and %WC were significantly increased when compared with the DM + Vehicle group on days 7 and 14. The tissue MDA content on day 14, and the number of infiltrated neutrophils on days 4 and 7 were significantly reduced in the DM + Combination group compared with those in the DM + Vehicle group. Furthermore, a strong positive correlation was revealed between %CV and %WC in the five groups on day 7 (r=0.736; P=0.0003). These findings indicated that topical application of combined PE and SIM could enhance wound healing by upregulating angiogenesis and reducing neutrophil infiltration in mice with diabetic wounds.

A Meta-Analysis of Neural Correlates of Reward Anticipation in Individuals at Clinical Risk for Schizophrenia.

BACKGROUND: Aberrant striatal responses to reward anticipation have been observed in schizophrenia. However, it is unclear whether these dysfunctions predate the onset of psychosis and whether reward anticipation is impaired in individuals at clinical high risk for schizophrenia (CHR). METHODS: To examine the neural correlates of monetary anticipation in the prodromal phase of schizophrenia, we performed a whole-brain meta-analysis of 13 functional neuroimaging studies that compared reward anticipation signals between CHR individuals and healthy controls (HC). Three databases (PubMed, Web of Science, and ScienceDirect) were systematically searched from January 1, 2000, to May 1, 2022. RESULTS: Thirteen whole-brain functional magnetic resonance imaging studies including 318 CHR individuals and 426 HC were identified through comprehensive literature searches. Relative to HC, CHR individuals showed increased brain responses in the medial prefrontal cortex and anterior cingulate cortex and decreased activation in the mesolimbic circuit, including the putamen, parahippocampal gyrus, insula, cerebellum, and supramarginal gyrus, during reward anticipation. CONCLUSIONS: Our findings in the CHR group confirmed the existence of abnormal motivational-related activation during reward anticipation, thus demonstrating the pathophysiological characteristics of the risk populations. These results have the potential to lead to the early identification and more accurate prediction of subsequent psychosis as well as a deeper understanding of the neurobiology of high-risk state of psychotic disorder.

Increased Expression Levels of Soluble Fms-Like Tyrosine Kinase-1 Inhibit the Development of the Nervous System.

INTRODUCTION: Preeclampsia (PE) remains a leading cause of maternal and perinatal morbidity. At present, only limited options are available for the treatment of PE. Consequently, many patients need to terminate their pregnancies to relieve the disease. Soluble fms-like tyrosine kinase-1 (sFlt-1) is a decoy receptor of placental growth factor and vascular endothelial growth factor which can promote angiogenesis. Throughout pregnancy, the expression level of sFlt-1 continues to increase in both the mother with PE and her offspring. MATERIAL AND METHODS: In this experiment, we generated a zebrafish line expressing high levels of sFlt-1 and investigated changes in behavior and development of the nervous system. RESULTS: At 96 h post-fertilization (hpf), the brain volume area of zebrafish in the experimental group (zFLT1+CasRx) was significantly smaller after injection than in the WT group (p < 0.05) and the negative control group (CasRx) (p < 0.05). At 96 hpf, compared with the WT group, the cerebral blood vessels in the CasRx control group and experimental group (zFLT1-sgRNA+CasRx) were significantly lower after injection (p < 0.05). Compared with the CasRx control group, the track movement distance and the mean track speed of zebrafish in the experimental group (zFLT1-sgRNA+CasRx) after the 6th injection were significantly decreased (p < 0.05). CONCLUSIONS: The increased expression levels of sFlt-1 in zebrafish inhibited the development of the cerebral blood vessels, influenced brain volumes, and inhibited behavioral activities. Our data suggest that the elevation of sFlt-1 in the pathological state of PE can inhibit the development of the nervous system in offspring.

The valence state of iron-based nanomaterials determines the ferroptosis potential in a zebrafish model.

Many nanomaterials containing different valences of iron have been designed for applications in biomedicine, energy, catalyzers, nanoenzymes, and so on. However, the toxic effects of the valence state of iron in iron-based nanomaterials are still unclear. Here, three different-valence iron-based nanomaterials (nFe@Fe3O4, nFe3O4 and nFe2O3) were synthesized and exposed to zebrafish embryos and mammalian cardiomyocytes. All of them induced ferroptosis along with an increase in valence through iron overload and the Fenton reaction. Specifically, we exposed Tg (cmlc2:EGFP) zebrafish to the three iron-based nanomaterials and found that nFe@Fe3O4 treatments led to enlarged ventricles, while nFe3O4 and nFe2O3 increased atrial size, which was consistent with the results from hematoxylin-eosin staining and in situ hybridization. Moreover, we used ferroptosis inhibitors (ferrostatin-1 or deferoxamine) to treat zebrafish along with nanoparticles exposure and found that the cardiac developmental defects caused by nFe3O4 and nFe2O3, but not nFe@Fe3O4, could be completely rescued by ferroptosis inhibitors. We further found that nFe@Fe3O4, rather than nFe3O4 and nFe2O3, reduced the dissolved oxygen in the medium, which resulted in hypoxia and acceleration of heart tube formation and ventricular enlargement, and both were fully rescued by oxygen donors combined with ferroptosis inhibitors. Consistently, these findings were also observed in mammalian cardiomyocytes. In summary, our study demonstrates that the valence state of iron-based nanomaterials determines the ferroptosis potential. Our study also clarifies that high-valence iron-based nanomaterials induce an enlarged atrium via ferroptosis, while low-valence ones increase the ventricular size through both hypoxia and ferroptosis, which is helpful to understand the potential adverse effects of different valences of iron-based nanomaterials on environmental health and assure the responsible and sustainable development of nanotechnology.

Fasudil Increased the Sensitivity to Gefitinib in NSCLC by Decreasing Intracellular Lipid Accumulation.

Tyrosine kinase inhibitors (TKIs) resistance is a challenge in patients with epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC). Here, we examined the effect of Fasudil in reversing TKIs resistance. The results of CCK8 assay, clone formation assay, cell cycle arrest analysis, and apoptosis analysis show that Fasudil treatment effectively suppressed the growth and induced apoptosis of the EGFR-mutant NSCLC cells. Furthermore, Fasudil in combination with gefitinib showed a synergistic anti-tumor effect in gefitinib-resistant NSCLC cells. RNA-seq analysis and immunoblotting indicated that Fasudil treatment significantly inhibited intracellular lipid accumulation and EGFR/PI3K/AKT pathway activation. Mechanistic investigations showed that Fasudil regulated lipogenic gene expressions via AMPK signal pathway. In vivo, Fasudil and gefitinib co-administration significantly attenuated the growth of H1975 nude mouse xenograft models, suggesting that Fasudil treatment combined with gefitinib can be applied as a therapy for gefitinib-resistant NSCLC cells.

[Characteristic Analysis and Source Apportionment of VOCs in Urban Areas of Beijing in Summer].

Refined characterization of volatile organic compound (VOCs) components and source apportionment can provide scientific and effective support for ozone (O3) pollution prevention and control. Using hourly-resolution VOCs online data monitored at urban sites in Beijing from July to August in 2020, the chemical characteristics of VOCs and ozone formation potential (OFP) in environmental receptors during high and low ozone concentration periods were analyzed, and refined source apportionment was conducted with a positive matrix factorization (PMF) model. The results showed that the average φ[total volatile organic compounds (TVOCs)] at the monitoring sites during the observation period was 12.65×10-9, and the φ(TVOCs) during the high and low ozone concentration periods were 13.44×10-9 and 12.33×10-9, respectively, with an OFP of 107.6 µg·m-3and 99.2 µg·m-3, respectively. Ozone production was controlled by VOCs, with the highest reactivity of aromatic hydrocarbons and the top three species contributing to OFP being isoprene, toluene, and m/p-xylene. The main sources of VOCs in environmental receptors during low O3 periods included vehicular emissions (26.4%), background emissions (15.7%), solvent using (13.0%), auto repair (12.8%), secondary generation sources (9.7%), biomass combustion (6.1%), printing industry (5.7%), LNG-fueled vehicles (5.5%), and vegetation emissions (5.0%), of which background emissions, secondary generation, and printing industry sources have been little discussed in recent studies of VOCs source apportionment in Beijing. The contribution of auto repair sources and secondary generation sources increased by 3.4% and 2.6%, respectively, during the high O3 periods compared to those during the low O3 periods, and vehicular emissions remained the most significant source of VOCs contribution in the urban area of Beijing. Vegetation emissions rose from 07:00 pm and reach a maximum in the late afternoon. The contribution of background emission sources was less variable; vehicular emissions and LNG-fueled vehicle sources showed a morning and evening peak, with a relatively low contribution in the afternoon.

Ischemia and reperfusion injury combined with cisplatin induces immunogenic cell death in lung cancer cells.

A first-line chemotherapeutic drug for non-small cell lung cancer (NSCLC), cisplatin (CDDP), fails to induce immunogenic cell death (ICD) because it fails to induce calreticulin (CRT) exposure on the cell surface. We investigated the potential of ischemia and reperfusion injury (I/R) combined with CDDP to induce ICD in lung cancer cells. The in vitro model of I/R, oxygen-glucose deprivation and reperfusion (OGD/R), effectively induced CRT exposure, ATP secretion, high mobility group box 1 (HMGB1) release and eIF2α phosphorylation in both Lewis lung carcinoma (LLC) and A549 cells when combined with CDDP. By using a vaccine assay and coculture with bone marrow-derived dendritic cells (BMDCs), we showed that OGD/R restored the immunogenicity of CDDP by phosphorylating eIF2α and demonstrated that OGD/R + CDDP (O + C) is an ICD inducer. Using the inguinal tumor model, we found that I/R significantly enhanced the tumor-killing effect of CDDP and Mitomycin C, and this effect relied on adaptive antitumor immunity. Consistently, I + C altered the ratio of interferon-gamma-secreting T lymphocytes, thus overcoming the immunosuppressive effect induced by CDDP. In conclusion, our research presents a new combination strategy and indicates that I/R is a potential anticancer immunogenic modality when combined with nonimmunogenic chemotherapy.