Interior decorative volatile organic compounds exposure induces sleep disorders through aberrant branched chain amino acid transaminase 2 mediated glutamatergic signaling resulting from a neuroinflammatory cascade.

Air pollution has been recognized as a contributing factor to sleep disorders (SD), which have been correlated with an elevated susceptibility to a variety of human diseases. Nevertheless, research has not definitively established a connection between SD and interior decorative volatile organic compounds (ID-VOCs), a significant indoor air pollutant. In this study, we employed a mouse model exposed to ID-VOCs to explore the impacts of ID-VOCs exposure on sleep patterns and the potential underlying mechanism. Of the 23 key compositions of ID-VOCs identified, aromatic hydrocarbons were found to be the most prevalent. Exposure to ID-VOCs in mice resulted in SD, characterized by prolonged wake fullness and decreased sleep during the light period. ID-VOCs exposure triggered neuroinflammatory responses in the suprachiasmatic nucleus (SCN), with microglia activation leading to the overproduction of inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1α (IL-1α), and complement component 1q (C1q), ultimately inducing A1 astrocytes. Consequently, the upregulation of branched chain amino acid transaminase 2 (BCAT2) in A1 astrocytes resulted in elevated extracellular glutamate and disruption of the wake-sleep transition mechanism, which might be the toxicological mechanism of SD caused by ID-VOCs.

Spatio-temporal distribution of cadmium levels in Chinese population and its potential risk factors.

Cadmium (Cd), a ubiquitous heavy metal, exists in numerous environmental matrices and has severe adverse effects on various human organs and tissues. This research evaluates blood and urine Cd levels in the Chinese population through data mining using Monte Carlo simulation (MCS). A total of 168 scientific studies (120 on urine and 48 on blood) published between January 1980 and December 2020, reflecting a population of 109,743 individuals in China, were included in the study. The results indicate that the blood and urine Cd levels in the Chinese population exhibited a peak from 1990 to 1995 and remained stable after 1995, averaging 1.21 µg/L of blood Cd (BCd) and 0.61 µg/L of urine Cd (UCd). The spatial trend of Cd levels varied significantly. Shandong, Zhejiang, Heilongjiang, and Guangdong provinces were identified as the top provinces with high Cd levels, which were related to factors such as tobacco sales, E-waste amounts, and contaminated rice. Additionally, the study highlights that BCd concentrations are highest among preschool-aged individuals, whereas school-age and adolescent groups exhibit the lowest levels. However, no significant difference existed among the different age groups. Males showed significantly higher Cd levels than females in the general population. Moreover, exposure to smoking, drinking, and staple food preferences had an impact on Cd levels. Furthermore, this comprehensive study, using biological monitoring and data mining, provides valuable information on Cd pollution levels in the Chinese population. It presents a statistical analysis that can aid decision-makers in implementing effective measures to control potential Cd pollution and improve the health of vulnerable populations.

Conductive interpenetrating network organohydrogels of gellan gum/polypyrrole with weather-tolerance, piezoresistive sensing and shape-memory capability.

To develop ecofriendly multifunctional gel materials for sustainable flexible electronic devices, composite organohydrogels of gellan gum (GG) and polypyrrole (PPy) with an interpenetrating network structure (IPN-GG/PPy organohydrogels) were developed first time, through fabrication of GG organohydrogels followed by in-situ oxidation polymerization of pyrrole inside. Combination of water with glycerol can not only impart environment-stability to GG hydrogels but promote the mechanics remarkably, with the compressive strength amplified by 1250 % from 0.02 to 0.27 MPa. Incorporation of PPy confers electrical conductivity to the GG organohydrogel as well as promoting the mechanical performance further. The maximum conductivity of the IPN-GG/PPy organohydrogels reached 1.2 mS/cm at 25 °C, and retained at 0.6 mS/cm under -20 °C and 0.56 mS/cm after 7 days' exposure in 25 °C and 60 % RH. The compression strength of that with the maximum conductivity increases by 170 % from 0.27 to 0.73 MPa. The excellent conductivity and mechanical properties endow the IPN-GG/PPy organohydrogels good piezoresistive strain/pressure sensing behavior. Moreover, the thermo-reversible GG network bestows them shape-memory capability. The multifunctionality and intrinsic eco-friendliness is favorable for sustainable application in fields such as flexible electronics, soft robotics and artificial intelligence, competent in motion recognition, physiological signal monitoring, intelligent actuation.

Polyhexamethylene guanidine accelerates the macrophage foamy formation mediated pulmonary fibrosis.

Polyhexamethylene guanidine (PHMG) is manufactured and applied extensively due to its superior disinfectant capabilities. However, the inhalatory exposure to PHMG aerosols is increasingly recognized as a potential instigator of pulmonary fibrosis, prompting an urgent call for elucidation of the underlying pathophysiological mechanisms. Within this context, alveolar macrophages play a pivotal role in the primary immune defense in the respiratory tract. Dysregulated lipid metabolism within alveolar macrophages leads to the accumulation of foam cells, a process that is intimately linked with the pathogenesis of pulmonary fibrosis. Therefore, this study examines PHMG's effects on alveolar macrophage foaminess and its underlying mechanisms. We conducted a 3-week inhalation exposure followed by a 3-week recovery period in C57BL/6 J mice using a whole-body exposure system equipped with a disinfection aerosol generator (WESDAG). The presence of lipid-laden alveolar macrophages and downregulation of pulmonary tissue lipid transport proteins ABCA1 and ABCG1 were observed in mice. In cell culture models involving lipid-loaded macrophages, we demonstrated that PHMG promotes foam cell formation by inhibiting lipid efflux in mouse alveolar macrophages. Furthermore, PHMG-induced foam cells were found to promote an increase in the release of TGF-ß1, fibronectin deposition, and collagen remodeling. In vivo interventions were subsequently implemented on mice exposed to PHMG aerosols, aiming to restore macrophage lipid efflux function. Remarkably, this intervention demonstrated the potential to retard the progression of pulmonary fibrosis. In conclusion, this study underscores the pivotal role of macrophage foaming in the pathogenesis of PHMG disinfectants-induced pulmonary fibrosis. Moreover, it provides compelling evidence to suggest that the regulation of macrophage efflux function holds promise for mitigating the progression of pulmonary fibrosis, thereby offering novel insights into the mechanisms underlying inhaled PHMG disinfectants-induced pulmonary fibrosis.

Pulmonary Surfactant Homeostasis Dysfunction Mediates Multiwalled Carbon Nanotubes Induced Lung Fibrosis via Elevating Surface Tension.

Multiwalled carbon nanotubes (MWCNTs) have been widely used in many disciplines and raised great concerns about their negative health impacts, especially environmental and occupational exposure. MWCNTs have been reported to induce fibrotic responses; however, the underlying mechanisms remain largely veiled. Here, we reported that MWCNTs inhalation induced lung fibrosis together with decreased lung compliance, increased elastance in the mice model, and elevated surface tension in vitro. Specifically, MWCNTs increased surface tension by impairing the function of the pulmonary surfactant. Mechanistically, MWCNTs induced lamellar body (LB) dysfunction through autophagy dysfunction, which then leads to surface tension elevated by pulmonary surfactant dysfunction in the context of lung fibrosis. This is a study to investigate the molecular mechanism of MWCNTs-induced lung fibrosis and focus on surface tension. A direct mechanistic link among impaired LBs, surface tension, and fibrosis has been established. This finding elucidates the detailed molecular mechanisms of lung fibrosis induced by MWCNTs. It also highlights that pulmonary surfactants are expected to be potential therapeutic targets for the prevention and treatment of lung fibrosis induced by MWCNTs.

Pulmonary Toxicity Assessment after a Single Intratracheal Inhalation of Chlorhexidine Aerosol in Mice.

Guanidine disinfectants are important chemical agents with a broad spectrum of activity that are effective against most microorganisms. Chlorhexidine, one of the most used guanidine disinfectants, is added to shampoo and mouthwash and applied in medical device sterilization. During the use of chlorhexidine, aerosols with micron particle size may be formed, which may cause inhalation toxicity. To assess the toxicity of inhaled chlorhexidine aerosol, mice underwent the intratracheal instillation of different concentrations of chlorhexidine (0, 0.125%, 0.25%, 0.5%, and 1%) using a MicroSprayer Aerosolizer. The mice were exposed for eight weeks and then sacrificed to obtain lung tissue for subsequent experiments. Histopathology staining revealed damaged lung tissues and increased collagen exudation. At the same time, pulmonary function tests showed that chlorhexidine exposure could cause restrictive ventilatory dysfunction, consistent with pulmonary fibrosis. The results of transcriptome analyses suggest that chlorhexidine may trigger an inflammatory response and promote the activation of pathways related to extracellular matrix deposition. Further, we identified that chlorhexidine exposure might enhance mucus secretion by up-regulating Muc5b and Muc5ac genes, thereby inducing fibrosis-like injury. These findings underscore the need for standardized use of disinfectants and the assessment of their inhalation toxicity.

Carbon dots induce pathological damage to the intestine via causing intestinal flora dysbiosis and intestinal inflammation.

BACKGROUND: Carbon dots (CDs), as excellent antibacterial nanomaterials, have gained great attention in treating infection-induced diseases such as periodontitis and stomatitis. Given the eventual exposure of CDs to the intestine, elucidating the effect of CDs on intestinal health is required for the safety evaluation of CDs. RESULTS: Herein, CDs extracted from ε-poly-L-lysine (PL) were chosen to explore the modulation effect of CDs on probiotic behavior in vitro and intestinal remodeling in vivo. Results verify that PL-CDs negatively regulate Lactobacillus rhamnosus (L. rhamnosus) growth via increasing reactive oxygen species (ROS) production and reducing the antioxidant activity, which subsequently destroys membrane permeability and integrity. PL-CDs are also inclined to inhibit cell viability and accelerate cell apoptosis. In vivo, the gavage of PL-CDs is verified to induce inflammatory infiltration and barrier damage in mice. Moreover, PL-CDs are found to increase the Firmicutes to Bacteroidota (F/B) ratio and the relative abundance of Lachnospiraceae while decreasing that of Muribaculaceae. CONCLUSION: Overall, these evidences indicate that PL-CDs may inevitably result in intestinal flora dysbiosis via inhibiting probiotic growth and simultaneously activating intestinal inflammation, thus causing pathological damage to the intestine, which provides an effective and insightful reference for the potential risk of CDs from the perspective of intestinal remodeling.

SWI/SNF complexes and cancers.

Epigenetics refers to the study of genetic changes that can affect gene expression without altering the underlying DNA sequence, including DNA methylation, histone modification, chromatin remodelling, X chromosome inactivation and non-coding RNA regulation. Of these, DNA methylation, histone modification and chromatin remodelling constitute the three classical modes of epigenetic regulation. These three mechanisms alter gene transcription by adjusting chromatin accessibility, thereby affecting cell and tissue phenotypes in the absence of DNA sequence changes. In the presence of ATP hydrolases, chromatin remodelling alters the structure of chromatin and thus changes the transcription level of DNA-guided RNA. To date, four types of ATP-dependent chromatin remodelling complexes have been identified in humans, namely SWI/SNF, ISWI, INO80 and NURD/MI2/CHD. SWI/SNF mutations are prevalent in a wide variety of cancerous tissues and cancer-derived cell lines as discovered by next-generation sequencing technologies. SWI/SNF can bind to nucleosomes and use the energy of ATP to disrupt DNA and histone interactions, sliding or ejecting histones, altering nucleosome structure, and changing transcriptional and regulatory mechanisms. Furthermore, mutations in the SWI/SNF complex have been observed in approximately 20 % of all cancers. Together, these findings suggest that mutations targeting the SWI/SNF complex may have a positive impact on tumorigenesis and cancer progression.

NCOA1/2/3 rearrangements in uterine tumor resembling ovarian sex cord tumor: A clinicopathological and molecular study of 18 cases.

Recurrent NCOA1/2/3 gene fusions emerged in uterine tumor resembling ovarian sex cord tumor (UTROSCT). More cases are required to consolidate these molecular alterations. In this study, the clinicopathological features and immunostaining profiles were reviewed in 18 UTROSCT. Fluorescence in situ hybridization for dual color break-apart probes of NCOA1, NCOA2, NCOA3, BCOR, YWHAE, PHF1 and JAZF1 were performed on 16 tumors. Eight cases were subjected to targeted next-generation sequencing to detect genomic alterations. We found that the tumors predominantly showed various sex-cord patterns without a recognizable endometrial stromal component. They exhibited a diverse immunohistochemical profile, frequently co-expressing sex cord (calretinin, inhibin, WT1, SF-1, and FOXL2), smooth muscle (SMA, desmin and caldesmon), epithelial (CK) and other markers (CD10 and IFITM1). Fourteen of 16 tumors (87.5%) showed NCOA1-3 gene rearranges, but none had BCOR, YWHAE, PHF1 and JAZF1 fusions. Five tumors contained 6 non-recurrent pathogenic (likely) mutations and one had gains in c-MYC. Our study supports frequent NCOA1-3 rearrangements in UTROSCT. Rare, non-recurrent mutations suggest that these gene rearrangements be potential drivers in tumorigenesis. Detection of gene rearrangements can contribute to the correct interpretation of UTROSCT. However, large comparative studies with molecular tests are required to confirm these findings.

MiT/TFE Family Renal Cell Carcinoma.

The microphthalmia-associated transcription factor/transcription factor E (MiT/TFE) family of transcription factors are evolutionarily conserved, basic helix-loop-helix leucine zipper (bHLH-Zip) transcription factors, consisting of MITF, TFEB, TFE3, and TFEC. MiT/TFE proteins, with the exception of TFEC, are involved in the development of renal cell carcinoma (RCC). Most of the MiT/TFE transcription factor alterations seen in sporadic RCC cases of MiT family translocation renal cell carcinoma (tRCC) are chimeric proteins generated by chromosomal rearrangements. These chimeric MiT/TFE proteins retain the bHLH-Zip structures and act as oncogenic transcription factors. The germline variant of MITF p.E318K has been reported as a risk factor for RCC. E 318 is present at the SUMOylation consensus site of MITF. The p.E318K variant abrogates SUMOylation on K 316, which results in alteration of MITF transcriptional activity. Only a few cases of MITF p.E318K RCC have been reported, and their clinical features have not yet been fully described. It would be important for clinicians to recognize MITF p.E318K RCC and consider MITF germline testing for undiagnosed familial RCC cases. This review outlines the involvement of the MiT/TFE transcription factors in RCC, both in sporadic and hereditary cases. Further elucidation of the molecular function of the MiT/TFE family is necessary for better diagnosis and treatment of these rare diseases.

Ex vivo coronary endothelial cell activation associated with indoor coal combustion initiated atherosclerosis.

Plenty of rural populations still chronically exposed to indoor coal burning, which tremendously raises the risk of cardiovascular disease, in China. This study aimed to further investigate the association between indoor coal burning exposure and atherosclerotic cardiovascular diseases to search for relevant markers for disease prevention. Herein, we conducted a cross-sectional study, carried out on 752 local long-term residents with or without bituminous coal for cooking and heating indoor, in Nangong County, Hebei Province, China. We utilized a nearest neighbor propensity score match (PSM) with a caliper distance equal to 0.001 to eliminate bias caused by confounding factors. The expression of genes associated with endothelial activation (CCL2, CCL5, CXCL8, CXCL12, VCAM, ICAM, SELP) in primary human coronary artery endothelial cells (HCAECs) were quantified through ex vivo biosensor assay. Multiple linear regression models with stratification analyses by gender and binary logit regression models were used to evaluate the association between mRNA expression of biosensor genes and indoor coal burning pollution or carotid atherosclerosis, respectively. Protein secretion level was detected by enzyme-linked immunosorbent assay (ELISA). The prevalence of carotid atherosclerosis in exposure group was higher than control (P = 0.023), before PSM. The gene expression of CCL2 in exposure group was significantly higher than control (P = 0.002). Indoor coal burning exposure was correlated with gene expression of CCL2 (ß = 3.45, 95 % CI: 0.04-6.87, P = 0.047) and CXCL8 (ß = 1.25, 95 % CI: 0.02-2.49, P = 0.046) in female. A higher risk of carotid atherosclerosis was observed in the same as the increase expression of CCL2 (OR = 1.07, 95 % CI: 1.01-1.14, P = 0.020). In conclusion, prolonged exposure to indoor coal burning could elevate the gene expression of CCL2 by activating vascular endothelial cells and was relative to the initiation of carotid atherosclerosis.

Chronic carbon black nanoparticles exposure increases lung cancer risk by affecting the cell cycle via circulatory inflammation.

As a widely used pure elemental carbon in colloidal particles, carbon black was listed as a group 2B carcinogen by IARC in 2010. The most available mechanism information about carbon black and carcinogenesis are from in vivo or in vitro studies. However, few studies concerned the nanoparticle's real-ambient exposure causing systemic change and further affecting the target organ. Herein, we used an ex vivo biosensor assay to investigate the transcriptome change of primary bronchial epithelial cells after treatment with the plasma from workers with long-term occupational carbon black exposure history. Based on ex vivo biosensor assay and transcriptome sequencing, we found the effect of internal systemic environment on epithelial cells after carbon black exposure was an inflammatory response, which mainly activates cell cycle-related pathways. After exposure to carbon black, the internal systemic environment could activate cancer-related pathways like epithelial-mesenchymal transition, hypoxia, TNF-α signaling via NF-κB. The hub genes in the carbon black group (CDC20 and PLK1) and their correlation with the systemic environment were uncovered by constructing the protein-protein interaction network. Inflammatory cytokines, especially CRP, were strongly correlated with the expression of CDC20 and PLK1. Besides, we also find a strong correlation between CDC20 and cytokinesis-block micronucleus endpoints in peripheral blood (rho = 0.591, P < 0.001). Our results show that long-term carbon black exposure might activate cell cycle-related pathways through circulating inflammation and increase the risk of cancer, while the oxidative stress caused by diesel exhaust particles are mainly related to PAHs exposure. After exposure to carbon black, the systemic environment could activate cancer-related pathways like diesel exhaust particles, increasing the risk of lung cancer. These attempts might provide a further understanding of the indirect effect of chronic occupational inhaled carbon black exposure on pulmonary carcinogenesis.

Inhaled tire-wear microplastic particles induced pulmonary fibrotic injury via epithelial cytoskeleton rearrangement.

Tire wear microplastic particles (TWMPs) are emerging microplastic pollutants that have gained increasing attention lately. However, the health effect of inhaled airborne TWMPs has never been explored before and may already be included in particulate matter morbidity and mortality. Here, we endeavored to address the preliminary study of TWMP inhalation-induced pulmonary toxic effects and its epigenetic mechanisms in C57BL/6 mice. As a result, restricted ventilatory dysfunction and fibrotic pathological changes were observed in TWMP-treaded mice. Further research found that attenuation of miR-1a-3p plays an important role in TWMP-induced lung injury. Results from in vitro study confirmed that cytoskeleton regulatory gene twinfilin-1 was one of the target genes of miR-1a-3p, and involved in cytoskeleton rearrangement caused by TWMP exposure. Mechanistically, miR-1a-3p inhibited the F-actin formation by targeting cytoskeletal regulatory proteins twinfilin-1, leading to TWMP-induced pulmonary fibrotic injury. While we are in the very early stages of explaining the role of epigenetics in TWMP-induced lung injury, the potential for the use of epigenetic marks as biomarkers is high and discoveries made in this field will likely bring us closer to better understanding this crucial mechanism.

Circulatory metabolites trigger ex vivo arterial endothelial cell dysfunction in population chronically exposed to diesel exhaust.

BACKGROUND: Chronic exposure to diesel exhaust has a causal link to cardiovascular diseases in various environmental and occupational settings. Arterial endothelial cell function plays an important role in ensuring proper maintenance of cardiovascular homeostasis and the endothelial cell dysfunction by circulatory inflammation is a hallmark in cardiovascular diseases. Acute exposure to diesel exhaust in controlled exposure studies leads to artery endothelial cells dysfunction in previous study, however the effect of chronic exposure remains unknown. RESULTS: We applied an ex vivo endothelial biosensor assay for serum samples from 133 diesel engine testers (DETs) and 126 non-DETs with the aim of identifying evidence of increased risk for cardiovascular diseases. Environmental monitoring suggested that DETs were exposed to high levels of diesel exhaust aerosol (282.3 µg/m3 PM2.5 and 135.2 µg/m3 elemental carbon). Surprisingly, chronic diesel exhaust exposure was associated with a pro-inflammatory phenotype in the ex vivo endothelial cell model, in a dose-dependent manner with CCL5 and VCAM as most affected genes. This dysfunction was not mediated by reduction in circulatory pro-inflammatory factors but significantly associated with a reduction in circulatory metabolites cGMP and an increase in primary DNA damage in leucocyte in a dose-dependent manner, which also explained a large magnitude of association between diesel exhaust exposure and ex vivo endothelial biosensor response. Exogenous cGMP addition experiment further confirmed the induction of ex vivo biosensor gene expressions in endothelial cells treated with physiologically relevant levels of metabolites cGMP. CONCLUSION: Serum-borne bioactivity caused the arterial endothelial cell dysfunction may attribute to the circulatory metabolites based on the ex vivo biosensor assay. The reduced cGMP and increased polycyclic aromatic hydrocarbons metabolites-induced cyto/geno-toxic play important role in the endothelial cell dysfunction of workers chronic exposure to diesel exhaust.

Olfactory bulb microglia activation mediated neuronal death in real-ambient particulate matter exposure mice with depression-like behaviors.

Growing evidence has indicated that air pollution is associated with depression, and damage of olfactory bulb (OB) is regarded as an early marker for depression. However, the toxicity of fine particulate matter (PM2.5) on OB and underlying mechanisms remains to be elucidated. In our study, a real-ambient PM2.5 exposure system was applied to explore the effects of PM2.5 on OB in C57BL/6 mice for 4 or 8 weeks. After 8 weeks exposure, the mice emerged potential depressive-like responses with reduction and disorder of cells in olfactory bulb tissues. Apoptosis and ultra-microstructure analysis indicated that the real-ambient PM2.5 exposure caused the neuronal death of OB. The immunofluorescence observation and KEGG pathway analysis revealed the real-ambient PM2.5 exposure induced microglia activation along with tumor necrosis factor α (TNFα)-mediated signaling enriched in OB of mice with depression-like behaviors. Moreover, results from ex vivo biosensor assay exhibited that PM2.5 might trigger systemic inflammation with increased levels of various proinflammatory factors to activate microglia. Further in vitro co-culture model identified that the PM2.5 evoked microglia cells activation with TNFα secretion and induced neuronal cells apoptosis via classical caspase3 signaling. Our findings provide new insights that PM2.5 induced microglia activation characterized by the release of TNFα to cause neurotoxicity either by direct action or by circulatory inflammation, resulting in OB damage, which may play a critical role in early diagnosis and pathogenic mechanisms for PM2.5 to cause depression.

Joint Effects of Carbon Black Exposure and Dietary Antioxidant Vitamin Intake on Small Airway Dysfunction.

Objectives: Small airway dysfunction is considered as a precursor of chronic obstructive pulmonary disease and asthma. Our aim was to explore the joint effects of carbon black (CB) exposure and antioxidant vitamin intake on small airway dysfunction. Methods: A total of 70 CB packers (CBPs) and 107 non-CBPs were enrolled from an established cohort of CBP. Carbon content in airway macrophage (CCAM) quantified in induced sputum was used as a bio-effective dosimetry for exposure to CB. Logistic regression models were used to examine the odds ratios (ORs) of CB and dietary intake of antioxidant vitamins on small airway dysfunction, and the dose-response association. Results: The prevalence of small airway dysfunction was 32.9% (23 of 70) among CBPs, and 19.6% (21 of 107) among non-CBPs. For each 2.72-fold increase in CCAM, the OR of small airway dysfunction was 2.31 (95% CI = 1.20-4.44). For every 10 mg day-1 increase of the vitamin C intake, the risk of small airway dysfunction decreased by 6% (OR = 0.94, 95% CI = 0.88-0.99). Compared to non-CB exposure and higher vitamin C intake, CB exposure and lower vitamin C intake (OR = 7.56, 95% CI = 1.80 to 31.81) were associated with an increased risk of small airway dysfunction. Conclusions: Chronic exposure to a high level of CB aerosol increased the risk of small airway dysfunction in CB baggers. Dietary intake of vitamin C might be a modifiable factor for preventing small airway dysfunction.

Blood leukocyte count as a systemic inflammatory biomarker associated with a more rapid spirometric decline in a large cohort of iron and steel industry workers.

OBJECTIVE: Iron and steel industry workers are exposed to high levels of inhalable dust particles that contain various elements, including metals, and cause occupational lung diseases. We aim to assess the relationship between occupational dust exposure, systemic inflammation, and spirometric decline in a cohort of Chinese iron and steel workers. METHODS: We studied 7513 workers who participated in a Health Surveillance program at Wugang Institute for Occupational Health between 2008 and 2017. Time-weighted exposure intensity (TWEI) of dust was quantified based on self-reported dust exposure history, the experience of occupational hygienists, and historical data of dust exposure for workers with certain job titles. A linear mixed-effects model was used for association analyses. RESULTS: The average annual change of lung function was - 50.78 ml/year in forced expiratory volume in 1 s (FEV1) and - 34.36 ml/year in forced vital capacity (FVC) in males, and - 39.06 ml/year in FEV1 and - 26.66 ml/year in FVC in females. Higher TWEI prior to baseline was associated with lower longitudinal measurements of FEV1 and FVC but not with their decline rates. Higher WBC and its differential at baseline were associated with lower longitudinal measurements and a more rapid decline of FEV1 and FVC in a dose-dependent monotonically increasing manner. Moreover, the increase of WBC and its differential post-baseline was also associated with a more rapid decline of FEV1 and FVC. CONCLUSIONS: Our findings support the important role of systemic inflammation in affecting the temporal change of lung function in iron and steel industry workers.

Polyhexamethylene guanidine aerosol triggers pulmonary fibrosis concomitant with elevated surface tension via inhibiting pulmonary surfactant.

Environmental chemicals inhalation exposure could induce pulmonary fibrosis, which is characterized by the excessive proliferation of fibroblasts and accumulation of extracellular matrix components, in which surface tension usually plays vital roles. Polyhexamethylene guanidine (PHMG) was first recognized as a potential hazard ingredient in humidifier disinfectants, which caused an outbreak of pulmonary fibrosis in South Korea. However, the underlying mechanisms involved in PHMG-induced pulmonary fibrosis have not yet been fully elucidated. Therefore, this study mainly focuses on the effect of PHMG on surface tension to unveil the influence and involved mechanisms in PHMG-induced pulmonary fibrosis. C57BL/6J mice were exposed to sub-acute PHMG aerosol for 8 weeks. The results indicated that PHMG induced pulmonary fibrosis combined with elevated surface tension. Results from in vitro study further confirmed PHMG elevated surface tension by inhibited pulmonary surfactant. Mechanistically, PHMG suppressed the key surfactant protein SP-B and SP-C by inhibiting protein expression and block their active sites. The present study, for the first time, revealed the molecular mechanism of PHMG-induced pulmonary fibrosis based on pulmonary surfactant inhibition mediated surface tension elevated. And pulmonary surfactant may be a potential target for further intervention to prevent PHMG-induced fibrosis or alleviate the symptom of relevant patients.