CD8+ tissue-resident memory T cells are essential in bleomycin-induced pulmonary fibrosis.

Human tissue-resident memory T (TRM) cells play a crucial role in protecting the body from infections and cancers. Recent research observed increased numbers of TRM cells in the lung tissues of idiopathic pulmonary fibrosis patients. However, the functional consequences of TRM cells in pulmonary fibrosis remain unclear. Here, we found that the numbers of TRM cells, especially the CD8+ subset, were increased in the mouse lung with bleomycin-induced pulmonary fibrosis. Increasing or decreasing CD8+ TRM cells in mouse lungs accordingly altered the severity of fibrosis. In addition, the adoptive transfer of CD8+ T cells containing a large number of CD8+ TRM cells from fibrotic lungs was sufficient to induce pulmonary fibrosis in control mice. Treatment with chemokine CC-motif ligand (CCL18) induced CD8+ TRM cell expansion and exacerbated fibrosis, whereas blocking C-C chemokine receptor 8 (CCR8) prevented CD8+ TRM recruitment and inhibited pulmonary fibrosis. In conclusion, CD8+ TRM cells are essential for bleomycin-induced pulmonary fibrosis, and targeting CCL18/CCR8/CD8+ TRM cells may be a potential therapeutic approach. NEW & NOTEWORTHY The role of CD8+ TRM cells in the development of pulmonary fibrosis was validated and studied in the classic model of pulmonary fibrosis. It was proposed for the first time that CCL18 has a chemotactic effect on CD8+ TRM cells, thereby exacerbating pulmonary fibrosis.

Size-resolved gas-particle partitioning of polycyclic aromatic hydrocarbons in a large temperature range of 50 ℃.

Size-resolved gas-particle partitioning of semi-volatile organic compounds (SVOCs) can affect their environmental behaviors and health effects, which has not been widely studied in comparing with the gas-total suspended particle partitioning. Herein, the size-resolved gas-particle partitioning quotient (KPi) of polycyclic aromatic hydrocarbons (PAHs) in a large temperature range (-20.6 â„ƒ ∼ 29.4 â„ƒ) was firstly comprehensively studied. The log KPi values of PAHs related to fine particles were significantly higher than those related to coarse particles. When the logarithm of subcooled liquid-vapor pressure (log PL0) ∈ [-7, -1), the regression slopes of log KPi vs log PL0 related to the particle size > 1.0 µm were shallower than those with the particle size range of 0.10-1.0 µm, which indicated the influence of particle size on KPi. Among the three previous prediction equations of gas-particle partitioning quotient, the empirical equation based on the ambient temperature matched better with the measured log KPi. Therefore, a new prediction equation including ambient temperature and particle size as the two major parameters was established. For most particle size ranges, the new equation showed better prediction performance than the three previous equations. In summary, this study provided new insights for the size-resolved gas-particle partitioning mechanism and quotient.

piR-27222 mediates PM2.5-induced lung cancer by resisting cell PANoptosis through the WTAP/m6A axis.

PM2.5 pollution has been associated with the incidence of lung cancer, but the underlying mechanism is still unclear. PIWI-interacting RNAs (piRNAs), initially identified in germline cells, have emerged as a novel class of small non-coding RNAs (26 - 32 nucleotides) with diverse functions in various diseases, including cancer. However, the role and mechanism of piRNAs in the development of PM2.5-induced lung cancer remain to be clarified. In the presented study, we used a PM2.5-induced malignant transformation cell model to analyze the change of piRNA profiles. Among the disturbed piRNAs, piR-27222 was identified as an oncogene that inhibited cell death in a m6A-dependent manner. Mechanistically, we found that piR-27222 could deubiquitinate and stabilize eIF4B by directly binding to eIF4B and reducing its interaction with PARK2. The enhanced expression of eIF4B, in turn, promoted the expression of WTAP, leading to increased m6A modification in the Casp8 transcript. Consequently, the stability of Casp8 transcripts was reduced, rendering lung cancer cells resistant to PANoptosis. Collectively, our findings reveal that PM2.5 exposure up-regulated piR-27222 expression, which could affect EIF4B/WTAP/m6A axis, thereby inhibiting PANoptosis of cells and promoting lung cancer. Our study provides new insights into understanding the epigenetic mechanisms underlining PM2.5-induced lung cancer.

New insights into the function and mechanisms of piRNA PMLCPIR in promoting PM2.5-induced lung cancer.

INTRODUCTION: Extensive studies have established the correlation between long-term PM2.5 exposure and lung cancer, yet the mechanisms underlying this association remain poorly understood. PIWI-interacting RNAs (piRNAs), a novel category of small non-coding RNAs, serve important roles in various diseases. However, their biological function and mechanism in PM2.5-induced lung cancer have not been thoroughly investigated. OBJECTIVES: We aimed to explore the oncogenic role of piRNA in lung cancer induced by PM2.5 exposure, as well as the underlying mechanisms. METHODS: We conducted a PM2.5-induced human lung epithelial cell malignant transformation model. Human samples were used to further verify the finding. In vitro proliferation, migration, and invasion assays were performed to study the function of piRNA. RNA-sequencing was used to elucidate the the mechanisms of how piRNA mediates cell functions. PiRNA pull-down and computational docking analysis were conducted to identify proteins that binding to piRNA. In vivo experiments were used to explore whether inhibition of PMLCPIR could have a therapeutic effect on lung cancer. RESULTS: We identified a new up-regulated piRNA, termed PM2.5-induced lung cancer up-regulation piRNA (PMLCPIR), which promotes the proliferation of PM2.5-transformed cells and lung cancer cells. RNA sequencing revealed ITGB1 as a downstream target of PMLCPIR. Importantly, PMLCPIR binds to nucleolin (NCL) and increases the expression of its target gene, ITGB1, thereby activating PI3K/AKT signaling. The inhibition of PMLCPIR could promote apoptosis in lung cancer cells and enhance their chemosensitivity to anti-tumor drugs. CONCLUSION: We systematically identified the alterations of piRNA expression profiles in the PM2.5-induced malignant transformation model. Then, PMLCPIR was recognized as a novel oncogenic piRNA in PM2.5-induced lung cancer. Mechanically, PMLCPIR binds to NCL, enhancing ITGB1 expression and activating the ontogenetic PI3K/AKT signaling, potentially contributing to lung cancer progression. This study provides novel insights into the revelation of a new epigenetic regulator in PM2.5-induced lung cancer.

Sclerotinia rot of Zephyranthes candida caused by Sclerotinia sclerotiorum and Sclerotinia minor.

Sclerotinia rot is a serious disease that occurs on Zephyranthes candida. A thorough understanding of the pathogenic fungal species and understanding the biological characteristics are important for controlling sclerotinia. Fungal strains were isolated from the diseased leaves of Z. candida through tissue isolation. Koch's hypothesis screened pathogenic strains by pathogenicity of healthy leaves, including re-isolation and identification. A multigene phylogenetic tree was constructed by extracting genomic DNA from pathogenic strains and measuring the nucleotide sequences at four sites, including the internal transcribed spacer (ITS), RNA polymerase II second largest subunit (RPB2), glyceraldehyde-3-phosphate dehydrogenase (G3PDH), and heat shock protein 60 (HSP60). Morphological characteristics of the fungal structures were evaluated through microscopic analysis. The growth of pathogens was observed and recorded under different pH, different temperatures, different carbon sources and different nitrogen sources to clarify their biological characteristics. Representative strains D7, D13, X4, and X15 infected Z. candida and caused sclerotinia rot. At the beginning of the culture, white flocculent fungal hyphae appeared on the potato dextrose agar (PDA) medium, and black spherical to irregular-shaped sclerotia appeared at the edge of the colony after 7 days. The diameter of the sclerotia was 2.4-8.6 mm and 0.4-0.9 mm, respectively. One sclerotium was able to germinate from 1 to 5 apothecia. Ascus were cylindrical or spindle-shaped, with a size of 110.0-120.0 × 9.2-11.6 µm. One ascus contained eight colorless, oval ascospores, with a size of 8.4-12.0 × 4.5-5.5 µm. Based on the phylogenetic tree constructed with the gene sequences for ITS, G3PDH, HSP60, and RPB2, D7 and D13 shared 99% homology with sclerotinia sclerotiorum, whereas X4 and X15 shared 99% homology with sclerotinia minor. S. sclerotiorum growth was more suitable when the culture temperature was 15°C-25°C, pH 5.0, carbon source was maltose and nitrogen source was yeast powder. S. minor growth was more suitable when the culture temperature was 15°C, pH 5.0, the carbon source was glucose, and the nitrogen source was yeast powder. The results identified the pathogens as S. sclerotiorum and S. minor. To the best of our knowledge, this is the first report of S. sclerotiorum and S. minor causing sclerotinia rot on Z. candida. We herein aimed to identify the causal agent of sclerotinia rot of Z. candida in China based on morphological characteristics, molecular identification, and pathogenicity tests. Performed the experiments on the biological characteristics, to understand the law of disease occurrence. We also evaluated methods for the effective control of this disease. Our findings provide support for further studies on the pathogenesis mechanism of sclerotinia rot.

Temperature dependence of the rain-gas and snow-gas partition coefficients for nearly a thousand chemicals.

Compared to the particle-gas partition coefficients (KPG), the rain-gas (KRG) and snow-gas (KSG) partition coefficients are also essential in studying the environmental behavior and fate of chemicals in the atmosphere. While the temperature dependence for the KPG have been extensively studied, the study for KRG and KSG are still lacking. Adsorption coefficients between water surface-air (KIA) and snow surface-air (KJA), as well as partition coefficients between water-air (KWA) and octanol-air (KOA) are vital in calculating KRG and KSG. These four basic adsorption and partition coefficients are also temperature-dependent, given by the well-known two-parameters Antoine equation logKXY = AXY + BXY/T, where KXY is the adsorption or partition coefficients, AXY and BXY are Antoine parameters (XY stand for IA, JA, WA, and OA), and T is the temperature in Kelvin. In this study, the parameters AXY and BXY are calculated for 943 chemicals, and logKXY can be estimated at any ambient temperature for these chemicals using these Antoine parameters. The results are evaluated by comparing these data with published experimental and modeled data, and the results show reasonable accuracy. Based on these coefficients, temperature-dependence of logKRG and logKSG is studied. It is found that both logKRG and logKSG are linearly related to 1/T, and Antoine parameters for logKRG and logKSG are also estimated. Distributions of the 943 chemicals in the atmospheric phases (gas, particle, and rain/snow), are illustrated in a Chemical Space Map. The findings reveal that, at environmental temperatures and precipitation days, the dominant state for the majority of chemicals is the gaseous phase. All the AXY and BXY values for logKSG, logKRG, and basic adsorption and partition coefficients, both modeled by this study and collected from published work, are systematically organized into an accessible dataset for public utilization.

Differences between the intestinal microbial communities of healthy dogs from plateau and those of plateau dogs infected with Echinococcus.

OBJECTIVE: Cystic echinococcosis (CE) represents a profoundly perilous zoonotic disease. The advent of viral macrogenomics has facilitated the exploration of hitherto uncharted viral territories. In the scope of this investigation, our objective is to scrutinize disparities in the intestinal microbiotic ecosystems of canines dwelling in elevated terrains and those afflicted by Echinococcus infection, employing the tool of viral macrogenomics. METHODS: In this study, we collected a comprehensive total of 1,970 fecal samples from plateau dogs infected with Echinococcus, as well as healthy control plateau dogs from the Yushu and Guoluo regions in the highland terrain of China. These samples were subjected to viral macrogenomic analysis to investigate the viral community inhabiting the canine gastrointestinal tract. RESULTS: Our meticulous analysis led to the identification of 136 viral genomic sequences, encompassing eight distinct viral families. CONCLUSION: The outcomes of this study hold the potential to enhance our comprehension of the intricate interplay between hosts, parasites, and viral communities within the highland canine gut ecosystem. Through the examination of phage presence, it may aid in early detection or assessment of infection severity, providing valuable insights into Echinococcus infection and offering prospects for potential treatment strategies.

Modelling the dynamic gas/particle partitioning process of semi-volatile organic compounds emitted from point sources: Quantitative analysis and impact assessment.

The deleterious impact of pollution point sources on the surrounding environment and human has long been a focal point of environmental research. When considering the local atmospheric dispersion of semi-volatile organic compounds (SVOCs) around the emission sites, it is essential to account the dynamic process for the gas/particle (G/P) partitioning, which involves the transition from an initial state to a steady state. In this study, we have developed a model that enables the prediction of the dynamic process for G/P partitioning of SVOCs, particularly considering the influence from emission. It is important to note that the dynamic processes of the concentrations of SVOCs in particle phase (CP) and in gas phase (CG) differ significantly. These differences arise due to the influence of two critical factors: particulate proportion of SVOCs in the emissions (ϕ0) and octanol-air partitioning coefficient (KOA). The validity of our model was assessed by comparing its predictions of the extremum value of the G/P partitioning quotient (KP) with the results obtained from the steady-state model. Remarkably, the characteristic time (tC), used to evaluate the timescale required for SVOCs to reach steady state, demonstrated different variations with KOA for CP and CG. Additionally, the values of tC were quite different for CP and CG, which were markedly influenced by ϕ0. For some SVOCs with high KOA values, it took approximately 35 h to reach steady state. Furthermore, it was found that the time to achieve 95 % of steady state (t95 ≈ 3tC) could reach approximately 105 h. This duration is sufficient for chemicals to disperse from their emission site to the surrounding areas. Therefore, it is crucial to consider the dynamic process of G/P partitioning in local atmospheric transport studies. Moreover, the influence of ϕ0 should be incorporated into future investigations examining the dynamic process of G/P partitioning.

DEC1 is involved in circadian rhythm disruption-exacerbated pulmonary fibrosis.

BACKGROUND: The alveolar epithelial type II cell (AT2) and its senescence play a pivotal role in alveolar damage and pulmonary fibrosis. Cell circadian rhythm is strongly associated with cell senescence. Differentiated embryonic chondrocyte expressed gene 1 (DEC1) is a very important circadian clock gene. However, the role of DEC1 in AT2 senescence and pulmonary fibrosis was still unclear. RESULTS: In this study, a circadian disruption model of light intervention was used. It was found that circadian disruption exacerbated pulmonary fibrosis in mice. To understand the underlying mechanism, DEC1 levels were investigated. Results showed that DEC1 levels increased in lung tissues of IPF patients and in bleomycin-induced mouse fibrotic lungs. In vitro study revealed that bleomycin and TGF-ß1 increased the expressions of DEC1, collagen-I, and fibronectin in AT2 cells. Inhibition of DEC1 mitigated bleomycin-induced fibrotic changes in vitro and in vivo. After that, cell senescence was observed in bleomycin-treated AT2 cells and mouse models, but these were prevented by DEC1 inhibition. At last, p21 was confirmed having circadian rhythm followed DEC1 in normal conditions. But bleomycin disrupted the circadian rhythm and increased DEC1 which promoted p21 expression, increased p21 mediated AT2 senescence and pulmonary fibrosis. CONCLUSIONS: Taken together, circadian clock protein DEC1 mediated pulmonary fibrosis via p21 and cell senescence in alveolar epithelial type II cells.

Cross-regional scale studies of organochlorine pesticides in air in China: Pollution characteristic, seasonal variation, and gas/particle partitioning.

Few simultaneous studies of organochlorine pesticides (OCPs) in the atmosphere have been conducted across Southeast and Northeast China, and no data on the gas/particle (G/P) partitioning behaviors of several current-use OCPs are available. In this study, a one-year synchronous monitoring program was conducted for OCPs in Chinese atmosphere spanning 30° latitude and 60 °C temperature. A total of 111 pairs of gas and particle samples were collected from Mohe and Harbin in Northeast China and from Shenzhen in Southeast China. The detection frequency for 66.7 % of the OCPs exceeded 80 %, indicating their prevalence in the atmosphere. The concentrations of individual OCPs spanned six orders of magnitude, indicating different pollution levels. Highest levels of hexachlorobenzene were observed at all sites. Banned OCPs were found predominantly in secondary distribution patterns, whereas current-use OCPs were dominated by primary distribution patterns. In Harbin and Mohe, the concentrations of OCPs were highest in summer, followed by autumn and winter. No obvious seasonal variation was observed in Shenzhen associated with different cultivation types. At all three sites, OCPs were predominantly found in the gas phase, and higher percentages of particle-phase OCPs were observed in Harbin and Mohe than in Shenzhen. In this study, G/P partitioning models were used to study the G/P partitioning mechanism of OCPs. The Li-Ma-Yang model provided the most accurate prediction of the G/P partitioning behavior of OCPs with high molecular weights and low vapor pressures, particularly at low temperatures. However, OCPs with lower molecular weights and higher vapor pressures were predominantly in the equilibrium state, for which the Junge-Pankow model was suitable. This systematic cross-scale study provides new insights into pollution, G/P partitioning, and the environmental behavior of OCPs in the atmosphere.

Ferroptosis contributes to ethanol-induced hepatic cell death via labile iron accumulation and GPx4 inactivation.

Alcohol abuse is a significant cause of global morbidity and mortality, with alcoholic liver disease (ALD) being a common consequence. The pathogenesis of ALD involves various cellular processes, including oxidative stress, inflammation, and hepatic cell death. Recently, ferroptosis, an iron-dependent form of programmed cell death, has emerged as a potential mechanism in many diseases. However, the specific involvement and regulatory mechanisms of ferroptosis in ALD remain poorly understood. Here we aimed to investigate the presence and mechanism of alcohol-induced ferroptosis and the involvement of miRNAs in regulating ferroptosis sensitivity. Our findings revealed that long-term ethanol feeding induced ferroptosis in male mice, as evidenced by increased expression of ferroptosis-related genes, lipid peroxidation, and labile iron accumulation in the liver. Furthermore, we identified dysregulation of the methionine cycle and transsulfuration pathway, leading to severe glutathione (GSH) exhaustion and indirect deactivation of glutathione peroxidase 4 (GPx4), a critical enzyme in preventing ferroptosis. Additionally, we identified miR-214 as a ferroptosis regulator in ALD, enhancing hepatocyte ferroptosis by transcriptionally activating the expression of ferroptosis-driver genes. Our study provides novel insights into the involvement and regulatory mechanisms of ferroptosis in ALD, highlighting the potential therapeutic implications of targeting ferroptosis and miRNAs in ALD management.

Spatial distribution and temporal trend of organochlorine pesticides in Chinese surface soil.

Although organochlorine pesticides (OCPs) in the Stockholm Convention List were banned for a period of time, the residue of OCPs in environment was still detected recently. Therefore, the continuous environmental monitoring was necessary and important for the deep understanding on the temporal trend of environmental fate of OCPs. In this study, the national scale surface soil samples in 26 provinces of China in 2012 were collected, and 28 OCPs were analyzed. The mean concentrations (ng/g dw) of Σhexachlorocyclohexanes (HCHs), Σdichlorodiphenyltrichloroethane (DDTs), hexachlorobenzene (HCB), and hexachlorobutadiene (HCBD) were 2.47 ± 5.4, 4.29 ± 8.28, 3.33 ± 7.68, and 0.041 ± 0.097, respectively. The correlations between OCPs concentrations with temperature, latitude, and longitude were conducted for the deep study of the spatial distribution pattern of OCPs. It was found that HCHs, HCB, and HCBD are positively correlated with latitude and longitude; however, the correlations were not significant. HCHs followed the secondary distribution pattern, and DDTs followed both the primary and/or secondary distribution patterns. Except for HCB, other OCPs showed a gradual downward trend from 2005 to 2012, indicating the effectiveness of the phase-out of OCPs. In summary, the results of the study provided new insight into the related studies, which will help us to better understand the long-term environmental fate of OCPs on large scales.

Removal of antibiotic resistant bacteria and genes by nanoscale zero-valent iron activated persulfate: Implication for the contribution of pH decrease.

The mechanism of removing antibiotic resistant bacteria (ARB) and antibiotic resistant genes (ARGs) by persulfate was attributed to the generation of reactive oxygen species (ROS). However, the potential contribution of decreased pH in persulfate system to ARB and ARGs removal has rarely been reported. Here, the efficiency and mechanism of removing ARB and ARGs by nanoscale zero-valent iron activated persulfate (nZVI/PS) were investigated. Results showed that the ARB (2 × 108 CFU/mL) could be completely inactivated within 5 min, and the removal efficiencies of sul1 and intI1 were 98.95% and 99.64% by nZVI/20 mM PS, respectively. Investigation of mechanism revealed that hydroxyl radicals was the dominant ROS of nZVI/PS in removing ARB and ARGs. Importantly, the pH of nZVI/PS system was greatly decreased, even to 2.9 in nZVI/20 mM PS system. Impressively, when the pH of the bacterial suspension was adjusted to 2.9, the removal efficiency of ARB, sul1 and intI1 were 60.33%, 73.76% and 71.51% within 30 min, respectively. Further excitation-emission-matrix analysis confirmed that decreased pH contributed to ARB damage. The above results on the effect of pH indicated that the decreased pH of nZVI/PS system also made an important contribution for the removal of ARB and ARGs.

BMAL1/p53 mediating bronchial epithelial cell autophagy contributes to PM2.5-aggravated asthma.

BACKGROUND: Fine particulate matter (PM2.5) is associated with increased incidence and severity of asthma. PM2.5 exposure disrupts airway epithelial cells, which elicits and sustains PM2.5-induced airway inflammation and remodeling. However, the mechanisms underlying development and exacerbation of PM2.5-induced asthma were still poorly understood. The aryl hydrocarbon receptor nuclear translocator-like protein 1 (BMAL1) is a major circadian clock transcriptional activator that is also extensively expressed in peripheral tissues and plays a crucial role in organ and tissue metabolism. RESULTS: In this study, we found PM2.5 aggravated airway remodeling in mouse chronic asthma, and exacerbated asthma manifestation in mouse acute asthma. Next, low BMAL1 expression was found to be crucial for airway remodeling in PM2.5-challenged asthmatic mice. Subsequently, we confirmed that BMAL1 could bind and promote ubiquitination of p53, which can regulate p53 degradation and block its increase under normal conditions. However, PM2.5-induced BMAL1 inhibition resulted in up-regulation of p53 protein in bronchial epithelial cells, then increased-p53 promoted autophagy. Autophagy in bronchial epithelial cells mediated collagen-I synthesis as well as airway remodeling in asthma. CONCLUSIONS: Taken together, our results suggest that BMAL1/p53-mediated bronchial epithelial cell autophagy contributes to PM2.5-aggravated asthma. This study highlights the functional importance of BMAL1-dependent p53 regulation during asthma, and provides a novel mechanistic insight into the therapeutic mechanisms of BMAL1. Video Abstract.

Association of occupational exposure to polycyclic aromatic hydrocarbons in workers with hypertension from a northeastern Chinese petrochemical industrial area.

Elevated urinary polycyclic aromatic hydrocarbon metabolites have been linked to an increased risk of cardiovascular diseases (CVDs). However, for petrochemical workers with potentially high PAH exposure, it remains largely unknown whether the link will be amplified. Thus, this work aimed to investigate 14 urinary mono-hydroxylated polycyclic aromatic hydrocarbons (OH-PAHs) in 746 petrochemical workers working in a Chinese petrochemical industrial area and their association with the risk of hypertension using the binary logistic regression. Metabolites of naphthalene, fluorene, phenanthrene, and pyrene were frequently detected in the 746 urine samples analyzed (>98%), with Σ10OH-PAH concentration in the range of 0.906-358 ng/mL. 2-hydroxynaphthalene accounted for the largest proportion of ten detected OH-PAHs (60.8% of Σ10OH-PAHs). There were significant correlations between these metabolites and other factors, including gender, age, and body mass index. Diastolic blood pressure, not systolic blood pressure, was significant positively associated with the urinary Σ10OH-PAH concentrations of the petrochemical workers. Elevated urinary 2/3-OH-Flu was significantly associated with an increased risk of hypertension (adjusted odds ratio: 1.96, 95% confidence interval: 1.20-3.18, p = 0.007), suggesting that PAH exposure in petrochemical workers was a driving factor of hypertension. In the stratified analysis, the association was more pronounced in those who were overweight with older age. Although the PAH exposure risk in petrochemical workers based on the estimated daily intakes was relatively low. Given the long-term impact, we call attention to CVDs of petrochemical workers.

Using a human bronchial epithelial cell-based malignant transformation model to explore the function of hsa-miR-200 family in the progress of PM2.5-induced lung cancer development.

Numerous studies have revealed that ambient long-term exposure to fine particulate matter (PM2.5) is significantly related to the development of lung cancer, but the molecular mechanisms of PM2.5 exposure-induced lung cancer remains unknown. As an important epigenetic regulator, microRNAs (miRNAs) play vital roles in responding to environment exposure and various diseases including lung cancer development. Here we constructed a PM2.5-induced malignant transformed cell model and found that miR-200 family, especially miR-200a-3p, was involved in the process of PM2.5 induced lung cancer. Further investigation of the function of miR-200 family (miR-200a-3p as a representative revealed that miR-200a-3p promoted cell migration by directly suppressing TNS3 expression. These results suggested that ambient PM2.5 exposure may increase the expression of miR-200 family and then promote the proliferation and migration of lung cancer cells. Our study provided novel model and insights into the molecular mechanism of ambient PM2.5 exposure-induced lung cancer.

Integration of metabolomics and proteomics reveals the underlying hepatotoxic mechanism of perfluorooctane sulfonate (PFOS) and 6:2 chlorinated polyfluoroalkyl ether sulfonic acid (6:2 Cl-PFESA) in primary human hepatocytes.

Perfluorooctane sulfonate (PFOS) and its alternative 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA) are ubiquitous in various environmental and human samples. They have been reported to have hepatotoxicity effects, but the potential mechanisms remain unclear. Herein, we integrated metabolomics and proteomics analysis to investigate the altered profiles in metabolite and protein levels in primary human hepatocytes (PHH) exposed to 6:2 Cl-PFESA and PFOS at human exposure relevant concentrations. Our results showed that 6:2 Cl-PFESA exhibited higher perturbation effects on cell viability, metabolome and proteome than PFOS. Integration of metabolomics and proteomics revealed that the alteration of glycerophospholipid metabolism was the critical pathway of 6:2 Cl-PFESA and PFOS-induced lipid metabolism disorder in primary human hepatocytes. Interestingly, 6:2 Cl-PFESA-induced cellular metabolic process disorder was associated with the cellular membrane-bounded signaling pathway, while PFOS was associated with the intracellular transport process. Moreover, the disruption effects of 6:2 Cl-PFESA were also involved in inositol phosphate metabolism and phosphatidylinositol signaling system. Overall, this study provided comprehensive insights into the hepatic lipid toxicity mechanisms of 6:2 Cl-PFESA and PFOS in human primary hepatocytes.

A Double-Blind Randomized Placebo-Controlled Phase 3 Trial of Tobramycin Inhalation Solution in Adults With Bronchiectasis With Pseudomonas aeruginosa Infection.

BACKGROUND: Few large-scale studies have demonstrated the efficacy of tobramycin nebulization in bronchiectasis. We evaluated the efficacy and safety of nebulized tobramycin inhalation solution (TIS) in adults with bronchiectasis with Pseudomonas aeruginosa infection. RESEARCH QUESTION: Can TIS effectively reduce sputum P aeruginosa density and improve the bronchiectasis-specific quality of life in patients with bronchiectasis with P aeruginosa infection? STUDY DESIGN AND METHODS: This was a phase 3, 16-week, multicenter, randomized, double-blind, placebo-controlled trial. Eligible adults with bronchiectasis were recruited from October 2018 to July 2021. On the basis of usual care, patients nebulized TIS (300 mg/5 mL twice daily) or normal saline (5 mL twice daily) via vibrating-mesh nebulizer. Treatment consisted of two cycles, each consisting of 28 days on-treatment and 28 days off-treatment. The coprimary end points included changes from baseline in P aeruginosa density and Quality-of-Life Bronchiectasis Respiratory Symptoms score on day 29. RESULTS: The modified intention-to-treat population consisted of 167 patients in the tobramycin group and 172 patients in the placebo group. Compared with placebo, TIS resulted in a significantly greater reduction in P aeruginosa density (adjusted mean difference, 1.74 log10 colony-forming units/g; 95% CI, 1.12-2.35; P < .001) and greater improvement in Quality-of-Life Bronchiectasis Respiratory Symptoms score (adjusted mean difference, 7.91; 95% CI, 5.72-10.11; P < .001) on day 29. Similar findings were observed on day 85. TIS resulted in a significant reduction in 24-h sputum volume and sputum purulence score on days 29, 57, and 85. More patients became culture negative for P aeruginosa in the tobramycin group than in the placebo group on day 29 (29.3% vs 10.6%). The incidence of adverse events and serious adverse events were comparable between the two groups. INTERPRETATION: TIS is an effective treatment option and has an acceptable safety profile in patients with bronchiectasis with P aeruginosa infection. TRIAL REGISTRATION: ClinicalTrials.gov; No. NCT03715322; URL: www. CLINICALTRIALS: gov.

National-scale monitoring of historic used organochlorine pesticides (OCPs) and current used pesticides (CUPs) in Chinese surface soil: Old topic and new story.

Along with the restriction and prohibition of historic used organochlorine pesticides (OCPs), current used pesticides (CUPs) were widely used as alternatives. In order to investigate the pollution characteristics of pesticides, the levels and spatial distributions of OCPs and CUPs in 154 surface soil across China were comprehensively compared. Totally, 107 target pesticides were screened, and 20 OCPs and 34 CUPs were detected. The numbers of co-occurred pesticides in single soil sample were from 17 to 36 indicating the diversity and complexity of pesticides pollution. The concentrations of OCPs in urban soils were higher than rural soils, while rural > urban for CUPs. Furthermore, obviously different spatial distribution patterns were found for OCPs and CUPs. For OCPs, the secondary distribution pattern was dominant. For CUPs, the primary distribution pattern was obviously observed due to their current extensive usage. In addition, higher concentrations of both CUPs and OCPs were accumulated in the Northeast China Plain due to long-range atmospheric transport and deposition. Along with the old topic of OCPs, the study pointed out the preliminary understanding of CUPs pollution characteristic in surface soil of China, which provided a new story with the deep understanding of their environmental fate in both China and the world.

Disulfiram-loaded hollow copper sulfide nanoparticles show anti-tumor effects in preclinical models of colorectal cancer.

Colorectal cancer is one of the most common malignancies causing the majority of cancer-related deaths. There is an urgent need to develop new anticancer modalities. Recently, efforts have been made to turn clinically approved drugs into anticancer agents in specific tumor microenvironments via NPs. Disulfiram (DSF) as an effective copper (Cu2+)-dependent anti-tumour drug, which has been more widely used in antitumor research. Here, we constructed a novel therapeutic nanoplatforms, DSF@CuS, by encapsulating DSF in hollow CuS NPs to enable in situ chemoselective activation of DSF and hyperthermal amplified chemotherapy. The anticancer effect of DSF was enhanced by the thermal energy generated under NIR irradiation through the intrinsic photothermal conversion of CuS. As a result, significant apoptosis was induced in vitro, and tumor elimination was achieved in vivo. Collectively, DSF@CuS combined with photothermal therapy can significantly promote the apoptosis of CT26 colorectal cancer cells both in vitro and in vivo, providing a potential theoretical agent for the treatment of colorectal cancer.