Gas/particle (G/P) partitioning is an important influencing factor for the environmental fate of semi-volatile organic compounds (SVOCs). The G/P partitioning of polycyclic aromatic hydrocarbons ...(PAHs) is an integrated complex process due to its formation and growth concurrently with particles. Based on the large dataset of gaseous and particulate samples in a wide ambient temperature range of 50 °C, the simple empirical equations based on ambient temperature were established to predict the G/P partitioning quotient (KP) of PAHs at the temperature range from 252 K to 307 K (−21 °C to 34 °C). The performance of the empirical equations was validated by comparison with the monitoring KP of PAHs worldwide. The empirical equations exhibited good performance for the prediction of KP of PAHs based on ambient temperature. Two deviations with the prediction lines of the previous G/P partitioning models from the monitoring data of KP were observed. It was found that the deviations might be attributed to some non-considered influencing factors with the previous G/P partitioning prediction models. Therefore, further research should be conducted to study the mechanism of the G/P partitioning of PAHs, and more influencing factors should be introduced into the establishment of G/P partitioning models of PAHs. In summary, the result of the present study provided a convenient method for the prediction of KP of PAHs, which should be useful for the study of environmental fate of PAHs in atmosphere.
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•Influence of temperature on the G/P partitioning of PAHs was studied.•Simple empirical equations based on ambient temperature were established.•G/P partitioning quotient (KP) of PAHs from 252 K to 307 K can be predicated.•Two deviations of G/P partitioning models from monitoring KP were observed.
Non-invasive estimation of cartilage material properties is useful for understanding cartilage health and creating subject-specific computational models. Bi-component T2 mapping measured using ...Multi-Component Driven Equilibrium Single Shot Observation of T1 and T2 (mcDESPOT) is sensitive for detecting cartilage degeneration within the human knee joint, but has not been correlated with cartilage composition and mechanical properties. Therefore, the purpose of this study was to investigate the relationship between bi-component T2 parameters measured using mcDESPOT at 3.0 T and cartilage composition and mechanical properties. Ex-vivo patellar cartilage specimens harvested from five human cadaveric knees were imaged using mcDESPOT at 3.0 T. Cartilage samples were removed from the patellae, mechanically tested to determine linear modulus and dissipated energy, and chemically tested to determine proteoglycan and collagen content. Parameter maps of single-component T2 relaxation time (T2), the T2 relaxation times of the fast relaxing macromolecular bound water component (T2F) and slow relaxing bulk water component (T2S), and the fraction of the fast relaxing macromolecular bound water component (FF) were compared to mechanical and chemical measures using linear regression. FF was significantly (p < 0.05) correlated with energy dissipation and linear modulus. T2 was significantly (p ≤ 0.05) correlated with elastic modulus at 1 Hz and energy dissipated at all frequencies. There were no other significant (p = 0.13–0.97) correlations between mcDESPOT parameters and mechanical properties. FF was significantly (p = 0.04) correlated with proteoglycan content. There were no other significant (p = 0.19–0.92) correlations between mcDESPOT parameters and proteoglycan or collagen content. This study suggests that FF measured using mcDESPOT at 3.0 T could be used to non-invasively estimate cartilage proteoglycan content, elastic modulus, and energy dissipation.
Despite the ubiquity and prevalence of lead (Pb) in the environment and industry, the mechanism of lead-induced neurotoxicity in the brain remains unclear, let alone its prevention and treatment. In ...this study, we hypothesized that exogenous cholesterol supplementation acts as an effective remedy for lead-induced neurodevelopmental impairments caused by lead. Forty 21-day-old male rats were randomly divided into four groups and administered 0.1 % lead water and/or 2 % cholesterol-containing feed for 30 d. Ultimately, rats in the lead group lost weight, accompanied by spatial learning and memory impairments as verified by the Morris water maze test, in which the escape latency of rats was prolonged, and the number of crossings in the target platform and the residence time in the target quadrant were significantly diminished compared to the control group. Hematoxylin-Eosin (H&E) staining and Nissl staining illustrated that typical pathological morphology occurred in the brain tissue of the lead group, where the tissue structure was loose, the number of hippocampal neurons and granulosa cells decreased significantly and were arranged loosely, along with enlarged intercellular space, light matrix staining, and decline in Nissl bodies. In addition, inflammatory response and oxidative stress were significantly induced by lead. Immunofluorescence experiments showed apparent activation of astrocytes and microglia, followed by the enhancement of TNF-α and IL-β levels. Moreover, the MDA content in the lead group was elevated dramatically, whereas the activities of SOD and GSH were significantly inhibited. As for the mechanism, western blot and qRT-PCR experiments were performed, where lead could significantly inhibit the BDNF-TrkB signaling pathway, lowering the protein expression of BDNF and TrkB. Cholesterol metabolism was also affected by lead exposure, in which cholesterol metabolism-related protein expression and gene transcription, including SREBP2, HMGCR, and LDLR, were downregulated. However, cholesterol supplementation efficiently detoxified the negative effects of lead-induced neurotoxicity, reversing the inflammatory response, oxidative stress, inactivation of the BDNF signaling pathway, and imbalance of cholesterol metabolism, thus improving the learning and memory ability of rats. In brief, our study demonstrated that cholesterol supplementation could ameliorate the deficiency of learning and memory induced by lead, which is closely associated with the initiation of the BDNF/TrkB signaling pathway and regulation of cholesterol metabolism.
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•Lead (Pb)-induced neurotoxicity might be associated with imbalance of cholesterol homeostasis.•Supplementation of cholesterol ameliorated Pb-induced learning and memory impairments.•Amelioration of Pb-induced injury may be linked with activation of BDNF signaling and cholesterol metabolism.
•Dechlorane compounds were measured in indoor dust across China.•Higher concentrations of DP were found in urban and public samples.•Sources of DP and “DP-like” compounds were different in indoor ...dust.•Health risk of exposure to DP and related compound were acceptable.
Levels of dechlorane plus (DP) and “DP-like” compounds were measured in indoor dust samples collected across China. The concentrations of ΣDP and “DP-like” compounds ranged from 0.35 to 1000ngg−1 and<0.21 to 2.4ngg−1, respectively. The total DP concentration in urban sites were significantly higher than those of rural sites, while no significant difference was found for “DP-like” compounds, suggesting different sources of these compounds. Significant positive correlations were found between fsyn and latitude, and between fsyn and longitude. The deleterious risk associated with DP exposure via indoor dust for the general population in China was low and safer than expectation. For estimating human exposure via indoor dust, sensitivity analysis showed that more attention should be given to the influential variables such as the level of pollutants, body weight, and the amount of ingestion and adsorption.
Abstract
Capn4 belongs to a family of calpains that participate in a wide variety of biological functions, but little is known about the role of Capn4 in cardiac disease. Here, we show that the ...expression of Capn4 was significantly increased in Angiotensin II (Ang II)-treated cardiomyocytes and Ang II-induced cardiac hypertrophic mouse hearts. Importantly, in agreement with the Capn4 expression patterns, the maximal calpain activity measured in heart homogenates was elevated in Ang II-treated mice and oral coadministration of SNJ-1945 (calpain inhibitor) attenuated the total calpain activity measured in vitro. Functional assays indicated that overexpression of Capn4 obviously aggravated Ang II-induced cardiac hypertrophy, whereas Capn4 knockdown resulted in the opposite phenotypes. Further investigation demonstrated that Capn4 maintained the activation of the insulin-like growth factor (IGF)-AKT signalling pathway in cardiomyocytes by increasing c-Jun expression. Mechanistic investigations revealed that Capn4 directly bound and stabilized c-Jun and knockdown of Capn4 increased the ubiquitination level of c-Jun in cardiomyocytes. Additionally, our results demonstrated that the antihypertrophic effect of Capn4 silencing was partially dependent on the inhibition of c-Jun. Overall, these data suggested that Capn4 contributes to cardiac hypertrophy by enhancing the c-Jun-mediated IGF-AKT signalling pathway and could be a potential therapeutic target for hypertrophic cardiomyopathy.
Graphical Abstract
Graphical Abstract
Tissue damage in diabetes is at least partly due to elevated reactive oxygen species production by the mitochondrial respiratory chain during hyperglycemia. Sustained hyperglycemia results in ...mitochondrial dysfunction and the abnormal expression of mitochondrial genes, such as NADH: Ubiquinone oxidoreductase subunit A13 (NDUFA13). Metformin, an AMP‑activated protein kinase (AMPK) activator, protects cardiomyocytes from oxidative stress by improving mitochondrial function; however, the exact underlying mechanisms are not completely understood. The aim of the present study was to investigated the molecular changes and related regulatory mechanisms in the response of H9C2 cardiomyocytes to metformin under high glucose conditions. H9C2 cells were subjected to CCK‑8 assay to assess cell viability. Reactive oxygen species generation was measured with DCFH‑DA assay. Western blotting was used to analyze the expression levels of NDUFA13, AMPK, p‑AMPK and GAPDH. Reverse transcription‑quantitative PCR was used to evaluate the expression levels of mitochondrial genes and transcription factors. It was observed that metformin protected H9C2 cardiomyocytes by suppressing high glucose (HG)‑induced elevated oxidative stress. In addition, metformin stimulated mitochondrial biogenesis, as indicated by increased expression levels of mitochondrial genes (NDUFA1, NDUFA2, NDUFA13 and manganese superoxide dismutase) and mitochondrial biogenesis‑related transcription factors peroxisome proliferator‑activated receptor‑gamma coactivator‑1α, nuclear respiratory factor (NRF)‑1, and NRF‑2 in the metformin + HG group compared with the HG group. Moreover, metformin promoted mitochondrial NDUFA13 protein expression via the AMPK signaling pathway, which was abolished by pretreatment with the AMPK inhibitor, Compound C. The results suggested that metformin protected cardiomyocytes against HG‑induced oxidative stress via a mechanism involving AMPK, NDUFA13 and mitochondrial biogenesis.
Indoor window films can represent short-term air pollution conditions of indoor environment through rapidly capturing organic contaminants as effective passive air samplers. To investigate the ...temporal variation, influence factors of polycyclic aromatic hydrocarbons (PAHs) in indoor window films, and the exchange behavior with gas phase in college dormitories, 42 pairs window films of interior and exterior window surfaces and corresponding indoor gas phase and dust samples were collected monthly in six selected dormitories, Harbin, China, from August to December 2019 and September 2020. The average concentration of ∑16PAHs in indoor window films (398 ng/m2) was significantly (p < 0.01) lower than that in outdoors (652 ng/m2). In addition, the median indoor/outdoor ∑16PAHs concentration ratio was close to 0.5, showing that outdoor air acted as a major PAH source to indoor environment. The 5-ring PAHs were mostly dominant in window films whereas the 3-ring PAHs contributed mostly in gas phase. 3-ring PAHs and 4-ring PAHs were both important contributors for dormitory dust. Window films showed stable temporal variation, i.e. PAH concentrations in heating months were higher than those in non-heating months. The atmospheric O3 concentration was the main influence factor of PAHs in indoor window films. PAHs with low molecular weight in indoor window films rapidly reached film/air equilibrium phase within in dozens of hours. The large deviation in the slope of the log KF-A versus log KOA regression line from that in reported equilibrium formula might be the difference between the window film composition and octanol.
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•Elevated heavy polycyclic aromatic hydrocarbon (PAH) accumulation in indoor films.•PAHs in films and gas phase showed similar temporal variation affected by heating.•Light PAHs rapidly reached indoor film/air equilibrium phase within dozens of hours.•Deviation in slope of regression line with film/air equilibrium formula was explored.
The search for traces of life is one of the principal objectives of Mars exploration. The global distribution of minerals associated with serpentinization in the Noachian terrains on Mars likely ...suggest that serpentinization commonly occurred early in the planets history. A consensus is that these reactions involved in the serpentinization may have provided the initial material and energy for the origin and early evolution of life on Earth. Comparably, the serpentine regions of Mars are potential target sites for the detection of the putative life on Mars. Herein, an actinobacterial species Streptomyces spp. FXJ8.102 is used as a model microbe to investigate the microbe-mediated dissolution of antigorite in liquid culture. The experimental results show that the strain can couple biomechanical and biochemical mechanisms in the serpentine dissolution, leading to the development of “cell-sized” and “cell-shaped” eroded pits/channels on the mineral surfaces, and the low Mg/Si ratios on the eroded sites. In addition, the cells can also induce the formation of secondary glushinskite during the dissolution process. By contrast, no distinguishable surface change on antigorite and secondary mineral formation can be observed in the control experiments without inoculation. Therefore, a collection of the features including the distinctive eroded texture and composition on serpentine surfaces, and the special mineral assemblage including the formation of secondary oxalate minerals may serve as a compelling biosignature for the search of life on Mars.
Colorectal cancer (CRC) is an extremely malignant tumor with a high mortality rate. Little is known about the mechanism by which forkhead Box q1 (FOXQ1) causes CRC invasion and metastasis through the ...epidermal growth factor receptor (EGFR) pathway.
To illuminate the mechanism by which FOXQ1 promotes the invasion and metastasis of CRC by activating the heparin binding epidermal growth factor (HB-EGF)/EGFR pathway.
We investigated the differential expression and prognosis of FOXQ1 and HB-EGF in CRC using the Gene Expression Profiling Interactive Analysis (GEPIA) website (http://gepia.cancer-pku.cn/index.html). Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting were used to detect the expression of FOXQ1 and HB-EGF in cell lines and tissues, and we constructed a stable low-expressing FOXQ1 cell line and verified it with the above method. The expression changes of membrane-bound HB-EGF (proHB-EGF) and soluble HB-EGF (sHB-EGF) in the low-expressing FOXQ1 cell line were detected by flow cytometry and ELISA. Western blotting was used to detect changes in the expression levels of HB-EGF and EGFR pathway-related downstream genes when exogenous recombinant human HB-EGF was added to FOXQ1 knockdown cells. Proliferation experiments, transwell migration experiments, and scratch experiments were carried out to determine the mechanism by which FOXQ1 activates the EGFR signaling pathway through HB-EGF, and then to evaluate the clinical relevance of FOXQ1 and HB-EGF.
GEPIA showed that the expression of FOXQ1 in CRC tissues was relatively high and was related to a lower overall survival rate. PCR array results showed that FOXQ1 is related to the HB-EGF and EGFR pathways. Knockdown of FOXQ1 suppressed the expression of HB-EGF, and led to a decrease in EGFR and its downstream genes
,
,
expression levels. After knockdown of FOXQ1 in CRC cell lines, cell proliferation, migration and invasion were attenuated. Adding HB-EGF restored the migration and invasion ability of CRC, but not the cell proliferation ability. Kaplan-Meier survival analysis results showed that the combination of FOXQ1 and HB-EGF may serve to predict CRC survival.
Based on these collective data, we propose that FOXQ1 promotes the invasion and metastasis of CRC
the HB-EGF/EGFR pathway.
Objective
Under current standards of treating highly aggressive hypopharyngeal cancer (HPC), oncological control and functional outcome are still unsatisfactory worldwide. This study explored the ...surgery-oriented comprehensive treatment approach based on 15 years of practice.
Methods
A retrospective cohort of HPC patients treated by the senior author at Chinese PLA General Hospital between Nov 2005 and Aug 2012 and Capital Medical University Beijing Friendship Hospital between May 2014 and Nov 2019 was studied. Oncological control, swallowing function, and quality of life (QoL) were assessed.
Results
In total, 122 patients were included in this study, with 11 (9.0%) cases in the early stage and 111 (91.0%) cases in the advanced stage. Five-year overall survival (OS) and disease-free survival (DFS) were 40.0% and 36.1%, respectively. The swallowing outcome was satisfactory in 90 (73.8%) patients. Tracheostomy-free survival was achieved in 55 (45.1%) patients. Multivariate cox regression analysis showed that the size of the surgical defect, local-regional recurrence, and distant metastasis were independent impact factors for OS and DFS (P < .05). Multivariate analysis showed that the logistic regression coefficients (standard error) of pharyngo-cutaneous fistula and local-regional recurrence on swallowing function were 1.274 (.532) and 1.283 (.496), respectively (P < .05). In addition, the logistic regression coefficients (standard error) of the clinical stage, local-regional recurrence, decannulation, and feeding tube on QoL were −7.803 (3.593), −7.699 (3.151), 13.853 (3.494), and −20.243 (3.696), respectively (P < .05).
Conclusions
Surgery-oriented comprehensive treatment can give rise to good swallowing function without jeopardizing oncological control. The size of the surgical defect, local-regional recurrence, and distant metastasis were independent factors impacting OS and DFS. Pharyngo-cutaneous fistula and local-regional recurrence were independent factors impacting swallowing function. Clinical stage, local-regional recurrence, decannulation, and feeding tube were independent factors impacting QoL.
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