Long-term exposure to the mixture of phthalates induced male reproductive toxicity in rats and the alleviative effects of quercetin.

Phthalates (PEs), such as di(2-ethylhexyl) phthalate (DEHP), dibutyl phthalate (DBP) and butyl benzyl phthalate (BBP) could cause reproductive and developmental toxicities, while human beings are increasingly exposed to them at low-doses. Phytochemical quercetin (Que) is a flavonoid that has estrogenic effect, anti-inflammatory and anti-oxidant effects. This study was conducted to assess the alleviative effect of Que. on male reproductive toxicity induced by the mixture of three commonly used PEs (MPEs) at low-dose in rats, and explore the underlying mechanism. Male rats were treated with MPEs (16 mg/kg/day) and/or Que. (50 mg/kg/d) for 91 days. The results showed that MPEs exposure caused male reproductive injuries, such as decreased serum sex hormones levels, abnormal testicular pathological structure, increased abnormal sperm rate and changed expressions of PIWIL1 and PIWIL2. Furthermore, MPEs also changed the expression of steroidogenic proteins in steroid hormone metabolism, including StAR, CYP11A1, CYP17A1, 17ß-HSD, CYP19A1. However, the alterations of these parameters were reversed by Que. MPEs caused male reproductive injuries in rats; Que. inhibited MPEs' male reproductive toxicity, which might relate to the improvement of testosterone biosynthesis.

Neferine alleviates ovariectomy-induced osteoporosis by enhancing osteogenic differentiation of bone marrow mesenchymal stem cells via regulation of the p38MAPK pathway.

OBJECTIVE: Osteoporosis, a skeletal ailment marked by bone metabolism imbalance and disruption of bone microarchitecture, Neferine, a bisbenzylisoquinoline alkaloid with diverse pharmacological activities, has received limited attention in the context of osteoporosis treatment. METHODS: We employed a bilateral ovariectomy (OVX) rat model to induce osteoporosis and subsequently administered Neferine treatment for four weeks following successful model establishment. Throughout the modeling and treatment phases, we closely monitored rat body weights. We assessed alterations in bone tissue microstructure through micro-CT, HE staining, and safranin O-fast green staining. Levels of bone formation and resorption markers in serum were evaluated using ELISA assay. Western blot analysis was employed to determine the expression levels of p38MAPK, p-p38MAPK, and bone formation-related genes in bone tissue. We isolated and cultured OVX rat BMSCs (OVX-BMSCs) and induced osteogenic differentiation while simultaneously introducing Neferine and the p38MAPK inhibitor SB203580 for intervention. RESULTS: Neferine treatment effectively curbed the rapid weight gain in OVX rats, ameliorated bone loss, and decreased serum levels of TRAP, CTX-I, PINP, and BALP. Most notably, Neferine promoted the expression of bone formation-related factors in bone tissue of OVX rats, while concurrently activating the p38MAPK signaling pathway. In in vitro experiments, Neferine facilitated the expression of bone formation-related factors in OVX-BMSCs, increased the osteogenic differentiation potential of OVX-BMSCs, and activated the p38MAPK signaling pathway. Nevertheless, SB203580 partially reversed Neferine's promotive effect. CONCLUSION: Neferine can boost the osteoblastic differentiation of BMSCs and alleviate OVX-induced osteoporosis in rats by activating the p38MAPK signaling pathway.

Acute exposure to seasonal PM2.5 induces toxicological responses in A549 cells cultured at the air-liquid interface mediated by oxidative stress and endoplasmic reticulum stress.

Atmospheric fine particulate matter (PM2.5) enters the human body through respiration and poses a threat to human health. This is not only dependent on its mass concentration in the atmosphere, but also related to seasonal variations in its chemical components, which makes it important to study the cytotoxicity of PM2.5 in different seasons. Traditional immersion exposure cannot simulate the living environment of human epithelial cells in the human body, making this method unsuitable for evaluating the inhalation toxicity of PM2.5. In this study, a novel air-liquid interface (ALI) particulate matter exposure device (VITROCELL Cloud 12 system) was used to evaluate the toxic effects and potential mechanisms of human lung epithelial cells (A549) after exposure to seasonal PM2.5. PM2.5 samples from four seasons were collected and analyzed for chemical components. After 6 h of exposure to seasonal PM2.5, winter PM2.5 exhibited the highest cytotoxicity among most toxicity indicators, especially apoptosis rate, reactive oxygen species (ROS), inflammatory responses and DNA damage (γ-H2AX). The effect of autumn PM2.5 on apoptosis rate was significantly higher than that in spring, and there was no significant difference in other toxicity indicators between spring and autumn. The cytotoxicity of summer PM2.5 was the lowest among the four seasons. It should be noted that even exposure to low doses of summer PM2.5 leads to significant DNA damage in A459 cells. Correlation analysis results showed that water-soluble ions, metallic elements, and polycyclic aromatic hydrocarbons (PAHs) were associated with most toxicological endpoints. Inhibitors of oxidative stress and endoplasmic reticulum (ER) stress significantly inhibited cellular damage, indicating that PM2.5-induced cytotoxicity may be related to the generation of ROS and ER stress. In addition, PM2.5 can induce ER stress through oxidative stress, which ultimately leads to apoptosis.

Alleviative effect of quercetin against reproductive toxicity induced by chronic exposure to the mixture of phthalates in male rats.

Phthalates (PEs) are widely used plasticizers in polymer products, and humans are increasingly exposed to them. This study was designed to investigate the alleviative effect of phytochemicals quercetin (Que) against male reproductive toxicity caused by the mixture of three commonly used PEs (MPEs), and further to explore the underlying mechanism. Forty-eight male SD rats were randomly and evenly divided into control group, Que group, MPEs group and MPEs+Que group (n = 12); The oral exposure doses of MPEs and Que were 450 mg/kg/d and 50 mg/kg/d, respectively. After 91 days of continuous intervention, compared with control group, the testes weight, epididymis weight, serum sex hormones, and anogenital distance were significantly decreased in MPEs group (P < 0.05); Testicular histopathological observation showed that all seminiferous tubules were atrophy, leydig cells were hyperplasia, spermatogenic cells growth were arrested in MPEs group. Ultrastructural observation of testicular germ cells showed that the edges of the nuclear membranes were indistinct, and the mitochondria were severely damaged with the cristae disrupted, decreased or even disappeared in MPEs group. Immunohistochemistry and Western blot analysis showed that testicular CYP11A1, CYP17A1 and 17ß-HSD were up-regulated, while StAR, PIWIL1 and PIWIL2 were down-regulated in MPEs group (P < 0.05); However, the alterations of these parameters were restored in MPEs+Que group. The results indicated MPEs disturbed steroid hormone metabolism, and caused male reproductive injuries; whereas, Que could inhibit MPEs' male reproductive toxicity, which might relate to the restored regulation of steroid hormone metabolism.

Ameliorative effects of zinc and vitamin E against phthalates-induced reproductive toxicity in male rats.

OBJECTIVE: Phthalates (PEs) could cause reproductive harm to males. A mixture of three widely used PEs (MPEs) was used to investigate the ameliorative effects of zinc (Zn) and vitamin E (VE) against male reproductive toxicity. METHODS: Fifty male SD rats were randomly divided into five groups (n = 10). Rats in MPEs group were orally treated with 160 mg/kg/d MPEs, while rats in MPEs combined Zn and/or VE groups were treated with 160 mg/kg/d MPEs plus 25 mg/kg/d Zn and/or 25 mg/kg/d VE. After intervention for 70 days, it's was measured of male reproductive organs' weight, histopathological observation of sperms and testes, serum hormones, PIWI proteins and steroidogenic proteins. RESULTS: Compared with control, anogenital distance, testes weight, epididymides weight, and sex hormones were significantly decreased, while the sperm malformation rate was markedly increased in MPEs group (p < .05); the testicular tissues were injured in MPEs group with disordered and decreased spermatids, and arrested spermatogenesis. PIWIL1, PIWIL2, StAR, CYP11A1 and CYP19A1 were down-regulated in MPEs group (p < .05). However, the alterations of these parameters were restored in MPEs combined Zn and/or VE groups (p < .05). CONCLUSION: Zn and/or VE improved steroid hormone metabolism, and inhibited MPEs' male reproductive toxicity.

Mixed-Lineage Leukemia 1 Inhibition Enhances the Differentiation Potential of Bovine Embryonic Stem Cells by Increasing H3K4 Mono-Methylation at Active Promoters.

Mixed-lineage leukemia 1 (MLL1) introduces 1-, 2- and 3-methylation into histone H3K4 through the evolutionarily conserved set domain. In this study, bovine embryonic stem cells (bESCs, known as bESCs-F7) were established from in vitro-fertilized (IVF) embryos via Wnt signaling inhibition; however, their contribution to the endoderm in vivo is limited. To improve the quality of bESCs, MM-102, an inhibitor of MLL1, was applied to the culture. The results showed that MLL1 inhibition along with GSK3 and MAP2K inhibition (3i) at the embryonic stage did not affect bESCs' establishment and pluripotency. MLL1 inhibition improved the pluripotency and differentiation potential of bESCs via the up-regulation of stem cell signaling pathways such as PI3K-Akt and WNT. MLL1 inhibition decreased H3K4me1 modification at the promoters and altered the distribution of DNA methylation in bESCs. In summary, MLL1 inhibition gives bESCs better pluripotency, and its application may provide high-quality pluripotent stem cells for domestic animals.

Utilization of sewage sludge ash in ultra-high performance concrete (UHPC): Microstructure and life-cycle assessment.

In this research, an economical and eco-friendly ultra-high performance concrete (UHPC) with compressive strength of more than 120 MPa was prepared with the dosage of sewage sludge ash (SSA) at 8 wt%. The results indicate that the addition of SSA has an adverse influence on the workability of UHPC samples due to its special morphology. Furthermore, the microstructure and phase assemblage of SSA-based UHPC were determined and the results show that SSA inhibits the early hydration of cement clinker, while promotes the precipitation of additional hydration products at later curing ages due to its pozzolanic reaction. The pore structure analysis of SSA-based UHPC determined by mercury intrusion porosimetry indicates that the addition of SSA increases the cumulative pore volume, while decreases the large pore volume of UHPC. Economic and environmental analysis indicates that using SSA-based UHPC greatly reduces the unit cost and the impacts on the environment.

Reproductive toxicity and underlying mechanisms of fine particulate matter (PM2.5) on Caenorhabditis elegans in different seasons.

Although numerous studies have investigated that atmospheric fine particulate matter (PM2.5) can be toxic to environmental organisms, the research on the reproductive toxicity of PM2.5 is limited, and the key toxic components and underlying mechanisms remain unknown. In this work, PM2.5 samples of four seasons in Nanjing from March 1, 2021, to February 28, 2022 were collected and the chemical components were analyzed. Caenorhabditis elegans (C. elegans) was employed to conduct the toxicological testing. The reproductive toxicity of PM2.5 to C. elegans in different seasons was evaluated by multiple reproductive endpoints. Exposure to high concentrations of PM2.5 significantly decreased the brood size and the number of fertilized eggs in utero. PM2.5 exposure also increased the number of germ cell corpses and caused abnormal expression of apoptosis-related genes (ced-9, ced-4, and ced-3), which confirmed that PM2.5 induced germline apoptosis. In addition, PM2.5 exposure significantly increased the production of reactive oxygen species (ROS) in C. elegans and the fluorescence intensity of HUS-1 protein in of transgenic strain WS1433. Meanwhile, the expression of genes related to DNA damage (cep-1, clk-2, egl-1, and hus-1) and oxidative stress (mev-1, isp-1, and gas-1) also significantly altered in C. elegans, suggesting induction of DNA damage and oxidative stress. According to Pearson correlation analyses, DNA damage and oxidative stress were significantly correlated with multiple reproductive endpoints in C. elegans. Thus, it was speculated that PM2.5 caused reproductive dysfunction and germ cell apoptosis in C. elegans may be by inducing ROS and DNA damage. In addition, heavy metals in PM2.5 were significantly correlated with multiple endpoints at physiological and biochemical, suggesting that the heavy metals might be an important contributor to the reproductive toxicity induced by PM2.5.

Smart Titanium Wire Used for the Evaluation of Hydrophobic/Hydrophilic Interaction by In-Tube Solid Phase Microextraction.

Evaluation of the hydrophobic/hydrophilic interaction individually between the sorbent and target compounds in sample pretreatment is a big challenge. Herein, a smart titanium substrate with switchable surface wettability was fabricated and selected as the sorbent for the solution. The titanium wires and meshes were fabricated by simple hydrothermal etching and chemical modification so as to construct the superhydrophilic and superhydrophobic surfaces. The micro/nano hierarchical structures of the formed TiO2 nanoparticles in situ on the surface of Ti substrates exhibited the switchable surface wettability. After UV irradiation for about 15.5 h, the superhydrophobic substrates became superhydrophilic. The morphologies and element composition of the wires were observed by SEM, EDS, and XRD, and their surface wettabilities were measured using the Ti mesh by contact angle goniometer. The pristine hydrophilic wire, the resulting superhydrophilic wire, superhydrophobic wire, and the UV-irradiated superhydrophilic wire were filled into a stainless tube as the sorbent instead of the sample loop of a six-port valve for on-line in-tube solid-phase microextraction. When employed in conjunction with HPLC, four kinds of wires were comparatively applied to extract six estrogens in water samples. The optimal conditions for the preconcentration and separation of target compounds were obtained with a sample volume of 60 mL, an injection rate of 2 mL/min, a desorption time of 2 min, and a mobile phase of acetonile/water (47/53, v/v). The results showed that both the superhydrophilic wire and UV-irradiated wire had the highest extraction efficiency for the polar compounds of estrogens with the enrichment factors in the range of 20-177, while the superhydrophobic wire exhibited the highest extraction efficiency for the non-polar compounds of five polycyclic aromatic hydrocarbons (PAHs). They demonstrated that extraction efficiency was mainly dependent on the surface wettability of the sorbent and the polarity of the target compounds, which was in accordance with the molecular theory of like dissolves like.

Topsentinol L Trisulfate, a Marine Natural Product That Targets Basal-like and Claudin-Low Breast Cancers.

Patients diagnosed with basal-like breast cancer suffer from poor prognosis and limited treatment options. There is an urgent need to identify new targets that can benefit patients with basal-like and claudin-low (BL-CL) breast cancers. We screened fractions from our Marine Invertebrate Compound Library (MICL) to identify compounds that specifically target BL-CL breast cancers. We identified a previously unreported trisulfated sterol, i.e., topsentinol L trisulfate (TLT), which exhibited increased efficacy against BL-CL breast cancers relative to luminal/HER2+ breast cancer. Biochemical investigation of the effects of TLT on BL-CL cell lines revealed its ability to inhibit activation of AMP-activated protein kinase (AMPK) and checkpoint kinase 1 (CHK1) and to promote activation of p38. The importance of targeting AMPK and CHK1 in BL-CL cell lines was validated by treating a panel of breast cancer cell lines with known small molecule inhibitors of AMPK (dorsomorphin) and CHK1 (Ly2603618) and recording the increased effectiveness against BL-CL breast cancers as compared with luminal/HER2+ breast cancer. Finally, we generated a drug response gene-expression signature and projected it against a human tumor panel of 12 different cancer types to identify other cancer types sensitive to the compound. The TLT sensitivity gene-expression signature identified breast and bladder cancer as the most sensitive to TLT, while glioblastoma multiforme was the least sensitive.

Pulmonary valve annular and right ventricular outflow tract size as predictions values for moderate to severe pulmonary regurgitation after repaired Tetralogy of Fallot.

OBJECTIVE: This study sought to investigate the variation of right heart structure pre- and post-operation as risk factors for moderate to severe pulmonary regurgitation (PR) after repaired Tetralogy of Fallot and the best "cutoff" values for the transannular patch (TAP). METHODS: We collected surgical, echocardiographic, and computed tomographic data of Teralogy of Fallot (TOF) patients over two years and calculated z-score values based on the echocardiographic data. Based on the PR level after follow-up, the patients were divided into two groups, trivial to mild PR and moderate to severe PR. A multivariate logistic regression analysis was performed, and the receiver operating characteristic curve analysis was used to find the best "cutoff" value for risk factors. RESULTS: A total of 104 TOF patients were included in our cohort study. From the multivariate analysis, correction strategy (P = .002), difference in zRVOT (OR 1.974, 95% CI 1.354 to 2.878, P < .0001), and zPVA (OR 3.605, 95% CI 1.980 to 6.562, P < .0001) were the significant risk factors for moderate to severe PR. The "cutoff" value for the difference in zPVA that could predict moderate to severe PR in the TAP group was 3, and the optimal "cutoff" value for TAP was -1.4. CONCLUSIONS: The TAP is a risk factor for significant PR after surgery. We recommend the optimal "cutoff" value for TAP is -1.4 calculated using Shan-Shan Wang's data set. During the procedure, to limit the RVOT resection and restrict the enlargement of pulmonary annulus within a variation of z-score as 3 would reduce significant PR.

The Lbc gene promotes differentiation of chicken embryo stem cell into spermatogonial stem cells via the regulation of transcriptional factor Hoxa5.

Recently, the surface marker genes of spermatogonial stem cells (SSCs) were increasingly excavated and verified. However, few studies focused on the key genes involved in the regulation of SSCs differentiation. Our laboratory has screened the Lbc gene (GenBank accession number: XM_429585.3), which is specifically expressed on the SSCs. The aim of this study is to investigate the function of Lbc and its regulatory mechanism for SSCs. The indirect immunofluorescence assay (IFA) showed that Lbc was located in both nucleus and cytoplasm. Lbc was also overexpressed and knocked out both in vitro and in vivo to verify its function in SSCs, respectively. As a result, the overexpressed Lbc could promote the formation of spermatogonial stem cells like cells (SSCs-like), while the deficiency of Lbc blocked the formation of SSCs-like. We also identified the core region of Lbc promoter that located into the upstream of the transcription initiation site -247 to -2bp. Moreover, the activity of Lbc promoter could be increased by histone acetylation which is leading to the higher expression of Lbc. When we mutated the transcription factor HOXA5 and SOX10 that bound to the core region of Lbc promoter, HOXA5 could reduce the transcription activity of Lbc whereas the SOX10 was not. Currently, we found Lbc is a new specific marker of SSCs. This gene can be modified by histone acetylated and promote the formation of chicken SSCs via the transcription factor HOXA5. The present research will lay the foundation for further study on the regulatory mechanism of SSCs.

Differential Activation of TRPA1 by Diesel Exhaust Particles: Relationships between Chemical Composition, Potency, and Lung Toxicity.

Diesel exhaust particulate (DEP) causes pulmonary irritation and inflammation, which can exacerbate asthma and other diseases. These effects may arise from the activation of transient receptor potential ankyrin-1 (TRPA1). This study shows that a representative DEP can activate TRPA1-expressing pulmonary C-fibers in the mouse lung. Furthermore, DEP collected from idling vehicles at an emissions inspection station, the tailpipe of an on-road "black smoker" diesel truck, waste DEP from a diesel exhaust filter regeneration machine, and NIST SRM 2975 can activate human TRPA1 in lung epithelial cells to elicit different biological responses. The potency of the DEP, particle extracts, and selected chemical components was compared in TRPA1 over-expressing HEK-293 and human lung cells using calcium flux and other toxicologically relevant end-point assays. Emission station DEP was the most potent and filter DEP the least. Potency was related to the percentage of ethanol extractable TRPA1 agonists and was equivalent when equal amounts of extract mass was used for treatment. The DEP samples were further compared using scanning electron microscopy, energy-dispersive X-ray spectroscopy, gas chromatography-mass spectrometry, and principal component analysis as well as targeted analysis of known TRPA1 agonists. Activation of TRPA1 was attributable to both particle-associated electrophiles and non-electrophilic agonists, which affected the induction of interleukin-8 mRNA via TRPA1 in A549 and IMR-90 lung cells as well as TRPA1-mediated mucin gene induction in human lung cells and mucous cell metaplasia in mice. This work illustrates that not all DEP samples are equivalent, and studies aimed at assessing mechanisms of DEP toxicity should account for multiple variables, including the expression of receptor targets such as TRPA1 and particle chemistry.

Human umbilical cord mesenchymal stem cells facilitate the up-regulation of miR-153-3p, whereby attenuating MGO-induced peritoneal fibrosis in rats.

MiRNAs contribute greatly to epithelial to mesenchymal transition (EMT) of peritoneal mesothelial cells (PMCs), which is a crucial step in peritoneal fibrosis (PF). In this study, we tried to profile whether miRNA expression differences exist after human umbilical cord mesenchymal stem cells (hUCMSCs) treatment in PF rats and investigate the possible role of miR-153-3p involved in anti-EMT process. We randomly assigned 34 rats into three groups: control group (Group Control), MGO-induced PF rats (Group MGO) and hUCMSCs-treated rats (Group MGO + hUCMSCs). MiRNA microarrays and real-time PCR analyses were conducted in three groups. α-SMA, Snail1 and E-cadherin expression were detected by Western blot. Luciferase reporter assays were used to detect the effects of miR-153-3p overexpression on Snai1 in rat peritoneal mesothelial cells (RPMCs). We identified differentially expressed miRNAs related to EMT, in which miR-153-3p demonstrated the greatest increase in Group MGO + hUCMSCs. Transient cotransfection of miR-153-3p mimics with luciferase expression plasmids resulted in a significant repression of Snai1 3'-untranslated region luciferase activity in RPMCs. These studies suggest that miR-153-3p is a critical molecule in anti-EMT effects of hUCMSCs in MGO-induced PF rats. MiR-153-3p might exert its beneficial effect through directly targeting Snai1.

Activation of TRPV3 by Wood Smoke Particles and Roles in Pneumotoxicity.

Wood/biomass smoke particulate materials (WBSPM) are pneumotoxic, but the mechanisms by which these materials affect lung cells are not fully understood. We previously identified transient receptor potential (TRP) ankyrin-1 as a sensor for electrophiles in WBSPM and hypothesized that other TRP channels expressed by lung cells might also be activated by WBSPM, contributing to pneumotoxicity. Screening TRP channel activation by WBSPM using calcium flux assays revealed TRPV3 activation by materials obtained from burning multiple types of wood under fixed conditions. TRPV3 activation by WBSPM was dependent on the chemical composition, and the pattern of activation and chemical components of PM agonists was different from that of TRPA1. Chemical analysis of particle constituents by gas chromatography-mass spectrometry and principal component analysis indicated enrichment of cresol, ethylphenol, and xylenol analogues, plus several other chemicals among the most potent samples. 2,3-, 2,4-, 2,5-, 2,6-, 3,4-, and 3,5-xylenol, 2-, 3-, and 4-ethylphenol, 2-methoxy-4-methylphenol, and 5,8-dihydronaphthol were TRPV3 agonists exhibiting preferential activation versus TRPA1, M8, V1, and V4. The concentration of 2,3- and 3,4-xylenol in the most potent samples of pine and mesquite smoke PM (<3 µm) was 0.1-0.3% by weight, while that of 5,8-dihydronaphthol was 0.03%. TRPV3 was expressed by several human lung epithelial cell lines, and both pine PM and pure chemical TRPV3 agonists found in WBSPM were more toxic to TRPV3-over-expressing cells via TRPV3 activation. Finally, mice treated sub-acutely with pine particles exhibited an increase in sensitivity to inhaled methacholine involving TRPV3. In summary, TRPV3 is activated by specific chemicals in WBSPM, potentially contributing to the pneumotoxic properties of certain WBSPM.

Onydecalins, Fungal Polyketides with Anti- Histoplasma and Anti-TRP Activity.

We report an unusual 3-substituted pyridine polyketide, onydecalin A (1), which was obtained along with 2 as a major constituent from the fungus Aioliomyces pyridodomos (order: Onygenales) following a two-month fermentation. Feeding studies demonstrated that the pyridine subunit originates via an unprecedented biosynthetic process in comparison to other polyketide-linked pyridines or derivatives such as pyridones. The slow growth of the fungus led us to perform a one-year fermentation, leading to production of compounds 2-4 as the major constituents. These compounds showed modest but selective inhibition against a variety of transient receptor potential channels, as well as against the human pathogenic fungus Histoplasma capsulatum.

Ophiobolins from the Mangrove Fungus Aspergillus ustus.

Seven new ophiobolins (1-5, 12, and 14) along with the 11 known analogues (6-11, 13, 15-18) were isolated from the ethyl acetate extracts of the liquid and solid cultures of the mangrove fungus Aspergillus ustus 094102. The structures including the absolute configurations of the seven new compounds were elucidated by spectroscopic analysis, chemical methods, and quantum ECD calculations. Compounds 4-8 and 11-15 showed cytotoxicities against the G3K, MCF-7, MD-MBA-231, MCF/Adr, A549, and HL-60 human cancer cell lines with the IC50 values ranging from 0.6 to 9.5 µM.

Ozone-induction coupled with plasma assistance to enhance cataluminescence for monitoring of volatile organic compounds.

The authors describe a strategy for ozone-induction coupling with plasma assistance (O3-I/PA) to enhance cataluminescence (CTL) based sensing of volatile organic compounds (VOCs). A homemade O3-I/PA CTL sensor system was constructed based on this strategy. O3-I/PA can significantly enhance the CTL response to many compounds that were hardly detectable previously with adequate sensitivity. Without any preconcentration, the limits of detection (for S/N = 3) are 20 µg.m-3 (= 5 ppbv) for toluene and 8 µg.m-3 (6.4 ppbv) for formaldehyde. VOCs including benzene, alkanes, halohydrocarbons, alkenes alcohols, aldehydes, ketones and ethers are found to produce a strong response when using this sensor system. Mechanistic studies showed that the synergistic effect of ozone-induction and plasma assistance promote the oxidation of the VOCs under formation of CO2. This strongly favors CTL emission. The sensor system can be used as a direct-reading detector for on-line and real-time monitoring of total VOCs. It also can be used as a detector in gas chromatography for the identification of individual VOCs. It is perceived that this work paves the way to both a new kind of vapor sensor and to a detection scheme in gas chromatography. Graphical abstract The synergistic effect of ozone-induction and plasma assistance promote the deep oxidation of the VOCs into CO2, which strongly favors cataluminescence emission.

Activation of Human Transient Receptor Potential Melastatin-8 (TRPM8) by Calcium-Rich Particulate Materials and Effects on Human Lung Cells.

To better understand how adverse health effects are caused by exposure to particulate materials, and to develop preventative measures, it is important to identify the properties of particles and molecular targets that link exposure with specific biologic outcomes. Coal fly ash (CFA) is a by-product of coal combustion that can affect human health. We report that human transient receptor potential melastatin-8 (TRPM8) and an N-terminally truncated TRPM8 variant (TRPM8-Δ801) are activated by CFA and calcium-rich nanoparticles and/or soluble salts within CFA. TRPM8 activation by CFA was potentiated by cold temperature involving the phosphatidylinositol 4,5-bisphosphate binding residue (L1008), but was independent of the icilin and menthol binding site residue Y745 and, essentially, the N-terminal amino acids 1-800. CFA, calcium nanoparticles, and calcium salts also activated transient receptor potential vanilloid-1 (TRPV1) and transient receptor potential ankyrin-1 (TRPA1), but not TRPV4. CFA treatment induced CXCL1 and interleukin-8 mRNA in BEAS-2B and primary human bronchial epithelial cells through activation of both TRPM8 and TRPV1. However, neither mouse nor rat TRPM8 was activated by these materials, and Trpm8 knockout had no effect on cytokine induction in the lungs of CFA-instilled mice. Amino acids S921 and S927 in mouse Trpm8 were identified as important for the lack of response to CFA. These results imply that TRPM8, in conjunction with TRPV1 and TRPA1, might sense selected forms of inhaled particulate materials in human airways, shaping cellular responses to these materials, and improving our understanding of how and why certain particulate materials elicit different responses in biologic systems, affecting human health.