Sub-ppt level detection of carbon monoxide and nitrous oxide enabled by mid-infrared doubly resonant photoacoustic spectroscopy.

We report highly sensitive detection of carbon monoxide (CO) and nitrous oxide (N2O) using doubly resonant photoacoustic spectroscopy paired with a quantum cascade laser (QCL) at 4.57 µm. The butterfly-packaged QCL is used to exploit the CO absorption line at 2190.02 cm-1 and the N2O absorption line at 2191.42 cm-1 by scanning the injection current. Leveraging the simultaneous acoustic and optical resonances and adopting a lower photoacoustic detection frequency, we achieve a minimum detection limit of 0.85 part-per-trillion (ppt) for CO over the 500 s averaging time, and 0.7 ppt for N2O over the 200 s averaging time. Our approach demonstrates record sensitivity for CO and N2O detection compared to state-of-the-art optical gas sensors.

PCK2 maintains intestinal homeostasis and prevents colitis by protecting antibody-secreting cells from oxidative stress.

Maintaining intracellular redox balance is essential for the survival, antibody secretion, and mucosal immune homeostasis of immunoglobulin A (IgA) antibody-secreting cells (ASCs). However, the relationship between mitochondrial metabolic enzymes and the redox balance in ASCs has yet to be comprehensively studied. Our study unveils the pivotal role of mitochondrial enzyme PCK2 in regulating ASCs' redox balance and intestinal homeostasis. We discover that PCK2 loss, whether globally or in B cells, exacerbates dextran sodium sulphate (DSS)-induced colitis due to increased IgA ASC cell death and diminished antibody production. Mechanistically, the absence of PCK2 diverts glutamine into the TCA cycle, leading to heightened TCA flux and excessive mitochondrial reactive oxygen species (mtROS) production. In addition, PCK2 loss reduces glutamine availability for glutathione (GSH) synthesis, resulting in a decrease of total glutathione level. The elevated mtROS and reduced GSH expose ASCs to overwhelming oxidative stress, culminating in cell apoptosis. Crucially, we found that the mitochondria-targeted antioxidant Mitoquinone (Mito-Q) can mitigate the detrimental effects of PCK2 deficiency in IgA ASCs, thereby alleviating colitis in mice. Our findings highlight PCK2 as a key player in IgA ASC survival and provide a potential new target for colitis treatment.

Dynamic changes in RNA m6A and 5 hmC influence gene expression programs during macrophage differentiation and polarisation.

RNA modifications are essential for the establishment of cellular identity. Although increasing evidence indicates that RNA modifications regulate the innate immune response, their role in monocyte-to-macrophage differentiation and polarisation is unclear. While m6A has been widely studied, other RNA modifications, including 5 hmC, remain poorly characterised. We profiled m6A and 5 hmC epitranscriptomes, transcriptomes, translatomes and proteomes of monocytes and macrophages at rest and pro- and anti-inflammatory states. Transcriptome-wide mapping of m6A and 5 hmC reveals enrichment of m6A and/or 5 hmC on specific categories of transcripts essential for macrophage differentiation. Our analyses indicate that m6A and 5 hmC modifications are present in transcripts with critical functions in pro- and anti-inflammatory macrophages. Notably, we also discover the co-occurrence of m6A and 5 hmC on alternatively-spliced isoforms and/or opposing ends of the untranslated regions (UTR) of mRNAs with key roles in macrophage biology. In specific examples, RNA 5 hmC controls the decay of transcripts independently of m6A. This study provides (i) a comprehensive dataset to interrogate the role of RNA modifications in a plastic system (ii) a resource for exploring different layers of gene expression regulation in the context of human monocyte-to-macrophage differentiation and polarisation, (iii) new insights into RNA modifications as central regulators of effector cells in innate immunity.

Characterization of moisture migration and diffusion in two types of tobacco biomass during the dehydration process by the TG-NMR analysis.

The tobacco waste generated from the tobacco agriculture and industry, including the discarded stem and leaf, often needs dehydration pretreatment before thermal conversion utilization. In order to study the water activity and migration of tobacco waste during the pretreatment process, TG-NMR (Thermogravimetric Nuclear Magnetic Resonance) was used to obtain the drying curves and LF-NMR (Low Field Nuclear Magnetic Resonance) T2 inversion spectrum at each stage of tobacco drying. Meanwhile, the variation pattern of pore distribution during the dehydration process of two types of tobacco waste has been obtained. Combined with the pore distribution changes, a possible spatial migration mode of water was proposed. The change of adsorption energy of water during tobacco drying was calculated, and verified the above hypothesis. This study results provide reference for the optimization of dehydration pretreatment process for different tobacco waste in order to reduce energy consumption during recycling of tobacco biomass.

Changes in biomarkers of exposure and withdrawal symptom among Chinese adult smokers after completely or partially switching from combustible cigarettes to an electronic nicotine delivery system.

This study assessed changes in biomarkers of exposure (BoE) after 5 days of completely or partially switching to an electronic nicotine delivery system (ENDS) use, compared with continued use of combustible cigarettes and smoking abstinence among Chinese adult smokers. A randomized, open-label, parallel-arm study was conducted among Chinese adult smokers who were naive ENDS users. Forty-six subjects were randomized to 4 study groups (n = 11-12 per group): exclusive ENDS use, dual use of ENDS and cigarettes, exclusive cigarettes use, and smoking abstinence. Subjects were confined in clinic for 5 consecutive days and product use was ad libitum. Nicotine and its metabolites (cotinine and 3-hydroxycotinine), and BoEs (AAMA, CEMA, HEMA, HMPMA, 3-HPMA, SPMA, exhaled CO, and exhaled NO) were measured. Withdrawal symptom was measured using MNWS throughout the 5-day period. Six urine BoEs of volatile organic compounds decreased by 55.1-84.1% in the exclusive ENDS use group, which is similar to the smoking abstinence group (67.2-87.4%). The level of decrease was 56.8-70.4% in the dual use group and 10.7-39.0% in the cigarettes group. Urine total nicotine exposure had a non-significant increase in the exclusive ENDS use group, and plasma nicotine and cotinine showed a trend of increasing day by day. After completely or partially switching to ENDS use among Chinese smokers, exposure to selected toxicants were significantly decreased. The results of this study add to the body of evidence that exposure to toxic substance decreased among smokers after complete or partial switch from combustible cigarettes to ENDS use. As part of transition to experienced ENDS use, this study found that smokers of the initial stage who have no prior ENDS experience may increase nicotine intake after switching to ENDS use.

Quantum cascade laser absorption sensor for in-situ, real-time and sensitive measurement of high-temperature SO2 and SO3.

We report a mid-infrared quantum cascade laser absorption sensor capable of measuring SO2 and SO3 simultaneously and sensitively at elevated temperatures. In the sensor development, the intense transitions of SO2 and SO3 in the mid-infrared region of 1129 cm-1 and 1398 cm-1 were exploited by two quantum cascade lasers. A high-temperature multipass cell was adopted to increase the absorption path length to 10 m. The quantitative concentrations of SOx were directly obtained from the calibration-free wavelength modulation spectroscopic method, which was validated at varied temperature and pressure conditions. From Allan deviation analysis, we achieved a minimum detection limit of 8 parts per billion (ppb) for SO2 and 3 ppb for SO3, with an average time of 100 s. Lastly, we successfully demonstrated the real-time and sensitive measurement of SO2 and SO3 during the oxidation reaction of SO2 by O3 at 460 K. Our laser sensor shows great potential for in-situ and real-time monitoring of SOx from combustion emissions.

Biochar derived from tobacco waste significantly reduces the accumulations of cadmium and copper in edible parts of two vegetables: an in-situ field study.

Biochar, as a soil amendment, can be applied to remediate heavy metal (HM) contaminated farmland. However, there is little research on the effect of tobacco biochar (TB) derived from tobacco waste on HM controlling in edible parts of vegetables. In this study, the impact of two TB levels on the plant growth, copper (Cu) and cadmium (Cd) accumulation in the edible parts of lettuce and chrysanthemum, and on Cu and Cd bioavailability of rhizosphere soil was investigated through in-situ field experiments. The results showed that TB has rich oxygen containing functional groups, high porosity, high nitrogen adsorption capacity. The addition of 5 t ha-1 and 10 t ha-1 TB significantly increased the shoot biomass of chrysanthemum, but had no effect on the growth of lettuce. Two levels of TB significantly increased the pH value, but decreased the available Cu and Cd concentrations of rhizosphere soil, thereby reducing the Cu and Cd accumulations in the edible parts of lettuce and chrysanthemum. The findings provided effective evidences that TB derived from tobacco waste is an efficient strategy for controlling Cu and Cd accumulation in the edible parts of vegetables to ensure agri-product safety production in HM-polluted farmland.

Inhalation of electronic cigarettes slightly affects lung function and inflammation in mice.

Electronic cigarettes have become increasingly popular, but the results of previous studies on electronic cigarette exposure in animals have been equivocal. This study aimed to evaluate the effects of electronic cigarette smoke (ECS) and cigarette smoke (CS) on lung function and pulmonary inflammation in mice to investigate whether electronic cigarettes are safer when compared to cigarettes. 32 specific pathogen-free BALB/c male mice were randomly grouped and exposed to fresh air (control), mint-flavored ECS (ECS1, 6 mg/kg), cheese-flavored ECS (ECS2, 6 mg/kg), and CS (6 mg/kg). After 3 weeks exposure to ECS or CS, we measured lung function (PIF and Penh) and blood oxygen saturation. The levels of TNF-α and IL-6 in the bronchoalveolar lavage fluid (BALF) and serum were measured using ELISA. HE staining was performed to observe the pathological changes in the lung tissues. The levels of IL-6 in BALF and serum, and TNF-α in BALF, were elevated similarly in the ECS and CS groups compared to the control group. Significant elevation was observed in serum TNF-α levels in the CS group. The total count of cells in BALF were increased after ECS1 exposure and CS exposure. PIF and oxygen saturation decreased, and Penh increased markedly in the CS group but not in the ECS groups. Compared with the ECS groups, mice in the CS group had widened lung tissue septa and increased inflammatory cell infiltration. However, we did not detect significant differences between mint-flavored and cheese-flavored e-cigarettes in our study. Overall, our findings suggested that both ECS and CS impair lung function and histopathology while promoting inflammation. In contrast, ECS has a less negative impact than CS.

The toxic effects of electronic cigarette aerosol and cigarette smoke on cardiovascular, gastrointestinal and renal systems in mice.

Electronic cigarette (EC) has been suggested to be less harmful than cigarette smoking, but the research on the full extent of their harm reduction potential is still lacking. This study aimed to evaluate the influence of EC aerosol and cigarette smoke (CS) on cardiovascular, gastrointestinal, and renal functions in mice after prolonged exposure. Forty-eight C57BL/6J male mice were randomly grouped and then exposed to fresh air (control), mung bean-flavored EC aerosol with low and high dose (EC1L, 6 mg/kg; EC1H, 12 mg/kg), watermelon-flavored EC aerosol with low and high dose (EC2L, 6 mg/kg; EC2H, 12 mg/kg), and finally a cigarette smoke (CS, 6 mg/kg), respectively. After 10 weeks of exposure, the heart rate increased for both the EC and CS groups, and the effect of CS on blood oxygen saturation was significantly higher than that of the EC group (P < 0.01). Proteomic analysis of the heart tissue showed that the overlapped differential expression protein from the EC and CS exposures was Crip2. For the gastrointestinal system, oral mucosa was significantly damaged in CS group. Compare with CS, EC had significantly fewer negative effects on most of the indictors which focused on in this study.

Actively tunable rasorber with broadband RCS reduction and low infrared emissivity.

In this paper, an actively tunable rasorber with broadband RCS reduction and low infrared emissivity is proposed. The rasorber can achieve flexible control of the peak of the transmission frequency and make the platform invisible in multiple spectrum. Based on the combination of varactor diodes and bandpass frequency-selective surface (FSS), the transmission window can be continuously tuned from 1.8 to 4.5 GHz. The designed rasorber has more than 10 dB RCS reduction from 5.4 to 14.1 GHz. Furthermore, an infrared low emissivity layer based on ITO resistance film is added above the rasorber, and the average infrared emissivity of the measured surface is 0.33. The experimental and simulation results are in good agreement. This work is expected to be applied to frequency hopping secure communication and ultra-wideband, multi-spectrum stealth.

Modelling extreme risks for green bond and clean energy.

Value at Risk and Expected Shortfall are two traditional tools used to measure extreme risk in financial markets. However, there is little research on measuring extreme risk in emerging markets such as green bonds and clean energy. This paper uses both semi-parametric models with simultaneous excitation functions and traditional models to estimate extreme risk in SP500 Green Bond (GB) and Global Clean Energy (GCE), selecting Expected Shortfall (ES) and Value at Risk (VaR) as the indices of extreme risk. Then, the paper uses a breakpoint scan of the predictions of the different types of models. The results find that the green bond market was relatively stable while the global clean energy market experienced sharp fluctuations after the COVID-19 pandemic outbreak. Representative models in GCE have at least two breakpoints, but those for GB have no breakpoints. The GARCH model with normal innovations performs the best among all target models, and the GARCH-FZ model fits the best among all semi-parametric candidates. Our research could help governments, companies, and investors with risk management and improve model accuracy and mechanisms for measuring extreme risks.

Preventive effect of LCZ696 on hypoxic pulmonary hypertension in rats via regulating the PI3K/AKT signaling pathway.

Hypoxic pulmonary hypertension (HPH) is a devastating disease worldwide; however, effective therapeutic drugs are lacking. This study investigated the effects and underlying mechanisms of LCZ696 treatment on hypoxia-induced pulmonary hypertension. Male Sprague-Dawley (SD) rats were kept in a hypobaric chamber with an oxygen concentration of 5% for 4 weeks. Rats were treated with either LCZ696 (18 mg/kg, 36 mg/kg, and 72 mg/kg) or sildenafil. The mean pulmonary artery pressure (mPAP), right ventricle hypertrophy index (RVHI), and lung system index were measured. Hematoxylin-eosin (HE) staining, Masson staining, and immunofluorescence staining were used for histological analysis. Enzyme linked immunosorbent assay (ELISA) kits were used to determine the concentrations of inflammatory and hypoxia-related factors. Western blotting was used to examine the expression of apoptotic and PI3K/AKT signaling pathway proteins in rat lung tissue. Hypoxia increased mPAP, RVHI, and lung system index and induced pulmonary vascular remodeling, pulmonary arteriomyosis, and pulmonary artery fibrosis. LCZ696 treatment reduced the increase in mPAP, RVHI, and the lung system index and ameliorated the induced pathological changes. Hypoxia upregulated expression of NF-kB, TNF-α, IL-6, HIF-1α, and Vascular endothelial growth factor (VEGF), decreased the ratio of Bax/Bcl-2, and activated the PI3K/AKT signaling pathway in lung tissue, and these effects were partially reversed by treatment with LCZ696. These results demonstrated that LCZ696 can ameliorate hypoxia-induced HPH by suppressing apoptosis, inhibiting the inflammatory response, and inhibiting the PI3K/AKT signaling pathway. It provides a reference for clinical rational drug use and lays a foundation for the study of HPH therapeutic drugs.

Ectomycorrhizal fungi, two species of Laccaria, differentially block the migration and accumulation of cadmium and copper in Pinus densiflora.

The root tips of host plant species can establish ectomycorrhizae with their fungal partners, thereby altering the responses of the host plants to heavy metal (HM) toxicity. Here, two species of Laccaria, L. bicolor and L. japonica, were investigated in symbiosis with Pinus densiflora to study their potential for promotion of phytoremediation of HM-contaminated soils in pot experiments. The results showed that L. japonica had significantly higher dry biomass than L. bicolor in mycelia grown on modified Melin-Norkrans medium containing elevated levels of cadmium (Cd) or copper (Cu). Meanwhile, the accumulations of Cd or Cu in L. bicolor mycelia were much higher than that in L. japonica at the same level of Cd or Cu. Therefore, L. japonica displayed a stronger tolerance to HM toxicity than L. bicolor in situ. Compared with non-mycorrhizal P. densiflora seedlings, inoculation with two Laccaria species significantly increased the growth of P. densiflora seedlings in absence or presence of HM. The mantle of host roots blocked the uptake and migration of HM, which led to the decrease of Cd and Cu accumulation in the P. densiflora shoots and roots, except for the root Cd accumulation of L. bicolor-mycorrhizal plants when 25 mg kg-1 Cd exposure. Furthermore, HM distribution in mycelia showed Cd and Cu are mainly retained in the cell walls of mycelia. These results provide strong evidence that the two species of Laccaria in this system may have different strategies to assist host tree against HM toxicity.

Cigarettes smoking and e-cigarettes using among university students: a cross-section survey in Guangzhou, China, 2021.

BACKGROUND: There is an increase in the use of cigarettes and e-cigarettes worldwide, and the similar trends may be observed in young adults. Since 2014, e-cigarettes have become the most commonly used nicotine products among young adults (Sun et al., JAMA Netw Open 4:e2118788, 2021). With the increase in e-cigarette use and the decrease in use of cigarettes and other tobacco products, however, there is limited information about Chinese smokers, e-cigarettes users and trends in cigarettes and e-cigarettes use among university students. Therefore, our objective was to investigate the using status of cigarettes, e-cigarettes and smoking behavior among the students from 7 universities in Guangzhou, China. METHODS: Students at 7 different universities in Guangzhou were investigated online in 2021 through a cross-sectional survey. A total of 10,008 students were recruited and after screening, 9361 participants were adopted in our statistics. Descriptive analysis, Chi-square analysis, and multiple logistic regression analysis were used to explore the smoking status and influencing factors. RESULTS: The average age of the 9361 university students was 22.4 years (SD = 3.6). 58.3% of participants were male. 29.8% of the participants smoked or used e-cigarettes. Among the smokers and users of e-cigarettes, 16.7% were e-cigarettes only users, 35.0% were cigarettes only users, and 48.3% were dual users. Males were more likely to smoke or use e-cigarettes. Medical students, students from prestigious Chinese universities, and students with higher levels of education were less likely. Students with unhealthy lifestyles (e.g., drinking alcohol frequently, playing video games excessively, staying up late frequently) were more likely to smoke or use e-cigarettes. Emotion can have significant impacts on both cigarettes and e-cigarettes dual users when choosing cigarettes or e-cigarettes to use. More than half of dual users said they would choose cigarettes when they were depressed and e-cigarettes when they were happy. CONCLUSION: We identified factors influencing the use of cigarettes and e-cigarettes among university students in Guangzhou, China. Gender, education level background, specialization, lifestyle habits and emotion all influenced the use of cigarettes and e-cigarettes among university students in Guangzhou, China. Male, low education level, from non-prestigious Chinese universities or vocational schools, non-medical specialization, and presence of unhealthy lifestyles were influencing factors for the use of cigarettes and e-cigarettes among university students in Guangzhou and students with these factors were more likely to smoke or use e-cigarettes. Besides, emotions can influence dual users' choice of products. This study provides more information to better understand young people's preferences for cigarettes and e-cigarettes by elucidating the characteristics of cigarettes and e-cigarettes use, as well as related influencing factors, among university students in Guangzhou. Further research involving more variables connected to the use of cigarettes and e-cigarettes will be required in our future study.

Citric Acid and Poly-glutamic Acid Promote the Phytoextraction of Cadmium and Lead in Solanum nigrum L. Grown in Compound Cd-Pb Contaminated Soils.

Phytoextraction is an efficient strategy for remediating heavy metal-contaminated soil. Chelators can improve the bioavailability of heavy metals and increase phytoextraction efficiency. However, traditional chelators have gradually been replaced due to secondary pollution. In this study, a typical organic acid (citric acid, CA) and a novel biodegradable chelator (poly-glutamic acid, PGA), were investigated using pot experiments to compare the phytoextraction efficiency of Solanum nigrum L. (a Cd (hyper)accumulator) for cadmium (Cd) and lead (Pb) in contaminated soil. The results showed CA and PGA significantly improved plant growth, and total Cd and Pb amounts of S. nigrum, both CA and PGA significantly increased the shoot Cd and Pb concentrations. However, only PGA significantly increased the root Pb concentration. CA and PGA application promoted the bioavailability of Cd and Pb in rhizosphere soils and their translocations from roots to shoots in S. nigrum. Both CA and PGA increased the phytoextraction efficiency of Cd and Pb in S. nigrum plants, and the PGA for Cd and Pb phytoextraction was more effective than CA. Our findings demonstrate that the biodegradable chelator PGA has great potential for enhancing phytoextraction from compound Cd-Pb contaminated soils, suggesting that biodegradable chelator-assisted phytoextraction with (hyper)accumulator is strongly recommended in severely contaminated sites.

Tanshinone functions as a coenzyme that confers gain of function of NQO1 to suppress ferroptosis.

Ferroptosis is triggered by the breakdown of cellular iron-dependent redox homeostasis and the abnormal accumulation of lipid ROS. Cells have evolved defense mechanisms to prevent lipid ROS accumulation and ferroptosis. Using a library of more than 4,000 bioactive compounds, we show that tanshinone from Salvia miltiorrhiza (Danshen) has very potent inhibitory activity against ferroptosis. Mechanistically, we found that tanshinone functions as a coenzyme for NAD(P)H:quinone oxidoreductase 1 (NQO1), which detoxifies lipid peroxyl radicals and inhibits ferroptosis both in vitro and in vivo. Although NQO1 is recognized as an oxidative stress response gene, it does not appear to have a direct role in ferroptosis inhibition in the absence of tanshinone. Here, we demonstrate a gain of function of NQO1 induced by tanshinone, which is a novel mechanism for ferroptosis inhibition. Using mouse models of acute liver injury and ischemia/reperfusion heart injury, we observed that tanshinone displays protective effects in both the liver and the heart in a manner dependent on NQO1. Our results link the clinical use of tanshinone to its activity in ferroptosis inhibition.

Cytotoxicity and cell injuries of flavored electronic cigarette aerosol and mainstream cigarette smoke: A comprehensive in vitro evaluation.

INTRODUCTION: Although electronic cigarettes (e-cigarettes) have attracted much attention due to their claimed harm-reduction effects compared with conventional cigarettes, the adverse effects of e-cigarette aerosol exposure on human health are still unclear. In this work we compared the cytotoxic effects of combustion cigarettes with four commercially available flavored electronic cigarettes and their main components on ten cell lines. Cell injury mechanism of e-cigarette aerosol and combustible cigarette smoke was also explored using cellular models. METHODS: Eleven kinds of e-cigarettes aerosol condensates (ECSCs) and cigarette smoke constituent's condensates (CSC) were collected by Cambridge filter pad, and the nicotine contents were determined by UPLC to provide an equivalent nicotine dosage. The CCK-8 assay was used to measure the cell viability differences between ECSC and CSC. Based on RNA-seq results, we compared the effects of ECSC and CSC on various cell injury pathways. Oxidative stress and inflammatory responses were further tested by Western Blot, immunofluorescence, and qRT-PCR assays. RESULTS: CSC was found to be more cytotoxic than flavored ECSC and their main components, and BEAS-2B cell line was the most sensitive cells by comparing the IC50 value. With prolonged exposure duration and higher doses, ECSC began to exhibit cytotoxicity at and above 72 µg/mL. The IC50 values of ECSC were 15-fold higher than that of CSC. Transcriptome analyses indicated that cell injury-related processes were enriched after the treatment of CSC. CSC could significantly induce more oxidative stress and inflammatory signals than ECSC. CONCLUSION: ECSCs and their components induced significantly less cytotoxicity than CSC under the laboratory exposure conditions, and CSC caused much severe cell injuries. Our study adds to the body of scientific evidence for a more comprehensive safety evaluation of e-cigarette products as compared to cigarettes.

Beneficial effects of arbuscular mycorrhizae on Cu detoxification in Mimosa pudica L. grown in Cu-polluted soils.

Arbuscular mycorrhizal (AM) fungi are known to have beneficial effects on host plants growing on contaminated soils. The present study aimed at investigating the influence of two different AM fungi (Rhizophagus intraradices and Funneliformis mosseae) on the growth of plants and Cu uptake by Mimosa pudica L. grown in polluted soils containing various levels of Cu (Control, 400, 500, or 600 mg kg-l soil) in pot experiments. Mycorrhizal colonisation rates by the two AM fungi decreased markedly with the increasing Cu levels in soils. This inhibition was more pronounced to F. mosseae than R. intraradices, indicating that R. intraradices was more tolerant to Cu than F. mosseae. Compared with non-mycorrhizal plants, R. intraradices inoculation increased plant growth (including shoot height, numbers of compound leaves and leaflets, and dry biomass) and P concentrations in the shoots and roots of M. pudica at all levels of Cu. Meanwhile, F. mosseae displayed a capability of growth promotion to M. pudica much later and lower than R. intraradices. F. mosseae and R. intraradices markedly decreased Cu concentration in shoots at 400-600 mg kg-1 Cu levels. However, R. intraradices was more efficient than F. mosseae in decreasing the shoot Cu concentrations. As for the increasing Cu tolerance by R. intraradices, possibly it was reached though the improvement of phosphorus nutrition and the decline of Cu transport from roots to shoots of M. pudica. R. intraradices showed a good potential for improving medicinal plants growth and declining toxic effects in Cu-contaminated soils.

TET2 deficiency sensitizes tumor cells to statins by reducing HMGCS1 expression.

TET2 (ten-eleven-translocation) protein is a Fe(II)- and α-ketoglutarate-dependent dioxygenase that catalyzes DNA demethylation to regulate gene expression. While TET2 gene is frequently mutated in hematological cancer, its enzymatic activity is also compromised in various solid tumors. Whether TET2 deficiency creates vulnerability for cancer cells has not been studied. Here we reported that TET2 deficiency is associated with the change of lipid metabolism processes in acute myeloid leukemia (AML) patient. We demonstrate that statins, the inhibitors of ß-Hydroxy ß-methylglutaryl-CoA (HMG-CoA) reductase and commonly used cholesterol-lowering medicines, significantly sensitize TET2 deficient tumor cells to apoptosis. TET2 directly regulates the expression of HMG-CoA synthase (HMGCS1) by catalyzing demethylation on its promoter region, and conversely TET2 deficiency leads to significant down-regulation of HMGCS1 expression and the mevalonate pathway. Consistently, overexpression of HMGCS1 in TET2-deficient cells rescues statin-induced apoptosis. We further reveal that decrease of geranylgeranyl diphosphate (GGPP), an intermediate metabolite in the mevalonate pathway, is responsible for statin-induced apoptosis. GGPP shortage abolishes normal membrane localization and function of multiple small GTPases, leading to cell dysfunction. Collectively, our study reveals a vulnerability in TET2 deficient tumor and a potential therapeutic strategy using an already approved safe medicine.

Combined biological effects and lung proteomics analysis in mice reveal different toxic impacts of electronic cigarette aerosol and combustible cigarette smoke on the respiratory system.

Combustible cigarettes produce many toxic substances that have been linked to diseases, such as lung cancer and chronic obstructive pulmonary disease. For those smokers unable or unwilling to quit, electronic cigarettes (e-cigarettes) could be used as an alternative to cigarettes. However, the effects and mechanisms of e-cigarette aerosol (ECA) on respiratory function have not been fully elucidated, and in vivo studies of its safety are limited compared to cigarette smoke (CS). In this article, we chose nicotine levels as dosing references and C57BL/6 mice for a 10-week subchronic inhalation toxicity study. A comprehensive set of toxicological endpoints was used to study the effect of exposure. Both CS (6 mg/kg) and ECA (6 or 12 mg/kg) inhalation had decreased the animal's lung function and increased levels of inflammation markers, along with pathological changes in the airways and lungs, with ECA displaying a relatively small effect at the same dose. Proteomic analysis of lung tissue showed greater overall protein changes by CS than that of ECA, with more severe inflammatory network perturbations. Compared with ECA, KEGG analysis of CS revealed upregulation of more inflammatory and virus-related pathways. Protein-protein interactions (PPI) showed that both ECA and CS significantly changed ribosome and complement system-related proteins in mouse lung tissue. The results support that e-cigarette aerosol is less harmful to the respiratory system than cigarette smoke at the same dose using this animal model, thus providing additional evidence for the relative safety of e-cigarettes.