US of thyroid nodules: can AI-assisted diagnostic system compete with fine needle aspiration?

OBJECTIVES: Artificial intelligence (AI) systems can diagnose thyroid nodules with similar or better performance than radiologists. Little is known about how this performance compares with that achieved through fine needle aspiration (FNA). This study aims to compare the diagnostic yields of FNA cytopathology alone and combined with BRAFV600E mutation analysis and an AI diagnostic system. METHODS: The ultrasound images of 637 thyroid nodules were collected in three hospitals. The diagnostic efficacies of an AI diagnostic system, FNA-based cytopathology, and BRAFV600E mutation analysis were evaluated in terms of sensitivity, specificity, accuracy, and the κ coefficient with respect to the gold standard, defined by postsurgical pathology and consistent benign outcomes from two combined FNA and mutation analysis examinations performed with a half-year interval. RESULTS: The malignancy threshold for the AI system was selected according to the Youden index from a retrospective cohort of 346 nodules and then applied to a prospective cohort of 291 nodules. The combination of FNA cytopathology according to the Bethesda criteria and BRAFV600E mutation analysis showed no significant difference from the AI system in terms of accuracy for either cohort in our multicenter study. In addition, for 45 included indeterminate Bethesda category III and IV nodules, the accuracy, sensitivity, and specificity of the AI system were 84.44%, 95.45%, and 73.91%, respectively. CONCLUSIONS: The AI diagnostic system showed similar diagnostic performance to FNA cytopathology combined with BRAFV600E mutation analysis. Given its advantages in terms of operability, time efficiency, non-invasiveness, and the wide availability of ultrasonography, it provides a new alternative for thyroid nodule diagnosis. CLINICAL RELEVANCE STATEMENT: Thyroid ultrasonic artificial intelligence shows statistically equivalent performance for thyroid nodule diagnosis to FNA cytopathology combined with BRAFV600E mutation analysis. It can be widely applied in hospitals and clinics to assist radiologists in thyroid nodule screening and is expected to reduce the need for relatively invasive FNA biopsies. KEY POINTS: • In a retrospective cohort of 346 nodules, the evaluated artificial intelligence (AI) system did not significantly differ from fine needle aspiration (FNA) cytopathology alone and combined with gene mutation analysis in accuracy. • In a prospective multicenter cohort of 291 nodules, the accuracy of the AI diagnostic system was not significantly different from that of FNA cytopathology either alone or combined with gene mutation analysis. • For 45 indeterminate Bethesda category III and IV nodules, the AI system did not perform significantly differently from BRAFV600E mutation analysis.

Knockdown of fat mass and obesity alleviates the ferroptosis in Parkinson's disease through m6A-NRF2-dependent manner.

Emerging evidence has suggested that N6 -methyladenosine (m6 A) regulates the pathology of Parkinson's disease (PD). Nevertheless, the function of demethylase fat mass and obesity (FTO) associated pathogenesis is still not fully elucidated. Here, this research findings revealed that m6 A-modification was decreased in PD models, meanwhile, the FTO level upregulated in the PD models. Functionally, in N-methyl-4-phenylpyridinium (MPP+) treated SH-SY5Y cells, the ferroptosis significantly upregulated and FTO silencing mitigated the ferroptosis phenotype. Moreover, in silico assays indicated that nuclear factor erythroid 2-related factor-2 (NRF2) acted as the target of FTO, and FTO demethylated the m6 A modification from NRF2 mRNA. Furthermore, FTO impaired the NRF2 mRNA stability via m6 A-dependent pathway. Thus, our findings illustrated an important role of FTO on PD through m6 A-NRF2-ferroptosis manner. Taken together, the study revealed the potential function of FTO on PD nervous system diseases.

UHRF1 plays an oncogenic role in small cell lung cancer.

Small cell lung cancer (SCLC) is a malignant tumor characterized by aggressiveness and dismal prognosis. The specific role of ubiquitin-like PHD and RING finger domain (UHRF1), a frequently overexpressed cancer-promoting gene in various tumors, is poorly understood in SCLC. Herein, we explored the potential carcinogenic role of UHRF1 in SCLC. First, public databases were used to analyze the expression of UHRF1 in SCLC, and tissue specimens in our center were examined to confirm the results while clinical outcomes were collected to analyze its relationship with UHRF1. Then, UHRF1 knockdown and overexpression cell lines were established to evaluate the carcinogenic function of UHRF1 in vitro and in vivo. The mechanism of the biological consequences was determined by co-inmunoprecipitation. Moreover, we also analyzed the influence of UHRF1 on cisplatin (DDP) sensitivity of SCLC. The expression of UHRF1 was significantly higher in SCLC tissues than in normal tissues, and high levels of UHRF1 suggested a poor prognosis for SCLC. Mechanistically, UHRF1 promoted SCLC growth through yes-associated protein 1 (YAP1). Specifically, UHRF1 bound to YAP1 and inhibited YAP1 ubiquitin degradation, thus stabilizing the YAP1 protein in SCLC cells. UHRF1 downregulation enhanced DDP sensitivity in SCLC cells and was correlated with a favorable prognosis in patients with SCLC treated with platinum-based chemotherapy. UHRF1 plays an oncogenic role in SCLC by modulating YAP1. Therefore, UHRF1 could be used as a biomarker to predict the prognosis of SCLC patients and serve as a potential therapeutic target for SCLC patients.

Exploring the correlation of metabolites changes and microbial succession in solid-state fermentation of Sichuan Sun-dried vinegar.

BACKGROUND: The traditional Sichuan Sun-dried vinegar (SSV) with unique flavor and taste is believed to be generated by the solid-state fermentation craft. However, how microorganisms and their metabolites change along with fermentation has not yet been explored. RESULTS: In this study, our results demonstrated that the middle and late stages of SSV fermentation were the periods showing the largest accumulation of organic acids and amino acids. Furthermore, in the bacterial community, the highest average relative abundance was Lactobacillus (ranging from 37.55 to 92.50%) in all fermentation stages, while Acetobacters ranked second position (ranging from 20.15 to 0.55%). The number of culturable lactic acid bacteria is also increased during fermentation process (ranging from 3.93 to 8.31 CFU/g). In fungal community, Alternaria (29.42%), Issatchenkia (37.56%) and Zygosaccharomyces (69.24%) were most abundant in different fermentation stages, respectively. Interestingly, Zygosaccharomyces, Schwanniomyces and Issatchenkia were first noticed as the dominant yeast genera in vinegar fermentation process. Additionally, spearman correlation coefficients exhibited that Lactobacillus, Zygosaccharomyces and Schwanniomyces were significant correlation with most metabolites during the fermentation, implying that these microorganisms might make a significant contribution to the flavor formation of SSV. CONCLUSION: The unique flavor of SSV is mainly produced by the core microorganisms (Lactobacillus, Zygosaccharomyces and Schwanniomyces) during fermentation. This study will provide detailed information related to the structure of microorganism and correlation between changes in metabolites and microbial succession in SSV. And it will be very helpful for proposing a potential approach to monitor the traditional fermentation process.

ncRNAs-mediated overexpression of STIL predict unfavorable prognosis and correlated with the efficacy of immunotherapy of hepatocellular carcinoma.

BACKGROUND: STIL centriolar assembly protein (STIL) is a cytoplasmic protein implicated in cellular growth and proliferation as well as chromosomal stability, which abnormal condition affected tumor immunity and tumor progression. However, the role of STIL in the biological mechanism of hepatocellular carcinoma (HCC) remains unclear. METHODS: Comprehensive bioinformatic approaches, in vitro functional assays, and validation were conducted to elucidate the oncogenic value of STIL in HCC. RESULTS: In the present study, we found that STIL may serve as an independent prognostic indicator and a potential oncogene in HCC. Gene set enrichment analysis (GSEA), and Gene set variation analysis (GSVA) showed that upregulated expression of STIL was positively associated with pathways enriched in the cell cycle and DNA damage response. Subsequently, we identified several non-coding RNAs (ncRNAs) accounting for the upregulation of STIL expression using a combination of in silico bioinformatics approaches (including expression analysis, correlation analysis, and survival analysis). Finally, CCNT2-AS1/SNHG1-has-miR-204-5p-STIL axis was screened out as the most potential upstream ncRNA-related pathway of STIL in HCC. Moreover, STIL expression is highly associated with the infiltration of immune cells, the expression of immune checkpoints, as well as the survival benefit of immunotherapy/chemotherapy. CONCLUSIONS: Our study discloses that ncRNAs-mediated overexpression of STIL independently predicted poor prognosis and correlated with the efficacy of PD-1-targeted immunotherapy in HCC.

Unveiling interactions of norfloxacin with microplastic in surface water by 2D FTIR correlation spectroscopy and X-ray photoelectron spectroscopy analyses.

Microplastics (MPs) has shown adsorption of hydrophilic organic matters (HOMs) in aqueous environments. However, it is still difficult to predict the adsorption behaviors of HOMs by different MPs, especially in authentic water systems. In this study, the adsorption behaviors and mechanisms of norfloxacin (NOR) onto polyamide (PA) MPs were investigated in both simulated and real surface water. The results showed that the adsorption equilibrium of NOR by PA in simulated surface water could be achieved within 15 h, while the adsorption rate of NOR in real surface was slowed down, with the equilibrium time of 25 h. Pseudo-second-order model could well describe the adsorption kinetics data. The experimental maximum adsorption capacity of NOR on PA in real surface water (e. g. 132.54 ug/g) was dramatically reduced by 37.5 % compared with that in simulated surface water (e. g. 212.25 ug/g), and the adsorption isotherm would obey Freundlich model. Besides, the leaching of NOR from the surface of PA could occur obviously at acidic environment. Furthermore, the salinity and natural organic matter exhibited significantly adverse effects on the NOR adsorption. Finally, the results of 2D Fourier transform infrared correlation spectroscopy and X-ray photoelectron spectroscopy indicated that the electrostatic, H-bond and van der Waals interactions were involved in the adsorption. More importantly, the sequential functional groups in the adsorption process followed the orders: 1638 (CO) > 1542 amide II (-NH-CO) > 717 (CH2) > 1445 (CO) > 973 amide IV (CONH). This study could provide an insight into the interactions between PA and NOR in different water environments.

Soil potentially toxic element pollution at different urbanization intensities: Quantitative source apportionment and source-oriented health risk assessment.

Potentially toxic element (PTE) pollution of urban soils has become the focus of social concern, but the differences of the sources, pollution levels and source-oriented human health risks (HHR) of PTE in urban soils among different urban intensity areas is rarely known. This study explored a comprehensive scheme that combined positive matrix factorization model and source-oriented assessment to quantitatively assess the priority pollution sources and HHR in urban soils from areas with different urbanization intensities. All the average values for PTE concentrations, except for Cr, were higher than their corresponding background values. The contributions made by the four sources (atmospheric deposition, agricultural activities, traffic activities, and natural sources) were relatively similar (22.29-29.89%) in the low urbanization intensity (LUI) area, whereas traffic activities and atmospheric deposition made the greatest contributions in the medium urbanization intensity (MUI) (29.12%) and the high urbanization intensity (HUI) (38.97%) areas, respectively. The geo-accumulation index results revealed that Cd was the most polluting element and the HUI area had the highest pollution levels. The content-oriented assessment of HHR demonstrated that the non-carcinogenic risks were acceptable, but the carcinogenic risks were unacceptable. According to the source-oriented HHR assessment, among the anthropogenic activities, atmospheric deposition contributed the most to carcinogenic risk of children in all areas, and atmospheric deposition, traffic activities and agricultural activities contributed the most to the carcinogenic risk of adults in HUI, MUI and LUI, respectively. This suggest that control measures need to be tailored to the appropriate urbanization intensity to effectively curb PTE pollution caused by anthropogenic activities.

Green remediation of Ni, Zn, and Cu in an electroplating contaminated site by wood vinegar with optimization and risk assessment.

Wood vinegar (WV) is a renewable organic compound, possessing characteristics such as high oxygenated compound content and low negative impact on soil. Based on its weak acid properties and complexing ability to potentially toxic elements (PTEs), WV was used to leach Ni, Zn, and Cu contaminated soil in electroplating sites. In addition, the response surface methodology (RSM) based on the Box-Behnken design (BBD) was established to clarify the interaction between each single factor, and finally completed the risk assessment of the soil. The amounts of PTEs leached from the soil climbed with the increase of WV concentration, liquid-solid ratio, and leaching time, while they surged with the decrease of pH. Under optimal leaching circumstances (the concentration of WV= 100 %; washing time= 919 min; pH= 1.00), the removal rates of Ni, Zn, and Cu could reach 91.7 %, 57.8 %, and 65.0 %, respectively, and the WV-extracted PTEs were mainly from the Fe-Mn oxides fraction. After leaching, the Nemerow integrated pollution index (NIPI) decreased from an initial value of 7.08 (indicating severe pollution) to 0.450 (indicating no pollution). The potential ecological risk index (RI) dropped from 274 (medium level) to 39.1 (low level). Additionally, the potential carcinogenic risk (CR) values reduced by 93.9 % for both adults and children. The results revealed that the washing process significantly reduced the pollution level, potential ecological risk, and health risk. Coupled with FTIR and SEM-EDS analysis, the mechanism of WV removal of PTEs could be explained from three aspects: acid activation, H+ ion exchange, and functional group complexation. In summary, WV is an eco-friendly and high-efficiency leaching material for the remediation of PTEs polluted sites, which will maintain soil function and protect human health.

Enhanced silicate remediation in cadmium-contaminated alkaline soil: Amorphous structure improves adsorption performance.

Silicates have been used as soil heavy metal passivators, but low remediation efficiency limited their development. In order to solve this problem, in this paper, an economical and environmentally friendly amorphous iron silicate was prepared by a simple co-precipitation method. It could be proved from the passivation experiments that the remediation efficiency of amorphous iron silicate (AIS) on Cd-contaminated soil was better than that of natural silicates (montmorillonite and diatomite), which reflected the superiority of amorphous materials. Plant experiments showed that AIS could effectively inhibit the absorption and accumulation of Cd2+ in the edible parts of garlic. In addition, it may effectively reduce the potential ecological risk assessment of soil, and its immobilization mechanism of Cd2+ includes electrostatic adsorption, co-precipitation, ion exchange, and complexation of surface functional groups. This study demonstrates the advantages of amorphous iron silicate as a new functional material in the remediation of Cd-contaminated soil and provides a reference for the development and application of environment-friendly passivators.

Rape Straw Supported FeS Nanoparticles with Encapsulated Structure as Peroxymonosulfate and Hydrogen Peroxide Activators for Enhanced Oxytetracycline Degradation.

Iron-based catalysts with high load content of iron sulfide (FeS) were commonly peroxymonosulfate (PMS) and hydrogen peroxide (H2O2) activators to degrade organic pollutants but limited catalytic efficiency and increased risk of ferrous ion leaching restricted their use. Meanwhile, various biomass materials such as straw, peel, and branch have been extensively prepared into biochar for mechanical support for iron-based catalysts; however, the preparation process of biochar was energy-intensive. In this study, FeS nanoparticles modified rape straw composites (RS-FeS) encapsulated with ethylenediaminetetraacetic acid (RS-EDTA-FeS) were successfully presented by in-situ synthesis method for efficiently activating PMS and H2O2 to degrade oxytetracycline (OTC), which was economical and environmentally friendly. The results showed that the modified rape straw can remove OTC efficiently, and the addition of EDTA also significantly enhanced the stability and the reusability of the catalyst. In addition, EDTA also promoted the activation of H2O2 at neutral pH. The OTC degradation efficiency of the two catalysts by PMS was faster than that of H2O2, but H2O2 had a stronger ability to remove OTC than PMS. The highest OTC removal efficiency of RS-FeS and RS-EDTA-FeS were 87.51 and 81.15%. O2•- and 1O2 were the major reactive oxidative species (ROS) in the PMS system. Furthermore, compared with RS-FeS, the addition of EDTA inhabited the generation of O2•- in the PMS system. Instead, O2•- and •OH were the major ROS in the H2O2 system, but 1O2 was also identified in RS-FeS/H2O2 system. RS-EDTA-FeS showed a trend of rising first and then decreasing in recycle test. Instead, the removal rate of OTC by RS-FeS decreased significantly with the increase in reuse times. In the actual wastewater test, the TOC removal of two catalysts active by H2O2 was better than PMS, which was consistent with the test results of OTC, indicating that the two catalysts have application value in the removal of organic pollutants in actual wastewater. This study directly used plant materials as catalysts and omits the preparation process of biochar, greatly reduces the preparation cost and secondary pollution of catalysts, and provides theoretical support for the deepening of advanced oxidation technology.

Response of microbiomes with different abundances to removal of metal fractions by soil washing.

Toxic metal contamination causes a great threat to soil ecosystem and human health. Soil washing is a fast practice for removing metals, but its influences on microbial diversity and the stability of soil ecosystem remain unknown. In this study, ethylenediaminetetraacetic acid (EDTA), citric acid (CA), and fermented pineapple peel residue (FPP) were used as representatives of chelates, low molecular organic acids and biological materials to wash Pb-polluted soils, and their impacts on microbial community were investigated. Washing with these agents effectively removed Pb, but altered microbial community structure. After washing with EDTA, CA, and FPP, 3-8 bacterial phyla and 1 fungal phylum greatly increased, while 7-20 bacterial and 0-6 fungal phyla severely decreased or even disappeared. The alterations of different microbiomes were closely related to soil metal fractions. The labile metal fraction had negative effects on most bacteria and fungi, but also showed positive influences on Actinobacteria, Patescibacteria, and Fusobacteria. The moderately stable and stable fractions were nontoxic to the most microbes, but still harmful to Patescibacteria and Deinococcus-Thermus. These findings provide new insights for the effects of soil washing remediation and toxicity of metal fractions on the microbiomes with different abundance.

Nitrogen addition may promote soil organic carbon storage and CO2 emission but reduce dissolved organic carbon in Zoige peatland.

With the increase of nitrogen (N) deposition, N input can affect soil C cycling since microbes may trigger a series of activities to balance the supply and demand of nutrients. However, as one of the largest C sinks on earth, the role of extra N addition in affecting peatland soil C and its potential mechanism remains unclear and debated. Therefore, this study chose the largest peatland in China (i.e., Zoige, mostly N-limited) to systematically explore the potential changes of soil C, microbes, and ecoenzymes caused by extra N input at the lab scale incubation. Three different types of soils were collected and incubated with different levels of NH4NO3 solution for 45 days. After incubation, N input generally increased soil organic C (SOC) but decreased dissolved organic carbon (DOC) in Zoige peatland soils. Moreover, CO2 and CH4 emissions were significantly increased after high N input (equal to 5 mg NH4NO3 g-1 dry soils). Through a series of analyses, it was observed that microbial communities and ecoenzyme activities mainly influenced the changes of different C components. Collectively, this study implied that the increasing N deposition might help C sequestration in N-limited peatland soils; simultaneously, the risk of increased CO2 and CH4 by N input in global warming should not be ignored.

Downregulation of breast cancer resistance protein by long-term fractionated radiotherapy sensitizes lung adenocarcinoma to SN-38.

Chemotherapy is usually the subsequent treatment for non-small cell lung cancer patients with acquired radioresistance after long-term fractionated radiotherapy. However, few studies have focused on the selection of chemotherapeutic drugs to treat lung adenocarcinoma patients with radioresistance. Our study compared the sensitivity changes of lung adenocarcinoma cells to conventional chemotherapeutic drugs under radioresistant circumstances by using three lung adenocarcinoma cell models, which were irradiated with fractionated X-rays at a total dose of 60 Gy. The results showed that the toxicities of paclitaxel, docetaxel and SN-38 were increased in radioresistant cells. The IC50 values of docetaxel and SN-38 decreased 0 ~ 3 times and 3 ~ 36 times in radioresistant cells, respectively. Notably, the A549 radioresistant cells were approximately 36 times more sensitive to SN-38 than the parental cells. Further results revealed that the downregulation of the efflux transporter BCRP by long-term fractionated irradiation was an important factor contributing to the increased cytotoxicity of SN-38. In addition, the reported miRNAs and transcriptional factors that regulate BCRP did not participate in the downregulation. In conclusion, these results presented important data on the sensitivity changes of lung adenocarcinoma cells to chemotherapeutic drugs after acquiring radioresistance and suggested that irinotecan (the prodrug of SN-38) might be a promising drug candidate for lung adenocarcinoma patients with acquired radioresistance.

Determination of intracellular anlotinib, osimertinib, afatinib and gefitinib accumulations in human brain microvascular endothelial cells by liquid chromatography/tandem mass spectrometry.

RATIONALE: Brain metastases are a common complication in patients with non-small-cell lung cancer (NSCLC). Anlotinib hydrochloride is a novel multi-target tyrosine kinase inhibitor (TKI) exhibiting a superior overall response rate for brain metastases from NSCLC. The penetrability of anlotinib and three generations of epidermal growth factor receptor (EGFR) TKIs (osimertinib, afatinib and gefitinib) into brain microvascular endothelial cells (HBMECs) was compared. METHODS: A sensitive quantification method for the four TKIs was developed using liquid chromatography coupled to tandem mass spectrometry (LC/MS/MS). Anlotinib and the three EGFR TKIs were separated on an ACQUITY BEH C18 column after a direct protein precipitation, and then analyzed using electrospray ionization in positive ion mode. The linearity, accuracy, precision, limit of quantification, specificity and stability were assessed. RESULTS: The four analytes could be efficiently quantified in a single run of 3.8 min. The validation parameters of all analytes satisfy the acceptance criteria of bioanalytical method guidelines. The calibration range was 0.2-200 ng mL-1 for anlotinib and gefitinib, 1-500 ng mL-1 for osimertinib and 1-200 ng mL-1 for afatinib. The penetration of anlotinib across HBMECs was comparable with that of afatinib and gefitinib but less than that of osimertinib. CONCLUSIONS: A sensitive LC/MS/MS method to simultaneously measure anlotinib, osimertinib, afatinib and gefitinib in cell extracts was successfully validated and applied to determine their uptake inside HBMECs, which could pave the way for future research on the role of anlotinib in NSCLC brain metastases.

Inhibition of histamine receptor H3 suppresses the growth and metastasis of human non-small cell lung cancer cells via inhibiting PI3K/Akt/mTOR and MEK/ERK signaling pathways and blocking EMT.

Recent evidence shows that the expression levels of histamine receptor H3 (Hrh3) are upregulated in several types of cancer. However, the role of Hrh3 in non-small cell lung cancer (NSCLC) has not been elucidated. In the present study, we showed that the expression levels of Hrh3 were significantly increased in NSCLC samples, and high levels of Hrh3 were associated with poor overall survival (OS) in NSCLC patients. In five human NSCLC cell lines tested, Hrh3 was significantly upregulated. In NSCLC cell lines H1975, H460, and A549, Hrh3 antagonist ciproxifan (CPX, 10-80 µM) exerted moderate and concentration-dependent inhibition on the cell growth and induced apoptosis, whereas its agonist RAMH (80 µM) reversed these effects. Furthermore, inhibition of Hrh3 by CPX or siRNA retarded the migration and invasion of NSCLC cells through inhibiting epithelial-mesenchymal transition (EMT) progression via reducing the phosphorylation of PI3K/Akt/mTOR and MEK/ERK signaling pathways. In nude mice bearing H1975 cell xenograft or A549 cell xenograft, administration of CPX (3 mg/kg every other day, intraperitoneal) significantly inhibited the tumor growth with increased E-cadherin and ZO-1 expression and decreased Fibronectin expression in tumor tissue. In conclusion, this study reveals that Hrh3 plays an important role in the growth and metastasis of NSCLC; it might be a potential therapeutic target against the lung cancer.

Highly efficient removal of phosphorus from agricultural runoff by a new akadama clay barrier-vegetated drainage ditch system (VDD) and its mechanism.

A vegetated drainage ditch (VDD) system is an effective management practice for removing excess phosphorus (P) from agricultural runoff. However, the maximization of P removing efficiency by VDD remains a challenge. In this study, new VDDs with akadama clay barriers (particle size of clay: 1-6 mm; height of barrier: 5-15 cm and length of barrier: 10-90 cm) were designed in lab scale, and the mechanism of phosphate removal by akadama clay was investigated. It was found that a new VDD with akadama clay barriers (particle size:1 mm; height:10 cm and length: 90 cm) exhibited the highest removal efficiency of total P (TP) (97.1%), particulate P(PP) (96.9%), and dissolved P (DP) (97.4%), respectively. The retained P was mainly adsorbed in akadama clay barrier sections, and a low concentration of P was observed in soil sections in the new VDD. The maximum adsorption capacity of phosphate to akadama clay was 5.06 mg/g at 298 K, and XPS analysis indicated that phosphate was adsorbed by the inner-sphere complexation formation with the metal elements (Al, Fe). This study indicates that the new VDD with akadama clay barriers is a promising technique to efficiently remove P from agricultural runoff and significantly minimize the risk of P release into streams through runoff.

Chalcomoracin inhibits cell proliferation and increases sensitivity to radiotherapy in human non-small cell lung cancer cells via inducing endoplasmic reticulum stress-mediated paraptosis.

Chalcomoracin (CMR) is a kind of Diels-Alder adduct extracted from the mulberry leaves. Recent studies showed that CMR has a broad spectrum of anticancer activities and induces paraptosis in breast cancer and prostate cancer cells. In this study, we investigated the effects of CMR against human non-small cell lung cancer cells and the underlying mechanisms. We found that CMR dose-dependently inhibited the proliferation of human lung cancer H460, A549 and PC-9 cells. Furthermore, exposure to low and median doses of CMR induced paraptosis but not apoptosis, which was presented as the formation of extensive cytoplasmic vacuolation with increased expression of endoplasmic reticulum stress markers, Bip and Chop, as well as activation of MAPK pathway in the lung cancer cells. Knockdown of Bip with siRNA not only reduced the cell-killing effect of CMR, but also decreased the percentage of cytoplasmic vacuoles in H460 cells. Moreover, CMR also increased the sensitivity of lung cancer cells to radiotherapy through enhanced endoplasmic reticulum stress. In lung cancer H460 cell xenograft nude mice, combined treatment of CMR and radiation caused greatly enhanced tumor growth inhibition with upregulation of endoplasmic reticulum stress proteins and activation of pErk in xenograft tumor tissue. These data demonstrate that the anticancer activity and radiosensitization effect of CMR result from inducing paraptosis, suggesting that CMR could be considered as a potential anticancer agent and radiation sensitizer in the future cancer therapeutics.

Remediation of heavy metal contaminated soil by biodegradable chelator-induced washing: Efficiencies and mechanisms.

Biodegradable chelators (BCs) are promising substitutes for conventional washing agents in the remediation of heavy metal contaminated soil with strong complexing ability and less cost. However, great challenges for the applications of BC-assisted washing still exist, such as the assessment of the factor affecting the efficiency of metal removal and the unclear of the metal removal mechanism. Batch washing was therefore explored to evaluate the potential for four BCs for removing Cd, Pb, and Zn from polluted soils. The soil spectroscopic characteristics before and after washing were also investigated. The results demonstrated that iminodisuccinic acid (ISA) and glutamate-N, N-diacetic acid (GLDA) were an appealing alternative to commonly used non-biodegradable ethylenediaminetetraacetic acid, but glucomonocarbonic acid (GCA) and polyaspartic acid (PASP) were less efficient. Optimal parameters of BCs were determined to be a concentration of 50 mmol L-1, a pH of 5.0, a contact time of 120 min, and a solid/liquid ratio of 1:5, considering metal removal efficiencies and the suitable cost. A single removal washing could be up to 52.39% of Cd, 71.79% of Pb, and 34.13% of Zn from mine soil, and 98.28% of Cd, 91.10% of Pb, and 90.91% of Zn from polluted farmland soil. After washing, the intensity of heavy metal binding to soil colloids increased while the metal mobility reduced because of weakly bound fractions removed by BCs. The BCs-induced soil washing revealed that the possible mechanisms of metal removal included the acid dissolution, ion exchange, and surface complexation. Our findings highlight the potential application of especially ISA and GLDA as efficient washing agents to remove potentially toxic elements from contaminated soils.

Removal of lead, zinc and cadmium from contaminated soils with two plant extracts: Mechanism and potential risks.

Screening appropriate washing agents to remediate soils contaminated with heavy metals is crucial for decreasing metal hazards posing to environment and human health. In this study, two plant washing agents-water-extracted from Fagopyrum esculentum and Fordiophyton faberi, were applied to remove soil Pb, Zn, and Cd by washing. Results indicated that metal removals augmented with increase of washing solution concentrations, decreased with increasing pH values of the solution and followed the pseudo-second-order model depending on contact duration. At concentration of 50 g/L, pH 3 and contact duration of 120 min, F. esculentum had higher removals of Pb (5.98-6.83%), Zn (21.82-27.94%), and Cd (39.90-40.74%) than those of F. faberi. And metal ions could be removed by binding with carboxyl, hydroxyl, amide, amine and aromatic groups in washing solutions. The potential risks of residual metals declined by 51.35-52.12% for mine soil and 48.51-49.96% for farmland soil with exchangeable and carbonate-bound fractions obviously extracted after a single washing (P < 0.05). And soil organic carbon and nutrients increased to some extent except for total phosphorus and available potassium. Moreover, soil phytotoxicity lowered except that some adverse effects on seed germination existed. Therefore, the water extract from F. esculentum is a promising washing agent for heavy metal removal.

Emission of CO2 and CH4 from a multi-ditches system in rice cultivation region: Flux, temporal-spatial variation and effect factors.

Man-made multi-level ditches system is designed to irrigate, drain and collect runoff from surrounding fields. It is not only the conduit of water and field carbon, but also the linear-like wetland with complex carbon cycling. However, the contribution of ditches system to CO2 and CH4 emission has rarely been assessed. To understand the emission pattern of CO2 and CH4 from ditches, this study investigated the emission fluxes of CO2 and CH4 in a three-level ditches system in Chengdu Plain, China. The results showed that the emission of CO2 and CH4 ranged from 70.38 to 950.40 mg C m-2 h-1 and 6.51-74.99 mg C m-2 h-1, respectively, and was higher in spring and summer than other seasons in all ditches (P < 0.05). On the other hand, the emission of CO2 and CH4 increased along with the decreasing ditches size. Besides, it is found that the precipitation, water table depth and water DO concentration might contribute to the emission of CO2, while CH4 was possibly influenced by precipitation, water table depth, temperature, water DO and DOC concentration. Moreover, it is suggested that terrestrial external input and in-situ metabolism might be the main sources of C emission, and in-situ source might largely contribute to CH4 emission. To reduce the C emission, it is necessary to improve fertilization and irrigation methods, limit soil pollutants transferring into ditches, and frequently dredge sediments in future.