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The unintended formation of disinfection byproducts (DBPs) may compromise the safety of drinking water. Since no specified DBPs have been found to be responsible for the overall adverse effects and over half of total organic halogen (TOX) remains unidentified, DBP mixture toxicity is gaining increasing interest as a potential indicator of how risky drinking water might be. In this study, a new approach to evaluating the toxicity of drinking water DBP mixtures was developed by combining freeze-drying or rotoevaporation pretreatment with an in vivo high-salinity-tolerance bioassay with the embryos of a marine polychaete Platynereis dumerilii. The DBP recoveries by freeze-drying or rotoevaporation were compared with those by commonly applied liquid-liquid-extraction (LLE). For drinking water subjected to typical disinfection processes (i.e., chlorination, chloramination, chlorine dioxide treatment, and ozonation with or without postchlorination), LLE led to the lowest TOX recovery (11-18%) and the loss of all inorganic DBPs, while freeze-drying and rotoevaporation recovered 28-58% and 35-61% of TOX, respectively, and effectively recovered 81-99% and 85-104% of inorganic DBPs, respectively. Thus, LLE caused an underestimation of the toxicity of DBP mixtures compared with freeze-drying and rotoevaporation. Besides, the comparative toxicity varied significantly for water samples pretreated with different methods due to the effect of inorganic DBPs and a synergistic effect of organic and inorganic DBPs. The new approach revealed that the bromide-rich source water disinfected with ozone caused the highest developmental toxicity, followed by those disinfected with chlorine, chlorine dioxide, and chloramine in that order.

Jianping Xu, Xiaoyan Liu, Sheng Yang, Xiangru Zhang, Yuankai Shi Department of Medical Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Beijing, People’s Republic of China Background: Treatment failure frequently occurs in patients with epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) who respond to EGFR tyrosine kinase inhibitors initially. This retrospective study tried to investigate the efficacy and safety of apatinib plus icotinib in patients with advanced NSCLC after icotinib treatment failure.Patients and methods: This study comprised 27 patients with advanced NSCLC who had progressed after icotinib monotherapy. Initially, patients received oral icotinib (125mg, tid) alone. When the disease progressed, they received icotinib plus apatinib (500mg, qd, orally). Treatment was continued until disease progression, unacceptable toxicity or consent withdrawal.Results: Followed up to December 2016, the median time of combined therapy was 7.47months, and eight of 27 patients were dead. The median overall survival was not reached, and median progression-free survival (PFS) was 5.33months (95% CI, 3.63–7.03months). Moreover, the objective response rate (ORR) was 11.1%, and the disease control rate (DCR) was 81.5%. A total of 14 patients received combined therapy as the second-line treatment, and the ORR and DCR were 7.1% and 78.6%, respectively; 13 patients received drugs as the third- or later-line treatment, with an ORR and a DCR of 15.4% and 84.6%, respectively. In addition, 11 patients experienced icotinib monotherapy failure within 6months with median PFS of 7.37months, and 16 patients had progression after 6months with median PFS of 2.60months. The common drug-related toxic effects were hypertension (44.4%) and fatigue (37.0%).Conclusion: Apatinib plus icotinib is efficacious in treating patients with advanced NSCLC after icotinib treatment failure, with acceptable toxic effects. Keywords: epidermal growth factor receptor mutation, non-small cell lung cancer, apatinib, icotinib, efficacy

When a bromide-containing water is treated by the ultraviolet (UV)/chlorine process, hydroxyl radicals (HO) and halogen radicals such as Cl or Br are formed due to the UV photolysis of free halogens. These reactive species may induce the formation of bromate, which is a probable human carcinogen. Bromate formation in the UV/chlorine process using low pressure (LP) and medium pressure (MP) lamps in the presence of bromide was investigated in the present study. The UV/chlorine process significantly enhanced bromate formation as compared to dark chlorination. The bromate formation was elevated with increasing UV fluence, bromide concentration, and pH values under both LP and MP UV irradiations. It was significantly enhanced at pH 9 compared to those at pH 6 and 7 with MP UV irradiation, while it was slightly enhanced at pH 9 with LP UV. The formation by UV/chlorine process started with the formation of free bromine (HOBr/OBr-) through the reaction of chlorine and bromide, followed by a subsequent oxidation of free bromine and formation of BrO and bromate by reacting with radicals.

On-line chemical cleaning with sodium hypochlorite (NaClO) has been extensively practiced for maintaining the stable permeability of membrane bioreactor (MBR), during which activated sludge is inevitably exposed to NaClO. The authors previously reported the NaClO-induced generation of dissolved organic matter (DOM) and halogenated byproducts, however their fate in terms of biodegradability and removability in MBR has been unknown. Therefore, this study investigated the removal mechanisms of generated DOM and byproducts in an aerobic MBR. It was found that about 39% of DOM produced was removed through biodegradation and membrane rejection. The fluorescence excitation-emission matrix (EEM) coupled with parallel factor analysis (PARAFAC) also revealed that protein-like substances were more readily biodegradable than humic-like substances. Moreover, 25 kinds of chlorinated and brominated byproducts were detected after the contact of biomass with NaClO by ultra performance liquid chromatography/electrospray ionization-triple quadrupole mass spectrometry, while nine of which were confirmed with standard compounds. 62.4–84.5% halogenated byproducts were ended up in permeate of MBR chemically cleaned with 5–20 mg/L of NaClO. This study raises a serious concern on reusing and recycling of such MBR permeate.

Chlorine dioxide (ClO2) is a widely used alternative disinfectant due to its high biocidal efficiency and low-level formation of trihalomethanes and haloacetic acids. A major portion of total organic halogen (TOX), a collective parameter for all halogenated DBPs, formed in ClO2-treated drinking water is still unknown. A commonly used pretreatment method for analyzing halogenated DBPs in drinking water is one-time liquid-liquid extraction (LLE), which may lead to a substantial loss of DBPs prior to analysis. In this study, characterization and identification of polar halogenated DBPs in a ClO2-treated drinking water sample were conducted by pretreating the sample with multiple extractions. Compared to one-time LLE, the combined four-time LLEs improved the recovery of TOX by 2.3 times. The developmental toxicity of the drinking water sample pretreated with the combined four-time LLEs was 1.67 times higher than that pretreated with one-time LLE. With the aid of ultra-performance liquid chromatography/electrospray ionization-triple quadrupole mass spectrometry, a new group of polar halogenated DBPs, trihalomethanols, were detected in the drinking water sample pretreated with multiple extractions; two of them, trichloromethanol and bromodichloromethanol, were identified with synthesized standard compounds. Moreover, these trihalomethanols were found to be the transformation products of trihalomethanes formed during ClO2 disinfection. The results indicate that multiple LLEs can significantly improve extraction efficiencies of polar halogenated DBPs and is a better pretreatment method for characterizing and identifying new polar halogenated DBPs in drinking water.

The nematicidal activity of furfural, biochar and urea on plant-parasitic nematodes is rather well documented and approved; however, there is no information about combination treatment with those anti-nematode agents. We tested the nematicidal effect of combinations that paired furfural and biochar (F0B, F2.5B, F5B and F10B) or biochar-coated urea (F0BCU, F8.25BCU, F16.5BCU and F33BCU) to the root-knot nematode, Meloidogyne incognita (RKN) in the absence and presence of tomato plant, and characterized their possible mode of action. After biochar or BCU being paired with furfural, the accompanying effect of FB or FBCU, at all their application rates, resulted in superior control of RKN to that obtained when each component was applied individually. All applied levels of furfural–biochar-based formulations significantly inhibited RKN criteria compared to untreated control. Specifically, the FBCU formulation showed more synergistic interactions and greater nematicidal activity than FB on RKN. Nevertheless, the potentiating effect was the most common interaction between furfural and biochar with FB formulations on RKN. Despite their nematicidal activity, the applied furfural–biochar-based formulations were favorable to tomato growth and free-living nematodes when containing furfural at rates

Chlorination is extensively applied for disinfecting sewage effluents, but it unintentionally generates disinfection byproducts (DBPs). Using seawater for toilet flushing introduces a high level of bromide into domestic sewage. Chlorination of sewage effluent rich in bromide causes the formation of brominated DBPs. The objectives of achieving a disinfection goal, reducing disinfectant consumption and operational costs, as well as diminishing adverse effects to aquatic organisms in receiving water body remain a challenge in sewage treatment. In this study, we have demonstrated that, with the same total chlorine dosage, a three-step chlorination (dosing chlorine by splitting it into three equal portions with a 5-min time interval for each portion) was significantly more efficient in disinfecting a primary saline sewage effluent than a one-step chlorination (dosing chlorine at one time). Compared to one-step chlorination, three-step chlorination enhanced the disinfection efficiency by up to 0.73-log reduction of Escherichia coli. The overall DBP formation resulting from one-step and three-step chlorination was quantified by total organic halogen measurement. Compared to one-step chlorination, the DBP formation in three-step chlorination was decreased by up to 23.4%. The comparative toxicity of one-step and three-step chlorination was evaluated in terms of the development of embryo-larva of a marine polychaete Platynereis dumerilii. The results revealed that the primary sewage effluent with three-step chlorination was less toxic than that with one-step chlorination, indicating that three-step chlorination could reduce the potential adverse effects of disinfected sewage effluents to aquatic organisms in the receiving marine water.

Halogenated disinfection byproducts (DBPs) are generated via reactions with natural organic matter (NOM) in chlorine disinfection of drinking water. How large NOM molecules are converted to halogenated aliphatic DBPs during chlorination remains a fascinating yet largely unresolved issue. Recently, many relatively toxic halogenated aromatic DBPs have been identified in chlorinated drinking waters, and they behave as intermediate DBPs to decompose to halogenated aliphatic DBPs. There is still one gap between NOM and halogenated aromatic DBPs. In this study, nine nonhalogenated aromatic compounds were identified as new intermediate DBPs in chlorination, including 4-hydroxybenzaldehyde, 4-hydroxybenzoic acid, 3-formyl-4-hydroxybenzoic acid, salicylic acid, 5-formyl-2-hydroxybenzoic acid, 4-hydroxyphthalic acid, 4'-hydroxyacetophenone, 4-methylbenzoic acid, and 4-hydroxy-3-methylbenzaldehyde. These nonhalogenated aromatic DBPs formed quickly and reached the maximum levels at relatively low chlorine doses within a short contact time, and their formation pathways were proposed. The formation kinetics of three nonhalogenated aromatic DBPs and their corresponding monochloro-/dichloro-substitutes during chlorination were then modeled. The nonhalogenated aromatic DBPs contributed up to 84% of the formed monochloro-substitutes and 22% of the formed dichloro-substitutes, demonstrating that they somewhat acted as intermediates between NOM and halogenated aromatic DBPs. Furthermore, the formed nonhalogenated aromatic DBPs were found to be removed by >50% by granular activated carbon adsorption.

Late Cretaceous evaporite in the Khorat Plateau (KP) is one of the largest potash deposits in the world. Previous researches reported that the origin of potash deposits in the KP is controversial; however, recent studies emphasized non-marine fluids (hydrothermal fluid or meteoric water) influenced geochemical behaviors of potash deposits. Eleven halite samples from halite and potash layers in a drilling core (NS007) in southwestern KP were collected and analyzed for δ37Cl values, Br− and Cl− concentrations in this study. The results show that (1) low δ37Cl values (− 1.31‰ ~ + 0.14‰) of halite from halite layer, combining with reported isotopic (δD and δ18O) values of fluid inclusions in halite in corresponding layer, suggest possible influence of hydrothermal fluid; (2) positive correlation between δ37Cl values and Br × 103/Cl ratios, high δ37Cl values (− 0.48‰ ~ + 0.41‰) and previous high 87Sr/86Sr values of halite from potash layer indicate meteoric water inputs into this layer. These comparisons demonstrate that hydrothermal or meteoric waters (non-marine fluids) influenced potash deposits in northeastern Thailand.

Chlorine disinfection is a vital treatment process to inactivate pathogens, but it also generates numerous halogenated disinfection byproducts (DBPs) via reactions with halides and natural organic matter (NOM). Epidemiological studies have shown that consumption of chlorinated drinking water with halogenated DBPs is related to increased spontaneous abortions, stillbirth, birth defects, and bladder and colorectal cancers. To control DBPs, efforts have been devoted to minimizing the formation of DBPs by removing the major DBP precursor, NOM, or by adopting alternative disinfectants. Notably, the precursor removal may not be very effective and the application of alternative disinfectants may generate their own sets of DBPs. It has remained a grand challenge to develop a new DBP control strategy which can effectively decrease the DBP formation and reduce the health risks of chlorinated drinking water. To solve this problem, Zhang’s group reported a new approach to effectively control halogenated DBPs by removing intermediate aromatic halogenated DBPs, which were formed from chlorine disinfection, via granular activated carbon (GAC) adsorption.

Potash plays an important role in agricultural production. The Qaidam Basin (QB) in western China is a typical inland evaporite basin, which contains an abundance of K-rich brines, including shallow brines (i.e., surface brines and intercrystalline brines) in salt lakes and deep brines (i.e., pore brines and oilfield brines) in the strata. Significant studies on these brines have been reported, however, the integrated studies on sources of K, its distribution, and the sedimentary pattern of the two brine types are still inadequate. In this study, the K+ concentrations of sixty-four intercrystalline brines from the Qarhan Salt Lake (QSL), the largest playa in the QB, are presented. After combining those results with the major ionic compositions of river waters and deep K-rich brines, and the K+ concentrations of shallow brines in the QB, we concluded that: (1) The K of brines in the QSL is mainly from the high&ndash, flux K input by rivers which gain K from silicate weathering, while the &ldquo, ancient Qaidam Lake&rdquo, contributed little K to the QSL, (2) the large K flux supplied by rivers, the appropriate concentration degree, and the mixing of river waters and spring waters, cooperatively account for the highest K concentrations of brines in the QSL in the QB. The different river K recharges in different sections and isolated depressions are responsible for uneven K+ concentrations of brines in the QSL. (3) The deep brines are mainly distributed in the western QB. The K source of pore brines is from the interaction of pore water with the overlying evaporite layer. While the K in oilfield brines may be meteoric water, salt dissolution, the mixing of hydrothermal fluids, and the conversion of clay minerals to K-feldspar may consume K in the oilfield brines.

On-line chemical cleaning with sodium hypochlorite (NaOCl) is widely employed for sustaining MBR permeability, during which the inevitable contact between activated sludge and NaOCl had been shown to trigger substantial release of dissolved organic matter (DOM). Therefore, this work further explored the formation mechanisms of such DOM by looking into the respective reactions of intracellular organic matter (IOM) and cell debris in activated sludge with NaOCl. The results showed that DOM was primarily produced from the dissolution of cell wall, while IOM release was insignificant at the NaOCl concentration of 25 mg/L as Cl2. On the basis of experimental observations, a three-step mechanism was proposed for elucidating the DOM formation from activated sludge upon NaOCl exposure: (i) NaOCl first damaged cells by perforating cellular wall, producing a considerable amount of humic-like substances and low-molecular-weight halogenated byproducts; (ii) IOM was released but rapidly degraded and humified by NaOCl, accompanied with the formation of relatively high-molecular-weight halogenated byproducts; (iii) the residual NaOCl and combined chlorine continued to react with cell wall or likely diffused into cells leading to the deactivation of DNA/enzymes. Consequently, this study offers mechanistic insights into the origination of emerging contaminants during on-line membrane cleaning of practical MBR.

Salt lakes on the Qinghai-Tibetan Plateau (QTP) are remarkable for Li-rich brines. Along with the surging demand of Li, the Li-rich brines in salt lakes on the QTP are of great importance for China’s Li supply. Previous studies reported the geological, geographical, geochemical signatures of numerous salt lakes on the QTP; however, conclusive work and the internal relationships among the hydrochemistry, distribution and geological setting of Li-rich salt lakes are still inadequate. In this study, major and trace (Li, B) ionic compositions of 74 Li-rich salt lakes on the QTP were reviewed. The Li-rich brines cover various hydrochemical types (carbonate, sodium sulfate, magnesium sulfate, and chloride types) and present horizontal zoning from the southwest to the northeast along with the stronger aridity. The Li concentrations and Mg/Li ratios in these salt lakes range from 23 to 2895 mg/L, 0.0 to 1549.4, respectively. The distribution of these salt lakes is close to the major suture zones. Geothermal water is proposed to be the dominant source of Li in the investigated salt lakes, while weathering of Li-bearing sediments and igneous rocks, and brine migration provide a minor part of Li. Four factors (sufficient Li sources, arid climate, endorheic basin and time) should be considered for the formation of Li-rich brines in salt lakes on the QTP.

The development of bus priority strategy is of great significance to solve urban traffic problems, and one of the issues that passengers are most concerned about in bus travel is bus arrival time. In this paper, firstly, the related technologies of bus GPS data processing and bus arrival time prediction are studied, and then the running time of historical section is analyzed by K-Means clustering method, and the rolling prediction model of bus arrival time is put forward; finally, taking No. 6 bus in Huangdao District of Qingdao as an example, the prediction results of bus arrival time between the proposed model and other comparative models are discussed. The results show that the model can accurately predict the bus arrival time and meet the travel demand of passengers.

The interaction of chlorine with nitrogenous constituents in water is being concerned due to the formation of relatively toxic nitrogenous disinfection byproducts during chlorine disinfection. In this study, the transformation pathways of the chlorination of adenine and cytosine are proposed based on the products analysis using a collision-energy-dependent method on triple quadrupole mass spectrometry coupled with electrospray ionization. Products with multiple chlorine addition on the heterocyclic ring and on the aliphatic amine were observed during the chlorination of adenine and cytosine. The primary amine functional group in adenine and cytosine can undergo chlorine substitution to form N-chloramine and undergo hydrolysis of the C-N bond to form carbonyl derivative. The transformation of adenine and cytosine depends on pH and the chlorine to precursor (Cl/P) ratio. An 8-chloro derivative of adenine was observed at pH 4, but not at pH 7. Substitution of 1-2 chlorine atoms for the hydrogen atoms in the N-heterocyclic ring was observed during adenine chlorination compared to substitution of 1-4 chlorine atoms during cytosine chlorination. Chlorination of adenine also led to ring cleavage products. Both 5-chlorocytosine and 4-N-chlorocytosine were identified as cytosine transformation products. At pH 7 and a Cl/P molar ratio of 2, the major products of chlorination of cytosine were found to be aromatic chloro-compounds, not aliphatic N-chloramine. The results of this study are significant for understanding the transformation mechanisms of compounds containing both N-heterocyclic and primary amines due to chlorination.

Water disinfection can result in the unintended formation of halogenated disinfection byproducts (DBPs), which have been the subject of intensive investigation over the past 40 years. Robust methods for evaluating and characterizing the formation of halogenated DBPs are prerequisites for ultimately controlling the formation of DBPs and ensuring quality and safe disinfected water. Only a fraction of the total organic halogen (TOX) formed during disinfection has been chemically identified or even well characterized by the classical (derivatization-)gas chromatography/mass spectrometry (GC/MS) method. Such a method may not be amenable to the detection of polar halogenated DBPs, which constitute a major portion of the TOX that is still unaccounted for. Accordingly, a novel precursor ion scan (PIS) method using (liquid chromatography/) electrospray ionization-triple quadrupole mass spectrometry was developed for the rapid selective detection of all polar halogenated DBPs-no matter whether the DBPs are known or unknown-in water. This article reviews recent literature on the application of the PIS method for evaluating the occurrence, formation and control of polar halogenated DBPs in disinfected waters. The challenges in developing the PIS method were briefly summarized. Application of the powerful method pinpointed >150 previously unknown DBPs and revealed the formation, speciation and transformation of halogenated DBPs in disinfected drinking water, wastewater effluents, and swimming pool water. For the same source water, positive correlations were found between the total ion intensity (TII) levels in the PIS spectra of m/z 35/79/126.9 and the total organic chlorine/bromine/iodine levels in the disinfected water sample, and a disinfected sample with a higher TII level generally showed a higher toxic potency. Accordingly, the TII value can be used as a surrogate to comparatively reflect the water quality and assess the efficiency of a DBP control approach. To achieve a more comprehensive and systematic understanding of the DBP compositions in different waters and thus better control the DBP formation and reduce their overall toxicity, topics for future work were discussed.

Chlorine disinfection of wastewater effluents rich in bromide and iodide ions results in the formation of relatively toxic bromo- and iodo-disinfection byproducts (DBPs), especially highly toxic bromophenolic and iodophenolic DBPs, which could harm the marine ecosystem when they are discharged into receiving seawater along with the wastewater effluents. In this study, we investigated the conversion of three individual halophenolic DBPs (5-bromosalicylic acid, 2,5-dibromohydroquinone, and 2,4,6-triiodophenol) and two chlorinated saline wastewater DBP mixtures in seawater. The conversion products were analyzed with ultra performance liquid chromatography/electrospray ionization-triple quadrupole mass spectrometry, and the conversion of overall halo-DBPs in the wastewater DBP mixtures was monitored by measuring total organic halogen. The photoconversion-induced variations in the toxicity were evaluated using the embryos of a marine polychaete. Halophenolic DBPs were found to undergo photoconversion in seawater. The conversion was triggered by photonucleophilic substitution: bromophenolic and iodophenolic DBPs were converted to their chlorophenolic or hydroxyphenolic analogues, via substituting the bromine and iodine atoms with chloride or hydroxide ions in seawater; chlorophenolic DBPs were converted to their hydroxyphenolic analogues, via substituting the chlorine atoms with hydroxide ions in seawater. The hydroxyphenolic analogues thus formed further decomposed and finally cleaved to aliphatic compounds. The photoconversion of chlorinated saline wastewater DBPs in receiving seawater was overall a dehalogenation and detoxification process.

Natural organic matter (NOM) is present in source water worldwide, and it is composed of numerous organic compounds produced in natural processes. NOM has been drawing increasing concerns because it not only affects drinking water treatment on many aspects (e.g., the performance of treatment techniques, necessity of advanced treatment, the dose of treatment chemicals, etc.), but also acts as the main precursor of hazardous drinking water disinfection byproducts (DBPs). Accordingly, to optimize treatment processes and to control the formation of DBPs, it is vital to analyze and characterize NOM for a better understanding of its property and reactivity. In this review, a summary of methods used in NOM analysis and characterization during drinking water treatment was provided, including analysis methods for general parameters (e.g., dissolved organic carbon, dissolved organic nitrogen, (specific) ultraviolet absorbance, fluorescence, polarity, and zeta potential) and characterization methods for elemental and structural identification (e.g., elemental analysis, Fourier transform infrared spectroscopy, nuclear magnetic resonance spectroscopy, pyrolysis-gas chromatography/mass spectrometry, liquid chromatography/mass spectrometry, and Fourier transform ion cyclotron resonance mass spectrometry). In addition, preparation and pretreatment methods for NOM were also covered in this review, including isolation and concentration methods (reverse osmosis, pressure-reducing evaporation, freeze-drying, and electrodialysis) as well as fractionation methods (size exclusion chromatography, resin fractionation, membrane filtration, polarity rapid assessment, field-flow fractionation, and reversed-phase high performance liquid chromatography).

Disinfection byproducts (DBPs) are a class of compounds generated during chemical disinfection processes. Their wide distribution in potable water supply systems and environmental waters has aroused concerns for both human health and aquatic organisms. Recent toxicological studies have demonstrated that most of the emerging DBPs are significantly more toxic than the regulated DBPs. Analysis techniques are prerequisites for fully understanding DBPs, as they involve identifying and quantifying DBPs, and studying their occurrence and toxicity. Accordingly, this paper reviews current trends in the analysis and identification of emerging DBPs produced in artificial water samples with model substances (e.g., natural organic matter and anthropogenic contaminants) and in real environmental waters (e.g., drinking water, wastewater effluents, swimming pool water, ballast water, cooling water from power stations, and brine reject from desalination plants).

Chlorine disinfection is required to inactivate pathogens in drinking water, but it inevitably generates potentially toxic halogenated disinfection byproducts (halo-DBPs). A previous study has reported that the addition of ascorbate to tap water before boiling could significantly decrease the concentration of overall halo-DBPs in the boiled water. Since the fruit lemon is rich in vitamin C (i.e., ascorbic acid), adding it to tap water followed by heating and boiling in an effort to decrease levels of halo-DBPs was investigated in this study. We examined three approaches that produce lemon water: (i) adding lemon to tap water at room temperature, termed “Lemon”; (ii) adding lemon to boiled tap water (at 100 °C) and then cooling to room temperature, termed “Boiling + Lemon”; and (iii) adding lemon to tap water then boiling and cooling to room temperature, termed “Lemon + Boiling”. The concentrations of total and individual halo-DBPs in the resultant water samples were quantified with high-performance liquid chromatography-tandem mass spectrometry and the cytotoxicity of DBP mixtures extracted from the water samples was evaluated using human epithelial colorectal adenocarcinoma Caco-2 cells and hepatoma HepG2 cells. Our results show that the “Lemon + Boiling” approach substantially decreased the concentrations of halo-DBPs and the cytotoxicity of tap water. This strategy could be applied to control halo-DBPs, as well as to lower the adverse health effects of halo-DBPs on humans through tap water ingestion.

In the railway locomotive reducer manufacturing industry, due to the characteristics of multi variety and small batch, the efficiency of process planning is low, the cycle is long, and the production link is seriously disconnected. To solve this problem, an integrated process planning system based on Manufacturing Execution System (MES) was proposed, this system used decision-making models of process based on typical process library to make process planning more efficient. At last, ASP.NET platform and C# programming language were used to complete the development of the system.

Chlorine disinfection inactivates pathogens in drinking water, but meanwhile it causes the formation of halogenated disinfection byproducts (DBPs), which may induce adverse health effects. Humans are unavoidably exposed to halogenated DBPs via tap water ingestion. Boiling of tap water has been found to significantly reduce the concentrations of halogenated DBPs. In this study, we found that compared with boiling only, adding ascorbate (vitamin C) or carbonate (baking soda) to tap water and then boiling the water further reduced the level of total organic halogen (a collective parameter for all halogenated DBPs) by up to 36% or 28%, respectively. Adding ascorbate removed the chlorine residual in tap water and thus prevented the formation of more halogenated DBPs in the boiling process. Adding carbonate elevated pH of tap water and consequently enhanced the hydrolysis (dehalogenation) of halogenated DBPs or led to the formation of more trihalomethanes that might volatilize to air during the boiling process. The comparative developmental toxicity of the DBP mixtures in the water samples was also evaluated. The results showed that adding a tiny amount of sodium ascorbate or carbonate (2.5–5.0 mg/L) to tap water followed by boiling for 5 min reduced the developmental toxicity of tap water to a substantially lower level than boiling only. The addition of sodium ascorbate or carbonate to tap water in household could be realized by preparing them in tiny pills. This study suggests simple and effective methods to reduce the adverse effects of halogenated DBPs on humans through tap water ingestion.

Halogenated disinfection byproducts (DBPs) are formed during chlorine disinfection of drinking water. The complicated natural organic matter in source water causes the formation of an even more complicated mixture of DBPs. To evaluate the toxicity of a DBP mixture in a disinfected water sample, the sample needs to be pretreated in order to attain an observable acute adverse effect in the toxicity test. During sample pretreatment, volatile DBPs including trihalomethanes, haloacetonitriles and haloketones may be lost, which could affect the toxicity evaluation of the DBP mixture. In this study, we intentionally prepared “concentrated” simulated drinking water samples, which contained sufficiently high levels of volatile and nonvolatile DBPs and thus enabled directly evaluating the toxicity of the DBP mixtures without sample pretreatment. Specifically, the natural organic matter and bromide concentrations and the chlorine dose in the concentrated water samples were 250 times higher than those in a typical drinking water sample. Each concentrated water sample was divided into two aliquots, and one of them was nitrogen sparged to eliminate volatile DBPs; then, both aliquots were used directly in a well-established developmental toxicity test. No significant difference (p > 0.10) was found between the developmental toxicity indexes of each concentrated water sample without and with nitrogen sparging, indicating that the contribution of volatile DBPs to the developmental toxicity of the DBP mixture might be marginal. A reasonable interpretation is that nonvolatile halogenated DBPs (especially the aromatic ones) in the DBP mixture could be the major developmental toxicity contributor that warrants more attention.

Background: Swimming in pools is a healthy activity that entails exposure to disinfection by-products (DBPs), some of which are irritant and genotoxic. Objectives: We evaluated exposure to DBPs during swimming in a chlorinated pool and the association with short-term changes in genotoxicity and lung epithelium permeability biomarkers. Methods: Non-smoker adults (N = 116) swimming 40 min in an indoor pool were included. We measured a range of biomarkers before and at different times after swimming: trihalomethanes (THMs) in exhaled breath (5 min), trichloroacetic acid (TCAA) in urine (30 min), micronuclei in lymphocytes (1 h), serum club cell protein (CC16) (1 h), urine mutagenicity (2 h) and micronuclei in reticulocytes (4 days in a subset, N = 19). Several DBPs in water and trichloramine in air were measured, and physical activity was extensively assessed. We estimated interactions with polymorphisms in genes related to DBP metabolism. Results: Median level of chloroform, brominated and total THMs in water was 37.3, 9.5 and 48.5, μg/L, respectively, and trichloramine in air was 472.6 μg/m3. Median exhaled chloroform, brominated and total THMs increased after swimming by 10.9, 2.6 and 13.4, μg/m3, respectively. Creatinine-adjusted urinary TCAA increased by 3.1 μmol/mol. Micronuclei in lymphocytes and reticulocytes, urine mutagenicity and serum CC16 levels remained unchanged after swimming. Spearman correlation coefficients showed no association between DBP exposure and micronuclei in lymphocytes, urine mutagenicity and CC16. Moderate associations were observed for micronuclei in reticulocytes and DBP exposure. Conclusions: The unchanged levels of the short-term effect biomarkers after swimming and null associations with personal estimates of exposure to DBPs suggest no measurable effect on genotoxicity in lymphocytes, urine mutagenicity and lung epithelium permeability at the observed exposure levels. The moderate associations with micronuclei in reticulocytes require cautious interpretation given the reduced sample size. © 2019 The Authors, We are grateful to all volunteers and the swimming pool facility. This work was funded by the EU 7th Framework Programme EXPOSOMICS Project (grant agreement 308610 ). We thank the Parc de Salut Mar Biobank (MARBiobanc) for providing support to the project. MARBiobanc is supported by grants from Instituto de Salud Carlos III / FEDER ( RD09/0076/00036 and PT13/0010/0005 ) and the “Xarxa de Bancs de tumors” sponsored by Pla Director d'Oncologia de Catalunya (XBTC). ISGlobal is a member of the CERCA Programme, Generalitat de Catalunya. We appreciate the work by Kate Jones (Health & Safety Laboratory, UK) for urinary TCAA analysis.

Edible salt is essential to the health of humans and serves as a seasoning universally. Besides chloride, edible salt also contains other anions such as bromide, fluoride, sulfate, and carbonate due to incomplete removal during raw salt refinement. In a household cooking (e.g., soup making) process, a chlorine/monochloramine residual in tap water could react with bromide in edible salt and organic matter in food (e.g., rice, wheat) to form numerous brominated disinfection byproducts (Br-DBPs) at significant levels, which might induce adverse health effects to human beings. In this study, we solicited 20 edible salts of different types (i.e., sea salts, well and rock salts, lake salts, and bamboo salts) from nine countries and determined their bromide levels to be 67–375 mg/kg, with an average level of 173 mg/kg. A total of 25 polar Br-DBPs were detected and identified with structures/formulae in cooking water samples using ultra performance liquid chromatography/electrospray ionization-triple quadruple mass spectrometry (UPLC/ESI-tqMS) and high-resolution mass spectrometry. Effects of cooking conditions (e.g., disinfectant type and level, edible salt dose, organic matter type and dose, sequence and time interval of adding organic matter and salt, etc.) on the formation of polar Br-DBPs were investigated, and optimized cooking conditions with minimized formation of polar Br-DBPs were determined. Further aided with an Hep G2 cell cytotoxicity assay, it was found that the overall cytotoxicity of chlorinated and chloraminated cooking water samples prepared after cooking condition optimization was reduced by 57% and 22%, respectively, compared with those prepared before cooking condition optimization.

The Qarhan Salt Lake (QSL) in the Qaidam Basin in western China is the largest brine potash deposit in the world. The formation of MgSO4-deficient evaporites in the QSL, whether from the evaporation of river waters with high Na+ and Cl− levels, bacterial sulfate reduction (BSR) in brines resulting in SO42− depletion, or the mixing of the river and spring waters, remains controversial. The δ34S values of 33 intercrystalline brines and 10 gypsum samples from a sediment core (ISL1A) collected in the QSL were presented in this study. Combining these results with previously reported major ionic concentrations, total dissolved solids (TDS) and δ34S values of different waters, and 87Sr/86Sr ratios of sediments, it was concluded that (1) δ34S values of the intercrystalline brines (+6.7‰ to +12.1‰) and gypsum (+8.1‰ to +10.1‰) suggested that the BSR was insignificant in the QSL. These values were dominated by those of inflowing waters and the evaporation process; (2) river waters with high Na+ and Cl− levels were unable to form MgSO4-deficient evaporites in the QSL. A strong positive correlation of Na and Cl equivalents coupled with high (Na+ + Cl−)/TDS ratios suggested that the large amount of solutes in Golmud River waters results from the dissolution of halite rather than the chemical weathering of rocks; and (3) the flowing system of the river and spring in the past 50 kyr was similar to the modern supplying system, and mixing of river and spring waters was responsible for the precipitation of evaporites in the QSL.

Cadmium (Cd) precipitation and dissolution in pore water is associated with dissolved organic carbon (DOC)-induced reduction-oxidation of sulfur (S) under waterlogging and is vital for controlling the bioavailability in paddy soil. A 120-day soil incubation experiment, including application of sulfur (S, 30 mg kg−1) and wheat straw (W, 1.0%) alone or in combination (W + S) into Cd-contaminated paddy soil under waterlogging, was conducted to investigate the dynamic of dissolved Cd and its relationship with DOC, S2−, Fe2+, pH, Eh and pe + pH in soil pore water. The results showed that the lowest dissolved Cd concentration was observed in the W + S-treated soil pore water among all treatments when the soil Eh remained at lower values during the period of 15–60 days of incubation, which could be attributed to CdS precipitation and/or co-precipitation of Cd absorbed by FeS2 because of the reduction in sulfur. The application of S resulted in a Cd rebound in the pore water irrespective of W addition when the Eh began to increase from its lowest values during the period of 45–75 days of incubation, and SOB genera were observed in the S added soil. This could be attributed to re-dissolution of the precipitated Cd in soils under the SOB-driven oxidation of sulfide such as CdS and FeS2. In conclusion, DOC-driven reduction-oxidation of sulfur controls Cd dissolution in the pore water of Cd-contaminated paddy soil under waterlogging conditions. Further studies are required to investigate the interaction of sulfur and SOM-induced DOC on Cd bioavailability in rice-planted paddy soils.

Haloacetic acids (HAAs) are the major disinfection byproducts (DBPs) that are formed during chlorination of drinking water. In this paper, the conversion of HAAs to amino acids (e.g., glycine) via ammonolysis was studied. First, a new and sensitive method for detecting glycine was developed by setting selected ion recording m/z 76 in positive electrospray ionization mass spectrometry coupled with ultra performance liquid chromatography. Second, among the mono-HAAs under the same test conditions, iodoacetic acid (49.3%) showed a considerably higher conversion to glycine during ammonolysis than chloroacetic acid (4.2%) and bromoacetic acid (27.7%). The conversion of iodoacetic acid to glycine increased with increasing temperature, increasing reaction time, or decreasing the ratio of (NH4)2CO3 to NH3·H2O in the aminating agent. Hydrolysis of iodoacetic acid to glycolic acid was also observed during ammonolysis, and it accounted for at most 50% of the iodoacetic acid conversion. The conversion to amino acids and the hydrolysis were the two major pathways during ammonolysis of HAAs. Third, compared with the iodoacetic acid sample and the simulated tap water sample without ammonolysis, the developmental toxicity of the corresponding samples with ammonolysis decreased by up to 10.4% and 32.1%, respectively. The ammonolysis was thus demonstrated to be a detoxification process for both individual HAAs and DBP mixture in chlorinated tap water. In practice, the ammonolysis of haloacid DBPs in tap water may be realized by simply adding an appropriate amount of an aminating agent during cooking.

Flushing toilet with seawater is an effective method for preserving freshwater resources, but it introduces iodide and bromide ions into domestic wastewater. During chlorine disinfection, iodide and bromide ions in the saline wastewater effluent lead to the formation of iodinated and brominated aromatic disinfection byproducts (DBPs). Examples of aromatic DBPs include iodophenolic, bromophenolic and chlorophenolic compounds, which generally display substantially higher toxicity than haloaliphatic DBPs. This paper presented for the first time the rates of phototransformation of 21 newly identified halophenolic DBPs in seawater, the receiving waterbody of the wastewater effluent. The phototransformation rate constants (k) were in the range from 7.75 × 10−4 to 4.62 × 10−1 h−1, which gave half-lives of 1.5–895 h. A quantitative structure−activity relationship was established for the phototransformation of halophenolic DBPs as log k = − 0.0100 × Δ G f 0 + 5.7528 × log M W + 0.3686 × p K a − 19.1607 , where ΔGf0 is standard Gibbs formation energy, MW is molecular weight, and pKa is dissociation constant. This model well predicted the k values of halophenolic DBPs. Among the tested DBPs, 2,4,6-triiodophenol and 2,6-diiodo-4-nitrophenol were found to exhibit relatively high risks on marine organisms, based on toxicity indices and half-lives. In seawater, the two DBPs underwent photonucleophilic substitutions by bromide, chloride and hydroxide ions, resulting in the conversion to their bromophenolic and chlorophenolic counterparts (which are less toxic than the parent iodophenolic DBPs) and to their hydroxyphenolic counterparts (iodo(hydro)quinones, which are more toxic than the parent iodophenolic DBPs). The formed iodo(hydro)quinones further transformed to hydroxyl-iodo(hydro)quinones, which have lower toxicity than the parent compounds.

Stonecutters Island Sewage Treatment Works is one of the largest sewage treatment plants in the world and consists mainly of a chemically enhanced primary treatment (CEPT) unit and a disinfection unit. It has long been realized that most of the dosed chlorine (15 mg/L) is lost at the beginning part of the disinfection unit during disinfection of the CEPT effluent. Lab-scale tests were therefore conducted in this study to determine the causes. Because ferric chloride is used in CEPT, ferrous iron in the CEPT effluent (from the reduction of ferric iron) was initially thought to be the main chlorine consumer. However, the chlorine consumption by ferrous iron was found to be 1.2 mg/L at most. Suspended solids and sulfide also did not contribute significantly to the chlorine consumption. Batch tests were therefore conducted to evaluate the effects of mixing condition and chlorine stock solution concentration on the chlorine consumption. Less chlorine was consumed upon increased mixing. Using a high-concentration chlorine stock solution (25000 mg/L) resulted in a 3-times-higher chlorine consumption in the absence of mixing than using a low-concentration chlorine stock solution (2500 mg/L). By correlating the losses of ammonia and total nitrogen with the chlorine consumption, we hypothesized that the use of a high-concentration chlorine stock solution under poor mixing leads to a localized high ratio of chlorine to ammonia, resulting in breakpoint chlorination and an unusually excessive chlorine consumption. A novel apparatus was developed to quantify the nitrogen gas generated during chlorination of a simulated wastewater, and the mass balance of nitrogen-containing species (i.e., ammonia, nitrogen gas, nitrite and nitrate) during the chlorination was inspected. The good fit between the measured chlorine consumption and that back-calculated from nitrogen-containing species verified our hypothesis. Finally, it needs mentioning that the high chlorine consumption and the breakpoint chlorination may occur during chlorine disinfection of any sewage effluents with relatively high ammonia levels; thus it is suggested that either not-too-high concentrations of chlorine stock solutions or sufficient mixing should be applied during disinfection of the sewage effluents.

Adsorbable organic halogen (AOX) is a bulk organic parameter conventionally used to indicate all adsorbable halogenated organic disinfection byproducts formed in disinfected water. Analytically, AOX is determined by three sequential steps: 1) concentration and separation of AOX from halides with activated carbon, 2) conversion of AOX into halides with pyrolysis, and 3) quantification of halides via microcoulometry or ion chromatography (IC). Because the approach is relatively costly and cannot effectively recover non-adsorbable compounds, we herein proposed a facile and green pretreatment tool to measure the nonionic portion of total organic halogen (NTOX) with a new three-step approach: 1) separation of NTOX and halides with electrodialysis (ED), 2) conversion of NTOX into halides with ultraviolet, and 3) analysis of halides with IC. To verify this proposal, this study presented the efficiency of ED in separating halides and NTOX under a variety of operational and environmental conditions. The results showed that ED removed ≥98.5% of fluoride, chloride, bromide, and iodide from all tested waters (up to 1000 mg-X/L) within 1.5 h. Meanwhile, ED recovered an average of 87.9% of fourteen small molecular weight model compounds with each at 100 μg/L. By using electrospray ionization-triple quadrupole mass spectrometry, the whole pictures of high molecular weight compounds in a chlorinated drinking water before and after ED pretreatment were compared, which revealed 79.7% and 83.6% recoveries of overall polar chlorinated and brominated compounds, respectively. In addition, the quantity and property of the dissolved organic matter were largely maintained by ED, and the retained organics may be used for later characterization. The study hence presents a novel use of ED as a pretreatment tool to enable subsequent NTOX measurement.

Toilet flushing with seawater results in saline wastewater, which may contain approximately 33-50% seawater. Halogenated disinfection byproducts (DBPs), especially brominated and iodinated DBPs, have recently been found in chlorinated saline wastewater effluents. With the occurrence of brominated and iodinated DBPs, the adverse effects of chlorinated saline wastewater effluents to marine ecology have been uncertain. By evaluating the developmental effects in the marine polychaete Platynereis dumerilii directly exposed to chlorinated saline/freshwater wastewater effluents, we found surprisingly that chlorinated saline wastewater effluents were less toxic than a chlorinated freshwater wastewater effluent. This was also witnessed by the marine alga Tetraselmis marina. The toxicity of a chlorinated wastewater effluent to the marine species was dominated by its relatively low salinity compared to the salinity in seawater. The organic matter content in a chlorinated wastewater effluent might be partially responsible for the toxicity. The adverse effects of halogenated DBPs on the marine species were observed pronouncedly only in the "concentrated" chlorinated wastewater effluents. pH and ammonia content in a wastewater effluent caused no adverse effects on the marine species. The results suggest that using seawater to replace freshwater for toilet flushing might mitigate the "direct" acute detrimental effect of wastewater to the marine organisms.

There is no consensus about the best technique to use for the surgical treatment for large rectal adenomas. The advent of laparoscopic surgery has led to the development of several new methods for the treatment of gastrointestinal tumors. This study was designed to introduce an innovative technique of totally laparoscopic resection with natural orifice specimen extraction (NOSE) for large rectal adenomas and to assess the feasibility and safety of the technique. Between February 2011 and January 2014, we performed totally laparoscopic resection with NOSE on 18 patients with a large rectal adenoma. This new technique was successful in all 18 patients. The average size of the adenoma was 4.2 cm. Mean operation time was 108.4 min, and mean intraoperative blood loss was 36.6 ml. The mean time to passing of the first flatus was 2.3 days, and the mean postoperative hospital stay was 7.2 days. Only one patient needed analgesics after the operation. All patients were able to walk within the first 2 days. There were no cases of morbidity and recurrence. Totally laparoscopic resection with NOSE appears to be suitable for selected patients with a large adenoma located in mid- or low rectum.

When bromide/iodide is present in source water, hypobromous acid/hypoiodous acid will be formed with addition of chlorine, chloramine, or other disinfectants. Hypobromous acid/hypoiodous acid undergoes reactions with natural organic matter in source water to form numerous brominated/iodinated disinfection byproducts (DBPs). In this study, tap water samples were collected from eight cities in China. With the aid of electrospray ionization-triple quadrupole mass spectrometry by setting precursor ion scans of m/z 35, m/z 81, and m/z 126.9, whole pictures of polar chlorinated, brominated, and iodinated DBPs in the tap water samples were revealed for the first time. Numerous polar halogenated DBPs were detected, including haloacetic acids, newly identified halogenated phenols, and many new/unknown halogenated compounds. Total organic chlorine, total organic bromine, and total organic iodine were also measured to indicate the total levels of all chlorinated, brominated, and iodinated DBPs in the tap water samples. The total organic chlorine concentrations ranged from 26.8 to 194.0 μg·L−1 as Cl, with an average of 109.2 μg·L−1 as Cl; the total organic bromine concentrations ranged from below detection limit to 113.3 μg·L−1 as Br, with an average of 34.7 μg·L−1 as Br; the total organic iodine concentrations ranged from below detection limit to 16.4 μg·L−1 as I, with an average of 9.1 μg·L−1 as I; the total organic halogen concentrations ranged from 31.3 to 220.4 μg·L−1 as Cl, with an average of 127.2 μg·L−1 as Cl.

There are two types of wastewater in Hong Kong, non-saline and saline wastewaters. When it comes to disinfection, iodide is an important inorganic ion in concern because it may involve in the formation of iodinated disinfection byproducts, which show significantly higher toxicity than their brominated and chlorinated analogues. In this study, it was found that a non-saline wastewater in Hong Kong contained an unexpected high level of iodine. To trace the iodine sources of this non-saline wastewater, the information of the corresponding area was collected to find the possible iodine sources; then, the water samples from the possible iodine sources were collected; the concentrations of iodine species (iodide, iodate and organic iodine) in these collected water samples were determined; finally, the contribution percentages of iodine species from different sources were calculated. The results revealed that a specific domestic wastewater was the major iodine source, contributing to 68.6% of total iodine, 66.3% of iodide, 57.0% of iodate, and 112% of organic iodine in the non-saline wastewater, while landfill leachate, industrial and hospital wastewaters were the minor iodine sources, contributing to 6.6%, 3.1%, and 3.0% of total iodine in the non-saline wastewater, respectively. Furthermore, it was found that the extensive use of salt might result in high levels of iodine in the domestic wastewater and thus lead to the high level of iodine in the non-saline wastewater.

The optimal strategy was not established for patients who initially responded to gefitinib although re-administration of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) has been proven to be an option. Gefitinib and erlotinib were compared as salvage treatment after gefitinib failure. Thirty-eight lung adenocarcinoma patients were analyzed retrospectively as they received the second EGFR-TKIs treatment with either gefitinib or erlotinib. All of them had obtained disease control from initial gefitinib. Sixteen patients received gefitinib (G-G group) and 22 patients received erlotinib (G-E group). Of all patients, progress free survival (PFS) and overall survival (OS) were three and 12 months, respectively, and the disease controlled rate (DCR) of the second EGFR-TKIs treatment was 52.6%. One patient (6.3%) had partial remission (PR) and 10 (62.5%) had stable disease (SD), in the G-G group, whereas, three (13.6%) had PR and six (27.2%) had SD, in the G-E group. There was no statistical significance observed, although the DCR in the G-G group was higher than that in G-E group (68.8% vs. 40.8%, P= 0.09). Adverse events of both gefitinib and erlotinib were mild and administered. The median PFS and OS in G-G and G-E groups were similar (PFS four vs. three months; OS 22 vs. 12 months). In multivariate analysis, patients with SD in initial gefitinib treatment had significantly longer OS (P= 0.04). Gefitinib as well as erlotinib could be an option for patients who benefited from prior gefitinib treatment. Patients with SD in initial gefitinib obtained a significantly longer OS than those with PR.

Aromatic iodinated disinfection byproducts (DBPs) are a newly identified category of highly toxic DBPs. Among the identified aromatic iodinated DBPs, 2,4,6-triiodophenol and 2,6-diiodo-4-nitrophenol have shown relatively widespread occurrence and high toxicity. In this study, we found that 4-iodophenol underwent transformation to form 2,4,6-triiodophenol and 2,6-diiodo-4-nitrophenol in the presence of monochloramine. The transformation pathways were investigated, the decomposition kinetics of 4-iodophenol and the formation of 2,4,6-triiodophenol and 2,6-diiodo-4-nitrophenol were studied, the factors affecting the transformation were examined, the toxicity change during the transformation was evaluated, and the occurrence of the proposed transformation pathways during chloramination of source water was verified. The results revealed that 2,4,6-triiodophenol and 2,6-diiodo-4-nitrophenol, which could account for 71.0% of iodine in the transformed 4-iodophenol, were important iodinated transformation products of 4-iodophenol in the presence of monochloramine. The transformation pathways of 4-iodophenol in the presence of monochloramine were proposed and verified. The decomposition of 4-iodophenol in the presence of monochloramine followed a pseudo-second-order decay. Various factors including monochloramine dose, pH, temperature, nitrite concentration, and free chlorine contact time (before chloramination) affected the transformation. The cytotoxicity of the chloraminated 4-iodophenol samples increased continuously with contact time. The proposed transformation pathways occurred during chloramination of source water.

Aim Apatinib, an oral tyrosine kinase inhibitor mainly targeting VEGFR-2, exerts both antiangiogenesis and antiproliferation effects. Apatinib shows clinical benefit in advanced non-small cell lung cancer (NSCLC) at an initial dose of 750 mg qd. We further assessed the efficacy and safety of apatinib at a more frequently used dose of 500 mg qd. The preliminary clinical outcome of apatinib in patients with brain metastases was also reported. Methods We retrospectively reviewed the clinical data of 25 patients who received apatinib between August 2015 and May 2016. Progression-free survival (PFS) was calculated by using the Kaplan-Meier method. Results The objective response rate and disease control rate were 8.0% and 68.0%, respectively. The median PFS was 5.17 (95% confidence interval [CI]: 0.76-9.57) months. In the second-line setting (n = 13), the median PFS was 7.37 (95% CI: 0.01-14.72) months, whereas the median PFS for the 12 patients treated with apatinib as third line or beyond therapy was 5.17 (95% CI: 1.78-8.55) months. Of the seven patients with brain metastases, four patients had stable disease. All patients were well tolerant to apatinib without any grade 3 or 4 adverse events. The most common grade 1 or 2 adverse events included hypertension (72.0%), hand-foot-skin reaction (24.0%), fatigue (24.0%) and abnormal liver function (20.0%). Conclusions Apatinib is effective and well tolerated in patients with advanced NSCLC, even at a dosage of 500 mg qd, and might offer a new option for the treatment of such patients with brain metastases.

Evaporites commonly occur in the Mesozoic-Cenozoic Tethyan domain, which characterized by extensive Late Cretaceous potash deposits in the Lanping-Simao Basin (LSB) in southwestern China and in the Khorat Plateau (KP) in Thailand and Laos. The LSB and the KP are located in the eastern Tethyan tectonic belt. The origin of the Late Cretaceous evaporites in these basins is controversial; possibilities include marine, continental, or hydrothermal origins. In addition, the recharge model for the major solutes into these evaporitic basins is inadequate, whether it is from the KP to the LSB or from the Qiangtang to the LSB to the KP. In this study, 34 gypsum, anhydrite, and halite samples from two sediment cores collected from the KP were analyzed to determine their stable B-Sr-S isotopic compositions. This is the first time that δ11B values have been reported for the anhydrite in the study area. The origin and evolutionary relationships of these evaporitic basins were investigated based on the geochemical data, sedimentary features, mineral sequences, and stratigraphic ages of the evaporites in the LSB and KP. The tectonic evolution and stratigraphic comparisons during the Triassic-Cretaceous in the eastern Tethyan domain were systematically reviewed and summarized in order to determine a preferred recharge model for the evaporites in the KP. The following conclusions were reached. (1) The reconstructed δ11B values (+38.20‰ to + 51.23‰) of the parent solution, which were based on those of the anhydrite (+8.20‰ to + 21.23‰), and the isotopic fractionation levels (30.2‰ to 32.7‰), 87Sr/86Sr ratios (0.70743–0.70846), and δ34S values (+14.39‰ to +15.94‰) of the anhydrite and halite in the KP overlap with those of Late Cretaceous seawater, suggesting a marine origin. (2) The similar mineral sequences and B-Sr-S isotopic signatures, and the comparable sedimentary features and inherited ore-forming ages indicate that evaporites in the LSB and KP have similar solute sources and evolutionary relationships. (3) The tectonic evolution and stratigraphy demonstrate that during the Late Cretaceous, paleoseawater from the Shan Boundary Ocean (the eastern segment of the Meso-Tethys Ocean) most likely passed through the southwestern part (Tengchong-Baoshan block) of Sibumasu and preferably recharged marine solutes into the LSB and KP.

Background This study was conducted to evaluate the efficacy and safety of paclitaxel-carboplatin combined with intercalated gefitinib in patients with advanced, untreated, nonsquamous non-small cell lung cancer. Methods A total of 29 patients were enrolled in the study. All patients were Chinese, with a histology type of adenocarcinoma, without a smoking history, and as a result of the limited tissue sample, an epidermal growth factor receptor (EGFR) mutation test could not be performed. All patients received chemotherapy of paclitaxel-carboplatin every 21 days for four cycles, and gefitinib (250 mg/day) was administered on days eight to 17 of the chemotherapy cycle. If the patient responded to chemotherapy, maintenance therapy of 250mg of gefitinib could be administered daily. Results All of the 29 patients received at least one cycle of chemotherapy and gefitinib, and 25 patients received four cycles of therapy. Eighteen patients selected maintenance therapy with gefitinib. The objective response rate was 74.1% (95% confidence interval, 53.7% to 88.9%). No complete response was achieved. The median progression-free survival was 16 months, however, the median overall survival was not available by the conclusion of the study. The major adverse event was hematologic toxicity. Conclusions The regimen of paclitaxel-carboplatin combined with intercalated gefitinib showed a high response rate and a favorable safety profile. Gefitinib maintenance therapy was proven to be beneficial. This study proposes a good pattern of chemotherapy combined with EGFR tyrosine kinase inhibitors.

The formation of brominated disinfection byproducts (Br-DBPs), which are generally significantly more cytotoxic and genotoxic than their chlorinated analogues, in chloramination has not been fully examined. In this work, the formation of new polar Br-DBPs in simulated drinking waters was examined using state-of-the-art ultraperformance liquid chromatography/electrospray ionization-triple quadrupole mass spectrometry. As many as 29 aliphatic, aromatic, or nitrogenous polar Br-DBPs were detected in chloramination, and five of them (including 2,4,6-tribromoresorcinol, 2,6-dibromo-4-nitrophenol, 2,2,4-tribromo-5-hydroxy-4-cyclopentene-1,3-dione, 2,2,4-dibromochloro-5-hydroxy-4-cyclopentene-1,3-dione, and 2,2,4-bromodichloro-5-hydroxy-4-cyclopentene-1,3-dione) were tentatively identified. Unlike chlorination, chloramination favored the formation of aromatic and nitrogenous polar Br-DBPs and was mild enough to allow polar intermediate Br-DBPs to accumulate. To further explore the formation mechanism of Br-DBPs in chloramination, a quantitative empirical model involving 33 major reactions was developed to describe the overall kinetics. According to the modeling results, bromochloramine and monobromamine were the major species responsible for 54.2-58.1% and 41.7-45.7%, respectively, of the formed Br-DBPs, while hypobromous acid accounted for only 0.2% of the formed Br-DBPs; direct reactions between monochloramine and natural organic matter accounted for the majority of the formed chlorinated DBPs (93.7-95.1%); hypochlorous acid and hypobromous acid in the chloramination were at ng/L or subng/L levels, which were not enough to cause polar intermediate Br-DBPs to decompose.

The fracture process zone (FPZ) of concrete under three-point bending was extensively investigated using the digital image correlation technique. Surface displacement, strain components, crack opening displacement, effective crack length, and crack tip position were calculated and analyzed. The development of crack and FPZ were obtained through data processing and applied to the analysis of mechanical response. The development of the FPZ, divided into three stages, was found to have strong consistency with the change of the mechanical behavior of concrete. Two characteristic parameters of FPZ were used to study the size effect of concrete. It is found that with the increase of size, the FPZ will develop deeper at peak load. However, the ratio of the maximum length of the FPZ to the initial ligament length does not vary with size, which is about 0.85 in this study.

Background Epidermal growth factor-tyrosine kinase inhibitors (EGFR-TKIs) are one of the effective medicines in advanced lung adenocarcinoma leptomeningeal metastasis (LM) treatment in recent years. Methods This paper reports two cases of advanced lung adenocarcinoma with exon-EGFR19 mutation. LM occurred during gefitinib treatment with an extracranial condition under control. Later, erlotinib was adopted with a recurrent response. Results The progression free survival of both patients was over six months and their LM was under control for six and a half and nine months, respectively. LM may be sensitive on different levels to different EGFR-TKIs. Conclusion Erlotinib can be used to replace gefitinib if intracranial tumor progress occurs during gefitinib treatment. However, our conclusion still needs to be proven by further clinical research.

The dissolved iodine species that dominate aquatic systems are iodide, iodate and organo-iodine. These species may undergo transformation to one another and thus affect the formation of iodinated disinfection byproducts during disinfection of drinking waters or wastewater effluents. In this study, a fast, sensitive and accurate method for determining these iodine species in waters was developed by derivatizing iodide and iodate to organic iodine and measuring organic iodine with a total organic iodine (TOI) measurement approach. Within this method, organo-iodine was determined directly by TOI measurement; iodide was oxidized by monochloramine to hypoiodous acid and then hypoiodous acid reacted with phenol to form organic iodine, which was determined by TOI measurement; iodate was reduced by ascorbic acid to iodide and then determined as iodide. The quantitation limit of organo-iodine or sum of organo-iodine and iodide or sum of organo-iodine, iodide and iodate was 5 μg/L as I for a 40 mL water sample (or 2.5 μg/L as I for an 80 mL water sample, or 1.25 μg/L as I for a 160 mL water sample). This method was successfully applied to the determination of iodide, iodate and organo-iodine in a variety of water samples, including tap water, seawater, urine and wastewater. The recoveries of iodide, iodate and organo-iodine were 91-109%, 90-108% and 91-108%, respectively. The concentrations and distributions of iodine species in different water samples were obtained and compared.

Using seawater for toilet flushing may introduce high levels of bromide and iodide into a city's sewage treatment works, and result in the formation of brominated and iodinated disinfection byproducts (DBPs) during chlorination to disinfect sewage effluents. In a previous study, the authors' group has detected the presence of many brominated DBPs and identified five new aromatic brominated DBPs in chlorinated saline sewage effluents. The presence of brominated DBPs in chlorinated saline effluents may pose adverse implications for marine ecology. In this study, besides the detection and identification of another seven new aromatic halogenated DBPs in a chlorinated saline sewage effluent, their developmental toxicity was evaluated using the marine polychaete Platynereis dumerilii. For comparison, the developmental toxicity of some commonly known halogenated DBPs was also examined. The rank order of the developmental toxicity of 20 halogenated DBPs was 2,5-dibromohydroquinone2,6-diiodo-4-nitrophenol ≥ 2,4,6-triiodophenol4-bromo-2-chlorophenol ≥ 4-bromophenol2,4-dibromophenol ≥ 2,6-dibromo-4-nitrophenol2-bromo-4-chlorophenol2,6-dichloro-4-nitrophenol2,4-dichlorophenol2,4,6-tribromophenol3,5-dibromo-4-hydroxybenzaldehydebromoform ≥ 2,4,6-trichlorophenol2,6-dibromophenol2,6-dichlorophenoliodoacetic acid ≥ tribromoacetic acidbromoacetic acidchloroacetic acid. On the basis of developmental toxicity data, a quantitative structure-activity relationship (QSAR) was established. The QSAR involved two physical-chemical property descriptors (log P and pKa) and two electronic descriptors (the lowest unoccupied molecular orbital energy and the highest occupied molecular orbital energy) to indicate the transport, biouptake, and biointeraction of these DBPs. It can well predict the developmental toxicity of most of the DBPs tested.

Total organic halogen (TOX) is a collective parameter and a toxicity indicator for all the halogenated organic disinfection byproducts (DBPs) in a water sample. TOX measurement involves concentration of halogenated organic DBPs by adsorption onto activated carbon. Prior to activated carbon adsorption, quenching the chlorine residual in a water sample is an indispensable step to eliminate the positive interference resulting from continued chlorination with organic compounds adsorbed on the activated carbon surface or with the activated carbon surface itself. Arsenite is generally applied as the quenching agent. In this study, the arsenite quenching agent dose that was 100% of the stoichiometric amount of the chlorine residual in a water sample was demonstrated to be most appropriate. In practice, to ensure complete reduction of chlorine residual, slight overdose of arsenite is often recommended, but this was found to cause negative interferences in the TOX measurement due to two reasons. First, the competi...