Functional hydrogels for hepatocellular carcinoma: therapy, imaging, and in vitro model.

Hepatocellular carcinoma (HCC) is among the most common malignancies worldwide and is characterized by high rates of morbidity and mortality, posing a serious threat to human health. Interventional embolization therapy is the main treatment against middle- and late-stage liver cancer, but its efficacy is limited by the performance of embolism, hence the new embolic materials have provided hope to the inoperable patients. Especially, hydrogel materials with high embolization strength, appropriate viscosity, reliable security and multifunctionality are widely used as embolic materials, and can improve the efficacy of interventional therapy. In this review, we have described the status of research on hydrogels and challenges in the field of HCC therapy. First, various preparation methods of hydrogels through different cross-linking methods are introduced, then the functions of hydrogels related to HCC are summarized, including different HCC therapies, various imaging techniques, in vitro 3D models, and the shortcomings and prospects of the proposed applications are discussed in relation to HCC. We hope that this review is informative for readers interested in multifunctional hydrogels and will help researchers develop more novel embolic materials for interventional therapy of HCC.

Viola yedoensis Makino alleviates lipopolysaccharide-induced intestinal oxidative stress and inflammatory response by regulating the gut microbiota and NF-κB-NLRP3/ Nrf2-MAPK signaling pathway in broiler.

Viola yedoensis Makino (Vy) is a well-known traditional Chinese medicine widely used to treat inflammatory diseases. However, the regulatory effects of dietary Vy supplementation on lipopolysaccharide (LPS)-induced intestinal damage in broilers and the underlying molecular mechanisms remain unclear. In this study, broilers were intraperitoneally injected with 1 mg/kg LPS on days 17, 19 and 21 to induce intestinal damage. Vy supplementation at 0.5, 1.5 and 4.5 % in the diet was administered separately for 21 days to investigate the potential protective effects of Vy supplementation against LPS-induced intestinal impairment in broilers. Vy supplementation improved intestinal morphology and restored growth performance. Vy supplementation attenuated intestinal inflammation by regulating the nuclear factor kappa B (NF-κB) / NLR family pyrin domain-containing 3 (NLRP3) signaling pathway and inhibited its downstream pro-inflammatory factor levels. In addition, Vy supplementation relieved intestinal oxidative impairment by regulating the nuclear factor erythroid-2 related factor 2 (Nrf2) / mitogen-activated protein kinase (MAPK) signaling pathway and downstream antioxidant enzyme activity. Vy supplementation reduced LPS-induced mitochondrial damage and apoptosis. Furthermore, Vy supplementation alleviated LPS-induced intestinal inflammation and oxidative damage in chickens by increasing the abundance of protective bacteria (Lactobacillus and Romboutsia) and reducing the number of pathogenic bacteria (unclassified_f_Ruminococcaceae, unclassified_f_Oscillospiraceae and norank_f_norank_o_Clostridia_vadinBB60_group). Overall, Vy supplementation effectively ameliorated LPS-induced intestinal damage by regulating the NF-κB-NLRP3/Nrf2-MAPK signaling pathway and maintaining intestinal microbiota balance. Vy supplementation can be used as a dietary supplement to protect broilers against intestinal inflammation and oxidative damage.

Dual Nickel/Photoredox-Catalyzed Arylsulfonylation of Allenes.

The nickel/photoredox dual catalysis system is an efficient conversion platform for the difunctionalization of unsaturated hydrocarbons. Herein, we disclose the first dual nickel/photoredox-catalyzed intramolecular 1,2-arylsulfonylation of allenes, which can accurately construct a C(sp2)-C(sp2) bond and a C(sp3)-S bond. The reaction exhibits excellent chemoselectivity and regioselectivity, allowing modular conformations of a diverse series of 3-sulfonylmethylbenzofuran derivatives. Control experiments showed that the bipyridine ligand is crucial for the formation of a stable σ-alkyl nickel intermediate, providing the possibility for sulfonyl radical insertion. Meanwhile, the electrophilic sulfonyl radical facilitates further oxidative addition of the σ-alkyl nickel intermediate and inhibits addition with allenes. In addition, control experiments, cyclic voltammetry tests, Stern-Volmer experiments, and density functional theory calculations afford evidence for the Ni(0)/Ni(I)/Ni(II)/Ni(III) pathway in this 1,2-arylsulfonylation.

Four-Component Radical 1,2-Selenosulfonylation of Allenes.

Selenosulfones, as pivotal pharmaceutical molecule frameworks, have become a research hotspot in modern organic synthesis due to their vital need for efficient preparation. Herein, we have developed an iron-catalyzed four-component controllable radical tandem reaction of allenes involving cycloketone oxime esters, 1,4-diazabicyclo[2.2.2]octane bis(sulfur dioxide) adduct (DABSO), and diphenyl diselenides for the synthesis of complex selenosulfones. This is the first case of achieving the 1,2-selenosulfonylation of allenes via a radical process, wherein precise control of radical rates and polarity matching enhance high regioselective conversion. The reaction conditions are ecofriendly and mild with step-efficiency by forming two new C-S bonds and one C-Se bond in one pot. Moreover, the 1,2-selenosulfonylation of allenes can be achieved by replacing cycloketone oxime esters with aryldiazonium tetrafluoroborates in this system.

Inhibition mechanism of theaflavins on matrix metalloproteinase-2: inhibition kinetics, multispectral analysis, molecular docking and molecular dynamics simulation.

Dental caries is a chronic and destructive disease and matrix metalloproteinase-2 (MMP-2) plays a major role in caries. The inhibitory mechanisms of theaflavins [theaflavin (TF1), theaflavin-3-gallate (TF2A), theaflavin-3'-gallate (TF2B), and theaflavin-3,3'-digallate (TF3)] on MMP-2 were investigated using techniques such as enzyme inhibition kinetics, multi-spectral methods, molecular docking, and molecular dynamics simulations. The results showed that TF1, TF2A, TF2B, and TF3 all competitively and reversibly inhibited MMP-2 activity. Fluorescence spectra and molecular docking indicated that four theaflavins spontaneously bind to MMP-2 through noncovalent interactions, driven by hydrogen bonds and hydrophobic interactions, constituting a static quenching mechanism and resulting in an altered tryptophan residue environment around MMP-2. Molecular dynamic simulations demonstrated that four theaflavins can form stable, compact complexes with MMP-2. In addition, the order of theaflavins' ability to inhibit MMP-2 was found to be TF1 > TF2B > TF2A > TF3. Interestingly, the order of binding capacity between MMP-2 and TF1, TF2A, TF2B, and TF3 was consistent with the order of inhibitory capacity, and was opposite to the order of steric hindrance of theaflavins. This may be due to the narrow space of the active pocket of MMP-2, and the smaller the steric hindrance of theaflavins, the easier it is to enter the active pocket and bind to MMP-2. This study provided novel insights into theaflavins as functional components in the exploration of natural MMP-2 inhibitors.

Effects of different rootstocks grafting on selenium accumulation in Cyphomandra betacea Sendt. seedlings under selenium-contaminated soil.

The effects of rootstocks tomato (Solanum lycopersicum L.), eggplant (Solanum melongena L.), and nightshade (Solanum nigrum L.) grafting on the growth and selenium (Se) accumulation of Cyphomandra betacea Sendt. seedlings were studied to identify the most suitable rootstock for increasing Se uptake of fruit trees grown in Se-contaminated soil. The rootstocks of tomato, eggplant, and nightshade grafting increased the scion biomass of C. betacea seedlings by 146.1%, 23.2%, and 94.5%, respectively, compared with the un-grafted seedlings. Moreover, tomato, eggplant, and nightshade rootstocks grafting increased the photosynthesis, superoxide dismutase activity, and peroxidase activity, while reducing the catalase activity and soluble protein content of C. betacea seedlings. Although all three rootstocks grafting decreased Se contents in rootstock roots and stems, only nightshade rootstock grafting increased Se content in the scions of C. betacea seedlings. Notably, root biomass, catalase activity, soluble protein content, rootstock root Se content, and rootstock stem Se content were closely related to the scion Se content. These findings suggest that only grafting onto nightshade rootstock significantly enhances Se uptake in C. betacea, whereas tomato and eggplant rootstocks grafting have no effect on Se uptake.

This study shows that under selenium (Se)-contaminated soil conditions, tomato, eggplant, and nightshade rootstocks can promote the growth of C. betacea seedlings and improve their stress resistance. The nightshade rootstock stands out for its ability to promote Se uptake in C. betacea seedlings, suggesting its suitability as a promising rootstock to enhance both growth and Se uptake in C. betacea.

Lenvatinib in hepatocellular carcinoma: Resistance mechanisms and strategies for improved efficacy.

Hepatocellular carcinoma (HCC), one of the most prevalent and destructive causes of cancer-related deaths worldwide, approximately 70% of patients with HCC exhibit advanced disease at diagnosis, limiting the potential for radical treatment. For such patients, lenvatinib, a long-awaited alternative to sorafenib for first-line targeted therapy, has become a key treatment. Unfortunately, despite some progress, the prognosis for advanced HCC remains poor because of drug resistance development. However, the molecular mechanisms underlying lenvatinib resistance and ways to relief drug resistance in HCC are largely unknown and lack of systematic summary; thus, this review not only aims to explore factors contributing to lenvatinib resistance in HCC, but more importantly, summary potential methods to conquer or mitigate the resistance. The results suggest that abnormal activation of pathways, drug transport, epigenetics, tumour microenvironment, cancer stem cells, regulated cell death, epithelial-mesenchymal transition, and other mechanisms are involved in the development of lenvatinib resistance in HCC and subsequent HCC progression. To improve the therapeutic outcomes of lenvatinib, inhibiting acquired resistance, combined therapies, and nano-delivery carriers may be possible approaches.

Antipsychotic drug-induced behavioral abnormalities in common carp: The potential involvement of the gut microbiota-brain axis.

The effects of antipsychotic drugs on aquatic organisms have received widespread attention owing to their widespread use and continued release in aquatic environments. The toxicological effects of antipsychotics on aquatic organisms, particularly fish, are unexplored, and the underlying mechanisms remain unelucidated. This study aimed to use common carp to explore the effects of antipsychotics (olanzapine [OLA] and risperidone [RIS]) on behavior and the potential mechanisms driving these effects. The fish were exposed to OLA (0.1 and 10 µg/L) and RIS (0.03 and 3 µg/L) for 60 days. Behavioral tests and neurological indicators showed that exposure to antipsychotics could cause behavioral abnormalities and neurotoxicity in common carp. Further, 16 S rRNA sequencing revealed gut microbiota alteration and decreased relative abundance of some strains related to SCFA production after OLA and RIS exposure. Subsequently, a pseudo-sterile common carp model was successfully constructed, and transplantation of the gut microbiota from antipsychotic-exposed fish caused behavioral abnormalities and neurotoxicity in pseudo-sterile fish. Further, SCFA supplementation demonstrated that SCFAs ameliorated the behavioral abnormalities and neurological damage caused by antipsychotic exposure. To our knowledge, the present study is the first to investigate the effects of antipsychotics on various complex behaviors (swimming performance and social behavior) in common carp, highlighting the potential health risks associated with antipsychotic drug-induced neurotoxicity in fish. Although these results do not fully elucidate the mechanisms underlying the effects of antipsychotic drugs on fish behavior, they serve as a valuable initial investigation and form the basis for future research.

Hepatic artery infusion chemotherapy combined with the FOLFOX regimen for the treatment of hepatocellular carcinoma: recent advances and literature review.

INTRODUCTION: The incidence of primary liver cancer (PLC) has experienced a significant global increase, primarily attributed to the rise in hepatocellular carcinoma (HCC). Unfortunately, HCC is often diagnosed in advanced stages, leaving patients with limited treatment options. Therefore, transformation therapy is a crucial approach for long-term survival and radical resection in patients with advanced HCC. Conversion therapy has demonstrated promise in the treatment of advanced HCC. When integrated with the FOLFOX regimen, hepatic artery infusion chemotherapy (HAIC) can significantly improve tumor response efficiency, leading to high conversion and resection rates. AREAS COVERED: We reviewed landmark trials of HAIC in combination with different drugs or means for the treatment of HCC to determine the clinical value of HAIC-centric translational therapies in HCC treatment. Furthermore, we specifically emphasize the advantages associated with employing FOLFOX-HAIC in the treatment of advanced HCC. EXPERT OPINION: The combination of HAIC with the FOLFOX regimen can help prevent the low intratumoral accumulation and high adverse reaction rate caused by the FOLFOX alone, holding significant potential in the comprehensive treatment of future HCC patients.

Cancer diagnosis and treatment platform based on manganese-based nanomaterials.

Cancer is a leading cause of death worldwide, and the development of new diagnostic and treatment methods is crucial. Manganese-based nanomaterials (MnNMs) have emerged as a focal point in the field of cancer diagnosis and treatment due to their multifunctional properties. These nanomaterials have been extensively explored as contrast agents for various imaging technologies such as magnetic resonance imaging (MRI), photoacoustic imaging (PAI), and near-infrared fluorescence imaging (NIR-FL). The use of these nanomaterials has significantly enhanced the contrast for precise tumor detection and localization. Moreover, MnNMs have shown responsiveness to the tumor microenvironment (TME), enabling innovative approaches to cancer treatment. This review provides an overview of the latest developments of MnNMs and their potential applications in tumor diagnosis and therapy. Finally, potential challenges and prospects of MnNMs in clinical applications are discussed. We believe that this review would serve as a valuable resource for guiding further research on the application of manganese nanomaterials in cancer diagnosis and treatment, addressing the current limitations, and proposing future research directions.

Betulinic acid attenuates T-2 toxin-induced lung injury by activating Nrf2 signaling pathway and inhibiting MAPK/NF-κB signaling pathway.

T-2 toxin, a type-A trichothecene mycotoxin, exists ubiquitously in mildewed foods and feeds. Betulinic acid (BA), a pentacyclic triterpenoid derived from plants, has the effect of relieving inflammation and oxidative stress. The purpose of this study was to investigate whether BA mitigates lung impairment caused by T-2 toxin and elucidate the underlying mechanism. The results indicated that T-2 toxin triggered the inflammatory cell infiltration, morphological alterations and cell apoptosis in the lungs. It is gratifying that BA ameliorated T-2 toxin-caused lung injury. The protein expression of nuclear factor erythrocyte 2-related factor 2 (Nrf2) pathway and the markers of antioxidative capability were improved in T-2 toxin induced lung injury by BA mediated protection. Simultaneously, BA supplementation could suppress T-2 toxin-induced mitogen-activated protein kinase (MAPK)/nuclear factor-kappa B (NF-κB)-dependent inflammatory response and mitochondrial apoptotic pathway. Therefore, T-2 toxin gave rise to pulmonary toxicity, but these changes were moderated by BA administration through regulation of the Nrf2/MAPK/NF-κB pathway, which maybe offer a viable alternative for mitigating the lung impairments caused by the mycotoxin.

The roles of theaflavins in reducing dentin erosion.

This study aimed to evaluate the effect of theaflavins [TFs] on the process of dentin erosion and investigation the potential mechanism. For erosion kinetics of the dentin, 7 experimental groups (n = 5) treated with 10% ethanol [EtOH] (negative control) are erosion for 1, 2, 3, 4, 5, 6, and 7 d erosion cycles (4 cycles/d). For the effect of TFs on dentin erosion, 6 experimental groups (n = 5) were treated with 1% epigallocatechin gallate [EGCG], 1% chlorhexidine [CHX], 1%, 2%, 4%, and 8% TFs for the 30 s and then subjected to erosion cycles (4 cycles/d for 7 d). The erosive dentin wear (µm) and surface morphology were evaluated and compared by laser scanning confocal microscope and scanning electron microscopy. The matrix metalloproteinase inhibition effects of TFs were investigated using in situ zymography and molecular docking. TFs-treated collagen was investigated by ultimate microtensile strength, Fourier-transform infrared spectroscopy, and molecular docking. Data were analyzed by ANOVA, Tukey's test (P < 0.05). The TFs-treated groups (7.56 ± 0.39, 5.29 ± 0.61, 3.28 ± 0.33, and 2.62 ± 0.99 µm for 1%, 2%, 4%, and 8% TFs) had significantly lower erosive dentin wear than the negative control group (11.23 ± 0.82 µm), and the effect was concentration-dependent at low concentrations (P < 0.05). TFs inhibit matrix metalloproteinase [MMP]. Moreover, TFs crosslink dentin collagen and cause hydrophilic changes in dentin collagen. TFs preserve organic matrix within the demineralized dentin by inhibiting MMP activity and simultaneously improving collagen's resistance to enzymes, both of which contribute to preventing or slowing down the progression of dentin erosion.

A fluorescent biosensor based on quantum dot-labeled streptavidin and poly-l-lysine for the rapid detection of Salmonella in milk.

Salmonella, as a common foodborne pathogen in dairy products, poses a great threat to human health. We studied a new detection method based on quantum dots (QD). A fluorescent biosensor with multiple fluorescent signal amplification based on a streptavidin (SA) biotin system and the polyamino linear polymer poly-l-lysine (PLL) were established to detect Salmonella in milk. First, Salmonella was captured on a black 96-well plate with paired Salmonella mAb to form a double-antibody sandwich. Second, SA was immobilized on biotin-modified mAb by SA-biotin specific bond. Then, the biotin-modified polylysine (BT-PLL) was bound on SA and specifically bonded again through the SA-biotin system. Finally, water-soluble CdSe/ZnS QD-labeled SA was added to a black 96-well plate for covalent coupling with BT-PLL. The fluorescent signal was amplified in a dendritic manner by the layer-by-layer overlap of SA and biotin and the covalent coupling of biotinylated PLL. Under optimal conditions, the detection limit was 4.9 × 103 cfu/mL in PBS. The detection limit was 10 times better than that of the conventional sandwich ELISA. In addition, the proposed biosensor was well specific and could be used for detecting Salmonella in milk samples.

A novel electrochemical immunosensor based on Fe3O4@graphene nanocomposite modified glassy carbon electrode for rapid detection of Salmonella in milk.

Foods contaminated by foodborne pathogens have always been a great threat to human life. Herein, we constructed an electrochemical immunosensor for Salmonella detection by using a Fe3O4@graphene modified electrode. Because of the excellent electrical conductivity and mechanical stability of graphene and the large specific surface area of Fe3O4, the Fe3O4@graphene nanocomposite exhibits an excellent electrical signal, which greatly increased the sensitivity of the immunosensor. Gold nanoparticles were deposited on Fe3O4@graphene nanocomposite by electrochemical technology for the immobilization of the antibody. Cyclic voltammetry was selected to electrochemically characterize the construction process of immunosensors. The microstructure and morphology of related nanocomposites were analyzed by scanning electron microscopy. Under optimized experimental conditions, a good linear relationship was achieved in the Salmonella concentration range of 2.4 × 102 to 2.4 × 107 cfu/mL, and the limit of detection of the immunosensor was 2.4 × 102 cfu/mL. Additionally, the constructed immunosensor exhibited acceptable selectivity, reproducibility, and stability and provides a new reference for detecting pathogenic bacteria in milk.

The complete chloroplast genome sequence of the endemic and rare orchid Nothodoritis zhejiangensis (Orchidaceae) in China.

Nothodoritis zhejiangensis (Orchidaceae) is a rare orchid unique to China of great horticultural value. The complete chloroplast (cp) genome of this species is 143,522 bp in length and the total GC content is 36.8%. It includes a large single copy (LSC) region of 83,830 bp in length, a small single copy (SSC) region of 10,764 bp, and a pair of inverted repeat regions (IRs) with 24,464 bp. The cp genome contains 120 functional genes, including 74 protein-coding genes, 38 tRNA genes, and eight rRNA genes. The phylogenetic tree constructed by the maximum-likelihood method showed that the taxonomic status of N. zhejiangensis was clustered with the species in Phalaenopsis.

The complete chloroplast genome sequences of an endangered orchid species Paphiopedilum parishii (Orchidaceae).

Paphiopedilum parishii (Rchb. f.) Stein is an endangered and rare species with highly ornamental value. In this study, we report the complete chloroplast genome of P. parishii using the Illumina sequencing data. The total genome of P. parishii is 154,689 bp in length and the GC content is 35.9%, with a pair of inverted repeats (IRs) regions of 32,690 bp each, a large single-copy region (LSC) of 86,863 bp and a small single-copy region (SSC) of 2,446 bp. The chloroplast genome encoded 127 genes, including 82 protein-coding genes (CDS), 8 rRNA genes and 37 tRNA genes. The phylogenetic tree showed that P. parishii was clustered with other species in Paphiopedilum with strong support based on the complete chloroplast genome.

Rapid detection of Salmonella in milk by a nuclear magnetic resonance biosensor based on the streptavidin-biotin system and O-carboxymethyl chitosan target gadolinium probe.

Rapid and sensitive detection of foodborne pathogens is of great importance for food safety. Here, a set of nuclear magnetic resonance (NMR) biosensors based on a O-carboxymethyl chitosan target gadolinium (Gd) probe was developed to quickly detect Salmonella in milk by combining NMR technology and bioimmunotechnology with membrane filtration technology. First, O-carboxymethyl chitosan (O-CMC) was biotinylated to prepare biotinylated O-carboxymethyl chitosan (biotin-O-CMC) through amide reaction, and biotinylated magnetic complexes (biotin-O-CMC-Gd) were obtained by using O-CMC, which has strong chelating adsorption on Gd. The target probe was obtained by combining biotin-O-CMC-Gd with the biotinylated antibody (biotin-antibody) via streptavidin (SA) by introducing the SA-biotin system. Then, Salmonella was captured by the target probe through antigen-antibody interaction. Finally, NMR was used to measure the longitudinal relaxation time (T1) of the filtrate collected by membrane filtration. This NMR biosensor with good specificity and high efficiency can detect Salmonella with the sensitivity of 1.8 × 103 cfu/mL within 2 h; in addition, it can realize the detection of complex samples because of its strong anti-interference capability and may open up a new method for rapid detection of Salmonella, which has a great application potential.

Takeaway food in Chengdu, Sichuan province, China: Composition and nutritional value.

BACKGROUND AND OBJECTIVES: The popularity of takeaway has caused health problems. To analyse the basic nutrients and composition of popular takeaway meals in Chengdu, China. METHODS AND STUDY DESIGN: We randomly collected 105 takeaway meals from takeaway platforms. The quality of ingredients such as grains, vegetables, and meat were assessed and weighed. The samples were then homogenised, and the nutrients were detected following the AOAC Official Methods of Analysis. RESULTS: Compared with Chinese and US dietary reference intakes, the average energy, protein, salt, fat, vitamin, and available carbohydrate contents exceeded dietary recommendations for one takeaway meal. By contrast, the whole grain, vegetable, fruit, dairy product, egg, mineral, and dietary fibre contents were insufficient. Food compositions and basic nutrients differed among takeaway meals prepared with various cooking methods and meats. Fried rice had the lowest nutritional value. The fried dish set meal had high energy density. The nutrient content of poultry takeaway meals was more balanced compared with other meals assessed, and salt and fat were excessive in mixed meat meals. In addition, meatless takeaway meals tended to have high fat content because of excess vegetable oil added for better taste. CONCLUSIONS: Takeaway meals should have lower contents of energy, fat, carbohydrate, and salt and higher contents of whole grains, vegetables, fruits, dairy products, and eggs. Attention should be paid to the high energy density of the fried dish set meal to prevent resultant health problems such as obesity. Consumers, takeaway outlets, and government agencies need to work together to address the health problems.

[Determination of 8-oxo-2'-deoxyguanosine and Cotinine in Urine by Hydrophilic Chromatography-tandem Mass Spectrometry with Isotope Dilution].

OBJECTIVE: To develop an assay for determination of 8-oxo-2'-deoxyguanosine and cotinine in human urine by hydrophilic chromatography tandem mass spectrometry (HILIC-MS/MS) with isotope dilution. METHODS: The urine supernatant was 1∶5 diluted with 3 mmol/L ammonium formate aqueous solution containing 15N 5-8-OHdG and D 3-cotinine as internal standard. After being filtered through a 0.22 µm water filter, the sample solution was injected into ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) for analysis. Separation was performed on ACQUITY UPLC® BEH HILIC column (50 mm×3.0 mm, 1.7 µm) with isocratic elution (A∶B=10∶90) at 40 ℃. The mobile phase was composed with acetonitrile (B) and 3 mmol/L ammonium formate water soulution (A). The flow rate was 0.3 mL/min. Positive ion scan-multiple reaction monitoring (MRM) mode were used for monitoring and internal standard curves were applied for quantification. RESULTS: Good linearity was obtained under the optimal conditions. Detection limits for 8-OHdG and cotinine were 0.064 µg/L and 0.035 µg/L respectively, the quantitation limits were 0.21 µg/L and 0.12 µg/L respectively, and the recoveries of the spiked urine samples were 92.6%-102% and 102%-106% respectively. Statistical analysis of 40 urine sample determination results obtained by using the above assay showed that there were significant differences in tobacco smoke exposure and tobacco-specific nitrosamine intake between active and passive smoker ( P<0.05). The concentration of NNAL and cotinine were higher in urine samples of active smoker. Tobacco smoke exposure was positively correlated with tobacco specific nitrosamine intake in both active and passive smokers (the correlation coefficients were 0.487 and 0.786 respectively, P<0.05). CONCLUSION: We successfully established a simple and fast assay for simultaneously detecting 8-oxo-2'-deoxyguanosine and cotinine in human urine. It was sensitive and accurate for quntification via the calibration by the isotope internal standards, and can meet the needs of batch analysis.

Target quantification and semi-target screening of halogenated carboxylic acids in drinking water using ultra-high performance liquid chromatography-quadrupole orbitrap high-resolution mass spectrometry.

To monitor the existing and emerging halogenated carboxylic acids (HCAs) in drinking water, a sensitive and rapid ultra-high performance liquid chromatography-quadrupole orbitrap high-resolution mass spectrometry method for simultaneous target quantification of 10 haloacetic acids (HAAs) and semi-target screening of 19 HCAs was developed. After filtration, drinking water samples were injected into the instrument. HCAs were separated on an HSS T3 column and detected by a type of non-target scan in the electrospray ionization negative mode. For target quantification of 10 HAAs, good linearity was obtained and the correlation coefficients were higher than 0.995. The limits of detection were in the range of 0.050-2.0 µg/L. The recoveries were in the range of 89.7%-108%, 83.4%-121%, 77.1%-116% and 80.2%-104% at levels of 2.5, 5.0, 10 and 20 µg/L, respectively, with relative standard deviations of 1.26%-16.9%. For semi-target screening of 19 HCAs, several criteria including accurate m/z, predicted retention time, deduced fragment ions and simulated isotope pattern were used for identification. The method was applied to analyzing 41 drinking water samples successfully. Five HAAs were detected by target quantification, with dichloroacetic acid and trichloroacetic acid exceeding the limits suggested by the U.S. Environmental Protection Agency and the World Health Organization. Eight HCAs were preliminary identified by semi-target screening, and three of them were further confirmed with reference standards purchased later.