Development, validation, and use of a monitoring method for fipronil and its metabolites in chicken eggs by QuEChERS with online-SPE-LC-Q/Orbitrap analysis.

RATIONALE: The residues of fipronil and its metabolites in chicken eggs pose a threat to human health, so regular monitoring is necessary. However, the pretreatments of the existing detection methods are complex and time-consuming. A simple and streamlined pretreatment method is needed to improve the detection efficiency. METHOD: A rapid, efficient, and facile approach employing the quick, easy, cheap, effective, rugged, and safe (QuEChERS) method with online solid-phase extraction liquid chromatography tandem Q Exactive Orbitrap high-resolution mass spectrometry (online-SPE-LC-HRMS) was established and evaluated for the determination of fipronil, fipronil-desulfinyl, fipronil-sulfone, and fipronil-sulfide in chicken eggs. An improved sample preparation technique combining QuEChERS and online-SPE was developed. Negative targeted ion fragmentation scanning and targeted-selected ion monitoring of HRMS were adopted to identify and quantify the target analytes. RESULTS: The proposed pretreatment method took a few steps in <13 min to achieve excellent recoveries and negligible interference. High selectivity was acquired with the adoption of Q/Orbitrap HRMS. The limit of quantification (LOQ) of the analytes was 2.5 µg kg-1 , meeting the detection requirements of the maximum residue level enacted by the Codex Alimentarius Commission, Japan, and the United States for the sum of fipronil and its metabolites. Extraction recoveries at three spiked concentration levels were within 84.56% to 93.84%, with relative standard deviation ≤5.87%. CONCLUSION: The established method is efficient and easy to operate and displays satisfactory LOQs, recoveries, accuracy, and precision. This approach serves as a reference method for monitoring eggs while providing potential solutions for fipronil determination in more complicated matrices.

Design and Synthesis of Scopoletin Sulfonate Derivatives as Potential Insecticidal Agents.

(1) Background: Scopoletin and scoparone, two naturally occurring coumarins, have garnered considerable attention and have been introduced to the market in China due to their high insecticidal efficacy and low toxicity. To investigate the structure-activity relationship of these coumarins, a series of scopoletin derivatives with aryl sulfate at C7 and different substitutes at C3 were designed and synthesized, and their insecticidal activity was studied. (2) Methods: A total of 28 new scopoletin derivatives were designed and synthesized. Most target compounds exhibited moderate insecticidal activity against the phytophagous mite Tetranychus cinnabarinus and the brine shrimp Artemia salina. (3) Results: Among these compounds, compounds 5a and 5j possessed the best insecticidal activities against T. cinnabarinus, with LC50 values of 57.0 and 20.0 µg/mL, respectively, whereas that of the control drug was 15.0 µg/mL. Compound 4j exhibited selective insecticidal activities against A. salina, with an LC50 value of 9.36 µg/mL, whereas its LC50 value against T. cinnabarinus was 93.0 µg/mL. The enzymatic inhibitory activity on acetylcholinesterase (AChE) showed a consistent tendency with the insecticidal activity. Further molecular docking analyses predicted the binding conformations of these compounds, which showed a good correlation between the insecticidal activity and the binding scores. (4) Conclusions: In general, a decreased electron cloud density of the Δ3,4 olefinic bond is beneficial for improving the insecticidal activity against both T. cinnabarinus and A. salina. In addition, naphthyl or benzene groups with a sulfate ester at the C7 position could further improve the insecticidal activity against A. salina. AChE was implied to be a site of action for potential insecticidal activity. The results provide insight into the rational design of a new generation of effective coumarin insecticides.

An automated streamlined method for the therapeutic drug monitoring of digoxin based on the online-solid-phase extraction liquid chromatography tandem high-resolution mass spectrometry.

RATIONALE: Digoxin is widely used in the clinical treatment of cardiovascular diseases. However, due to its extremely narrow therapeutic window, therapeutic drug monitoring (TDM) is vitally important. In consideration of the time-consuming and labor-intensive nature of the traditional techniques, an automated and efficient method was required for the clinical individualized TDM of digoxin. METHODS: An online solid-phase extraction liquid chromatography tandem high-resolution mass spectrometry (online-SPE-LC-HRMS) method was developed and applied for the determination of digoxin in plasma. The online SPE-LC steps included pretreatment and separation of plasma samples that were carried out using a Waters Oasis HLB cartridge and XBridge Shield RP18 column, respectively. A high-resolution Q Orbitrap mass spectrometer with targeted-selected ion monitoring in negative scan mode was applied to monitor formate-adduct ions [M + HCOO]- m/z 825.42781 for digoxin. RESULTS: Linearity was shown over the range 0.1-10 ng mL-1 for digoxin with correlation coefficients of R2 > 0.999. The lower limit of quantitation (LLOQ) for digoxin was 0.1 ng mL-1 . Extraction recoveries ranged from 82.61% to 94.28% for digoxin. The intra- and inter-day precision values were < 5.53% with accuracy ranging from 84.97% to 96.75%. The total running time was 10 min for each sample. CONCLUSION: The established method displayed satisfactory recoveries, accuracy, precision, and stability, and successfully applied on the TDM of digoxin. This automated streamlined method provides a powerful tool to guide the individualized administration of digoxin, which is significant for the practice of precision medicine.

Statistical Inference for Periodic Self-Exciting Threshold Integer-Valued Autoregressive Processes.

This paper considers the periodic self-exciting threshold integer-valued autoregressive processes under a weaker condition in which the second moment is finite instead of the innovation distribution being given. The basic statistical properties of the model are discussed, the quasi-likelihood inference of the parameters is investigated, and the asymptotic behaviors of the estimators are obtained. Threshold estimates based on quasi-likelihood and least squares methods are given. Simulation studies evidence that the quasi-likelihood methods perform well with realistic sample sizes and may be superior to least squares and maximum likelihood methods. The practical application of the processes is illustrated by a time series dataset concerning the monthly counts of claimants collecting short-term disability benefits from the Workers' Compensation Board (WCB). In addition, the forecasting problem of this dataset is addressed.

An integrated strategy for rapid on-site screening and determination of prometryn residues in herbs.

We produced a prometryn-specific monoclonal antibody and propose a strategy for convenient on-site detection of prometryn residues in herbs for the first time. This strategy has perfect applicability in a complex herbal medicine matrix. The strategy combines a semiquantitative immunochromatographic strip assay with a heterologous indirect competitive ELISA. When there was no matrix interference, the ELISA had a half-maximal inhibitory concentration of 2.6 ng·mL-1 and a limit of detection of 0.2 ng·mL-1. The immunochromatographic strip assay can be completed within 5 min with a visual limit of detection of 1 ng·mL-1. Although the sample matrix had different effects on the sensitivity of the antibody, excellent repeatability and accuracy were achieved. The method was successfully applied for the screening and determination of prometryn residue in multiple complex herb samples for the first time, and the results were in good agreement with those obtained by liquid chromatography-tandem mass spectrometry. The proposed strategy is rapid, of high-throughput, and of low cost, and may be a promising choice for on-site detection of prometryn in different kinds of herbs. Graphical abstract.

Distribution and elimination of quinocetone and its major metabolites in Cherry Valley ducks.

We examined the tissue distribution and elimination of quinocetone (QCT) and its major metabolites 1-desoxyquinocetone (1-DQCT), di-desoxyquinocetone (BDQCT), and 3-methyl-quinoxaline-2-carboxylic (MQCA) in ducks. The analytes were simultaneously quantitated using a UPLC-MS/MS method after oral administration of QCT at 100 mg·kg-1 day-1 for 7 days. We found that QCT and its major metabolites were widely distributed in duck tissues. The concentrations indicated that the primary compound in the liver, kidney, and heart was MQCA and the primary compound in the stomach, intestine, spleen, and lung was QCT. We also identified that MQCA was the most appropriate compound for QCT residue monitoring. The liver and kidney are the primary QCT target organs in ducks, and this study provides clear monitoring tools and important data to evaluate its safety.

Fluorometric competitive immunoassay for chlorpyrifos using rhodamine-modified gold nanoparticles as a label.

A new kind of labelled antibody was synthesized by modifying gold nanoparticles (AuNPs) with the fluorophore rhodamine B isothiocyanate (RBITC) and a secondary antibody (IgG). The conjugate thus obtained was used in a competitive sandwich assay with a turn-on signal change. It was designed to detect the organophosphorus pesticide chlorpyrifos. The fluorescence of the RBITC-labeled gold immunoprobe with emission at 575 nm and excitation at 556 nm is almost completely quenched. If, however, cysteamine is added, the fluorophore is released from the labeled secondary antibody and fluorescence increases in accordance with the quantity of secondary antibody bound to the sandwich. This assay was applied to determine chlorpyrifos in dried tangerine peels. The detection results were also independently confirmed by LC-MS/MS. The method allows the concentrations of chlorpyrifos to be quantified down to 4.9 ng·mL-1, which is equivalent to 61 µg·kg-1 in dried tangerine peels. In our perception, this approach has a wide potential to be applied in the determination of numerous analytes for which antibodies are available. Graphical abstract A new kind of labelled antibody was synthesized by modifying gold nanoparticles with fluorophore rhodamine B isothiocyanate (RBITC) and a secondary antibody (IgG). The conjugate was used in fluoroimmunoassay with a turn-on signal change. The method was designed to detect the organophosphorus pesticide chlorpyrifos.

Bifurcation analysis of a Morris-Lecar neuron model.

In this paper, we investigate the dynamical behaviors of a Morris-Lecar neuron model. By using bifurcation methods and numerical simulations, we examine the global structure of bifurcations of the model. Results are summarized in various two-parameter bifurcation diagrams with the stimulating current as the abscissa and the other parameter as the ordinate. We also give the one-parameter bifurcation diagrams and pay much attention to the emergence of periodic solutions and bistability. Different membrane excitability is obtained by bifurcation analysis and frequency-current curves. The alteration of the membrane properties of the Morris-Lecar neurons is discussed.

Quinone derivatives from the genus Rubia and their bioactivities.

The extracts and phytochemicals of the genus Rubia have drawn much attention due to their potent effects; among them, naphthoquinone and cyclopeptide derivatives, with significant biological activities, have great potential to be developed to new drugs. This review updates and compiles a total of 142 quinone derivatives including anthraquinone and naphthoquinone derivatives, occuring in twelve Rubia species. These compounds were listed together with their sources, melting points, bioactivities, as well as 112 corresponding references. Furthermore, the structureactivity relationships of these quinone derivatives were discussed.

Development and in vitro evaluation of a transdermal hydrogel patch for ferulic acid.

Current work aimed to develop and evaluate a transdermal delivery system of hydrogel patch for ferulic acid to treat skin damage induced by UV radiation. VISCOMATE(TM) NP700, dihydroxy aluminium aminoacetate, glycerine, tartaric acid were used in combination in different ratios to design the hydrogel patch. In vitro release rate was selected as an index to optimize the formulation. The formulated hydrogel patch was evaluated by several parameters like tacking strength, cohesive strength, peeling strength, residuals after peeling and drug content determination. The in vitro penetration was determined by Franz diffusion technology with hairless mouse skin as permeability media. Different kinetics models were employed to simulate the release and penetrate patterns of ferulic acid from patches in order to investigate the drug transport mechanism. The residual drugs in the patch and skin were determined after the penetration experiment. The optimized preparation was dihydroxy aluminium aminoacetate: NP700: glycerine: ferulic acid as a ratio of 0.02:0.4:1.5:1.25:0.25. The cumulative percentage of release was 60.4465±1.7679% for 24h, which results from a combination of diffusion effect and polymer erosion effect. For the barrier of stratum corneum, the cumulative penetrate rate was only 1.3156±0.3588% and the release mechanism turn out to be the effect of erosion of polymer surface. The residual drugs in the patch were 97.5949±1.4932%. The in vitro data revealed that it was easy for ferulic acid to release from the paste while difficult to permeate through the skin barrier, which resulted in most of drugs residued in the paste. Hence, further experiments will be necessary for finding the penetration enhancer in ferulic acid transdermal delivery.

[Study on in vitro penetration of imperatorin].

The object of this paper was to study the in vitro percutaneous factors that affect permeability of imperatorin. Excised abdominal skin of SD rats was used as the permeation model. Modified Franz diffusion cell was used to evaluate receiving solution, skin treatment and drug concentration on the effect of permeation. HPLC was established to determine drug content in recetpor at specified time points. The result showed that 20% ethanol and 0.5% Tween-80 could significantly increase the steady-state infiltration rate (Jass) of imperatorin. Skin treated of 20% ethanol, 20% ethanol-1% Tween-80 before experiments got an increased transdermal rate, whereas, those only accepted the treatment of 1% Tween-80 showed a decreased transdermal rate. The steady-state infiltration rate of imperatorin had a relationship with drug concentration, with the concentration increase, a bigger steady-state infiltration rate was obtained. When the drug concentration reached a certain concentration, the value was no longer changed. From the above research it could be found that ethanol could change the structure of the skin stratum corneum, which resulted in the increase of steady-state infiltration rate. The effect of Tween-80 on the steady-state permeation rate had nothing to do with skin structure. The concentration of drug in the diffusing cell had an effect on the penetration of imperatorin, which was the combined action of different diffusion route.

[Pharmacokinetics of ferulic acid in transdermal delivery].

OBJECTIVE: To study the pharmacokinetics of ferulic acid in transdermal delivery; the influence factors such as temperature, flow rate, and drug concentration on the probe recovery are also investigated to obtain accurate data. METHOD: The stability of in vitro and in vivo recovery was determined by loss but the influence factor on the recovery was determined by gain. Appling dermal microdialysis to ferulic acid analytes, the concentration of ferulic acid in the dialysate was detected by HPLC. RESULT: There is a significant effect on the probe recovery for the in vitro recovery is much bigger at a higher temperature. When the flow rate rises, the in vitro recovery is down at index rate instead. Within the measuring rage, the drug concentration doesn't have effect on the recovery. The steady and reproduce of recovery is well within the measuring time, and the average recovery of in vitro is (24.82 +/- 1.01)% without temperature control and in vivo is (16.50 +/- 1.92)%. The C(max) of ferulic acid is 86 min and MRT is 291 min after dermal administration. CONCLUSION: Dermal microdialyis can be used in the ferulic acid study. For the ferulic acid can permeate the corneum quciky, it is practical to develop a transdermal delivery.

[Study on transdermal behavior of Zhitong cataplasm].

The aim of the present research was to study the transdermal absorbability of ferulic acid and imperatorin in Zhitong cataplasm. Using methanol to extract the effective components, HPLC was established to determine drug content in Zhitong cataplasm. The excised abdominal skin of nude rats was used as the permeation model Utilizing the modified Franz diffusion cell, the suitable receiving solution was elected. The contents of ferulic acid and imperatorin in Zhitong cataplasm were 455.10, 371.66 microg x g(-1), respectively. Taken 20% ethanol- PBS (pH 8) as receiving solution, ferulic acid and imperatorin could be detected maximize, with the steady-state infiltration rates of 1.29, 0.15 microg x h(-1) x cm(-2), respectively. After 24 h, their penetration quantities were 30.03, 3.31 microg x cm(-2), with the penetration rates of 41.45%, 5.60%, respectively. The residual quantities of ferulic acid and imperatorin in skin were 0.69, 2.60 microg x cm(-2), with the retention rates of 0.95%, 4.40%, respectively. The in vitro transdermal behavior of ferulic acid in Zhitong cataplasm was close to a zero-order process, with the stratum corneum playing a rate-limiting role; whereas the percutaneous behavior of imperatorin was closer to Higuchi model, where diffusion played an important role in drugs permeation.

[Study on in vitro/in vivo correlation of extracts from Ligusticum chuanxiong after transdermal administration].

OBJECTIVE: To study the transdermal permeation and in vivo pharmacokinetics of effective constituent ferulic acid from Ligusticum chuanxiong, in order to establish the in vitro/in vivo correlation in transdermal permeation. METHOD: Franz diffusion cell was adopted in the in vitro transdermal permeation, with CD-1 nude rat abdominal skin as the permeation medium. Linear probes were implanted in CD-1 nude rats. With PBS as perfusate, microdialysis was employed to study the pharmacokinetics. Ferulic acid concentrations in the receptor solution and dialysate were assessed by high performance liquid chromatography (HPLC). The study on correlation between in vitro and in vivo data was conducted by deconvolution methods. RESULT: The transdermal permeation rate of ferulic acid from Ligusticum chuanxiong was (0.094 4 +/- 0.049 4) microg x cm2 x min, with Cmax of ferulic acid being 808.91 microg x L(-1), and Tmax being 183 min after dermal administration. The in vitro/in vivo correlation was 93.61. CONCLUSION: Ferulic acid in extracts from L. chuanxiong can quickly penetrate skins. By using the in vitro/in vivo correlation in transdermal permeation, simple in vitro transdermal permeation method can be adopted to study the changes in its pharmacokinetics.

A simple and rapid strategy for monitoring vancomycin concentration in serum using a multicolor immunosensor based on the ratio of gold nanobipyramids and a product of cetyltrimethylammonium bromide-blue oxide of 3,3',5,5'-tetramethylbenzidine interaction.

Rapid and simple monitoring of vancomycin (VAN) concentration in blood is a vital strategy for maximizing therapeutic efficacy, minimizing toxicity and developing a personalized treatment plan. In this work, a simple multicolor immunosensor is proposed to enable rapid monitoring of VAN concentration in serum, without using any expensive and bulky instrument. The multicolor immunosensor platform is a system that works based on the principle that the product of cetyltrimethylammonium bromide-blue oxide of 3,3',5,5'-tetramethylbenzidine interaction (CTAB/TMB+) and TMB+ increases simultaneously with the decrease in VAN concentration, whereas AuNBPs are insensitive to VAN. The result indicates that the reaction system has multiple distinct color variants. These distinct vivid color changes can be easily distinguished with the naked eye, and smartphone-relied red-green-blue (RGB) analysis can be used for quantitative detection, without the need for any sophisticated apparatus. The construction of this multicolor system omitted the hydrochloric acid (HCl) addition step, growth or etch procedure of noble metal nanoparticles in traditional multicolor immunosensors, which can improve the time-cost and tedious operation. The proposed method achieves a good linear relationship (r2 = 0.9679), accuracy (recoveries, 99.25-126.96%) and repeatability (n = 3, RSD, 1.27-2.17%). Moreover, a good correlation was observed between the results obtained from the new method and liquid chromatography-tandem mass spectrometry (r2 = 0.8993, n = 8). In summary, this work provides a new low-cost, facile and user-friendly immunosensor platform with high potential for rapid detection of VAN and various other drugs at home, hospital rooms and rural areas.

Environmental geochemical baseline determination and pollution assessment of heavy metals in farmland soil of typical coal-based cities: A case study of Suzhou City in Anhui Province, China.

Soil is the foundation of agricultural green development and human survival; the study of local environmental geochemical baselines can guide soil management and ensure the safe use of soil. In this study, a total of 100 shallow farmland soil samples were collected in each township of Yongqiao District, Suzhou City, Anhui Province, China. Herein, the contents of 10 heavy metal elements including As, Hg, Cd, Pb, Cr, Cu, Mn, Ni, Zn and Fe were determined. In addition, the geochemical baseline of heavy metals was calculated based on the relative cumulative frequency curve method, and the soil pollution status was evaluated. The results show that the average contents of As, Hg, Cd, Cu, Mn and Zn exceeded the soil background values of Anhui Province by 3.82%-64.74% (1.04-1.65 times), meanwhile, the average contents of Pb and Cr were lower than the soil background values of Anhui Province. The average contents of Cd, Cr, Cu, Mn and Ni exceeded the Chinese soil background values by 1.61%-64.74% (0.98-1.65 times). The geochemical baseline values of As, Hg, Cd, Pb, Cr, Cu, Mn, Ni, Zn and Fe were 9.585 mg/kg, 0.028 mg/kg, 0.112 mg/kg, 21.59 mg/kg, 53.66 mg/kg, 19.31 mg/kg, 543.8 mg/kg, 24.93 mg/kg, 50.57 mg/kg and 2.654%, respectively. The pollution assessment results also showed that most of the farmland soil samples in the study area were non-polluting or slightly polluted based on geochemical baselines. Hg and Cu in a few samples were moderately polluted, and Cd in only one sample was moderately intensely polluted. Combined with the distribution of pollution and field investigation, it is considered that Hg comes from atmospheric deposition and agricultural non-point source pollution of industrial pollution. Cu comes from animal husbandry and agricultural pollution. Meanwhile, Cd is related to natural sources, wood processing and agricultural fertiliser application. The study demonstrated that the calculation of soil geochemical background value should take full account of the differences between the various regions, combined with the current state, particularly the pre-consideration of the distribution of elements or pollutants. Then, reasonably select the evaluation standard value so that the evaluation results can truly reflect the state of soil pollution.

Ameliorative effect of Berberidis radix polysaccharide selenium nanoparticles against carbon tetrachloride induced oxidative stress and inflammation.

Berberidis radix polysaccharide (BRP) extracted as capping agents was applied to prepare BRP-selenium nanoparticles (BRP-SeNPs) in the redox reaction system of sodium selenite and ascorbic acid. The stability and characterization of BRP-SeNPs were investigated by physical analysis method. The results revealed that BRP were tightly wrapped on the surface of SeNPs by forming C-O⋯Se bonds or hydrogen bonding interaction (O-H⋯Se). BRP-SeNPs presented irregular, fragmented and smooth surface morphology and polycrystalline nanoring structure, and its particle size was 89.4 nm in the optimal preparation condition. The pharmacologic functions of BRP-SeNPs were explored in vitro and in vivo. The results showed that BRP-SeNPs could heighten the cell viabilities and the enzyme activity of GSH-Px and decrease the content of MDA on H2O2-induced AML-12 cells injury model. In vivo tests, the results displayed that BRP-SeNPs could increase the body weight of mice, promote the enzyme activity like SOD and GSH-Px, decrease the liver organ index and the hepatic function index such as ALT, AST, CYP2E1, reduce the content of MDA, and relieve the proinflammation factors of NO, IL-1ß and TNF-α in CCl4-induced mice injury model. Liver tissue histopathological studies corroborated the improvement of BRP-SeNPs on liver of CCl4-induced mice. The results of Western blot showed that BRP-SeNPs could attenuate oxidant stress by the Nrf2/Keap1/MKP1/JNK pathways, and downregulate the proinflammatory factors by TLR4/MAPK pathway. These findings suggested that BRP-SeNPs possess the hepatoprotection and have the potential to be a green liver-protecting and auxiliary liver inflammation drugs.

Flood Routing Model Coupled with Dynamic Leakage Losses for Ephemeral Rivers with Large Potholes.

Ephemeral rivers commonly occur in regions with a shortage of water resources, and their channel configuration tends to change substantially owing to long drying times and artificial sand extraction. During short-term water conveyance, water storage in large potholes and leakage along the dry riverbed retards the flow, which is detrimental for the river landscape and ecological water demand. The objective of this study is to evaluate the flow process corresponding to a certain release scheme. A coupled dynamic leakage loss and flood routing model was established to predict the flood routing distance for dry rivers with potholes and strong leakage. The model mainly includes three sub-models of flow dynamics, dynamic leakage loss and water balance along multiple cross sections of the river channel. The water head was dominated by flow velocity and the overflow from potholes. The model was applied to Yongding River, a typical ephemeral river in northern China, and the model parameters were calibrated and verified using monitoring data from ecological water releases into the Yongding River in 2019 and 2020, thus, making the model more stable and reliable. Finally, the model was used to evaluate the impact of cross section optimization and pothole treatment on the flow process. This study can provide scientific guidance for ecological water conveyance and the ecological restoration of ephemeral rivers.

Acid rain leaching behavior of Zn-contaminated soils solidified/stabilized using cement-soda residue.

Cement-soda residue (CSR) has been proven to be an effective binder for treating heavy metal-contaminated soils, and the durability is its most important characteristic. In this study, the effects of acid rain (AR) on the leaching behavior of CSR-solidified/stabilized, zinc-contaminated soils were investigated using flexible-wall soil column leaching tests. After leaching, some parameters were determined such as the unconfined compressive strength (UCS) and permeability coefficient of the samples, the concentrations of Zn2+ and Ca2+ in the filtrate. The test results showed that after AR leaching, the UCS of the solidified soil samples decreased and the permeability coefficient increased, while the zinc concentration in the filtrate always met the third grade of the applicable standard, the Chinese National Environmental Quality Standards (<1 mg⋅L-1). To reveal the binding mechanism, scanning electron microscopy (SEM) and mercury intrusion testing (MIP) were used to observe the microscopic characteristics of the soil samples. At the micro scale, the MIP and SEM results confirmed that the hydration products in the soil samples-hydrated calcium silicate, calcium hydroxide, and calcium zincate hydrate-partially dissolved during AR leaching, resulting in the loss of their internal structure. Consequently, the high alkalinity of the soda residue contributed to H+ neutralization in the AR leaching agent, indicating that soda residue can not only solidify heavy metal zinc ions effectively but can also buffer the erosive effect of AR on soil.

Evaluation of Poly(ADP-ribose) Polymerase Inhibitor, Pamiparib (BGB-290) in Treating Acute Myeloid Leukemia and the Characterization of Its Nanocarrier.

Despite the continuous improvement of leukemia treatment in the clinic, the overall 5-year disease-free survival of acute myeloid leukemia (AML) is only approximately 30%-60% due to relapse and the refractoriness of AML after traditional chemotherapy. Inhibition of poly(ADP-ribose) polymerase (PARP), a member of the DNA damage repair complex, has a strong antitumor effect in solid tumors. However, the role of PARP in AML remains unclear. We found that high levels of PARP1 and PARP2 were positively related to chemotherapy resistance and poor prognosis in patients with AML. Doxorubicin (DOX)-resistant AML cells highly expressed PAPR1 and PARP2. Knockdown of PARP1 and PARP2, or pharmaceutical inhibition of PARP by the PARP inhibitor (PARPi) BGB-290, significantly enhanced the cytotoxicity of DOX in AML cells due to increased DNA damage. PLGA-loading BGB-290 was properly self-assembled into stable BGB-290@PLGA nanoparticles (NPs), which is uniform particle size and good stability. BGB-290@PLGA is easily uptake by AML cell lines and stays for a long time. Combined with DOX, BGB-290@PLGA can significantly improve the chemosensitivity of AML cell lines. Furthermore, BGB-290 and DOX combination treatment dramatically repressed the onset of leukemia and prolonged the survival of THP-1 xenografted mice. Overall, this study demonstrated that PARPi with traditional chemotherapy could be an efficient therapeutic strategy for AML.