Search Results (6)

The fungicide pyraclostrobin is the main measure used to control apple alternaria blotch in production. To evaluate the potential dietary risks for consumers, the dissipation and terminal residues of pyraclostrobin were investigated using ultra-high performance liquid chromatography–mass spectrometry (UHPLC–MS/MS). Pyraclostrobin in apples was extracted by acetonitrile with 2% ammonia and then purified using primary secondary amine (PSA) and graphitized carbon black (GCB). The method showed good linearity within the concentration range of 0.005–0.1 mg L⁻¹, with a coefficient of determination (R²) ≥ 0.9958. The recoveries ranged from 96.0% to 103.8%, with relative standard deviations (RSDs) between 0.8% and 2.3%. The limit of quantification (LOQ) was 0.01 mg kg⁻¹. Pyraclostrobin dispersible oil suspension was applied in 12 apple fields across China according to good agricultural practices (GAPs). In Beijing and Shandong, the dissipation of pyraclostrobin followed first-order kinetic equations, with a half-life of 11 days. The terminal residues ranged from <0.01 to 0.09 mg kg⁻¹. The national estimated daily intake (NEDI) of pyraclostrobin was compared with the acceptable daily intake (ADI), resulting in risk quotient (RQ_c) of 80.8%. These results suggest that pyraclostrobin poses a low health risk to consumers under GAP conditions and according to recommended dosages. Full article

Serum prostate-specific antigen (PSA) needs to be monitored with ultrasensitive PSA assays (uPSAs) for oncologists to be able to start salvage radiotherapy (SRT) while PSA is <0.5 µg/L for patients with prostate cancer (PCa) relapsing after a radical prostatectomy (RP). Our systematic review (SR) aimed to summarize uPSAs for patients with localized PCa. The SR was registered as InPLASY2023110084. We searched for studies on Google Scholar, PUBMED and reference lists of reviews and studies. We only included studies on uPSAs published in English and excluded studies of women, animals, sarcoidosis and reviews. Of the 115 included studies, 39 reported PSA assay methods and 76 reported clinical findings. Of 67,479 patients, 14,965 developed PSA recurrence (PSAR) and 2663 died. Extremely low PSA nadir and early developments of PSA separated PSAR-prone from non-PSAR-prone patients (cumulative p value 3.7 × 10¹²). RP patients with the lowest post-surgery PSA nadir and patients who had the lowest PSA at SRT had the fewest deaths. In conclusion, PSA for patients with localized PCa in the pre-PSAR phase of PCa is strongly associated with later PSAR and survival. A rising but still exceedingly low PSA at SRT predicts a good 5-year overall survival. Full article

A method was developed for the determination of matrine residues in quinoa (Chenopodium quinoa Willd.) plants and soil by liquid chromatography triple quadrupole tandem mass spectrometry (LC-MS/MS) with QuEChERS clean-up. Matrine from soil, quinoa roots, stems, leaves and seeds was extracted with 25% ammonia, 20 mL acetonitrile/methanol, salted with sodium chloride (NaCl) and purified with anhydrous magnesium sulfate (MgSO₄), N-propyl ethylenediamine (PSA) and graphitized carbon black (GCB). Then a chromatographic separation was performed on a Shim-pack XR-ODS II (75 mm × 2.0 mm, i. d., 2.2 µm) column with a gradient elution of 5 mmol/L ammonium formate-methanol as the mobile phase and monitored in multiple reaction monitoring modes (MRM) in electrospray positive ionization mode. The results showed that in the range of 0.005~1 mg/L, the linear correlation coefficients of matrine in the five matrices were all above 0.999. The LOQs for soil, quinoa roots, stems, leaves and seeds were 0.005, 0.005, 0.01, 0.01 and 0.005 mg/kg, respectively. The mean recoveries ranged from 74.42% to 98.37%, with RSDs of 1.25–6.84% at the three concentration addition levels. The average intra-day and inter-day recoveries were 73.92–92.36% and 78.56–90.18%, respectively, with RSDs below 8.72% and 9.43%. The recoveries and reproducibility of the method were superior. The method was used to determine the actual samples, which indicated that the half-lives of matrine in quinoa seeds, leaves, stems and soil were 1.28–1.32, 1.03–1.21, 0.81–0.92 and 0.93–0.97 d. It has a half-life below 30 d, which is an easily dissipated pesticide. The method is simple, sensitive, accurate, reliable and applicable to a wide range of applications, and it can achieve the rapid multi-residue determination of matrine to a certain extent. Next Generation Sequencing was used to explore the effects of exposure to high and low doses of matrine on soil bacterial communities and the composition of the three soils in the Qinghai Province (Haixi, Haidong and Haibei). The results showed that the number of ASVs increased significantly after treatment with matrine at an effective dose of 0.1 mg/kg than after treatment with matrine at an effective dose of 5.0 mg/kg. Similarly, bacterial abundance was higher after 0.1 mg/kg of matrine treatment than after 5.0 mg/kg of matrine treatment. The inhibitory effect on some bacterial flora was enhanced with an increase in matrine application, while the inhibitory effect on bacterial flora was weakened with time. Applying a certain dose of matrine e changed the relative abundance of the dominant bacterial genera of the soil bacteria. Full article

Clofazimine (CFZ) is a poorly soluble, weakly basic, small molecule antibiotic clinically used to treat leprosy and is now in clinical trials as a treatment for multidrug resistant tuberculosis and COVID-19. CFZ exhibits complex, context-dependent pharmacokinetics that are characterized by an increasing half-life in long term treatment regimens. The systemic pharmacokinetics of CFZ have been previously represented by a nonlinear, 2-compartment model incorporating an expanding volume of distribution. This expansion reflects the soluble-to-insoluble phase transition that the drug undergoes as it precipitates out and accumulates within macrophages disseminated throughout the organism. Using mice as a model organism, we studied the mechanistic underpinnings of this increasing half-life and how the systemic pharmacokinetics of CFZ are altered with continued dosing. To this end, M. tuberculosis infection status and multiple dosing schemes were studied alongside a parameter sensitivity analysis (PSA) to further understanding of systemic drug distribution. Parameter values governing the sigmoidal expansion function that captures the phase transition were methodically varied, and in turn, the systemic concentrations of the drug were calculated and compared to the experimentally measured concentrations of drug in serum and spleen. The resulting amounts of drug sequestered were dependent on the total mass of CFZ administered and the duration of drug loading. This phenomenon can be captured by altering three different parameters of an expansion function corresponding to key biological determinants responsible for the precipitation and the accumulation of the insoluble drug mass in macrophages. Through this analysis of the context dependent pharmacokinetics of CFZ, a predictive framework for projecting the systemic distribution and self-assembly of precipitated drug complexes as intracellular mechanopharmaceutical devices of this and other drugs exhibiting similarly complex pharmacokinetics can be constructed. Full article

Yersinia pestis is responsible for plague and major pandemics in Asia and Europe. This bacterium has shown resistance to an array of drugs commonly used for the treatment of plague. Therefore, effective therapeutics measurements, such as designing a vaccine that can effectively and safely prevent Y. pestis infection, are of high interest. To fast-track vaccine development against Yersinia pestis, herein, proteome-wide vaccine target annotation was performed, and structural vaccinology-assisted epitopes were predicted. Among the total 3909 proteins, only 5 (rstB, YPO2385, hmuR, flaA1a, and psaB) were shortlisted as essential vaccine targets. These targets were then subjected to multi-epitope vaccine design using different linkers. EAAK, AAY, and GPGPG as linkers were used to link CTL, HTL, and B-cell epitopes, and an adjuvant (beta defensin) was also added at the N-terminal of the MEVC. Physiochemical characterization, such as determination of the instability index, theoretical pI, half-life, aliphatic index, stability profiling, antigenicity, allergenicity, and hydropathy of the ensemble, showed that the vaccine is highly stable, antigenic, and non-allergenic and produces multiple interactions with immune receptors upon docking. In addition, molecular dynamics simulation confirmed the stable binding and good dynamic properties of the vaccine–TLR complex. Furthermore, in silico and immune simulation of the developed MEVC for Y. pestis showed that the vaccine triggered strong immune response after several doses at different intervals. Neutralization of the antigen was observed at the third day of injection. Conclusively, the vaccine designed here for Y. pestis produces an immune response; however, further immunological testing is needed to unveil its real efficacy. Full article

Kresoxim-methyl is a high-efficiency and broad-spectrum fungicide used for the control of rice fungal diseases; however, its residues after application potentially threaten human health. Investigations on the dissipation of kresoxim-methyl residue in rice field systems and dietary risk assessment of kresoxim-methyl in humans are limited. The present study employed the QuEChERS-GC-MS/MS method for residue analysis of kresoxim-methyl in rice plants, brown rice, and rice husks. The samples were extracted with acetonitrile and purified by PSA, C₁₈ column, and GCB. The average recovery of the spiked target compounds in the three matrices was between 80.5% and 99.3%, and the RSD was between 2.1% and 7.1%. The accuracy and precision of the method is in accordance with the requirements of residue analysis methods. Dissipation dynamic testing of kresoxim-methyl in rice plants indicated a half-life within the range of 1.8–6.0 days, and a rapid dissipation rate was detected. Dietary intake risk assessment showed that the national estimated daily intake (NEDI) of kresoxim-methyl in various Chinese subpopulations was 0.022–0.054 μg/(kg bw·days), and the risk quotient (RQ) was 0.0000055–0.00014%. These findings indicate that the risk for chronic dietary intake of kresoxim-methyl in brown rice is relatively low. The present study provides information and theoretical basis for guiding the scientific use of kresoxim-methyl in rice fields and evaluating its dietary risk in brown rice. Full article