Rapid Detection of Extensive Drug Resistance by Xpert MTB/XDR Optimizes Therapeutic Decision-Making in Rifampin-Resistant Tuberculosis Patients.

The Xpert MTB/XDR assay met the critical need for etiologic diagnosis of tuberculosis and rifampin resistance in previous studies. However, its benefits in tailoring the treatment regimen and improving the outcome for patients with rifampin-resistant tuberculosis (RR-TB) require further investigation. In this study, the Xpert MTB/XDR assay was used to determine the resistance profile of second-line drugs for RR-TB patients in two registered multicenter clinical trials, TB-TRUST (NCT03867136) and TB-TRUST-plus (NCT04717908), with the aim of testing the efficacy of all-oral shorter regimens in RR-TB patients in China. Patients would receive the fluoroquinolone-based all-oral shorter regimen, the injectable-containing regimen, or the bedaquiline-based regimen depending on fluoroquinolone susceptibility by using Xpert MTB/XDR. Among the 497 patients performed with Xpert MTB/XDR, 128 (25.8%) had infections resistant to fluoroquinolones and/or second-line injectable drugs (SLIDs). A total of 371 participants were recruited for the trials, and whole-genome sequencing (WGS) was performed on all corresponding culture-positive baseline strains. Taking the WGS results as the standard, the accuracy of the Xpert MTB/XDR assay in terms of resistance detection was 95.2% to 99.0% for all drugs. A total of 33 cases had inconsistent results, 9 of which were due to resistance heterogeneity. Most of the patients (241/281, 85.8%) had sputum culture conversion at 2 months. In conclusion, the Xpert MTB/XDR assay has the potential to serve as a quick reflex test in patients with RR-TB, as detected via Xpert MTB/RIF, to provide a reliable drug susceptibility profile of the infecting Mycobacterium tuberculosis strain and to initiate optimized treatment promptly.

Optimizing (O) rifapentine-based (RI) regimen and shortening (EN) the treatment of drug-susceptible tuberculosis (T) (ORIENT) using an adaptive seamless design: study protocol of a multicenter randomized controlled trial.

BACKGROUND: Standard treatment for drug-susceptible tuberculosis (DS-TB) includes a multidrug regimen requiring at least 6 months of treatment, and this lengthy treatment easily leads to poor adherence. There is an urgent need to simplify and shorten treatment regimens to reduce interruption and adverse event rates, improve compliance, and reduce costs. METHODS: ORIENT is a multicenter, randomized controlled, open-label, phase II/III, non-inferiority trial involving DS-TB patients to evaluate the safety and efficacy of short-term regimens compared with the standardized six-month treatment regimen. In stage 1, corresponding to a phase II trial, a total of 400 patients are randomly divided into four arms, stratified by site and the presence of lung cavitation. Investigational arms include 3 short-term regimens with rifapentine 10 mg/kg, 15 mg/kg, and 20 mg/kg, while the control arm uses the standardized six-month treatment regimen. A combination of rifapentine, isoniazid, pyrazinamide, and moxifloxacin is administered for 17 or 26 weeks in rifapentine arms, while a 26-week regimen containing rifampicin, isoniazid, pyrazinamide, and ethambutol is applied in the control arm. After the safety and preliminary effectiveness analysis of patients in stage 1, the control arm and the investigational arm meeting the conditions will enter into stage 2, which is equivalent to a phase III trial and will be expanded to recruit DS-TB patients. If all investigational arms do not meet the safety conditions, stage 2 will be canceled. In stage 1, the primary safety endpoint is permanent regimen discontinuation at 8 weeks after the first dose. The primary efficacy endpoint is the proportion of favorable outcomes at 78 weeks after the first dose for both two stages. DISCUSSION: This trial will contribute to the optimal dose of rifapentine in the Chinese population and suggest the feasibility of the short-course treatment regimen containing high-dose rifapentine and moxifloxacin for DS-TB. TRIAL REGISTRATION: The trial has been registered on ClinicalTrials.gov on 28 May 2022 with the identifier NCT05401071.

Ability of the MeltPro MTB/PZA Assay to Detect Susceptibility to Pyrazinamide in Rifampin-Resistant Tuberculosis Patients.

Prediction of susceptibility to pyrazinamide (PZA) directly from sputum has been challenging. The MeltPro MTB/PZA assay, based on melting curve analysis, can simultaneously detect Mycobacterium tuberculosis and the resistance to PZA from sputum. We aimed to evaluate the MeltPro MTB/PZA assay to predict PZA resistance among rifampin-resistant tuberculosis (RR-TB) patients. We prospectively enrolled RR-TB patients in the registered trials, and their baseline sputum samples were obtained to perform the assay and culture. DNA sequencing of culture isolates was analyzed and used as the reference standard. Sanger sequencing was performed for samples with discrepant results between next-generation sequencing (NGS) and the investigational assay. The main analysis was conducted in the population of patients with interpretable results by both NGS and the assay. A total of 239 patients with RR-TB were screened, and 220 underwent the MeltPro MTB/PZA assay. The assay provided no information for 25 of 220 patients (11.4%). Among the remaining 195 patients, 13 had negative culture or insufficient raw NGS sequencing data, and 15 had indeterminate assay results. A total of 167 patients were included in the main analysis. Against DNA sequencing, the sensitivity, specificity, and negative predictive value of the assay for detecting resistance to PZA were 91.4% (95% confidence interval [CI], 87.1% to 95.6%), 89.9% (95% CI, 85.3% to 94.5%), and 95.2% (95% CI, 91.9% to 98.4%), respectively. In conclusion, the MeltPro MTB/PZA assay is a fast semiautomatic molecular platform to rapidly predict resistance to PZA from sputum and holds promise as a screening tool with satisfactory sensitivity. IMPORTANCE This study evaluated the accuracy of the MeltPro MTB/PZA assay at detecting the presence of PZA resistance through registered clinical trials. Compared to DNA sequencing, the assay had high sensitivity and negative predictive value, suggesting its potential utility as a screening tool in clinical practice. The assay could serve as an ideal primary screening tool in low PZA-resistant M. tuberculosis prevalence settings and could be used as an additional test to identify PZA resistance rapidly and initially in the RR-TB population.

Epidemiological characteristics and transmission dynamics of the outbreak caused by the SARS-CoV-2 Omicron variant in Shanghai, China: A descriptive study.

Background: In early March 2022, a major outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant spread rapidly throughout Shanghai, China. Here we aimed to provide a description of the epidemiological characteristics and spatiotemporal transmission dynamics of the Omicron outbreak under the population-based screening and lockdown policies implemented in Shanghai. Methods: We extracted individual information on SARS-CoV-2 infections reported between January 1 and May 31, 2022, and on the timeline of the adopted non-pharmaceutical interventions. The epidemic was divided into three phases: i) sporadic infections (January 1-February 28), ii) local transmission (March 1-March 31), and iii) city-wide lockdown (April 1 to May 31). We described the epidemic spread during these three phases and the subdistrict-level spatiotemporal distribution of the infections. To evaluate the impact on the transmission of SARS-CoV-2 of the adopted targeted interventions in Phase 2 and city-wide lockdown in Phase 3, we estimated the dynamics of the net reproduction number (Rt ). Findings: A surge in imported infections in Phase 1 triggered cryptic local transmission of the Omicron variant in early March, resulting in the largest outbreak in mainland China since the original wave. A total of 626,000 SARS-CoV-2 infections were reported in 99.5% (215/216) of the subdistricts of Shanghai until the end of May. The spatial distribution of the infections was highly heterogeneous, with 37% of the subdistricts accounting for 80% of all infections. A clear trend from the city center towards adjacent suburban and rural areas was observed, with a progressive slowdown of the epidemic spread (from 463 to 244 meters/day) prior to the citywide lockdown. During Phase 2, Rt remained well above 1 despite the implementation of multiple targeted interventions. The citywide lockdown imposed on April 1 led to a marked decrease in transmission, bringing Rt below the epidemic threshold in the entire city on April 14 and ultimately leading to containment of the outbreak. Interpretation: Our results highlight the risk of widespread outbreaks in mainland China, particularly under the heightened pressure of imported infections. The targeted interventions adopted in March 2022 were not capable of halting transmission, and the implementation of a strict, prolonged city-wide lockdown was needed to successfully contain the outbreak, highlighting the challenges for containing Omicron outbreaks. Funding: Key Program of the National Natural Science Foundation of China (82130093); Shanghai Rising-Star Program (22QA1402300).

Epidemiological characteristics and transmission dynamics of the outbreak caused by the SARS-CoV-2 Omicron variant in Shanghai, China: a descriptive study.

Background: In early March 2022, a major outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant spread rapidly throughout Shanghai, China. Here we aimed to provide a description of the epidemiological characteristics and spatiotemporal transmission dynamics of the Omicron outbreak under the population-based screening and lockdown policies implemented in Shanghai. Methods: We extracted individual information on SARS-CoV-2 infections reported between January 1 and May 31, 2022, and on the timeline of the adopted non-pharmacological interventions. The epidemic was divided into three phases: i) sporadic infections (January 1-February 28), ii) local transmission (March 1-March 31), and iii) city-wide lockdown (April 1 to May 31). We described the epidemic spread during these three phases and the subdistrict-level spatiotemporal distribution of the infections. To evaluate the impact on the transmission of SARS-CoV-2 of the adopted targeted interventions in Phase 2 and city-wide lockdown in Phase 3, we estimated the dynamics of the net reproduction number ( R t ). Findings: A surge in imported infections in Phase 1 triggered cryptic local transmission of the Omicron variant in early March, resulting in the largest coronavirus disease 2019 (COVID-19) outbreak in mainland China since the original wave. A total of 626,000 SARS-CoV-2 infections were reported in 99.5% (215/216) of the subdistricts of Shanghai. The spatial distribution of the infections was highly heterogeneous, with 40% of the subdistricts accounting for 80% of all infections. A clear trend from the city center towards adjacent suburban and rural areas was observed, with a progressive slowdown of the epidemic spread (from 544 to 325 meters/day) prior to the citywide lockdown. During Phase 2, R t remained well above 1 despite the implementation of multiple targeted interventions. The citywide lockdown imposed on April 1 led to a marked decrease in transmission, bringing R t below the epidemic threshold in the entire city on April 14 and ultimately leading to containment of the outbreak. Interpretation: Our results highlight the risk of widespread outbreaks in mainland China, particularly under the heightened pressure of imported infections. The targeted interventions adopted in March 2022 were not capable of halting transmission, and the implementation of a strict, prolonged city-wide lockdown was needed to successfully contain the outbreak, highlighting the challenges for successfully containing Omicron outbreaks. Funding: Key Program of the National Natural Science Foundation of China (82130093). Research in context: Evidence before this study: On May 24, 2022, we searched PubMed and Europe PMC for papers published or posted on preprint servers after January 1, 2022, using the following query: ("SARS-CoV-2" OR "Omicron" OR "BA.2") AND ("epidemiology" OR "epidemiological" OR "transmission dynamics") AND ("Shanghai"). A total of 26 studies were identified; among them, two aimed to describe or project the spread of the 2022 Omicron outbreak in Shanghai. One preprint described the epidemiological and clinical characteristics of 376 pediatric SARS-CoV-2 infections in March 2022, and the other preprint projected the epidemic progress in Shanghai, without providing an analysis of field data. In sum, none of these studies provided a comprehensive description of the epidemiological characteristics and spatiotemporal transmission dynamics of the outbreak.Added value of this study: We collected individual information on SARS-CoV-2 infection and the timeline of the public health response. Population-based screenings were repeatedly implemented during the outbreak, which allowed us to investigate the spatiotemporal spread of the Omicron BA.2 variant as well as the impact of the implemented interventions, all without enduring significant amounts of underreporting from surveillance systems, as experienced in other areas. This study provides the first comprehensive assessment of the Omicron outbreak in Shanghai, China.Implications of all the available evidence: This descriptive study provides a comprehensive understanding of the epidemiological features and transmission dynamics of the Omicron outbreak in Shanghai, China. The empirical evidence from Shanghai, which was ultimately able to curtail the outbreak, provides invaluable information to policymakers on the impact of the containment strategies adopted by the Shanghai public health officials to prepare for potential outbreaks caused by Omicron or novel variants.

Global landscape of SARS-CoV-2 genomic surveillance and data sharing.

Genomic surveillance has shaped our understanding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. We performed a global landscape analysis on SARS-CoV-2 genomic surveillance and genomic data using a collection of country-specific data. Here, we characterize increasing circulation of the Alpha variant in early 2021, subsequently replaced by the Delta variant around May 2021. SARS-CoV-2 genomic surveillance and sequencing availability varied markedly across countries, with 45 countries performing a high level of routine genomic surveillance and 96 countries with a high availability of SARS-CoV-2 sequencing. We also observed a marked heterogeneity of sequencing percentage, sequencing technologies, turnaround time and completeness of released metadata across regions and income groups. A total of 37% of countries with explicit reporting on variants shared less than half of their sequences of variants of concern (VOCs) in public repositories. Our findings indicate an urgent need to increase timely and full sharing of sequences, the standardization of metadata files and support for countries with limited sequencing and bioinformatics capacity.

Prediction of long-term kinetics of vaccine-elicited neutralizing antibody and time-varying vaccine-specific efficacy against the SARS-CoV-2 Delta variant by clinical endpoint.

BACKGROUND: Evidence on vaccine-specific protection over time, in particular against the Delta variant, and protection afforded by a homologous third dose is urgently needed. METHODS: We used a previously published model and neutralization data for five vaccines-mRNA-1273, BNT162b2, NVX-CoV2373, V01, and CoronaVac- to evaluate long-term neutralizing antibody dynamics and predict time-varying efficacy against the Delta variant by specific vaccine, age group, and clinical severity. RESULTS: We found that homologous third-dose vaccination produces higher neutralization titers compared with titers observed following primary-series vaccination for all vaccines studied. We estimate the efficacy of mRNA-1273 and BNT162b2 against Delta variant infection to be 63.5% (95% CI: 51.4-67.3%) and 78.4% (95% CI: 72.2-83.5%), respectively, 14-30 days after the second dose, and that efficacy decreases to 36.0% (95% CI: 24.1-58.0%) and 38.5% (95% CI: 28.7-49.1%) 6-8 months later. Fourteen to 30 days after administration of homologous third doses, efficacy against the Delta variant would be 97.0% (95% CI: 96.4-98.5%) and 97.2% (95.7-98.1%). All five vaccines are predicted to provide good protection against severe illness from the Delta variant after both primary and homologous third dose vaccination. CONCLUSIONS: Timely administration of third doses of SARS-CoV-2-prototype-based vaccines can provide protection against the Delta variant, with better performance from mRNA vaccines than from protein and inactivated vaccines. Irrespective of vaccine technology, a homologous third dose for all types of vaccines included in the study will effectively prevent symptomatic and severe COVID-19 caused by the Delta variant. Long-term monitoring and surveillance of antibody dynamics and vaccine protection, as well as further validation of neutralizing antibody levels or other markers that can serve as correlates of protection against SARS-CoV-2 and its variants, are needed to inform COVID-19 pandemic responses.

Neutralizing Antibodies Against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Variants Induced by Natural Infection or Vaccination: A Systematic Review and Pooled Analysis.

Recently emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants may pose a threat to immunity. A systematic landscape of neutralizing antibodies against emerging variants is needed. We systematically searched for studies that evaluated neutralizing antibody titers induced by previous infection or vaccination against SARS-CoV-2 variants and collected individual data. We identified 106 studies meeting the eligibility criteria. Lineage B.1.351 (beta), P.1 (gamma) and B.1.617.2 (delta) significantly escaped natural infection-mediated neutralization, with an average of 4.1-fold (95% confidence interval [CI]: 3.6-4.7-fold), 1.8-fold (1.4-2.4-fold), and 3.2-fold (2.4-4.1-fold) reduction in live virus neutralization assay, while neutralizing titers against B.1.1.7 (alpha) decreased slightly (1.4-fold [95% CI: 1.2-1.6-fold]). Serum from vaccinees also led to significant reductions in neutralization of B.1.351 across different platforms, with an average of 7.1-fold (95% CI: 5.5-9.0-fold) for nonreplicating vector platform, 4.1-fold (3.7-4.4-fold) for messenger RNA platform, and 2.5-fold (1.7-2.9-fold) for protein subunit platform. Neutralizing antibody levels induced by messenger RNA vaccines against SARS-CoV-2 variants were similar to, or higher, than that derived from naturally infected individuals.

Global landscape of SARS-CoV-2 genomic surveillance, public availability extent of genomic data, and epidemic shaped by variants.

Genomic surveillance has shaped our understanding of SARS-CoV-2 variants, which have proliferated globally in 2021.We collected country-specific data on SARS-CoV-2 genomic surveillance, sequencing capabilities, public genomic data from multiple public repositories, and aggregated publicly available variant data. Then, different proxies were used to estimate the sequencing coverage and public availability extent of genomic data, in addition to describing the global dissemination of variants. We found that the COVID-19 global epidemic clearly featured increasing circulation of Alpha since the start of 2021, which was rapidly replaced by the Delta variant starting around May 2021. SARS-CoV-2 genomic surveillance and sequencing availability varied markedly across countries, with 63 countries performing routine genomic surveillance and 79 countries with high availability of SARS-CoV-2 sequencing. We also observed a marked heterogeneity of sequenced coverage across regions and countries. Across different variants, 21-46% of countries with explicit reporting on variants shared less than half of their variant sequences in public repositories. Our findings indicated an urgent need to expand sequencing capacity of virus isolates, enhance the sharing of sequences, the standardization of metadata files, and supportive networks for countries with no sequencing capability.

Prediction of vaccine efficacy of the Delta variant.

The emergence of SARS-CoV-2 variants have raised concerns over the protective efficacy of the current generation of vaccines, and it remains unclear to what extent, if any, different variants impact the efficacy and effectiveness of various SARS-CoV-2 vaccines. We systematically searched for studies of SARS-CoV-2 vaccine efficacy and effectiveness, as well as neutralization data for variants, and used a previously published statistical model to predict vaccine efficacy against variants. Overall, we estimate the efficacy of mRNA-1273 and ChAdOx1 nCoV-19 against infection caused by the Delta variant to be 25-50% lower than that of prototype strains. The predicted efficacy against symptomatic illness of the mRNA vaccines BNT162b2 and mRNA-1273 are 95.1% (UI: 88.4-98.1%) and 80.8% (60.7-92.3%), respectively, which are higher than that of adenovirus-vector vaccines Ad26.COV2.S (44.8%, UI: 29.8-60.1%) and ChAdOx1 nCoV-19 (41.1%, 19.8-62.8%). Taken together, these results suggest that the development of more effective vaccine strategies against the Delta variant may be needed. Finally, the use of neutralizing antibody titers to predict efficacy against variants provides an additional tool for public health decision making, as new variants continue to emerge.

Comprehensive mapping of neutralizing antibodies against SARS-CoV-2 variants induced by natural infection or vaccination.

Background: Immunity after SARS-CoV-2 infection or vaccination has been threatened by recently emerged SARS-CoV-2 variants. A systematic summary of the landscape of neutralizing antibodies against emerging variants is needed. Methods: We systematically searched PubMed, Embase, Web of Science, and 3 pre-print servers for studies that evaluated neutralizing antibodies titers induced by previous infection or vaccination against SARS-CoV-2 variants and comprehensively collected individual data. We calculated lineage-specific GMTs across different study participants and types of neutralization assays. Findings: We identified 56 studies, including 2,483 individuals and 8,590 neutralization tests, meeting the eligibility criteria. Compared with lineage B, we estimate a 1.5-fold (95% CI: 1.0-2.2) reduction in neutralization against the B.1.1.7, 8.7-fold (95% CI: 6.5-11.7) reduction against B.1.351 and 5.0-fold (95% CI: 4.0-6.2) reduction against P.1. The estimated neutralization reductions for B.1.351 compared to lineage B were 240.2-fold (95% CI: 124.0-465.6) reduction for non-replicating vector platform, 4.6-fold (95% CI: 4.0-5.2) reduction for RNA platform, and 1.6-fold (95% CI: 1.2-2.1) reduction for protein subunit platform. The neutralizing antibodies induced by administration of inactivated vaccines and mRNA vaccines against lineage P.1 were also remarkably reduced by an average of 5.9-fold (95% CI: 3.7-9.3) and 1.5-fold (95% CI: 1.2-1.9). Interpretation: Our findings indicate that the antibody response established by natural infection or vaccination might be able to effectively neutralize B.1.1.7, but neutralizing titers against B.1.351 and P.1 suffered large reductions. Standardized protocols for neutralization assays, as well as updating immune-based prevention and treatment, are needed. Funding: Chinese National Science Fund for Distinguished Young Scholars.

Refining MDR-TB treatment regimens for ultra short therapy (TB-TRUST): study protocol for a randomized controlled trial.

BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) are unsatisfied to treat, pressing more effective and innovative treatment regimens. New efficient regimens for MDR-TB have obtained high treatment success rates. However, those regimens without drug susceptibility testing (DST) are also likely to contribute to the emergence of resistance. Precision treatments guided by DST might optimize the patients' treatment outcome individually and minimize resistance amplification. METHODS: TB-TRUST is a phase III, multicenter, open-label, randomized controlled clinical trial of non-inferiority comparing the treatment success rate between the World Health Organization (WHO) shorter regimen and the refined ultra-short regimen for fluoroquinolones and second-line injectable drugs susceptible rifampicin-resistant TB. The control arm uses the WHO injectable-containing shorter regimen for 36-44 weeks depending on time of sputum smear conversion. The investigational arm uses a refined ultra-short regimen guided by molecular DST to pyrazinamide via whole-genome sequencing (WGS) to optimize the treatment of pyrazinamide-susceptible patients with levofloxacin, linezolid, cycloserine and pyrazinamide for 24-32 weeks and pyrazinamide-resistant with levofloxacin, linezolid, cycloserine and clofazimine for 36-44 weeks. The primary outcome is the treatment success rate without relapse at 84 weeks after treatment initiation. Secondary outcomes include the time of sputum culture conversion and occurrence of adverse events. Assuming α = 0.025 level of significance (one-sided test), a power of 80%, a < 10% difference in treatment success rate between control arm and investigational (80% vs. 82%), and a 5% lost follow-up rate, the number of participants per arm to show non-inferiority was calculated as 177(354 in total). DISCUSSION: Rapid molecular testing distinguishes patients who are eligible for shorter regimen with fluoroquinolone and the WGS-guided results shorten the treatment to 6 months for pyrazinamide susceptible patients. It's foreseeable that not only novel developed medicines, but also traditional powerful medicines with the susceptibility confirmed by DST are the key factors to ensure the effect of anti-MDR-TB drugs. As a DST-guided precision treatment, TB-TRUST are expected to optimize therapy outcome in more patients who cannot afford the expensive new medicines and minimize and even avoid resistance amplification with the rational use of anti-TB drugs. TRAIL REGISTRATION: ClinicalTrial.gov, NCT03867136 . Registered on March 7, 2019.

Determination of nitenpyram dissipation and residue in kiwifruit by LC-MS/MS.

To investigate the presence of nitenpyram in kiwifruit, a field experiment was conducted in six kiwifruit producing regions in China. A modified quick, easy, cheap, effective, rugged and safe method (QuEChERS) method based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed for the determination of nitenpyram in kiwifruit. Quantitative detection was performed by LC-MS/MS in multiple reaction monitoring (MRM) mode under positive-ion electrospray ionisation. The proposed method is linear and accurate in the range of 0.005 to 4.5 µg/mL. The recovery of nitenpyram was satisfactory (71.96-96.67%) with reasonable RSDs (9.83 %) for 0.01-4.5 mg/kg spiked levels. The limit of quantification (LOQ) was 0.01 mg/kg for nitenpyram. Nitenpyram degraded rapidly in kiwifruit with a half-life <4 days. Residues of nitenpyram were <0.01 - 0.54 mg/kg in kiwifruit 7, 14 and 21 days after spraying at six sites.

Enantioselective Degradation and Chiral Stability of Glufosinate in Soil and Water Samples and Formation of 3-Methylphosphinicopropionic Acid and N-Acetyl-glufosinate Metabolites.

Two enantiomers of glufosinate were separated under reverse-phase conditions on a chiral crown stationary phase (CROWNPAK CR(+)). An efficient and reliable chiral analytical method was developed to determine the glufosinate enantiomers and two metabolites in soil and water samples using high-performance liquid chromatography-high-resolution mass spectrometry (HPLC-HRMS). The linearities of the matrix-matched calibration curves in five water and four soil samples were good with a correlation coefficient R2 > 0.998, and the mean recoveries were 85.2-100.4%, with relative standard deviations of 1.0-7.1%. l-Glufosinate was degraded faster than d-glufosinate in four nonsterile natural soil and two nonsterile natural water samples. The degradation half-lives of the enantiomers ranged from 3.4 to 33.0 days in the soil samples, but glufosinate was stable in the five water samples, less than 22% of the applied substance degraded at the end of the experiment (100 days). Degradation in sterile soil was not enantioselective. The two enantiomers were configurationally stable in the four soil and five water samples. In most cases of glufosinate degradation in soils, the percentage of 3-methylphosphinicopropionic in relation to the parent was higher than that of N-acetyl-glufosinate. l-Glufosinate was preferentially degraded in the four soils, and formation of 3-methylphosphinicopropionic acid and N-acetyl-glufosinate was enantiomer dependent.

Deposition amount and dissipation kinetics of difenoconazole and propiconazole applied on banana with two commercial spray adjuvants.

A rapid and sensitive method for the simultaneous determination of difenoconazole and propiconazole residues in banana matrices was established using GC-MS/MS. The average recovery rates of difenoconazole and propiconazole from various matrices ranged from 76.7% to 94.9%. The relative standard deviation was between 0.9% and 7.4%. The effect of adding organosilicon and mineral oil adjuvants after being applied to the residues of difenoconazole and propiconazole in banana leaves was examined. The initial deposition amount 2 hours after the adjuvant treatment with organosilicon and mineral oil was 1.22-2.13 times higher than that after water treatment. After adding the two spray adjuvants, the residues of the two pesticides at 2 hours on three samples followed the order leaves > soil > fruit. The degradation half-lives of the two pesticides were in the range of 1.91-7.30 days for all the three treatments in two typical banana-growing areas in China. The degradation half-lives of the two pesticides in the water treatment group and the mineral oil treatment group were similar. However, organosilicon could apparently increase the half-life of difenoconazole on banana leaves. The final levels of difenoconazole and propiconazole residues on whole banana fruits were ≤0.1 mg kg-1 (MRL) 14 days after application. The results of this work may aid the safe use of difenoconazole and propiconazole in banana production, especially when used with organosilicon and mineral oil adjuvants.

Monitoring residue levels and dietary risk assessment of pymetrozine for Chinese consumption of cauliflower.

The present study investigates the occurrence of pymetrozine residues in cauliflower samples obtained from six cauliflower-producing areas of China during fixed time periods in 2017 and estimates the dietary risk of pymetrozine in cauliflower. A liquid chromatography with tandem mass spectrometry method was developed and validated to detect pymetrozine in cauliflower. The samples were extracted using 20 mL of acetonitrile and purified with dispersive solid-phase extraction using C18 as sorbent. The limit of quantification of pymetrozine was 0.008 mg/kg in cauliflower. The recoveries of the analyte were 82.04-95.18% with RSD <8.45%. The calibration curves for pymetrozine showed good linearities in the concentration range 0.004-2.0 mg/L with determination coefficients (R2 ) >0.999. Pymetrozine dissipated rapidly in cauliflower with a half-life of <4 days. The terminal residues of pymetrozine were <0.008-0.0881 mg/kg in cauliflower at 7, 10 and 14 days after spraying from six sites. The routine washing process removed about half amount of the pymetrozine in cauliflower; the reduction ratios were 51.0-52.8%. The dietary risk assessment indicated that pymetrozine did not exhibit obvious dietary health risks in cauliflower when good agricultural practices were implemented.

Synthesis of novel (E)-2-(4-(1H-1,2,4-triazol-1-yl)styryl)-4- (alkyl/arylmethyleneoxy)quinazoline derivatives as antimicrobial agents.

A series of novel (E)-2-(4-(1H-1,2,4-triazol-1-yl)styryl)-4-(alkyl/arylmethyleneoxy)quinazoline derivatives (4a-4s) were synthesized in good to excellent yields, and their structures were fully characterized by [Formula: see text] NMR, [Formula: see text] NMR, HRMS and IR spectra. The structure of compound 4b was further confirmed via single-crystal X-ray diffraction analysis. The bioassay results indicated that compounds 4s, 4q and 4n inhibit phytopathogenic bacterium Xanthomonas axonopodis pv. citri (Xac) more potently than commercial bactericide bismerthiazol. However, not a single compound can effectively inhibit three pathogenic fungi tested at 50 [Formula: see text].