N6-methyladenosine promotes induction of ADAR1-mediated A-to-I RNA editing to suppress aberrant antiviral innate immune responses.

Among over 150 distinct RNA modifications, N6-methyladenosine (m6A) and adenosine-to-inosine (A-to-I) RNA editing represent 2 of the most studied modifications on mammalian mRNAs. Although both modifications occur on adenosine residues, knowledge on potential functional crosstalk between these 2 modifications is still limited. Here, we show that the m6A modification promotes expression levels of the ADAR1, which encodes an A-to-I RNA editing enzyme, in response to interferon (IFN) stimulation. We reveal that YTH N6-methyladenosine RNA binding protein 1 (YTHDF1) mediates up-regulation of ADAR1; YTHDF1 is a reader protein that can preferentially bind m6A-modified transcripts and promote translation. Knockdown of YTHDF1 reduces the overall levels of IFN-induced A-to-I RNA editing, which consequently activates dsRNA-sensing pathway and increases expression of various IFN-stimulated genes. Physiologically, YTHDF1 deficiency inhibits virus replication in cells through regulating IFN responses. The A-to-I RNA editing activity of ADAR1 plays important roles in the YTHDF1-dependent IFN responses. Therefore, we uncover that m6A and YTHDF1 affect innate immune responses through modulating the ADAR1-mediated A-to-I RNA editing.

Construction of Uniform LiF Coating Layers for Stable High-Voltage LiCoO2 Cathodes in Lithium-Ion Batteries.

Stabilizing LiCoO2 (LCO) at 4.5 V rather than the common 4.2 V is important for the high specific capacity. In this study, we developed a simple and efficient way to improve the stability of LiCoO2 at high voltages. After a simple sol-gel method, we introduced trifluoroacetic acid (TA) to the surface of LCO via an afterwards calcination. Meanwhile, the TA reacted with residual lithium on the surface of LCO, further leading to the formation of uniform LiF nanoshells. The LiF nanoshells could effectively restrict the interfacial side reaction, hinder the transition metal dissolution and thus achieve a stable cathode-electrolyte interface at high working-voltages. As a result, the LCO@LiF demonstrated a much superior cycling stability with a capacity retention ratio of 83.54% after 100 cycles compared with the bare ones (43.3% for capacity retention), as well as high rate performances. Notably, LiF coating layers endow LCO with excellent high-temperature performances and outstanding full-cell performances. This work provides a simple and effective way to prepare stable LCO materials working at a high voltage.

Trajectories of α-fetoprotein and unresectable hepatocellular carcinoma outcomes receiving atezolizumab plus bevacizumab: a secondary analysis of IMbrave150 study.

BACKGROUND: α-fetoprotein (AFP) response has been demonstrated as a biomarker for unresectable hepatocellular carcinoma (uHCC) patients receiving immunotherapy, but its definition is still unclear. This exploratory study investigated the AFP trajectory and clinical outcomes of receiving atezolizumab plus bevacizumab (Atez/Bev) therapy. METHODS: This secondary analysis used the Atez/Bev arm data of phase III IMbrave150 study to distinguish potential AFP changing rate trajectories through latent class trajectory models. The multivariable Cox models were applied to calculate adjusted hazard ratios (HRs) and 95% CIs for clinical outcomes. RESULTS: Three distinct trajectories were identified among the uHCC patients with 7 times (range, 3 to 28) of AFP measurements: low-stable (50.0%, n = 132), sharp-falling (13.3%, n = 35), and high-rising (36.7%, n = 97). Compared with the high-rising class, HRs of disease progression were 0.52 (95% CI: 0.39, 0.70) and 0.26 (95% CI: 0.16, 0.43) for the low-stable class and sharp-falling class, respectively. In contrast, HRs of death were 0.59 (95% CI: 0.40, 0.81) and 0.30 (95% CI: 0.16, 0.57) for the two groups after propensity score adjustment. Besides, AFP trajectories had the highest relative importance of each covariate to survival. DISCUSSION: There are three distinct AFP trajectories in uHCC patients receiving Atez/Bev, and it is an independent biomarker for clinical outcomes.

RNA Modifications in Cancer Stem Cell Biology.

Post-transcriptional regulation of gene expression shapes the cell state both in health and disease. RNA modifications-especially N6-methyladenosine (m6A)-have recently emerged as key players in RNA processing that depends on a sophisticated interplay between proteins of the RNA modification machinery. Importantly, the RNA epitranscriptome becomes dysregulated in cancer and promotes cancer-associated gene expression programs as well as cancer cell adaptation to the tumor microenvironment. At the top of the tumor hierarchy, cancer stem cells (CSCs) are master regulators of tumorigenesis and resistance to therapeutic intervention. Therefore, defining how RNA modifications influence the CSC state is of great importance for cancer drug development. In this chapter, we summarize the current knowledge of the roles of RNA modifications in shaping the CSC state and driving gene expression programs that confer stem-like properties to CSCs, promote CSC adaptation to the local microenvironment, and endow CSCs with metastatic potential and drug resistance.

Yield and cost of government-organized colorectal cancer screening in young high-risk population in Northeast China.

Guidelines for colorectal cancer (CRC) screening recommend screening at age 40 for high-risk population in China. However, the yield and cost of CRC screening in younger population are lacking. This analysis aimed to evaluate the yield and cost of CRC screening in high-risk 40- to 54-year-olds. Individuals aged 40-54 years who were determined to have a high risk of CRC were recruited from December 2012 to December 2019. We calculated odds ratios (OR) and 95% confidence intervals (CI) for the detection rate of colorectal lesions among the three age groups and further calculated number of colonoscopies needed to screen (NNS) to detect one advanced lesion and cost of each group. The detection rates of advanced colorectal neoplasm in men aged 45-49 years (OR = 2.00, 95% CI: 0.93-4.30) and 50-54 years (OR = 2.19, 95% CI: 1.04-4.62) were higher than that aged 40-44 years. The detection rates of colorectal adenoma in women aged 50-54 years was higher than that aged 40-44 years (OR = 1.64, 95% CI: 1.23-2.19). Among the male screening population, NNS and cost to detect one advanced lesion in participants aged 45-49 years were similar to that aged 50-54 years, saving approximately half endoscopic resources and financial expenses compared with screening that aged 40-44 years. From the perspective of screening results and costs, it might be beneficial to delay the starting age of screening by gender. This study may provide reference for optimizing CRC screening strategies.

Incorporating Bioaccessibility into Inhalation Exposure Assessment of Emamectin Benzoate from Field Spraying.

The inhalation exposure of pesticide applicators and residents who live close to pesticide-treated fields is a worldwide concern in public health. Quantitative assessment of exposure to pesticide inhalation health risk highlights the need to accurately assess the bioaccessibility rather than the total content in ambient air. Herein, we developed an in vitro method to estimate the inhalation bioaccessibility of emamectin benzoate and validated its applicability using a rat plasma pharmacokinetic bioassay. Emamectin benzoate was extracted using the Gamble solution, with an optimized solid-to-liquid ratio (1/250), extraction time (24 h), and agitation (200 rpm), which obtained in vitro inhalation bioaccessibility consistent with its inhalation bioavailability in vivo (32.33%). The margin of exposure (MOE) was used to assess inhalation exposure risk. The inhalation unit exposures to emamectin benzoate of applicators and residents were 11.05-28.04 and 0.02-0.04 ng/m3, respectively, varying markedly according to the methods of application, e.g., formulations and nozzles. The inhalation risk assessment using present application methods appeared to be acceptable; however, the MOE of emamectin benzoate might be overestimated by 32% without considering inhalation bioaccessibility. Collectively, our findings contribute insights into the assessment of pesticide inhalation exposure based on bioaccessibility and provide guidance for the safe application of pesticides.

The Protective Effects of Goitrin on LPS-Induced Septic Shock in C57BL/6J Mice via Caspase-11 Non-Canonical Inflammasome Inhibition.

Septic shock is defined as a subset of sepsis, which is associated with a considerably high mortality risk. The caspase-11 non-canonical inflammasome is sensed and activated by intracellular lipopolysaccharide (LPS) leading to pyroptosis, it plays a critical role in septic shock. However, there are few known drugs that can control caspase-11 non-canonical inflammasome activation. We report here that goitrin, an alkaloid from Radix Isatidis, shows protective effects in LPS-induced septic shock and significant inhibitory effect in caspase-11 non-canonical inflammasome pathway. Male C57BL/6J were injected intraperitoneally with LPS (20 mg/kg) to induce experimental septic shock. The results demonstrated that the survival rates of mice pretreated with goitrin or Toll-like receptor 4 (TLR4) inhibitor TKA-242 increased, and LPS-induced hypothermia and lung damage improved by inhibiting inflammatory response. Elucidating the detailed mechanism, we surprisingly found goitrin is really different from TAK-242, it independent of the TLR4 signal activation, but significantly inhibited the activation of caspase-11 non-canonical inflammasome, including cleaved caspase-11 and N-terminal fragment of gasdermin D (GSDMD-NT). Furthermore, with a nonlethal dose of the TLR3 agonist poly(I:C)-primed and subsequently challenged with LPS to induce caspase-11-mediated lethal septic shock, the efficacy of goitrin had been verified. Those results revealed the effect of goitrin in protective against LPS-induced septic shock via inhibiting caspase-11 non-canonical inflammasome, which provided a new therapeutic strategy for clinical treatment of septic shock.

Features and development trends in international standardization of Chinese materia medica in ISO/TC 249.

Chinese materia medica (CMM) is indispensable component of Traditional Chinese Medicine (TCM) therapy. With the widespread of TCM around the world, the quality control and safe use of CMM become a major concern. This paper introduces the role of ISO standards for industrial development and current development status of CMM standards in ISO/TC 249. Through the comparison of similarities and differences between CMM standards in ISO/TC 249 and pharmacopoeias of main stakeholders, this paper suggests strengthening standard formulation in the following areas to provide more appropriate documents to facilitate the international trade and promote the industrial development of CMM: (1) Develop standards to fill the blanks among the whole industry chain of CMM; (2) Develop standards for new forms of CMM and services; (3) Develop specification and grade standards for CMM with large quantity and high value.

Pharmacokinetics-based identification of pseudoaldosterogenic compounds originating from Glycyrrhiza uralensis roots (Gancao) after dosing LianhuaQingwen capsule.

LianhuaQingwen capsule, prepared from an herbal combination, is officially recommended as treatment for COVID-19 in China. Of the serial pharmacokinetic investigations we designed to facilitate identifying LianhuaQingwen compounds that are likely to be therapeutically important, the current investigation focused on the component Glycyrrhiza uralensis roots (Gancao). Besides its function in COVID-19 treatment, Gancao is able to induce pseudoaldosteronism by inhibiting renal 11ß-HSD2. Systemic and colon-luminal exposure to Gancao compounds were characterized in volunteers receiving LianhuaQingwen and by in vitro metabolism studies. Access of Gancao compounds to 11ß-HSD2 was characterized using human/rat, in vitro transport, and plasma protein binding studies, while 11ß-HSD2 inhibition was assessed using human kidney microsomes. LianhuaQingwen contained a total of 41 Gancao constituents (0.01-8.56 µmol/day). Although glycyrrhizin (1), licorice saponin G2 (2), and liquiritin/liquiritin apioside (21/22) were the major Gancao constituents in LianhuaQingwen, their poor intestinal absorption and access to colonic microbiota resulted in significant levels of their respective deglycosylated metabolites glycyrrhetic acid (8), 24-hydroxyglycyrrhetic acid (M2D; a new Gancao metabolite), and liquiritigenin (27) in human plasma and feces after dosing. These circulating metabolites were glucuronized/sulfated in the liver and then excreted into bile. Hepatic oxidation of 8 also yielded M2D. Circulating 8 and M2D, having good membrane permeability, could access (via passive tubular reabsorption) and inhibit renal 11ß-HSD2. Collectively, 1 and 2 were metabolically activated to the pseudoaldosterogenic compounds 8 and M2D. This investigation, together with such investigations of other components, has implications for precisely defining therapeutic benefit of LianhuaQingwen and conditions for its safe use.

When glia meet induced pluripotent stem cells (iPSCs).

The importance of glial cells, mainly astrocytes, oligodendrocytes, and microglia, in the central nervous system (CNS) has been increasingly appreciated. Recent advances have demonstrated the diversity of glial cells and their contribution to human CNS development, normal CNS functions, and disease progression. The uniqueness of human glial cells is also supported by multiple lines of evidence. With the discovery of induced pluripotent stem cells (iPSCs) and the progress of generating glial cells from human iPSCs, there are numerous studies to model CNS diseases using human iPSC-derived glial cells. Here we summarize the basic characteristics of glial cells, with the focus on their classical functions, heterogeneity, and uniqueness in human species. We further review the findings from recent studies that use iPSC-derived glial cells for CNS disease modeling. We conclude with promises and future directions of using iPSC-derived glial cells for CNS disease modeling.

Potential dissemination mechanism of the tetC gene in Aeromonas media from the aerobic biofilm reactor under oxytetracycline stresses.

The tetC gene has been found to be one of the most widely distributed tetracycline resistance (tet) genes in various environmental niches, but the detailed dissemination mechanisms are still largely unknown. In the present study, 11 tetC-containing Aeromonas media strains were isolated from an aerobic biofilm reactor under oxytetracycline stresses, and the genome of one strain was sequenced using the PacBio RSII sequencing approach to reveal the genetic environment of tetC. The tetC gene was carried by an IS26 composite transposon, named Tn6434. The tetC-carrying Tn6434 structure was detected in all of the A. media strains either in a novel plasmid pAeme2 (n=9) or other DNA molecules (n=2) by PCR screening. The NCBI database searching result shows that this structure was also present in the plasmids or chromosomes of other 13 genera, indicating the transferability of Tn6434. Inverse PCR and sequencing confirmed that Tn6434 can form a circular intermediate and is able to incorporate into a preexisting IS26 element, suggesting that Tn6434 might be responsible for the dissemination of tetC between different DNA molecules. This study will be helpful in uncovering the spread mechanism of tet genes in water environments.

[Pharmacological effects of Huangqin Decoction prepared from roots of multi-originated peony on ulcerative colitis in mice:a comparative study].

Huangqin Decoction(HQD) is a classic prescription for treating dysentery in the Treatise on Cold Damage and now is mainly used for the treatment of ulcerative colitis(UC). Since there are no requirements on specific Paeonia species, both Paeoniae Radix Alba(white peony root, WPR) and Paeoniae Radix Rubra(red peony root, RPR) are clinically used in HQD now. Although the two types of peony roots are close in origin and similar in primary components, the medicinal properties and efficacies are different. Furthermore, the systematic comparative analysis on the efficacy differences in treating UC of HQD with the roots of multi-originated peony has been seldom reported. This study compared and evaluated the pharmacological effects of HQD prepared from the roots of multi-originated peony, including WPR, RPR-l(derived from P. lactiflora), and RPR-v(derived from P. veitchii) based on the mouse model of UC induced by dextran sodium sulfate(DSS) by animal behaviors, pathological section(colon), and cytokine expression(IL-1ß and IL-6), aiming to provide evidence for the identification of the original resource of peony root in HQD. The results indicated that all HQD samples prepared from WPR, RPR-l, and RPR-v could improve the symptoms of UC. Compared with the HQD-WPR, HQD-RPR-l and HQD-RPR-v were significantly different in weight loss, colon length, and disease activity index(DAI) score, but there was no significant difference between HQD-RPR-l and HQD-RPR-v. Moreover, HQD-RPR-v exhibited the most significant improvement in the pathological morphology of colonic tissue and mucosal defects. According to the previous comparative analysis of chemical profiling and content distribution of HQD prepared from the roots of multi-originated peony, RPR-v in HQD was potent in protecting against UC, which was presumedly attributed to a large number of monoterpene glycosides and galloyl glucoses. This study provided a scientific basis for the determination of peony root in HQD and its clinical medication.

Apatinib plus Chemotherapy as a Second-Line Treatment in Unresectable Non-Small Cell Lung Carcinoma: A Randomized, Controlled, Multicenter Clinical Trial.

LESSONS LEARNED: The efficacy of second-line treatment for advanced non-small cell lung carcinoma (NSCLC) without a sensitizing driver gene mutation is still unsatisfactory. The combination of apatinib and chemotherapy improved progression-free survival in the second-line therapy of advanced NSCLC without a sensitizing mutation. This study offers a new treatment strategy for second-line treatment of such patients but requires confirmation in a larger multi-institutional trial. BACKGROUND: This study explored the efficacy and safety of apatinib combined with single-agent chemotherapy versus single-agent chemotherapy in the second-line treatment of advanced non-small-cell lung carcinoma (NSCLC) without driver mutations. METHODS: In this double-arm, open label, exploratory clinical study, we enrolled patients with unresectable locally advanced or advanced NSCLC without driver mutations that had progressed following first-line chemotherapy. The subjects were allocated into an experimental group and a control group by 2:1. The experimental group received apatinib combined with four cycles of docetaxel or pemetrexed until disease progression, intolerable toxicity, or discontinuation at the patient' request. The control group only received four cycles of docetaxel or pemetrexed. The primary endpoints were progression-free survival (PFS), and the secondary endpoints were overall survival (OS), disease control rate (DCR), and safety. RESULTS: Thirty-seven patients were enrolled. The efficacy of 33 patients was evaluated. The median PFS was 5.47 versus 2.97 months, the DCR was 95% versus 73%, and the objective response rate (ORR) was 27% versus 9% in the experimental versus control group. The OS was still under follow-up. The most common adverse effects included hypertension, hand-foot skin reaction (HFSR), and fatigue. CONCLUSION: Apatinib combined with single-agent chemotherapy may be a novel option for second-line treatment of advanced NSCLC.

Micro/Nanoengineered α-Fe2 O3 Nanoaggregate Conformably Enclosed by Ultrathin N-Doped Carbon Shell for Ultrastable Lithium Storage and Insight into Phase Evolution Mechanism.

The Fe-based transition metal oxides are promising anode candidates for lithium storage considering their high specific capacity, low cost, and environmental compatibility. However, the poor electron/ion conductivity and significant volume stress limit their cycle and rate performances. Furthermore, the phenomena of capacity rise and sudden decay for α-Fe2 O3 have appeared in most reports. Here, a uniform micro/nano α-Fe2 O3 nanoaggregate conformably enclosed in an ultrathin N-doped carbon network (denoted as M/N-α-Fe2 O3 @NC) is designed. The M/N porous balls combine the merits of secondary nanoparticles to shorten the Li+ transportation pathways as well as alleviating volume expansion, and primary microballs to stabilize the electrode/electrolyte interface. Furthermore, the ultrathin carbon shell favors fast electron transfer and protects the electrode from electrolyte corrosion. Therefore, the M/N-α-Fe2 O3 @NC electrode delivers an excellent reversible capacity of 901 mA h g-1 with capacity retention up to 94.0 % after 200 cycles at 0.2 A g-1 . Notably, the capacity rise does not happen during cycling. Moreover, the lithium storage mechanism is elucidated by ex situ XRD and HRTEM experiments. It is verified that the reversible phase transformation of α↔γ occurs during the first cycle, whereas only the α-Fe2 O3 phase is reversibly transformed during subsequent cycles. This study offers a simple and scalable strategy for the practical application of high-performance Fe2 O3 electrodes.

Analysis on the current quality standards of Chinese materia Medica used in COVID-19 prevention and treatment.

PURPOSE: Traditional Chinese medicine (TCM) has fully engaged and played an essential role in the prevention and treatment of Coronavirus Disease 2019 (COVID-19). This study compares relevant standards on high-frequent Chinese Materia Medicia (CMM) used in this pandemic aiming at reaching a global consensus and ensuring the use of Chinese medicines safely. METHODS: 141 representative Chinese formulas and Chinese Patent Medicines from the National Protocol and the most of Provincial Protocols for controlling COVID-19 in China have been collected to statistical analyze the composition and characteristics of CMM. Among them, the domestic and international standards of 47 varieties with the frequency usage over 10 times were selected to compare their quality requirements in the mainstream pharmacopoeias and international standards. RESULTS: The quality requirements of used CMM for fighting COVID-19 on the terms of overall quality control, marker compounds, and safety indicators showed different patterns in these mainstream pharmacopoeias and international standards. The uniformed and scientific quality standards of CMM were urgently needed to promote global acceptation and trade. CONCLUSIONS: These findings will provide evidence for building unified quality and safety standards that can adapt to the characteristics of CMM and promote international trade, and also will be stated that it is of the highest priority for ISO/TC 249 to formulate high-quality standards that consolidate international consensus to ensure quality and safety of the urgently needed CMM.

Novel Transposon Tn6433 Variants Accelerate the Dissemination of tet(E) in Aeromonas in an Aerobic Biofilm Reactor under Oxytetracycline Stresses.

Little is known about the mechanisms that disseminate antibiotic resistance genes (ARGs) in wastewater microbial communities under antibiotic stress. The role of horizontal transfer mechanisms in dissemination of ARGs in an aerobic biofilm reactor under incremental oxytetracycline doses from 0 to 50 mg/L was studied. Aeromonas strains were the most common culturable bacteria in the reactor, with tet(E) as the most prevalent ARGs (73.3%) being possibly responsible for the oxytetracycline resistance phenotype. Genomic sequencing demonstrated that tet(E) was mainly carried by a Tn3 family transposon named Tn6433, whose incidence increased from 14.6% to 75.0% across the treatments. Tn6433 carrying tet(E) was initially detected in Aeromonas chromosomes at an oxytetracycline dose of 1 mg/L but subsequently detected on plasmids pAeca1-a variants (pAeca1-a, pAeca1-b, and pAeme6) and pAeca2 under higher oxytetracycline stress. The core region of the Tn6433-tet(E) structure was highly conserved, consisting of a transposition and resolution module, a class 1 integron, core passenger genes, and a Tn1722/Tn501-like transposon. Such a structure was found on both the chromosome and plasmids, suggesting that Tn6433 mediated the transposition of tet(E) from the chromosome to plasmid pAeca2 under increasing stresses. Bacteria carrying the transferable plasmid pAeca1-a were dominant in high antibiotic treatments, suggesting that Tn6433 disseminated tet(E), conferring selective advantages to recipients of this ARG.

Development and optimization of a method for determining betaine and trigonelline in the fruits of Lycium species by using solid-phase extraction combined with high-performance liquid chromatography-diode array detector.

Betaine is an essential nutrient for humans and a source of methyl donors for methionine and S-adenosylmethionine formation, and it is used as a biomarker for pharmacological activities and to evaluate the quality of Lycium species and common foods. However, because of its special structural features, poor ultraviolet-chromophore, and high polarity, the existing methods for betaine extraction and quantification cannot provide higher extraction efficiency, better sensitivity, or resolution degree. A simple, fast, and efficient high-performance liquid chromatography-diode array detector coupled with solid-phase extraction was adopted for simultaneous separation and quantification of betaine in four types of Lycium species. The results revealed that after degreasing with dichloromethane, extraction with 80% ethanol (pH adjusted to 1.0 with hydrochloric acid), and elution with aluminum oxide (OH- form), the improvement in the average yield rate of betaine was thrice of that of the existing methods. In addition, trigonelline was identified as the interfering substance of betaine for the first time in Lycium species, and betaine and trigonelline were simultaneously separated and quantified. Furthermore, their chemical characteristics and content distribution in different Lycium species were carried out.

Chemical profiling and marker characterization of Huangqin decoction prepared with three types of peony root by liquid chromatography with electrospray ionization mass spectrometry.

Clarification of the quality and biological effect equivalence of traditional Chinese medicines containing multi-origin species is essential to improve their current quality standards, and also is the core problem to clarify the origins of single herbs with multi-species in Chinese formulas that will guarantee their clinical application. Huangqin decoction is the typical one of multi-origin formulas frequently used in traditional Chinese medicine and Kampo medicine. An ultra high performance liquid chromatography with electrospray ionization-tandem mass spectrometry was developed for chemical profiling and marker quantification of Huangqin decoction prepared with two different original types of peony root, white and red peony root. Forty-seven main peaks in chemical profiling of Huangqin decoction prepared with white and red peony root were identified: nine were from peony root, 20 from baical skullcap root, 17 from licorice root, and one from jujubae fruit. The markers characteristics of the respective types of peony root in Huangqin decoction differ from that in single herbs, especially in terms of monoterpenoids and hydrolysable tannins. Subsequently, 17 representative markers in Huangqin decoction prepared with three types of peony root and their chemical characteristics and content distribution were carried out.

Removal of prothioconazole using screened microorganisms and identification of biodegradation products via UPLC-QqTOF-MS.

Degradation of the prothioconazole by three strains of microorganisms isolated from activated sludge obtained from a pesticide factory was assessed, and an ultrahigh-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QqTOF-MS) method for the determination of prothioconazole and its metabolites was established. The optimal conditions for the degradation of prothioconazole were determined by single factor optimization experiments. A degradation rate of 93.32% is achieved when the prothioconazole is co-cultured with the strain W313 at a cultivation time of 60 h, a cultivation temperature of 30 °C, a pH of 6.33, a prothioconazole concentration of 50 mg L-1, a microorganism volume of 10%, and a dextrose volume of 4%. The three effective microorganism strains were identified by morphological and molecular biology to be Candida tropicalis, Enterobacter cloacae, and Pseudomonas aeruginosa. UPLC-QqTOF-MS analysis allowed the identification of 62 different prothioconazole degradation products produced by the strain cultures, with prothioconazole-desthio, prothioconazole-dechloropropyl, and oxidizing prothioconazole being the main products. In addition, degradation products from different strains and conditions were compared. The results of scatter plot (S-Plot) analysis indicated that C9H7NO, C10H17N7, and C12H13ClN2O were only detected in the products incubated with Enterobacter cloacae. Thus, this study demonstrates that Enterobacter cloacae and Pseudomonas aeruginosa possesses high potential for bioremediation of prothioconazole-contaminated environments.