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Personalized cancer immunotherapies such as therapeutic vaccines and adoptive transfer of T cell receptor-transgenic T cells rely on the presentation of tumor-specific peptides by human leukocyte antigen class I molecules to cytotoxic T cells. Such neoepitopes can for example arise from somatic mutations and their identification is crucial for the rational design of new therapeutic interventions. Liquid chromatography mass spectrometry (LC-MS)-based immunopeptidomics is the only method to directly prove actual peptide presentation and we have developed a parameter optimization workflow to tune targeted assays for maximum detection sensitivity on a per peptide basis, termed optiPRM. Optimization of collision energy using optiPRM allows for the improved detection of low abundant peptides that are very hard to detect using standard parameters. Applying this to immunopeptidomics, we detected a neoepitope in a patient-derived xenograft from as little as 2.5 × 106 cells input. Application of the workflow on small patient tumor samples allowed for the detection of five mutation-derived neoepitopes in three patients. One neoepitope was confirmed to be recognized by patient T cells. In conclusion, optiPRM, a targeted MS workflow reaching ultra-high sensitivity by per peptide parameter optimization, makes the identification of actionable neoepitopes possible from sample sizes usually available in the clinic.

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Arterial spin labeling (ASL) has emerged as a promising noninvasive tool for the evaluation of both pediatric and adult arteriovenous malformations (AVMs). This paper reviews the advantages and challenges associated with the use of ASL in AVM assessment. An assessment of the diagnostic workup of AVMs and their variants in both adult and pediatric populations is proposed. Evaluation after treatments, whether endovascular or microsurgical, was similarly examined. ASL, with its endogenous tracer and favorable safety profile, offers functional assessment and arterial feeder identification. ASL has demonstrated strong performance in identifying feeder arteries and detecting arteriovenous shunting, although some studies report inferior performance compared with digital subtraction angiography (DSA) in delineating venous drainage. Challenges include uncertainties in sensitivity for specific AVM features. Detecting AVMs in challenging locations, such as the apical cranial convexity, is further complicated, demanding careful consideration due to the risk of underestimating total blood flow. Navigating these challenges, ASL provides a noninvasive avenue with undeniable merits, but a balanced approach considering its limitations is crucial. Larger-scale prospective studies are needed to comprehensively evaluate the diagnostic performance of ASL in AVM assessment.

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Microbial species capable of co-existing with healthy individuals, such as the commensal fungus Candida albicans, exploit multifarious strategies to evade our immune defenses. These strategies include the masking of immunoinflammatory pathogen-associated molecular patterns (PAMPs) at their cell surface. We reported previously that C. albicans actively reduces the exposure of the proinflammatory PAMP, ß-1,3-glucan, at its cell surface in response to host-related signals such as lactate and hypoxia. Here, we show that clinical isolates of C. albicans display phenotypic variability with respect to their lactate- and hypoxia-induced ß-1,3-glucan masking. We have exploited this variability to identify responsive and non-responsive clinical isolates. We then performed RNA sequencing on these isolates to reveal genes whose expression patterns suggested potential association with lactate- or hypoxia-induced ß-1,3-glucan masking. The deletion of two such genes attenuated masking: PHO84 and NCE103. We examined NCE103-related signaling further because NCE103 has been shown previously to encode carbonic anhydrase, which promotes adenylyl cyclase-protein kinase A (PKA) signaling at low CO2 levels. We show that while CO2 does not trigger ß-1,3-glucan masking in C. albicans, the Sch9-Rca1-Nce103 signaling module strongly influences ß-1,3-glucan exposure in response to hypoxia and lactate. In addition to identifying a new regulatory module that controls PAMP exposure in C. albicans, our data imply that this module is important for PKA signaling in response to environmental inputs other than CO2.IMPORTANCEOur innate immune defenses have evolved to protect us against microbial infection in part via receptor-mediated detection of "pathogen-associated molecular patterns" (PAMPs) expressed by invading microbes, which then triggers their immune clearance. Despite this surveillance, many microbial species are able to colonize healthy, immune-competent individuals, without causing infection. To do so, these microbes must evade immunity. The commensal fungus Candida albicans exploits a variety of strategies to evade immunity, one of which involves reducing the exposure of a proinflammatory PAMP (ß-1,3-glucan) at its cell surface. Most of the ß-1,3-glucan is located in the inner layer of the C. albicans cell wall, hidden by an outer layer of mannan fibrils. Nevertheless, some ß-1,3-glucan can become exposed at the fungal cell surface. However, in response to certain specific host signals, such as lactate or hypoxia, C. albicans activates an anticipatory protective response that decreases ß-1,3-glucan exposure, thereby reducing the susceptibility of the fungus to impending innate immune attack. Here, we exploited the natural phenotypic variability of C. albicans clinical isolates to identify strains that do not display the response to ß-1,3-glucan masking signals observed for the reference isolate, SC5314. Then, using genome-wide transcriptional profiling, we compared these non-responsive isolates with responsive controls to identify genes potentially involved in ß-1,3-glucan masking. Mutational analysis of these genes revealed that a sensing module that was previously associated with CO2 sensing also modulates ß-1,3-glucan exposure in response to hypoxia and lactate in this major fungal pathogen of humans.

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Objective.To develop a novel, unenhanced magnetic resonance angiography (MRA) exploiting cardiac-gated, single-slab 3D chemical-shift-encoded gradient- and spin-echo (GRASE) imaging for robust background suppression.Approach.The proposed single-slab 3D GRASE employs variable-flip-angles (VFA) in the refocusing radio-frequency (RF) pulse train to promote sensitivity to blood flow as well as imaging encoding efficiency. Phase encoding blips are inserted between adjacent lobes of the switching readout gradients such that chemical shift-induced phase information is encoded into different locations in k-space. Based on the assumption that most background signals in the angiogram come from the fatty tissues, the proposed method directly separates angiograms from fatty background tissue signals from highly incomplete measurements by solving a constrained optimization problem with sparsity prior. Numerical simulations and experiments were performed to validate the effectiveness of the proposed method in healthy volunteers as compared with conventional fresh blood imaging (FBI).Main results.Compared with conventional FBI, the proposed method yields clearer delineation of small branching arteries and robust fatty background suppression without apparent loss of signals.Significance.We have successfully demonstrated the feasibility of the proposed, single-slab 3D VFA GRASE with chemical-shift-encoded reconstruction for the generation of robust unenhanced peripheral MRA.

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Background: Coronary artery disease (CAD) is one of the most common diseases seriously harmful to human health caused by atherosclerosis. Besides coronary computed tomography angiography (CCTA) and invasive coronary angiography (ICA), coronary magnetic resonance angiography (CMRA) has become an alternative examination. The purpose of this study was to prospectively evaluate the feasibility of 3.0 T free-breathing whole-heart non-contrast-enhanced coronary magnetic resonance angiography (NCE-CMRA). Methods: After Institutional Review Board approval, the NCE-CMRA data sets of 29 patients acquired successfully at 3.0 T were evaluated independently by two blinded readers for visualization and image quality of coronary arteries using the subjective quality grade. The acquisition times were recorded in the meantime. A part of the patients had undergone CCTA, we represented stenosis by scores and used the Kappa to evaluate the consistency between CCTA and NCE-CMRA. Results: Six patients did not get diagnostic image quality because of severe artifacts. The image quality score assessed by both radiologists is 3.2±0.7, which means the NCE-CMRA can show the coronary arteries excellently. The main vessels of the coronary artery on NCE-CMRA images are considered reliably assessable. The acquisition time of NCE-CMRA, is 8.8±1.2 min. The Kappa of CCTA and NCE-CMRA on detecting stenosis is 0.842 (P<0.001). Conclusions: The NCE-CMRA results in reliable image quality and visualization parameters of coronary arteries within a short scan time. The NCE-CMRA and CCTA have a good agreement for detecting stenosis.

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Chlamydomonas reinhardtii evolved a CO2-concentrating mechanism (CCM) because of the limited CO2 in its natural environment. One critical component of the C. reinhardtii CCM is the limiting CO2 inducible B (LCIB) protein. LCIB is required for acclimation to air levels of CO2. C. reinhardtii cells with a mutated LCIB protein have an 'air-dier' phenotype when grown in low CO2 conditions, meaning they die in air levels of CO2 but can grow in high and very low CO2 conditions. The LCIB protein functions together with its close homolog in C. reinhardtii, limiting CO2 inducible C protein (LCIC), in a hexameric LCIB-LCIC complex. LCIB has been proposed to act as a vectoral carbonic anhydrase (CA) that helps to recapture CO2 that would otherwise leak out of the chloroplast. Although both LCIB and LCIC are structurally similar to ßCAs, their CA activity has not been demonstrated to date. We provide evidence that LCIB is an active CA using a Saccharomyces cerevisiae CA knockout mutant (∆NCE103) and an Arabidopsis thaliana ßCA5 knockout mutant (ßca5). We show that different truncated versions of the LCIB protein complement ∆NCE103, while the full length LCIB protein complements ßca5 plants, so that both the yeast and plant mutants can grow in low CO2 conditions.

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The fruit peel of a color mutant jujube cultivar, 'Sanbianhong' (SBF), was investigated using an ultra-high performance liquid chromatography quadrupole Orbitrap mass spectrometry (UHPLC-Q-Orbitrap MS) at five ripening stages (S1, Young fruit stage; S2, swelling stage; S3, white-mature stage; S4, pre-mature stage and S5, mature stage). Lutein, ß-carotene, chlorophyll a, chlorophyll b, and 13 anthocyanins were identified. Chlorophyll a and cyanidin 3-O-galactoside were considered key color metabolites in S1 with the content of 1.083 mg/g of fresh weight (FW) and 4.585 mg/g of FW, respectively. Delphinidin (0.488 mg/g FW) and cyanidin (6.259 mg/g FW) were identified as the key pigments in S3. Delphinidin 3-O-glucoside (0.256 mg/g FW) was identified as the key anthocyanin in maturity S5. Herein, the identification and quantitation of pigment-related metabolites of SBF were studied for the first time, and the results provide a theoretical basis for understanding the pigment changes of jujube fruit during ripening.

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Background: Patients with phenylketonuria (PKU) must maintain a lifelong natural protein-restricted diet to prevent neuro-cognitive damage. Early diagnosis is established with newborn screening, with diet subsequently controlled by regular phenylalanine (Phe) monitoring. During the COVID-19 pandemic, significant lockdown measures were introduced that may have influenced the above. Aim of our study: To establish whether the diagnosis was delayed in neonates during the pandemic. In addition, metabolic control was further assessed during the COVID-19 pandemic era (CE) compared to the same period a year prior (non-COVID-19 era, NCE). The lockdown periods (LD) were also compared with unrestricted periods (URP). Patients methods: Six neonates born during the CE and eight neonates born during NCE were included in the newborn screening analysis. Seventy-two classical PKU patients aged 2-18 years and categorized as children (2-12 years; 51 patients) and adolescents (>13 years; 21 patients) were included in the metabolic control analysis. The frequency of dried blood spot (DBS) sampling and Phe levels were assessed according to the different periods. Results: There was no diagnostic or therapeutic delay in reaching the recommended Phe range in neonates born during CE compared to those born in NCE (median [interquartile range, IQR]: 23.5 [22.5-24] vs. 22 [18.0-27] days, p = NS). The cumulative DBS sampling frequency in children increased by 9.9% in the CE while no change was noted in the adolescent group. The median Phe level increased significantly in both age groups in the CE, but remained within the recommended target range. During CE, changes in Phe levels differed in the two age groups: children had the highest median Phe in the second lockdown period (LD2), while the adolescents had an increased Phe in URP.There were significant negative correlations between DBS sampling frequencies and Phe levels in both age groups in NCE (children: r - 0.43, p = 0.002; adolescents r = -0.37, p = 0.012), and in adolescents in CE (r = -0.62, p = 0.006). Conclusion: The pandemic did not impact newborn metabolic screening. The increased frequency of DBS sampling in CE and good target Phe levels suggest a better compliance in a very sensitive period. Since many factors may impact metabolic control in the different age groups, further studies are needed to analyse their respective role.

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Past research has demonstrated the effectiveness of teacher-implemented, function-based treatments for problem behavior, but no studies have evaluated the impact of distractions on teachers' procedural integrity. In this proof-of-concept study, the experimenters employed a laboratory analog to examine the impact of distractions on levels of integrity when 5 teachers implemented 3 different treatments. Although integrity was similar across treatments when the setting was free of distractions, integrity declined for all teachers in the presence of student-driven distractions. In general, distractions had a greater impact on the integrity of differential negative reinforcement of alternative behavior (DNRA) compared to differential negative reinforcement of other behavior (DNRO) and noncontingent escape (NCE), particularly for the delivery of reinforcement. However, teachers tended to have lower levels of integrity when responding to problem behavior during DNRO. These findings support the potential viability of this approach for studying factors that impede procedural integrity in the classroom.

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BACKGROUND: Cardiac surgery-associated acute kidney injury (AKI) can increase the mortality and morbidity, and the incidence of chronic kidney disease, in critically ill survivors. The purpose of this research was to investigate possible links between urinary metabolic changes and cardiac surgery-associated AKI. METHODS: Using ultra-high-performance liquid chromatography coupled with Q-Exactive Orbitrap mass spectrometry, non-targeted metabolomics was performed on urinary samples collected from groups of patients with cardiac surgery-associated AKI at different time points, including Before_AKI (uninjured kidney), AKI_Day1 (injured kidney) and AKI_Day14 (recovered kidney) groups. The data among the three groups were analyzed by combining multivariate and univariate statistical methods, and urine metabolites related to AKI in patients after cardiac surgery were screened. Altered metabolic pathways associated with cardiac surgery-induced AKI were identified by examining the Kyoto Encyclopedia of Genes and Genomes database. RESULTS: The secreted urinary metabolome of the injured kidney can be well separated from the urine metabolomes of uninjured or recovered patients using multivariate and univariate statistical analyses. However, urine samples from the AKI_Day14 and Before_AKI groups cannot be distinguished using either of the two statistical analyses. Nearly 4000 urinary metabolites were identified through bioinformatics methods at Annotation Levels 1-4. Several of these differential metabolites may also perform essential biological functions. Differential analysis of the urinary metabolome among groups was also performed to provide potential prognostic indicators and changes in signalling pathways. Compared with the uninjured kidney group, the patients with cardiac surgery-associated AKI displayed dramatic changes in renal metabolism, including sulphur metabolism and amino acid metabolism. CONCLUSIONS: Urinary metabolite disorder was observed in patients with cardiac surgery-associated AKI due to ischaemia and medical treatment, and the recovered patients' kidneys were able to return to normal. This work provides data on urine metabolite markers and essential resources for further research on AKI.

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BACKGROUND: Emerging evidence suggests the potential role of atrial cardiomyopathy (AC) as a direct thromboembolic determinant in embolic stroke of undetermined source (ESUS). OBJECTIVE: We aimed to quantify the prevalence of potential AC markers among ESUS, non-cardioembolic (NCE) and cardioembolic (CE) stroke patients. METHODS: PubMed and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched for publications from inception to October 2021, with duplicate data extraction and risk of bias assessment. The Newcastle-Ottawa assessment scale was used to evaluate study quality. RESULTS: Among 398 screened studies, 11 observational studies with 2009 ESUS patients (mean age 66.5 years) fulfilled the inclusion criteria. Of electrocardiographic markers, increased P-wave terminal force in lead V1 was more prevalent in ESUS vs NCE (OR=2.26, 95%CI: 1.40-3.66). Of imaging markers, left atrial volume index (LAVI) and left atrial diameter (LAd) were higher in ESUS vs NCE (OR=1.04, 95%CI: 1.02-1.06 and OR=3.41, 95%CI: 1.35-8.61 respectively). Non-chicken wing morphology of the left atrial appendage was more frequent in ESUS compared to NCE patients in the majority of studies. Of serum biomarkers, the prevalence of NT-proBNP >250 pg/ml did not differ among ESUS vs NCE (OR=0.73, 95%CI: 0.39 -1.35). CONCLUSIONS: Electrocardiographic, echocardiographic markers and advanced imaging modalities able to assess the morphologic characteristics of left atrial appendage and left atrial function may be important tools to discriminate AC among ESUS vs NCE stroke patients. Prospective studies exploring the association of potential AC markers with ESUS occurrence are warranted to validate their clinical utility.

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Using polymers as additives to formulate ternary amorphous solid dispersions (ASDs) has successfully been established to increase the bioavailability of poorly soluble drugs, when one polymer is not able to provide both, stabilizing the drug in the matrix and the supersaturated solution. Therefore, we investigated the influence of low-viscosity hydroxypropyl cellulose (HPC) polymers as an additive in HPMC based ternary ASD formulations made by hot-melt extrusion (HME) on the bioavailability of itraconazole (ITZ). The partitioning potential of the different HPC grades was screened in biphasic supersaturation assays. Solid-state analytics were performed using differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD). The addition of HPCs, especially HPC-UL, resulted in a superior partitioned amount of ITZ in biphasic supersaturation assays. Moreover, the approach in using HPCs as an additive in HPMC based ASDs led to an increase in partitioned ITZ compared to Sporanox® in biorelevant biphasic dissolution studies. The results from the biphasic dissolution experiments correlated well with the in vivo studies, which revealed the highest oral bioavailability for the ternary ASD comprising HPC-UL and HPMC.

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Genotoxicity of the mixture of generic pesticides imidacloprid + imazalil + tebuconazole in a ratio of 14.0/1.7/1.0 by weight was assessed using Ames test (Salmonella typhimurium) and micronucleus test in vivo on mammalian bone marrow erythrocytes (CD-1 mice) supporting the data creation for the Real Life Risk Simulation (RLRS) approach. This pesticides' combination is used in the commercial formulation for seed treatment in advance of or immediately before sowing. Tested pesticides' technical grade active ingredients (TGAIs) showed no evidence of genotoxicity upon separate treatments. In combination, the three pesticides demonstrated negative results in the Ames test but induced a statistically significant, dose-depended increase in MN-PCEs in mice bone marrow at doses lower than those used separately. The observed effect may be mediated by the synergistic action of the tested TGAIs, their metabolites or impurities.

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BACKGROUND AND OBJECTIVE: The objective of our work was to establish a facile and scalable synthesis of imidazopyridone for further use in medicinal chemistry applications. An easy synthesis of a core scaffold will enable the medicinal chemistry community to use imidazopyridone as a privileged scaffold in new chemical entity (NCE) synthesis. MATERIALS AND METHODS: The synthesis was achieved from commercially available and cheap raw materials like amino acetonitrile hydrochloride or commercially available guanidine. RESULTS: Simple transformation starting from amino acetonitrile hydrochloride leads to the synthesis of a versatile imidazo [1, 5-a] pyrimidine-2-(1H)-one core structure. Using suitable functionalized starting materials, a set of NCEs were synthesized to demonstrate the application of the developed synthetic scheme. Similarly, guanidine was also used to synthesize a regioisomer of imidazopyridone in moderate to good yields. CONCLUSION: We demonstrate the synthesis of two different regio-isomers of imidazopyrimidinone using simple chemical transformations. Its application in synthesizing NCEs has also been exhibited in the present work.

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Pathogenic yeasts Candida albicans and Candida parapsilosis possess a ß-type carbonic anhydrase Nce103p, which is involved in CO2 hydration and signaling. C. albicans lacking Nce103p cannot survive in low CO2 concentrations, e.g., in atmospheric growth conditions. Candida carbonic anhydrases are orthologous to the Saccharomyces cerevisiae enzyme, which had originally been detected as a substrate of a non-classical export pathway. However, experimental evidence on localization of C. albicans and C. parapsilosis carbonic anhydrases has not been reported to date. Immunogold labeling and electron microscopy used in the present study showed that carbonic anhydrases are localized in the cell wall and plasmatic membrane of both Candida species. This localization was confirmed by Western blot and mass spectrometry analyses of isolated cell wall and plasma membrane fractions. Further analysis of C. albicans and C. parapsilosis subcellular fractions revealed presence of carbonic anhydrases also in the cytosolic and mitochondrial fractions of Candida cells cultivated in shaken liquid cultures, under the atmospheric conditions.

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Ubiquitin ligases (E3s) serve as key regulators for the ubiquitylation-mediated pathway. The identification of the corresponding relationship between E3 and its substrates is challenging but required for understanding the regulatory network of ubiquitylation. The low abundance of ubiquitinated conjugates and high redundancy of E3 substrate regulation made the screening pretty hard. Herein, we combined SILAC-based quantitative proteomics with two contrary genetic methods (overexpression and knockout) in theory for E3 (Hrt3, the F-box subunit of the SCF complex) substrate screening. The knockout method could not overcome the constraint mentioned above, while the overexpression approach turned on the access to the potential substrates of E3. Subsequently, we obtained 77 candidates, which are involved in many critical biological processes and need to be verified in the future. Within these candidates, we confirmed the relationship between one of the candidates Nce103 and Hrt3 and linked Hrt3 with oxygen sensitivity and oxidative stress response in which Nce103 took part as well. This research is also beneficial for understanding the impact of oxygen supply on regulation of yeast growth through the ubiquitination of Nce103.

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BACKGROUND: In view of many current mosquito-borne diseases there is a need for the design of novel repellents. OBJECTIVE: The objective of this article is to review the results of the researches carried out by the authors in the computer-assisted design of novel mosquito repellents. METHODS: Two methods in the computational design of repellents have been discussed: a) Quantitative Structure Activity Relationship (QSAR) studies from a set of repellents structurally related to DEET using computed mathematical descriptors, and b) Pharmacophore based modeling for design and discovery of novel repellent compounds including virtual screening of compound databases and synthesis of novel analogues. RESULTS: Effective QSARs could be developed using mathematical structural descriptors. The pharmacophore based method is an effective tool for the discovery of new repellent molecules. CONCLUSION: Results reviewed in this article show that both QSAR and pharmacophore based methods can be used to design novel repellent molecules.

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BACKGROUND: Ginsenosides have been widely used clinically for many years and were regarded as very safe. However, a few researches on the toxicities of these kinds of agents showed that some ginsenosides may have side-effect on the rats or dogs. So it is extremely necessary to further clarify the potential toxicity of ginsenosides. This study was carried out to investigate long-term toxicity and genotoxicity of 25-methoxydammarane-3, 12, 20-triol (25-OCH3-PPD), a new derivative of ginsenoside, in beagle dogs. METHODS: Twenty-four beagle dogs were divided randomly into four treatment groups and repeatedly orally administered with 25-OCH3-PPD capsule at 60, 120, and 240 mg/kg/day for 91 consecutive days. Ames, micronucleus, and chromosomal aberration tests were established to analyze the possible genotoxicity of 25-OCH3-PPD. RESULTS: There was no 25-OCH3-PPD-induced systemic toxicity in beagle dogs at any doses. The level of 25-OCH3-PPD at which no adverse effects were observed was found to be 240 mg/kg/day. The result of Ames test showed that there was no significant increase in the number of revertant colonies of 25-OCH3-PPD administrated groups compared to the vehicle control group. There were also no significant differences between 25-OCH3-PPD administrated groups at all dose levels and negative group in the micronucleus test and chromosomal aberration assay. CONCLUSION: The highest dose level of 25-OCH3-PPD at which no adverse effects were observed was found to be 240 mg/kg per day, and it is not a genotoxic agent either in somatic cells or germs cells. 25-OCH3-PPD is an extremely safe candidate compound for antitumor treatment.

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Uterine cervical carcinoma (CACX) is one of the leading causes of deaths in Indian women. Chromosomal alterations including 11p15.5 locus were reported in CACX. Consequently, we strived for the first time to understand the molecular status of the candidate gene Insulin-like growth factor 2, IGF2 (11p15.5) in Indian CACX patients (n = 128). DNA copy number (CN) analysis using CGH-SNP analysis showed no genetic alteration and it was further validated by comparison with publicly available CN datasets. But promoter hypo-methylation during the progression of CACX was observed and also found to be concordant with publicly available DNA methylation datasets. Interestingly, we found diverse expression of IGF2 transcript in both normal cervical epithelium (NCE) and CACX tumors. Similar heterogeneous expression pattern was seen in publicly available expression datasets as well. Finally, protein expression analysis in NCE showed concordance with transcript expression but tumors showed frequent low expression. Log-rank test showed a difference (p-value = 0.057) in overall survival between cases with and without alteration for IGF2 in Indian CACX patients. Collectively, our study proposes that regulation of IGF2 expression in NCE appeared to be multifaceted and deregulation during the development of CACX resulted in the differential expression.

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Effects of technical materials of pesticide active ingredients, belonging to various chemical classes, on erythropoiesis in mouse bone marrow were studied as part of the research on the pesticide mutagenic activity in micronucleus test. The purpose of the present study was to estimate the toxic action of the test substances on the target organ and the validity of the results of the micronucleus assay under conditions of erythropoiesis suppression. It was demonstrated that intragastrically administrated triazole pesticides reached bone marrow (target organ where micronucleus induction was assessed) and exerted an inhibitory effect on erythropoiesis. The effects of triazole pesticides were enhanced in the following order: difenoconazole ≤ tebuconazole < cyproconazole < flutriafol. Furthermore, an association between structural features of molecules and specific target organ activity of the test pesticides was observed. Based on the data on the general toxicity and the results of the evaluation of the effects on erythropoiesis, the maximum tolerated doses (MTDs) of 79 different technical materials of pesticides for CD-1 mice were determined.