Discovery of new N-Phenylamide Isoxazoline derivatives with high insecticidal activity and reduced honeybee toxicity.

Isoxazoline is a novel structure with strong potential for controlling agricultural insect pests, but its high toxicity to honeybees limits its development in agriculture. Herein, a series of N-phenylamide isoxazoline derivatives with low honeybee toxicity were designed and synthesized using the intermediate derivatization method. Bioassay results showed that these compounds exhibited good insecticidal activity. Compounds 3b and 3f showed significant insecticidal effects against Plutella xylostella (P. xylostella) with median lethal concentrations (LC50) of 0.06 and 0.07 mg/L, respectively, comparable to that of fluralaner (LC50 = 0.02 mg/L) and exceeding that of commercial insecticide fluxametamide (LC50 = 0.52 mg/L). It is noteworthy that the acute honeybee toxicities of compounds 3b and 3f (LD50 = 1.43 and 1.63 µg/adult, respectively) were significantly reduced to 1/10 of that of fluralaner (LD50 = 0.14 µg/adult), and were adequate or lower than that of fluxametamide (LD50 = 1.14 µg/adult). Theoretical simulation using molecular docking indicates that compound 3b has similar binding modes with fluralaner and a similar optimal docking pose with fluxametamide when binding to the GABA receptor, which may contribute to its potent insecticidal activity and relatively low toxicity to honey bees. This study provides compounds 3b and 3f as potential new insecticide candidates and provides insights into the development of new isoxazoline insecticides exhibiting both high efficacy and environmental safety.

Influence of Spider Silk Protein Structure on Mechanical and Biological Properties for Energetic Material Detection.

Spider silk protein, renowned for its excellent mechanical properties, biodegradability, chemical stability, and low immune and inflammatory response activation, consists of a core domain with a repeat sequence and non-repeating sequences at the N-terminal and C-terminal. In this review, we focus on the relationship between the silk structure and its mechanical properties, exploring the potential applications of spider silk materials in the detection of energetic materials.

Advance toward isolation, extraction, metabolism and health benefits of kaempferol, a major dietary flavonoid with future perspectives.

As a major ubiquitous secondary metabolite, flavonoids are widely distributed in planta. Among flavonoids, kaempferol is a typical natural flavonol in diets and medicinal plants with myriad bioactivities, such as anti-inflammatory activity, anti-cancer activity, antioxidant activity, and anti-diabetic activity. However, the natural sources, absorption and metabolism as well as the bioactivities of kaempferol have not been reviewed comprehensively and systematically. This review highlights the latest research progress and the effect of kaempferol in the prevention and treatment of various chronic diseases, as well as its protective health effects, and provides a theoretical basis for future research to be used in nutraceuticals. Further, comparison of the different extraction and analytical methods are presented to highlight the most optimum for PG recovery and its detection in plasma and body fluids. Such review aims at improving the value-added applications of this unique dietary bioactive flavonoids at commercial scale and to provide a reference for its needed further development.

Dearomatization Silylation of Benzofurans and Furopyridines via Silyl Radical Addition and Endocyclic C-O Bond Scission.

Direct introduction of silyl radicals to forge C-Si bonds is of central importance in organic synthesis, owing to the formidable potential of silyl groups as coupling partners for further derivatization reactions to achieve more valuable compounds. Cleavage of heteroaromatic endocyclic carbon-heteroatom bonds to assemble C-Si bonds is scarce. Here, we demonstrate a dearomatization silylation of benzofurans and furopyridines via silyl radical addition and C(2)-O bond scission under metal-catalyst-free and mild conditions. Preliminary mechanistic experiments suggest that these transformations involve radical/single-electron transfer and [1,5]-Brook rearrangement processes. This protocol for the total synthesis of Doxepin and oxyresveratrol derivatives is carried out. The silylated products in several transformation reactions have proven to be useful as synthetic intermediates.

Toxicity prediction of 1,2,4-triazoles compounds by QSTR and interspecies QSTTR models.

1,2,4-triazole derivatives exhibit various biological activities, including antibacterial and antifungal properties. On the other hand, these chemicals may have unique cumulative and harmful effects on living organisms. The goal of this work is to use quantitative structure-toxicity relationship (QSTR) and interspecies quantitative toxicity-toxicity relationship (iQSTTR) models to predict the acute toxicity of 1,2,4-triazole derivatives. The QSTR models were generated by multiple linear regression (MLR) following the OECD recommendations for QSAR model development and validation. The iQSTTR models were constructed using data on acute oral toxicity in rats and mice, as well as the 2D descriptor. The application domain (AD) analysis was used to identify model outliers and determine if the forecast was credible. Six QSTR models were successfully constructed in rats and mice using various delivery methods, and the scatter plots demonstrated excellent consistency across training and test sets. According to external and internal validation criteria, all six QSTR models may be broadly accepted; however, the orally administered mice model was the optimum one among the six species. Several chemicals with leverage values above the requirements were identified as response or structural outliers in the training sets for six QSTR and two iQSTTR models. All outliers, however, fell slightly outside the threshold or had low prediction errors, which may have had little impact on the capacity to forecast and were therefore preserved in the final models. In fact, neither the QSTR nor the iQSTTR test sets contained any response outliers. Additionally, all external and internal validation results for the iQSTTR models were approved, with the iQSTTR models outperforming the comparable QSTR models, which are deemed more dependable. The QSTR and iQSTTR models performed well in predicting toxicity using test sets, which would be beneficial in evaluating and synthesizing newly discovered 1,2,4-triazoles derivatives with low toxicity and environmental hazard.

Six genes involved in prognosis of hepatocellular carcinoma identified by Cox hazard regression.

BACKGROUND: Hepatocellular carcinoma (HCC), derived from hepatocytes, is the main histological subtype of primary liver cancer and poses a serious threat to human health due to the high incidence and poor prognosis. This study aimed to establish a multigene prognostic model to predict the prognosis of patients with HCC. RESULTS: Gene expression datasets (GSE121248, GSE40873, GSE62232) were used to identify differentially expressed genes (DEGs) between tumor and adjacent or normal tissues, and then hub genes were screened by protein-protein interaction (PPI) network and Cytoscape software. Seventeen genes among hub genes were significantly associated with prognosis and used to construct a prognostic model through COX hazard regression analysis. The predictive performance of this model was evaluated with TCGA data and was further validated with independent dataset GSE14520. Six genes (CDKN3, ZWINT, KIF20A, NUSAP1, HMMR, DLGAP5) were involved in the prognostic model, which separated HCC patients from TCGA dataset into high- and low-risk groups. Kaplan-Meier (KM) survival analysis and risk score analysis demonstrated that low-risk group represented a survival advantage. Univariate and multivariate regression analysis showed risk score could be an independent prognostic factor. The receiver operating characteristic (ROC) curve showed there was a better predictive power of the risk score than that of other clinical indicators. At last, the results from GSE14520 demonstrated the reliability of this prognostic model in some extent. CONCLUSION: This prognostic model represented significance for prognosis of HCC, and the risk score according to this model may be a better prognostic factor than other traditional clinical indicators.

Combination of tetrandrine and 3-n-butylphthalide protects against cerebral ischemia-reperfusion injury via ATF2/TLR4 pathway.

OBJECTIVE: Cerebral infarction (CI) is the mayor reason of death in China. Reperfusion is the only immediate treatment for acute cerebral infarction. However, blood reperfusion recovery may cause ischemia-reperfusion (I/R) injuries. The purpose of this study was to investigate the effects of Tetrandrine (TTD) and 3-n-Butylphthalide (NBP) on cerebral I/R injury. MATERIALS AND METHODS: I/R was used to establish CI model in vivo. TTD was performed to analyze cerebral infarction volume. OGD was applied to establish CI model in vitro. Flow cytometry and TUNEL assays were utilized to determine the cell death. ELISA was conducted to determine the release of cytokines. mRNA and protein expressions were detected using qRT-PCR and western blot. RESULTS: We found that NBP + TTD treatment significantly reduced cerebral infarction volume and inhibited the death of neurons in vivo. Moreover, NBP + TTD treatment suppressed the apoptosis and inflammatory response of neurons in vitro. Additionally, NBP + TTD suppressed the expression of activator transcription factor 2 (ATF2). However, overexpression of ATF2 contributed to the degeneration of neurons. Moreover, ATF2 transcriptionally activated Toll-like receptor 4 (TLR4). NBP + TTD inactivated ATF2/TLR4 signaling. CONCLUSIONS: Taken together, TTD combined with NBP protected against cerebral infarction by inhibiting the inflammatory response and neuronal cell apoptosis via inactivating ATF2/TLR4 signaling pathways. This may provide an alternative for I/R injury.

Insights into gastrointestinal microbiota-generated ginsenoside metabolites and their bioactivities.

The gastrointestinal microbiota and host co-evolve into a complex 'super-organism,' and this relationship plays a vital role in many physiological processes, such as drug metabolism. Ginseng is an important medicinal resource and the main ingredients are ginsenosides, which are less polar, difficult to absorb, and have low bioavailability. However, studies have shown that the biological activity of ginsenosides such as compound K (CK), ginsenoside Rg3 (Rg3), ginsenoside Rh2 (Rh2), 20(S)-protopanaxatriol (20(S)-PPT), and 20(S)-protopanaxadiol (20(S)-PPD) is closely related to the gastrointestinal microbiota. In this paper, the metabolic pathway of gastrointestinal microbiota-generated ginsenosides and the main pharmacological effects of these metabolites are discussed. Furthermore, our study provides a new insight into the discovery of novel drugs. Specifically, in new drug screening process, candidates with low biological activity and bioavailability should not be excluded. Because their metabolites may exhibit good pharmacological effects due to the involvement of the gastrointestinal microbiota. In addition, in further research studies to develop probiotics, a combination of agents could exert greater efficacy than single agents. Moreover, differences in lifestyle and diet lead to differences in the gastrointestinal microbiota in the human body. Therefore, administration of the same drug dose to different individuals could elicit different therapeutic effects, owing to the involvement of the gastrointestinal microbiota. Thus, treatment accuracy could be achieved by detecting the gastrointestinal microbiota before drug treatment.HighlightsGastrointestinal microbiota plays a decisive role in bioactivities of ginsenosides.The metabolic pathway and main pharmacological effects of ginsenoside metabolites are discussed.It provides new insights into novel drug discovery and further research to find probiotic, combinations to exert greater efficacy.Differences in lifestyle and diet, varies the gastrointestinal microbiota in the human body. However, the same dose of a drug producing different therapeutic effects may involve gastrointestinal microbiota.

Identification of gene modules associated with survival of diffuse large B-cell lymphoma treated with CHOP-based chemotherapy.

Diffuse Large B-cell Lymphoma (DLBCL), a heterogeneous disease, is influenced by complex network of gene interactions. Most previous studies focused on individual genes, but ignored the importance of intergenic correlations. In current study, we aimed to explore the association between gene networks and overall survival (OS) of DLBCL patients treated with CHOP-based chemotherapy (cyclophosphamide combination with doxorubicin, vincristine and prednisone). Weighted gene co-expression network analysis was conducted to obtain insights into the molecular characteristics of DLBCL. Ten co-expression gene networks (modules) were identified in training dataset (n = 470), and their associations with patients' OS after chemotherapy were tested. The results were validated in four independent datasets (n = 802). Gene ontology (GO) biological function enrichment analysis was conducted with Metascape. Three modules (purple, brown and red), which were enriched in T-cell immune, cell-cell adhesion and extracellular matrix (ECM), respectively, were found to be related to longer OS. Higher expression of several hub genes within these three co-expression modules, for example, LCP2 (HR = 0.77, p = 5.40 × 10-2), CD2 (HR = 0.87, p = 6.31 × 10-2), CD3D (HR = 0.83, p = 6.94 × 10-3), FYB (HR = 0.82, p = 1.40 × 10-2), GZMK (HR = 0.92, p = 1.19 × 10-1), FN1 (HR = 0.88, p = 7.06 × 10-2), SPARC (HR = 0.82, p = 2.06 × 10-2), were found to be associated with favourable survival. Moreover, the associations of the modules and hub genes with OS in different molecular subtypes and different chemotherapy groups were also revealed. In general, our research revealed the key gene modules and several hub genes were upregulated correlated with good survival of DLBCL patients, which might provide potential therapeutic targets for future clinical research.

An integrated prognosis model of pharmacogenomic gene signature and clinical information for diffuse large B-cell lymphoma patients following CHOP-like chemotherapy.

BACKGROUND: As the most common form of lymphoma, diffuse large B-cell lymphoma (DLBCL) is a clinical highly heterogeneous disease with variability in therapeutic outcomes and biological features. It is a challenge to identify of clinically meaningful tools for outcome prediction. In this study, we developed a prognosis model fused clinical characteristics with drug resistance pharmacogenomic signature to identify DLBCL prognostic subgroups for CHOP-based treatment. METHODS: The expression microarray data and clinical characteristics of 791 DLBCL patients from two Gene Expression Omnibus (GEO) databases were used to establish and validate this model. By using univariate Cox regression, eight clinical or genetic signatures were analyzed. The elastic net-regulated Cox regression analysis was used to select the best prognosis related factors into the predictive model. To estimate the prognostic capability of the model, Kaplan-Meier curve and the area under receiver operating characteristic (ROC) curve (AUC) were performed. RESULTS: A predictive model comprising 4 clinical factors and 2 pharmacogenomic gene signatures was established after 1000 times cross validation in the training dataset. The AUC of the comprehensive risk model was 0.78, whereas AUC value was lower for the clinical only model (0.68) or the gene only model (0.67). Compared with low-risk patients, the overall survival (OS) of DLBCL patients with high-risk scores was significantly decreased (HR = 4.55, 95% CI 3.14-6.59, log-rank p value = 1.06 × 10-15). The signature also enables to predict prognosis within different molecular subtypes of DLBCL. The reliability of the integrated model was confirmed by independent validation dataset (HR = 3.47, 95% CI 2.42-4.97, log rank p value = 1.53 × 10-11). CONCLUSIONS: This integrated model has a better predictive capability to ascertain the prognosis of DLBCL patients prior to CHOP-like treatment, which may improve the clinical management of DLBCL patients and provide theoretical basis for individualized treatment.

Iodine-promoted radical alkyl sulfuration of imidazopyridines with dialkyl azo compounds and elemental sulfur.

Dialkyl azo compounds were found to be effective alkyl radical sources for direct alkyl sulfuration with imidazopyridines using elemental sulfur under metal-free conditions. Iodine, an inexpensive and mild reagent, could promote alkyl sulfuration. A variety of quaternary cyanoalkyl radicals were successfully coupled with elemental sulfur. A subsequent C-H sulfuration of imidazopyridines afforded a diverse array of imidazopyridine derivatives bearing cyanoalkylthio groups. The cyano group could be modified and further underwent condensation with 2-aminothiazole to afford an interesting heterocyclic amide. Control experiments showed that iodine could greatly suppress the self-coupling of cyanoalkyl radicals, thus making the sulfuration proceed smoothly.

Taurine decreased uric acid levels in hyperuricemic rats and alleviated kidney injury.

Hyperuricemia can lead to direct kidney damage. Taurine participates in several renal physiological processes and has been shown as a renoprotective agent. It has been reported that taurine could reduce uric acid levels in diabetic rats, but to date there was no research on the effects of taurine on hyperuricemic rats with kidney injury. In present study, hyperuricemic rat models were induced by intragastric administration of adenine and ethambutol hydrochloride for 10 days, and taurine (1% or 2%) were added in the drinking water 7 days in advance for consecutively 17 days. The results showed that taurine alleviated renal morphological and pathological changes as well as kidney dysfunction in hyperuricemic rats. Taurine could efficiently decrease the elevated xanthine oxidase activities in hyperuricemic rats, indicating its effect on the regulation of uric acid formation. The reabsorption and secretion of uric acid are dependent on a number of urate transporters. Expressions of three urate transporters were significantly down-regulated in hyperuricemic rats, while taurine prevented the decrease of mRNA and protein expression levels of these urate transporters. The results indicate that taurine might play a role in the regulation of renal uric acid excretion. Therefore, taurine could be a promising agent for the treatment of hyperuricemia.

Cancer Nanobombs Delivering Artoxplatin with a Polyigniter Bearing Hydrophobic Ferrocene Units Upregulate PD-L1 Expression and Stimulate Stronger Anticancer Immunity.

Poor immunogenicity seriously hampers the broader implementation of antitumor immunotherapy. Enhanced immunogenicity capable of achieving greater antitumor immunity is urgently required. Here, a novel polymer that contains hydrophobic ferrocene (Fc) units and thioketal bonds in the main chain, which further delivered a prodrug of oxaliplatin and artesunate, i.e., Artoxplatin, to cancer cells is described. This polymer with Fc units in the nanoparticle can work as a polyigniter to spark the peroxide bonds in Artoxplatin and generate abundant reactive oxygen species (ROS) to kill cancers as nanobombig for cancer therapy. Moreover, ROS can trigger the breakdown of thioketal bonds in the polymer, resulting in the biodegradation of the polymer. Importantly, nanobombig can facilitate the maturation of dendritic cells and promote the activation of antitumor immunity, through the enhanced immunogenic cell death effect by ROS generated in situ. Furthermore, metabolomics analysis reveals a decrease in glutamine in nanobombig -treated cancer cells, resulting in the upregulation of programmed death ligand 1 (PD-L1). Consequently, it is further demonstrated enhanced tumor inhibitory effects when using nanobombig combined with anti-PD-L1 therapy. Overall, the nanosystem offers a rational design of an efficient chemo-immunotherapy regimen to promote antitumor immunity by improving tumor immunogenicity, addressing the key challenges cancer immunotherapy faced.

Single-nucleus transcriptome unveils the role of ferroptosis in ischemic stroke.

Multiple cell death pathways are involved in neuronal death in ischemic stroke (IS). However, the role of different cell death pathways in different cell types has not been elucidated. By analyzing three single-nucleus RNA sequencing (snRNA-seq) data of IS, we first found that a variety of programmed cell death (PCD) -related genes were significantly changed in different cell types. Based on machine learning and virtual gene knockout, we found that ferroptosis related genes, ferritin heavy chain 1 (Fth1) and ferritin light chain (Ftl1), play a key role in IS. Ftl1 and Fth1 can promote microglia activation, as well as the production of inflammatory factors and chemokines. Cell communication analysis showed that activated microglia could enhance chemotactic peripheral leukocyte infiltration, such as macrophages and neutrophils, through Spp1-Cd44 and App-Cd74 signaling, thereby aggravating brain tissue damage. Furthermore, real-time quantitative polymerase chain reaction (RT-qPCR) showed that P2ry12 and Mef2c were significantly decreased in oxygen-glucose deprivation (OGD) group, while Ftl1, Fth1, Apoe, Ctsb, Cd44 and Cd74 were significantly increased in OGD group. Collectively, our findings suggested targeted therapy against microglia Ftl1 and Fth1 might improve the state of microglia, reduce the infiltration of peripheral immune cells and tissue inflammation, and then improve the ischemic brain injury in mouse.

Combined analysis of cross-population healthy adult human microbiome reveals consistent differences in gut microbial characteristics between Western and non-Western countries.

Despite extensive research on the gut microbiome of healthy individuals from a single country, there are still a limited number of population-level comparative studies. Moreover, the sequencing approach used in most related studies involves 16 S ribosomal RNA (rRNA) sequencing with a limited resolution, which cannot provide detailed functional profiles. In the present study, we applied a combined analysis approach to analyze whole metagenomic shotgun sequencing data from 2035 healthy adult samples from six countries across four continents. Analysis of core species revealed that 13 species were present in more than 90 % of all investigated individuals, the majority of which produced short-chain fatty acids (SCFA)-producing bacteria. Our analysis revealed consistently significant differences in gut microbial species and pathways between Western and non-Western countries, such as Escherichia coli and the relation of MetaCyc pathways to the TCA cycle. Specific changes in microbial species and pathways are potentially related to lifestyle and diet. Furthermore, we identified several noteworthy microbial species and pathways that exhibit distinct characteristics specific to China. Interestingly, we observed that China (CHN) was more similar to the United States (USA) and United Kingdom (GBR) in terms of the taxonomic and functional composition of the gut microbiome than India (IND) and Madagascar (MDG), which were more similar to the China (CHN) diet. The current study identified consistent microbial features associated with population and geography, which will inspire further clinical translations that consider paying attention to differences in microbiota backgrounds and confounding factors.

Synergistic effects of taurine and L-arginine on attenuating insulin resistance hypertension.

To elucidate the synergistic effects of taurine and L-arginine on hypertension, 25% fructose were administered to male Wistar rats for 3 months to establish insulin resistance hypertensive models. Rats with the systolic blood pressure (SBP) higher than 150 mmHg were considered as model rats. Forty-two model rats were randomly divided into six groups and administered with 3% taurine, 2.7% taurine + 0.3% L-arginine, 2.1% taurine + 0.9% L-arginine, 1.5% taurine + 1.5% L-arginine and 3% L-arginine in drinking water respectively. The results showed that coadministration of taurine (1.5%) and L-arginine (1.5%) could bring the levels of SBP, blood glucose, and insulin down to normal levels after 4 weeks. The thickness of blood vessels increased significantly in model group, which could be reversed by taurine and L-arginine. Serum NO, cGMP, and ET levels could return to normal levels. These data indicated that both taurine and L-arginine could ameliorate vascular remodeling and showed obvious antihypertensive effects, and taurine (1.5%) and L-arginine (1.5%) in the drinking water showed a better result in the cure of hypertension.

A survey of epidemic management data models.

The COVID-19 epidemic has demonstrated the important role that data plays in the response to and management of public health emergencies. It has also heightened awareness of the role that ontologies play in the design of semantically precise data models that improve data interoperability among stakeholders. This paper surveys vocabularies and ontologies relevant to the task of achieving epidemic-related data interoperability. The paper first reviews 16 vocabularies and ontologies with respect to the use cases. Next it identifies patterns of knowledge that are common across multiple vocabularies and ontologies, followed by an analysis of patterns that are missing, based on the use cases. Conclusions show that existing vocabularies and ontologies provide significant coverage of the concepts underlying epidemic use cases, but there remain gaps in the coverage. More work is required to cover missing but significant concepts.

Salidroside protect Chinese hamster V79 cells from genotoxicity and oxidative stress induced by CL-20.

Hexanitrohexaazaisowurtzitane (CL-20) is a high-energy elemental explosive widely used in chemical and military fields. CL-20 harms environmental fate, biosafety, and occupational health. However, there is little known about the genotoxicity of CL-20, in particular its molecular mechanisms. Therefore, this study was framed to investigate the genotoxic mechanisms of CL-20 in V79 cells and evaluate whether the genotoxicity could be diminished by pretreating the cells with salidroside. The results showed that CL-20-induced genotoxicity in V79 cells primarily through oxidative damage to DNA and mitochondrial DNA (mtDNA) mutation. Salidroside could significantly reduce the inhibitory effect of CL-20 on the growth of V79 cells and reduce the levels of reactive oxygen species (ROS), 8-hydroxy-2 deoxyguanosine (8-OHdG), and malondialdehyde (MDA). Salidroside also restored CL-20-induced superoxide dismutase (SOD) and glutathione (GSH) in V79 cells. As a result, salidroside attenuated the DNA damage and mutations induced by CL-20. In conclusion, oxidative stress may be involved in CL-20-induced genotoxicity in V79 cells. Salidroside could protect V79 cells from oxidative damage induced by CL-20, mechanism of which may be related to scavenging intracellular ROS and increasing the expression of proteins that can promote the activity of intracellular antioxidant enzymes. The present study for the mechanisms and protection of CL-20-mediated genotoxicity will help further to understand the toxic effects of CL-20 and provide information on the therapeutic effect of salidroside in CL-20-induced genotoxicity.

Preparation and Characterization of Insecticide/Calix[4]arene Complexes and Their Enhanced Insecticidal Activities against Plutella xylostella.

Applications of supramolecular materials in plant protection have attracted significant interest in recent years. To develop a feasible method to improve the efficacy and reduce the usage of chemical pesticides, the effect of calix[4]arene (C4A) inclusion on enhancing the insecticidal activity of commercial insecticides was investigated. Results showed that all three tested insecticides (chlorfenapyr, indoxacarb, and abamectin) with distinct molecular sizes and modes of action were able to form stable 1:1 host-guest complexes with C4A through simple preparation steps. The insecticidal activities of the complexes against Plutella xylostella were effectively enhanced compared to the guest molecule, with the synergism ratio being up to 3.05 (for indoxacarb). An obvious correlation was found between the enhanced insecticidal activity and the high binding affinity between insecticide and C4A, while the improvement in water solubility may not be a determining factor. The work would provide hints for the further development of functional supramolecular hosts as synergists in pesticide formulations.

Application of QSAR models for acute toxicity of tetrazole compounds administrated orally and intraperitoneally in rat and mouse.

Tetrazoles and their derivatives possess various biological activities, such as antibacterial, anti-fungal, and other activities. However, these compounds may induce specific cumulative and toxic effects in living organisms. Therefore, quantitative structure-activity relationship (QSAR) models were constructed to study the acute oral toxicity of tetrazoles in rats and mice. The toxicity data of 111 tetrazole compounds were collected using the ChemIDplus, ChEMBL and ECHA databases as response variables, while the PaDEL-descriptor generated the 2D descriptors as independent variables. The models were developed and validated following the OECD guidelines by the DTC-QSAR tool. Three QSAR models were successfully established for the oral routes of rat and mouse and the intraperitoneal route of mouse, respectively. The scatter plots showed high consistency between the training and test data sets. All the models successfully met the external and internal validation criteria. Most of the descriptors kept in the final models exhibited positive correlations with toxicity, whereas only 6 descriptors exhibited negative associations. Several chemicals were identified as response or structural outliers, based on the standardized residuals and leverage values. In conclusion, the findings of this investigation demonstrate that the proposed QSAR models hold promise in forecasting the acute toxicity of recently developed or synthesized tetrazole compounds, thereby mitigating potential risks to human health and the environment.