Physiology, Biochemistry, and Transcriptomics Jointly Reveal the Phytotoxicity Mechanism of Acetochlor on Pisum sativum L.

Acetochlor, as a commonly used pre-emergent herbicide, can be toxic to crops and affect production if used improperly. However, the toxic mechanism of acetochlor on plants is not fully understood. The present study used a combination of transcriptomic analysis and physiological measurements to investigate the effects of short-term (15-day) exposure to different concentrations of acetochlor (1, 10, 20 mg/kg) on the morphology, physiology, and transcriptional levels of pea seedlings, aiming to elucidate the toxic response and resistance mechanisms in pea seedlings under herbicide stress. The results showed that the toxicity of acetochlor to pea seedlings was dose-dependent, manifested as dwarfing and stem base browning with increasing concentrations, especially at 10 mg/kg and above. Analysis of the antioxidant system showed that from the 1 mg/kg treatment, malondialdehyde, superoxide dismutase, peroxidase, and glutathione peroxidase in peas increased with increasing concentrations of acetochlor, indicating oxidative damage. Analysis of the glutathione (GSH) metabolism system showed that under 10 mg/kg treatment, the GSH content of pea plants significantly increased, and GSH transferase activity and gene expression were significantly induced, indicating a detoxification response in plants. Transcriptomic analysis showed that after acetochlor treatment, differentially expressed genes in peas were significantly enriched in the phenylpropane metabolic pathway, and the levels of key metabolites (flavonoids and lignin) were increased. In addition, we found that acetochlor-induced dwarfing of pea seedlings may be related to gibberellin signal transduction. Environ Toxicol Chem 2024;00:1-15. © 2024 SETAC.

Classification of Caries Based on CBCT: A Deep Learning Network Interpretability Study.

This study aimed to create a caries classification scheme based on cone-beam computed tomography (CBCT) and develop two deep learning models to improve caries classification accuracy. A total of 2713 axial slices were obtained from CBCT images of 204 carious teeth. Both classification models were trained and tested using the same pretrained classification networks on the dataset, including ResNet50_vd, MobileNetV3_large_ssld, and ResNet50_vd_ssld. The first model was used directly to classify the original images (direct classification model). The second model incorporated a presegmentation step for interpretation (interpretable classification model). Performance evaluation metrics including accuracy, precision, recall, and F1 score were calculated. The Local Interpretable Model-agnostic Explanations (LIME) method was employed to elucidate the decision-making process of the two models. In addition, a minimum distance between caries and pulp was introduced for determining the treatment strategies for type II carious teeth. The direct model that utilized the ResNet50_vd_ssld network achieved top accuracy, precision, recall, and F1 score of 0.700, 0.786, 0.606, and 0.616, respectively. Conversely, the interpretable model consistently yielded metrics surpassing 0.917, irrespective of the network employed. The LIME algorithm confirmed the interpretability of the classification models by identifying key image features for caries classification. Evaluation of treatment strategies for type II carious teeth revealed a significant negative correlation (p < 0.01) with the minimum distance. These results demonstrated that the CBCT-based caries classification scheme and the two classification models appeared to be acceptable tools for the diagnosis and categorization of dental caries.

Novel 4-triazole phenyl amide (4-TPA) molecules: Potent promoters of α-synuclein fibril disassembly.

Parkinson's disease profoundly compromises patients' daily lives, and the disassembly of α-synuclein aggregates, a primary pathological factor, represents a promising therapeutic approach. In this study, we conducted a systematic screening and optimization process to identify the novel scaffold B37, a 4-triazolyl-phenylamine derivative, exhibiting a potent disassembly activity of 1.1 µM against α-synuclein preformed fibrils. Notably, B37 demonstrated significant neuroprotective effects, ameliorated autophagic dysfunction induced by preformed fibrils, mitigated oxidative stress, and restored the co-localization of preformed fibrils with lysosomes. Transmission electron microscopy corroborated its in vitro disassembly function. Pharmacokinetic profiling revealed favorable parameters with a receptible blood-brain barrier permeability. B37 emerges as a promising lead compound for further optimization, aiming to develop a highly effective agent targeting the disassembly of α-synuclein aggregates to treat neurodegenerative diseases like Parkinson's disease.

New insights into the occurrence of continuous cropping obstacles in pea (Pisum sativum L.) from soil bacterial communities, root metabolism and gene transcription.

BACKGROUND: Continuous cropping is a significant obstacle to sustainable development in the pea (Pisum sativum L.) industry, but the underlying mechanisms of this remain unclear. In this study, we used 16 S rDNA sequencing, transcriptomics, and metabolomics to analyze the response mechanism of roots and soil bacteria to continuous cropping and the relationship between soil bacteria and root phenotypes of different pea genotypes (Ding wan 10 and Yun wan 8). RESULTS: Continuous cropping inhibited pea growth, with a greater effect on Ding wan 10 than Yun wan 8. Metabolomics showed that the number of differentially accumulated metabolites (DAMs) in pea roots increased with the number of continuous cropping, and more metabolic pathways were involved. Transcriptomics revealed that the number of differentially expressed genes (DEGs) increased with the number of continuous cropping. Continuous cropping altered the expression of genes involved in plant-pathogen interaction, MAPK signal transduction, and lignin synthesis pathways in pea roots, with more DEGs in Ding wan 10 than in Yun wan 8. The up-regulated expression of genes in the ethylene signal transduction pathway was evident in Ding wan 10. Soil bacterial diversity did not change, but the relative abundance of bacteria significantly responded to continuous cropping. Integrative analysis showed that the bacteria with significant relative abundance in the soil were strongly associated with the antioxidant synthesis and linoleic acid metabolism pathway of pea roots under continuous cropping once. Under continuous cropping twice, the bacteria with significant relative abundance changes were strongly associated with cysteine and methionine metabolism, fatty acid metabolism, phenylpropanoid biosynthesis, terpenoid backbone biosynthesis, linoleic acid, and amino sugar and nucleotide sugar metabolism. CONCLUSION: Ding wan 10 was more sensitive to continuous cropping than Yun wan 8. Continuous cropping times and pea genotypes determined the differences in root metabolic pathways. There were common metabolic pathways in the two pea genotypes in response to continuous cropping, and the DEGs and DAMs in these metabolic pathways were strongly associated with the bacteria with significant changes in relative abundance in the soil. This study provides new insights into obstacles to continuous cropping in peas.

Transcriptome and metabolite integrated analysis reveals that exogenous ethylene controls berry ripening processes in grapevine.

Although grapevine (Vitis vinifera L.) is generally classified as a non-climacteric fruit, the regulatory mechanisms of ethylene in the ripening of non-climacteric fruit are still poorly understood. In this study, exogenous ethephon (ETH) strongly stimulated fruit color and anthocyanin accumulation, which was consistent with the increased expression of anthocyanin structural, regulatory, and transport genes. ETH application increased ABA content and decreased IAA content by coordinating ABA and auxin biosynthesis regulatory network. ETH treatment also accelerated sugar (glucose and fructose) accumulation by enhancing the gene expression involved in sugar transport and sucrose cleavage. ETH treatment blocked the synthesis of cellulose and accelerated the degradation of pectin, which was strongly associated with berry softening. To further confirm the function of ethylene biosynthesis and signaling genes, transient overexpression of VvACO4 and VvEIL3 were performed in both in tomato and strawberry fruits. These findings of the ethylene cascade add to our understanding of ethylene in non-climacteric berry ripening regulation and revealed a complex involvement of ethylene and its interplay with phytohormones during grapevine berry ripening.

Comparative effectiveness of traditional Chinese medicine and angiotensin converting enzyme inhibitors, angiotensin receptor blockers, and sodium glucose cotransporter inhibitors in patients with diabetic kidney disease: A systematic review and network meta-analysis.

Angiotensin converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB), and sodium glucose cotransporter inhibitors (SGLT2i) are commonly used to treat diabetic kidney disease (DKD). Currently, increasing evidence also suggests traditional Chinese medicine (TCM) as an effective strategy. We assessed the efficacy of ACEI, ARB, SGLT2i, and TCM on major renal outcomes. We searched the electronic literature published up to March 2021 from CNKI, VIP, WanFang, SinoMed, PubMed, Embase, Cochrane Library, Web of Science, and clinicaltrials.gov; a total of 56 studies and 5464 participants were included. We found that TCM plus ACEI, TCM plus ARB, and TCM alone are very effective treatment methods compared with ACEI, ARB, and the placebo in reducing 24-h urine protein, serum creatinine, and blood urea nitrogen. TCM plus ACEI was the most effective treatment (TCM plus ACEI vs. the placebo in 24-h urine protein [mean difference (MD) - 757.18, 95% confidence interval-1177.41 to - 353.31], serum creatinine [MD - 25.81, 95% confidence interval - 35.51 to - 16.03], and blood urea nitrogen [MD - 3.48, 95% confidence interval - 5.04 to - 1.90]). Although the incidence of end-stage renal disease while receiving an TCM plus ARB compared with a placebo was not statistically significant, the treatment ranking showed this combination therapy to have the greatest probability (72.8%) of reducing end-stage renal disease mortality, followed by SGLT2i (68%). Our analyses showed that combining TCM with conventional treatments for patients with DKD can improve renoprotective effects and superiority, and ACEI plus TCM may be the most effective option for treating DKD.