Predicting drug side effects is an important topic in the drug discovery. Although several machine learning methods have been proposed to predict side effects, there is still space for improvements. ...Firstly, the side effect prediction is a multi-label learning task, and we can adopt the multi-label learning techniques for it. Secondly, drug-related features are associated with side effects, and feature dimensions have specific biological meanings. Recognizing critical dimensions and reducing irrelevant dimensions may help to reveal the causes of side effects.
In this paper, we propose a novel method 'feature selection-based multi-label k-nearest neighbor method' (FS-MLKNN), which can simultaneously determine critical feature dimensions and construct high-accuracy multi-label prediction models.
Computational experiments demonstrate that FS-MLKNN leads to good performances as well as explainable results. To achieve better performances, we further develop the ensemble learning model by integrating individual feature-based FS-MLKNN models. When compared with other state-of-the-art methods, the ensemble method produces better performances on benchmark datasets.
In conclusion, FS-MLKNN and the ensemble method are promising tools for the side effect prediction. The source code and datasets are available in the Additional file 1.
Rhizosphere microbes are essential partners for plant stress tolerance. Recent studies indicate that arbuscular mycorrhizal fungi (AMF) can facilitate the revegetation of soils contaminated by heavy ...metals though interacting with rhizosphere microbiome. However, it is unclear how AMF affect rhizosphere microbiome to improve the growth of plant under rare earth elements (REEs) stress. AMF (Claroideoglomus etunicatum) was inoculated to maize grown in soils spiked with Lanthanum (0 mg kg−1, La0; 10 mg kg−1, La10; 100 mg kg−1, La100; 500 mg kg−1, La500). Plant biomass, nutrient uptake, REE uptake and rhizosphere bacterial and fungal community were evaluated. The results indicated that La100 and La500 decreased significantly root colonization rates and nutrition uptake (K, P, Ca and Mg content). La500 decreased significantly α-diversity indexes of bacterial and fungal community. AMF enhanced significantly the shoot and root fresh and dry weight of maize in all La treatments (except for the root fresh and dry weight of La0 and La10 treatment). For La100 and La500 treatments, AMF increased significantly nutrition uptake (K, P, Ca and Mg content) in shoot of maize by 27.40–441.77%. For La500 treatment, AMF decreased significantly shoot La concentration by 51.53% in maize, but increased significantly root La concentration by 30.45%. In addition, AMF decreased bacterial and fungal Shannon index in La0 treatment, but increased bacterial Shannon index in La500 treatment. Both AMF and La500 affected significantly the bacterial and fungal community composition, and AMF led to more influence than La. AMF promoted the enrichment of bacteria, including Planomicrobium, Lysobacter, Saccharothrix, Agrococcus, Microbacterium, Streptomyces, Penicillium and other unclassified genus, and fungi (Penicillium) in La500, which showed the function for promoting plant growth and tolerance of heavy metal. The study revealed that AMF can regulate the rhizosphere bacterial and fungal composition and foster certain beneficial microbes to enhance the tolerance of maize under La stress. Phytoremediation assisted by AMF is an attractive approach to ameliorate REEs-contaminated soils.
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•La100 and La500 decreased root colonization rates and nutrition uptake of maize.•AMF promoted growth and nutrition uptake of maize in different La-stressed soil.•AMF and La500 significantly altered α-diversity indexes and rhizosphere microbiome.•Microbial community structure was mainly influenced by AMF more than La stress.•AMF assisted phytoremediation is an approach to repair REE contaminated soils.
Plant roots and soil microorganisms interact with each other mainly in the rhizosphere. Changes in the community structure of the rhizosphere microbiome are influenced by many factors. In this study, ...we determined the community structure of rhizosphere bacteria in cotton, and studied the variation of rhizosphere bacterial community structure in different soil types and developmental stages using TM-1, an upland cotton cultivar (Gossypium hirsutum L.) and Hai 7124, a sea island cotton cultivar (G. barbadense L.) by high-throughput sequencing technology. Six bacterial phyla were found dominantly in cotton rhizosphere bacterial community including Acidobacteria, Actinobacteria, Bacteroidetes, Planctomycetes, Proteobacteria, and Verrucomicrobia. The abundance of Acidobacteria, Cyanobacteria, Firmicutes, Planctomycetes and Proteobacteria were largely influenced by cotton root. Bacterial α-diversity in rhizosphere was lower than that of bulk soil in nutrient-rich soil, but higher in cotton continuous cropping field soil. The β-diversity in nutrient-rich soil was greater than that in continuous cropping field soil. The community structure of the rhizosphere bacteria varied significantly during different developmental stages. Our results provided insights into the dynamics of cotton rhizosphere bacterial community and would facilitate to improve cotton growth and development through adjusting soil bacterial community structure artificially.
Oxidative stress is an important cause of neurodegenerative diseases. Antioxidant is an potential important method to treat such diseases. The aim of this study is to discover new and effective ...antioxidants and their mechanism. The neuroprotective effect of six curcumin pyrozole compounds were first evaluated on sodium nitroprusside (SNP) - induced PC12 cell injury by testing cell viability and LDH release. The results showed that four compounds (C1-C4) have more significant protective effects compared to curcumin and edaravone. Furthermore, compounds C1-C4 can attenuate the intracellular ROS, and compound C3 is the most effective one which can preservate the mitochondria function by inhibiting the mitochondrial membrane potential loss and enhance nuclear translocation of Nrf2 in PC12 cell. These results indicated that C3 may be a potential candidate drug for treating neurodegenerative diseases.
•Curcumin pyrazole derivatives C1-C4 can alleviate oxidative stress-induced PC12 neuronal damage.•C1-C4 can effectively reduce intracellular ROS, and C3 is the most effective.•The protective effect of C3 is related to the protection of mitochondrial function.•The protective effect of C3 is related to activation of Nrf2 signaling pathway.•C3 may be a potential candidate compound for neuroprotectants in the future.
Doxorubicin, an anthracycline chemotherapeutic agent, is widely used in the treatment of many cancers. However, doxorubicin posts a great risk of adverse cardiovascular events, which are thought to ...be caused by oxidative stress. We recently reported that the ubiquitin E3 ligase TRIM21 interacts and ubiquitylates p62 and negatively regulates the p62-Keap1-Nrf2 antioxidant pathway. Therefore, we sought to determine the role TRIM21 in cardiotoxicity induced by oxidative damage.
Using TRIM21 knockout mice, we examined the effects of TRIM21 on cardiotoxicity induced by two oxidative damage models: the doxorubicin treatment model and the Left Anterior Descending (LAD) model. We also explored the underlying mechanism by RNA-sequencing of the heart tissues, and by treating the mouse embryonic fibroblasts (MEFs), immortalized rat cardiomyocyte line H9c2, and immortalized human cardiomyocyte line AC16 with doxorubicin.
TRIM21 knockout mice are protected from heart failure and fatality in both the doxorubicin and LAD models. Hearts of doxorubicin-treated wild-type mice exhibit deformed mitochondria and elevated level of lipid peroxidation reminiscent of ferroptosis, which is alleviated in TRIM21 knockout hearts. Mechanistically, TRIM21-deficient heart tissues and cultured MEFs and H9c2 cells display enhanced p62 sequestration of Keap1 and are protected from doxorubicin-induced ferroptosis. Reconstitution of wild-type but not the E3 ligase-dead and the p62 binding-deficient TRIM21 mutants impedes the protection from doxorubicin-induced cell death.
Our study demonstrates that TRIM21 ablation protects doxorubicin-induced cardiotoxicity and illustrates a new function of TRIM21 in ferroptosis, and suggests TRIM21 as a therapeutic target for reducing chemotherapy-related cardiotoxicity.
NIH (CA129536; DK108989): data collection, analysis.
Shanghai Pujiang Program (19PJ1401900): data collection.
National Natural Science Foundation (31971161): data collection.
Department of Veteran Affairs (BX004083): data collection.
Tianjin Science and Technology Plan Project (17ZXMFSY00020): data collection.
Acute ischemic stroke is a leading cause of disability and death. The development of neuroprotectants is an emerging strategy for the treatment of ischemic stroke. In this work, we designed and ...synthesized a series of 1,3,5-triaryl substituent triazole derivatives by introducing a phenolic group and phenyl ring to 3,5-diaryl substituents oxadiazole. Structure-activity relationship (SAR) analysis showed that compounds with alkyl groups or with substituents at the 3-position possessed better protective effects. Among the derivatives, 3,5-dimethyl substituted compound 24 exhibited the best neuroprotective effect with weak cytotoxicity. Compound 24 possessed a high plasma protein binding rate, moderate hERG inhibition, low acute toxicity, and suitable pharmacokinetic properties. In vivo experiments demonstrated that compound 24 exerted a protective effect by reducing cerebral infarction size, improving neurological behavior, and restoring redox balance in middle cerebral artery occlusion rats. Further investigation indicated that compound 24 exerted a protective effect against sodium nitroprusside (SNP) induced cell damage by scavenging intracellular reactive oxygen species and restoring mitochondrial membrane potential. Moreover, compound 24 induced the nuclear translocation of Nuclear factor erythroid 2-related factor (Nrf2) and promoted the generation of antioxidative proteins, including Heme oxygenase-1 (HO-1), NAD(P)H quinone dehydrogenase (NQO1), and glutamate-cysteine ligase catalytic (GCLC). Surface plasmon resonance (SPR) experiments indicated that compound 24 might activate the Nrf2 signaling pathway by interacting with the Keap1 Kelch domain. Taken together, these facts indicate that compound 24 might have potential in the treatment of ischemic stroke.
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•Protecting cells from sodium nitroprusside-induced oxidative stress.•Elimination of ROS and restoration of mitochondrial transmembrane potential.•The mechanism relies on the activation of Nrf2 signaling pathway.•Low acute toxicity and suitable pharmacokinetic properties in vivo.•Ameliorating the infarct size and neurological deficits of MCAO rats.
Rare earth elements (REEs) have been widely used in traditional and high-tech fields, and high doses of REEs are considered a risk to the ecosystem. Although the influence of arbuscular mycorrhizal ...fungi (AMF) in promoting host resistance to heavy metal (HM) stress has been well documented, the molecular mechanism by which AMF symbiosis enhances plant tolerance to REEs is still unclear. A pot experiment was conducted to investigate the molecular mechanism by which the AMF Claroideoglomus etunicatum promotes maize (Zea mays) seedling tolerance to lanthanum (La) stress (100 mg·kg−1 La). C. etunicatum symbiosis significantly improved maize seedling growth, P and La uptake and photosynthesis. Transcriptome, proteome, and metabolome analyses performed alone and together revealed that differentially expressed genes (DEGs) related to auxin /indole-3-acetic acid (AUX/IAA) and the DEGs and differentially expressed proteins (DEPs) related to ATP-binding cassette (ABC) transporters, natural resistance-associated macrophage proteins (Nramp6), vacuoles and vesicles were upregulated. In contrast, photosynthesis-related DEGs and DEPs were downregulated, and 1-phosphatidyl-1D-myo-inositol 3-phosphate (PI(3)P) was more abundant under C. etunicatum symbiosis. C. etunicatum symbiosis can promote plant growth by increasing P uptake, regulating plant hormone signal transduction, photosynthesis and glycerophospholipid metabolism pathways and enhancing La transport and compartmentalization in vacuoles and vesicles. The results provide new insights into the promotion of plant REE tolerance by AMF symbiosis and the possibility of utilizing AMF–maize interactions in REE phytoremediation and recycling.
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•Arbuscular mycorrhizal fungi improved maize growth and La accumulation.•Arbuscular mycorrhizal fungi upregulated AUX/IAA and ARF gene expression.•Arbuscular mycorrhizal fungi upregulated ABC transporter gene and protein expression.•Arbuscular mycorrhizal fungi downregulated photosynthesis gene and protein expression.•Highly abundant PI(3)P contributed to mycorrhizal maize La compartmentalization.
Rhizosphere fungal communities exert important influencing forces on plant growth and health. However, information on the dynamics of the rhizosphere fungal community structure of the worldwide ...economic crop cotton (Gossypium spp.) is limited. In the present study, next-generation sequencing of nuclear ribosomal internal transcribed spacer-1 (ITS1) was performed to characterize the rhizosphere fungal communities of G. hirsutum cv. TM-1 (upland cotton) and G. barbadense cv. Hai 7124 (island cotton). The plants were grown in field soil (FS) that had been continuously cropped with cotton and nutrient-rich soil (NS) that had not been cropped. The fungal species richness, diversity, and community composition were analyzed and compared among the soil resources, cotton genotypes, and developmental stages. We found that the fungal community structures were different between the rhizosphere and bulk soil and the difference were significantly varied between FS and NS. Our results suggested that cotton rhizosphere fungal community structure variation may have been primarily influenced by the interaction of cotton roots with different soil resources. We also found that the community composition of the cotton rhizosphere fungi varied significantly during different developmental stages. In addition, we observed fungi that was enriched or depleted at certain developmental stages and genotypes in FS and NS, and these insights can lay a foundation for deep research into the dynamics of pathogenic fungi and nutrient absorption of cotton roots. This research illustrates the characteristics of the cotton rhizosphere fungal communities and provides important information for understanding the potential influences of rhizosphere fungal communities on cotton growth and health.
► We report sediment bacterial communities in the Xiangjiang River. ► We examine ecological impact of heavy metals on bacterial community. ► Heavy metal pollution affected sediment microbial ...community diversity. ► Moderate polluted sediment sample has the largest species diversity. ► Microbial richness and evenness are not linear relations with metals.
Understanding the ecology of sediments that are contaminated with heavy metals is critical for bioremediating these sediments, which has become a public concern over the course of the development of modern industry. To investigate the bacterial community composition of sediments that are contaminated with heavy metals in the Xiangjiang River, a total of four sediment samples contaminated with multiple heavy metals were obtained, and a culture-independent molecular analysis, polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP), was performed. The results revealed that heavy metal pollution affected the sediment microbial community diversity, and the greatest species diversity appeared in the moderately polluted sediment X sample. The dominant family in these sediments includes α-Proteobacteria, β-Proteobacteria and Firmicutes. Moreover, α-Proteobacteria was significantly increased with increases in heavy metal. A redundancy analysis (RDA) also confirmed this phenomenon.
Abstract
While previous studies have emphasised several important factors associated with the spread of COVID-19 and strategies to reduce transmission, few studies have focused on the social and ...cultural factors that may influence its spread. This study analyses the spread of COVID-19 from a cross-country/region cultural perspective and finds that countries and regions with a collectivistic, Confucian or tight (restrictive) culture experience a lower spread rate of COVID-19. The results are robust to controlling for several factors, including population, age structure, gross domestic product (GDP) per capita, previous SARS occurrence, smoking prevalence, and religion. A one standard deviation increase in the collectivism score is associated with a 1.38% reduction of the weekly growth rate of COVID-19 cases. More importantly, the effect of culture on the spread of COVID-19 becomes stronger during national or regional lockdowns. Corroborating these main results, supporting analyses find a significant effect of culture on national and regional COVID-19 death rates. These findings suggest that to manage the ongoing surges in COVID-19 outbreaks, governments should implement public health policies that emphasise the ideas of common interest, personal responsibility and strong cultural norms, and sense of community, as this pandemic has revealed that people all live together in a small global village.
Why did Korea, Japan & Taiwan have so few deaths? I see face-covering and the Confucian idea of common good as key
. –Michael Levitt, the Nobel Prize Laureate (2020)
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