Interpretable Predictive Models to Understand Risk Factors for Maternal and Fetal Outcomes.

Although most pregnancies result in a good outcome, complications are not uncommon and can be associated with serious implications for mothers and babies. Predictive modeling has the potential to improve outcomes through a better understanding of risk factors, heightened surveillance for high-risk patients, and more timely and appropriate interventions, thereby helping obstetricians deliver better care. We identify and study the most important risk factors for four types of pregnancy complications: (i) severe maternal morbidity, (ii) shoulder dystocia, (iii) preterm preeclampsia, and (iv) antepartum stillbirth. We use an Explainable Boosting Machine (EBM), a high-accuracy glass-box learning method, for the prediction and identification of important risk factors. We undertake external validation and perform an extensive robustness analysis of the EBM models. EBMs match the accuracy of other black-box ML methods, such as deep neural networks and random forests, and outperform logistic regression, while being more interpretable. EBMs prove to be robust. The interpretability of the EBM models reveal surprising insights into the features contributing to risk (e.g., maternal height is the second most important feature for shoulder dystocia) and may have potential for clinical application in the prediction and prevention of serious complications in pregnancy.

Genome Mining and Heterologous Expression Guided the Discovery of Antimicrobial Naphthocyclinones from Streptomyces eurocidicus CGMCC 4.1086.

A type II polyketide synthase biosynthetic gene cluster (nap) was identified in Streptomyces eurocidicus CGMCC 4.1086 via genome mining. The heterologous expression of the cryptic nap gene cluster in Streptomyces albus J1074 generated dimerized aromatic polyketide naphthocyclinones (1-3), whose structures were determined via extensive analysis using nuclear magnetic resonance and high-resolution electrospray ionization mass spectroscopy. The biological pathway of naphthocyclinone synthesis was revealed via in vivo gene deletion, in vitro biochemical reactions, and comparative genomics. Remarkably, 3 played a crucial role in inhibiting Phytophthora capsici and Phytophthora sojae, with EC50 values of 6.1 and 20.2 µg/mL, respectively. Furthermore, 3 exhibited a potent protective effect against P. capsici and P. sojae in greenhouse tests.

New metabolites from Streptomyces pseudovenezuelae NA07424 and their potential activity of inducing resistance in plants against Phytophthora capsici.

BACKGROUND: The lack of novel fungicide and appearance of resistance are the most emergent problems in the control of Phytophthora diseases. Plant immunity elicitors that induce systemic resistance in plants are regarded as the new strategy for plant disease control. Streptomyces can produce a variety of bioactive natural products, which are important resources for lead compounds of plant immunity elicitors. RESULTS: A novel peptidendrocin C (1) together with the known analog peptidendrocin B (2) were isolated from Streptomyces pseudovenezuelae NA07424. Their structures were confirmed by spectroscopic data and Marfey's reaction. In bioactive assays, compound 1 played an important role in inducing systemic resistance of Nicotiana benthamiana against Phytophthora capsici growth, with a 90.5% inhibition ratio at 400 µg/mL, while compound 2 showed moderate activity, inhibiting P. capsici growth by a 50.8% decrease at 400 µg/mL. Simultaneously, two compounds promoted enhanced expression of the PR1 gene and callose accumulation in N. benthamiana and Arabidopsis thaliana. In this paper, we also provide the first insights into their biosynthesis by confirming their biosynthesis gene cluster and related functional genes. CONCLUSION: Our findings show that 1 and 2 have the potential to be used as lead compounds for development of new plant immunity elicitors to control Phytophthora diseases. The study of the biosynthesis pathway lays the groundwork for further application of the bioactive natural products. © 2022 Society of Chemical Industry.

Fault diagnosis of rolling bearings using an Improved Multi-Scale Convolutional Neural Network with Feature Attention mechanism.

Machine learning techniques have been successfully applied for the intelligent fault diagnosis of rolling bearings in recent years. This study has developed an Improved Multi-Scale Convolutional Neural Network integrated with a Feature Attention mechanism (IMS-FACNN) model to address the poor performance of traditional CNN-based models under unsteady and complex working environments. The proposed IMS-FACNN has a good extrapolation performance because of the novel IMS coarse grained procedure with training interference and the introduced the feature attention mechanism, which improves the model's generalization ability. The proposed IMS-FACNN model has a better performance than existing methods in all the examined scenarios including diagnosing the bearing fault of a real wind turbine. The results show that the reliability and superiority of the IMS-FACNN model in diagnosing faults of rolling bearings.

Novel Polyketide-Terpenoid Hybrid Metabolites and Increased Fungal Nematocidal Ability by Disruption of Genes 277 and 279 in Nematode-Trapping Fungus Arthrobotrys oligospora.

Nematode-trapping fungus Arthrobotrys oligospora can produce a type of sesquiterpenyl epoxy-cyclohexenoid (SEC) metabolites that are regarded as characteristic chemtaxonomic markers. Here, we reported investigation on the functions of a putatively cupin-like family gene 277 and a dehydrogenase gene 279 by gene engineering, chemical metabolite profiling and phenotype analysis. Ten targeted metabolites were isolated from two mutants Δ277 and Δ279 and four novel metabolites including three polyketide-terpenoid (PK-TP) hybrid ones were characterized. Metabolite C277-1 from mutant Δ277 shared the characteristic feature of the first and simplest PK-TP hybrid precursor, prenyl toluquinol, and metabolites C279-1 and C279-2 from mutant Δ279 shared the basic carbon skeleton of the key PK-TP hybrid precursor, farnesyl toluquinol, for biosynthesis of SEC metabolites. These results suggested that gene 277 should be involved in biosynthesis of the second prenyl unit for farnesyl toluquinol precursor, and gene 279 might be responsible for the diagnostic epoxy formation. Further analysis revealed that genes 277 and 279 might play roles in fungal conidiation, predatory trap formation, and nematode-capturing ability.

Development of a Wearable Electrical Impedance Tomographic Sensor for Gesture Recognition With Machine Learning.

A wearable electrical impedance tomographic (wEIT) sensor with 8 electrodes is developed to realize gesture recognition with machine learning algorithms. To optimize the wEIT sensor, gesture recognition rates are compared by using a series of electrodes with different materials and shapes. To improve the gesture recognition rates, several Machine Learning algorithms are used to recognize three different gestures with the obtained voltage data. To clarify the gesture recognition mechanism, an electrical model of the electrode-skin contact impedance is established. Experimental results show that: rectangular copper electrodes realize the highest recognition rate; the existence of the electrode-skin contact impedance could improve the gesture recognition rate; Medium Gaussian SVM (Support Vector Machine) algorithm is the optimal algorithm with an average recognition rate of 95%.

Selected Mutations Revealed Intermediates and Key Precursors in the Biosynthesis of Polyketide-Terpenoid Hybrid Sesquiterpenyl Epoxy-cyclohexenoids.

Sesquiterpenyl epoxy-cyclohexenoids (SECs) show impressive biological activities. However, the key pathways for SECs still remain unambiguous. Unexpectedly, 11 new SECs and derivatives with diverse oxidation patterns were isolated after the deletion of gene 274. A high accumulation of toluquinol and its new glycosides in mutant Δ276 and further isolation of the most crucial precursors farnesyl hydroquinone, farnesyl quinone, and three new derivatives from mutant Δ278 confirm that farnesylation at toluquinol is the key step for SECs.

Potent Nematicidal Activity and New Hybrid Metabolite Production by Disruption of a Cytochrome P450 Gene Involved in the Biosynthesis of Morphological Regulatory Arthrosporols in Nematode-Trapping Fungus Arthrobotrys oligospora.

Types of polyketide synthase-terpenoid synthase (PKS-TPS) hybrid metabolites, including arthrosporols with significant morphological regulatory activity, have been elucidated from nematode-trapping fungus Arthrobotrys oligospora. A previous study suggested that the gene cluster AOL_s00215 in A. oligospora was involved in the production of arthrosporols. Here, we report that disruption of one cytochrome P450 monooxygenase gene AOL_s00215g280 in the cluster resulted in significant phenotypic difference and much aerial hyphae. A further bioassay indicated that the mutant showed a dramatic decrease in the conidial formation but developed numerous traps and killed 85% nematodes within 6 h in contact with prey, in sharp contrast to the wild-type strain with no obvious response. Chemical investigation revealed huge accumulation of three new PKS-TPS epoxycyclohexone derivatives with different oxygenated patterns around the epoxycyclohexone moiety and the absence of arthrosporols in the cultural broth of the mutant ΔAOL_s00215g280. These findings suggested that a study on the biosynthetic pathway for morphological regulatory metabolites in nematode-trapping fungus would provide an efficient way to develop new fungal biocontrol agents.

Nematicidal Key Precursors for the Biosynthesis of Morphological Regulatory Arthrosporols in the Nematode-Trapping Fungus Arthrobotrys oligospora.

Arthrobotrys oligospora is the first recognized nematode-trapping fungus and by far the most abundant in the environment. Our recent study revealed the polyketide synthase (PKS) gene AOL_s00215g283 in A. oligospora involved in the production of many secondary metabolites and the trap formation of the fungus. Here we report that the disruption of two genes in the upstream flanking region of the gene AOL_s00215g283, AOL_s00215g281 and AOL_s00215g282, which putatively encoded one amidohydrolase and one cytochrome P450 monooxygenase, respectively, both resulted in significant nematicidal activity of the cultural broths of the mutants and loss of morphological regulatory arthrosporols. Chemical investigation revealed the huge accumulation of 6-methylsalicylic acid in the cultural broth of the mutant ΔAOL_s00215g281 and the high production of m-cresol in the mutant ΔAOL_s00215g282, respectively. Further bioassay revealed that 6-methylsalicylic acid and m-cresol displayed significant nematicidal activity toward root-knot nematodes Meloidogyne incognita with IC90 values of 300 and 100 µg/mL, respectively. The mutant ΔAOL_s00215g282 displayed a more complex metabolite profile than the mutant ΔAOL_s00215g281, suggesting that m-cresol was a more versatile key precursor than 6-methylsalicylic acid. These findings not only demonstrated that the gene AOL_s00215g283 encodes the 6-methylsalicylic acid synthase and the gene AOL_s00215g281 encodes the decarboxylase for 6-methylsalicylic acid but also provided evidence for the potential functions of the precursors in fungal complex biosynthetic pathways and had more implications for the establishment of efficient fungal biocontrol agents.

High Trap Formation and Low Metabolite Production by Disruption of the Polyketide Synthase Gene Involved in the Biosynthesis of Arthrosporols from Nematode-Trapping Fungus Arthrobotrys oligospora.

A group of morphology regulatory arthrosporol metabolites have been recently characterized from carnivorous fungus Arthrobotrys oligospora that can develop trapping networks to capture their prey. A combination of genetic manipulation and chemical analyses was applied to characterize the function of one polyketide synthase (PKS) gene AOL_s00215g283 in A. oligospora, which was putatively involved in the production of 6-methylsalicylic acid. High-performance liquid chromatography analysis showed that the disruption of the PKS gene not only led to the total loss of the arthrosporol A but also resulted in significant reduction in the production of secondary metabolites in the cultural broth of the mutant ΔAOL_s00215g283 strain. Interestingly, the mutant strain displayed significant increases in the trap formation and the nematicidal activity by 10 and 2 times, respectively, higher than the wild-type strain. These findings revealed a pathogenicity-related biosynthetic gene of this agriculturally important biological agent and have implications for establishment of efficient fungal biocontrol agents.