The Current Developments in Medicinal Plant Genomics Enabled the Diversification of Secondary Metabolites' Biosynthesis.

Medicinal plants produce important substrates for their adaptation and defenses against environmental factors and, at the same time, are used for traditional medicine and industrial additives. Plants have relatively little in the way of secondary metabolites via biosynthesis. Recently, the whole-genome sequencing of medicinal plants and the identification of secondary metabolite production were revolutionized by the rapid development and cheap cost of sequencing technology. Advances in functional genomics, such as transcriptomics, proteomics, and metabolomics, pave the way for discoveries in secondary metabolites and related key genes. The multi-omics approaches can offer tremendous insight into the variety, distribution, and development of biosynthetic gene clusters (BGCs). Although many reviews have reported on the plant and medicinal plant genome, chemistry, and pharmacology, there is no review giving a comprehensive report about the medicinal plant genome and multi-omics approaches to study the biosynthesis pathway of secondary metabolites. Here, we introduce the medicinal plant genome and the application of multi-omics tools for identifying genes related to the biosynthesis pathway of secondary metabolites. Moreover, we explore comparative genomics and polyploidy for gene family analysis in medicinal plants. This study promotes medicinal plant genomics, which contributes to the biosynthesis and screening of plant substrates and plant-based drugs and prompts the research efficiency of traditional medicine.

[Professional responsibility in obstetrics in Morocco: analyzes of litigation files between 2015-2018]. / La responsabilité médicale en obstétrique au Maroc: analyse des dossiers des contentieux judiciaires entre 2015-2018.

Reflections on professional responsibility in Morocco are in clear development. Health professionals and especially obstetricians are reporting a dire situation due to limited resources and the lack of a clear legal framework that protects them, given that litigations are on the rise in recent years. We collected medical records of obstetric litigations adjudicated at the litigation department of the Ministry of Health in Morocco over a period of three years (2015-2018), with the aim of assessing the current situation of professional responsibility in obstetrics and indentifying failures in obstetric litigation management as well as developing recommendations tailored to the Moroccan context. Among the 111 medical litigations adjudicated over the study period, 56% (n=62) concerned obstetric activity and 84% (n=54) complications during labor; brachial plexus was the most registered complaint (61.3%; n=39). The analysis of data on medical expertise from these medical records revealed a non-compliance with quality in 88.7% of cases (n=55), the condemnation of professional birth attendants in 93.5% (n=58), a lack of documentation in the medical records in 35 % of cases (n=22). Litigations are more recorded in obstetrics than in other areas of the public health sector in Morocco. The lack of documentation and the complexity of management of the litigation process as well as the tendency to compensate patients in the absence of a structure of medical care for victims of therapeutic hazards are the most frequent causes of claimants´ gain.

Rhizosphere microbial diversity in rhizosphere of Pinellia ternata intercropped with maize.

Dry tubers of Pinellia ternata (Thunb.) Breit are used in traditional Chinese medicine. Commonly known as "banxia" in China, the tubers contain valuable compounds, including alkaloids and polysaccharides that are widely used in pharmaceuticals. The quantity and quality of these important compounds are affected by whether P. ternata is grown as a sole crop or as an intercrop, and P. ternata cultivation has become challenging in recent years. By intercropping P. ternata, its maximum yield, as well as large numbers of chemical components, can be realized. Here, a large data set derived from next-generation sequencing was used to compare changes in the bacterial communities in rhizosphere soils of P. ternata and maize grown as sole crops and as intercrops. The overall microbial population in the rhizosphere of intercropped P. ternata was significantly larger than that of sole-cropped P. ternata, whereas the numbers of distinct microbial genera, ranging from 552 to 559 among treatments, were not significantly different between the two rhizospheres. The relative abundances of the genera differed. Specifically, the numbers of Acidobacteria and Anaerolineaceae species were significantly greater, and those of Bacillus were significantly lower, in the intercropped P. ternata rhizosphere than in the sole-cropped rhizosphere. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-021-03011-3.

Network Pharmacology and Molecular Docking Combined to Analyze the Molecular and Pharmacological Mechanism of Pinellia ternata in the Treatment of Hypertension.

Hypertension is a cardiovascular disease that causes great harm to health and life, affecting the function of important organs and accompanied by a variety of secondary diseases, which need to be treated with drugs for a long time. P. ternata alone or combination with western medicine has played an important role in traditional Chinese medicine. Although P. ternata is used clinically to treat hypertension, its functional molecular mechanism and pharmacological mechanism have not been elucidated. Therefore, in this study, the potentially effective components, and targets of P. ternata in the treatment of hypertension were screened by the method of network pharmacology, and the mechanism of P. ternata in the treatment of hypertension was analyzed by constructing a component-target relationship network, PPI interaction network, targets' function analysis, and molecular docking. In the study, 12 potentially effective components and 88 targets were screened, and 3 potential protein modules were found and analyzed after constructing a PPI network using targets. In addition, 10 targets were selected as core targets of the PPI network. After that, the targets were analyzed by Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Finally, the molecular docking method is used to study the interaction between the targets and the active components. The above evidence shows that the mechanism of P. ternata in the treatment of hypertension is complicated, as it acts in many ways, mainly by affecting nerve signal transmission, cell proliferation, and apoptosis, calcium channels, and so on. The binding between targets and active components mainly depends on Pi bonds and hydrogen bonds. Using the method of network pharmacology and molecular docking to analyze the mechanism of P. ternata in the treatment of hypertension will help to provide a better scientific basis for the combined use of traditional Chinese medicine and western medicine, and will better help to improve the quality of P. ternata and point out its direction.

Analysis of the Coptis chinensis genome reveals the diversification of protoberberine-type alkaloids.

Chinese goldthread (Coptis chinensis Franch.), a member of the Ranunculales, represents an important early-diverging eudicot lineage with diverse medicinal applications. Here, we present a high-quality chromosome-scale genome assembly and annotation of C. chinensis. Phylogenetic and comparative genomic analyses reveal the phylogenetic placement of this species and identify a single round of ancient whole-genome duplication (WGD) shared by the Ranunculaceae. We characterize genes involved in the biosynthesis of protoberberine-type alkaloids in C. chinensis. In particular, local genomic tandem duplications contribute to member amplification of a Ranunculales clade-specific gene family of the cytochrome P450 (CYP) 719. The functional versatility of a key CYP719 gene that encodes the (S)-canadine synthase enzyme involved in the berberine biosynthesis pathway may play critical roles in the diversification of other berberine-related alkaloids in C. chinensis. Our study provides insights into the genomic landscape of early-diverging eudicots and provides a valuable model genome for genetic and applied studies of Ranunculales.

Structure, Function, Diversity, and Composition of Fungal Communities in Rhizospheric Soil of Coptis chinensis Franch under a Successive Cropping System.

Soil types and cropping systems influence the diversity and composition of the rhizospheric microbial communities. Coptis chinensis Franch is one of the most important medicinal plants in China. In the current study, we provide detailed information regarding the diversity and composition of rhizospheric fungal communities of the C. chinensis plants in continuous cropping fields and fallow fields in two seasons (winter and summer), using next-generation sequencing. Alpha diversity was higher in the five-year C. chinensis field and lower in fallow fields. Significant differences analysis confirmed more fungi in the cultivated field soil than in fallow fields. Additionally, PCoA of beta diversity indices revealed that samples associated with the cultivated fields and fallow fields in different seasons were separated. Five fungal phyla (Ascomycota, Basidiomycota, Chytridiomycota, Glomeromycota and Mucoromycota) were identified from the soil samples in addition to the unclassified fungal taxa and Cryptomycota, and among these phyla, Ascomycota was predominantly found. FUNGuild fungal functional prediction revealed that saprotroph was the dominant trophic type in all two time-series soil samples. Redundancy analysis (RDA) of the dominant phyla data and soil physiochemical properties revealed the variations in fungal community structure in the soil samples. Knowledge from the present study could provide a valuable reference for solving the continuous cropping problems and promote the sustainable development of the C. chinensis industry.

Stochastic Modeling of Groundwater Fluoride Contamination: Introducing Lazy Learners.

While it remains the primary source of safe drinking and irrigation water in northwest Iran's Maku Plain, the region's groundwater is prone to fluoride contamination. Accordingly, modeling techniques to accurately predict groundwater fluoride concentration are required. The current paper advances several novel data mining algorithms including Lazy learners [instance-based K-nearest neighbors (IBK); locally weighted learning (LWL); and KStar], a tree-based algorithm (M5P), and a meta classifier algorithm [regression by discretization (RBD)] to predict groundwater fluoride concentration. Drawing on several groundwater quality variables (e.g., Ca 2 + , Mg 2 + , Na + , K + , HCO 3 - , CO 3 2 - , SO 4 2 - , and Cl - concentrations), measured in each of 143 samples collected between 2004 and 2008, several models predicting groundwater fluoride concentrations were developed. The full dataset was divided into two subsets: 70% for model training (calibration) and 30% for model evaluation (validation). Models were validated using several statistical evaluation criteria and three visual evaluation approaches (i.e., scatter plots, Taylor and Violin diagrams). Although Na+ and Ca2+ showed the greatest positive and negative correlations with fluoride (r = 0.59 and -0.39, respectively), they were insufficient to reliably predict fluoride levels; therefore, other water quality variables, including those weakly correlated with fluoride, should be considered as inputs for fluoride prediction. The IBK model outperformed other models in fluoride contamination prediction, followed by KStar, RBD, M5P, and LWL. The RBD and M5P models were the least accurate in terms of predicting peaks in fluoride concentration values. Results of the current study can be used to support practical and sustainable management of water and groundwater resources.

Nosocomial Infections: Multicenter surveillance of antimicrobial resistance profile of Staphylococcus aureus and Gram negative rods isolated from blood and other sterile body fluids in Iran.

BACKGROUND AND OBJECTIVE: Antibiotic resistance is increasing, especially in healthcare-associated infections causing significant public health concerns worldwide. National information is required to make appropriate policies, update list of essential drugs for treatment, and evaluate the effects of intervention strategies. A nationwide surveillance of antimicrobial resistant bacteria in nosocomial infections was established in Iran in 2008, so that the data obtained through the surveillance would enable us to construct a database. MATERIALS AND METHODS: Seven major teaching hospitals in Shiraz, Tabriz, Sari, Mashhad, Sanandaj, Ahwaz and Isfahan participated in this study. A total of 858 strains isolated from blood and other sterile body fluids were tested. Identification at the species level was performed with conventional biochemical methods and the API system. Susceptibility tests were done using disk diffusion method. The methicillin-resistance in S. aureus (MRSA) was determined by the oxacillin agar screen plate and respective MIC values were assessed using the E-test strips. The confirmatory disk diffusion methods were applied for phenotypic identification of extended-spectrum ß- lactamase (ESBL) production for E. coli and K. pneumoniae, according to CLSI guidelines. RESULTS: Cultivation and re-identification of the strains yielded 858 isolates, consisting of 224 S. aureus, 148 Klebsiella spp., 105 Serratia spp., 146 E. coli, 67 Acinetobacter spp., 38 Enterobacter spp., 95 Pseudomonas spp., 71 P.aeruginosa. 35 Stenotrophomonas sp., and 8 other organisms. MRSA was detected in 37.5% of the isolates. No vancomycin-resistant or vancomycin-intermediate resistant S. aureus was detected. With the exception of Acinetobacter and Stenotrophomonas, 85% of the Gram-negative isolates were found to be susceptible in vitro to imipenem. Overall, about 61% of K. pneumoniae and 35% of E. coli isolates were ESBL producing. CONCLUSION: Multidrug resistant isolates of Gram-negative organisms and methicillin-resistant strains of S. aureus have been detected in many hospitals in this study.

Risk factors associated with life-threatening infections in children with febrile neutropenia: a data mining approach.

PURPOSE: To determine risk factors (RFs) and their relationship with life-threatening infection (LTI) in children with febrile neutropenia (FN). METHOD: In this cross-sectional study, from December 2008 to November 2009, all children with FN admitted to Dr Sheikh Pediatric Hospital were enrolled. For each patient, demographic, clinical, and laboratory data were recorded and they were followed up for occurrence of LTI. RESULTS: One hundred and twenty episodes of FN in 68 patients were analyzed. The most common underlying disease was acute lymphoblastic leukemia (53.3%), 9 (7.5%) died from an infection and 35 patients (29.1%) had a LTI. Five variables were identified as RFs for LTI, that is, body temperature ≥39°C (P=0.000), presence of mucositis (P=0.000), abnormal chest x-ray (P=0.001), platelet count <20,000/mm (P=0.000), and absolute neutrophil count <100/mm (P=0.001). Risk of LTI was increasing according to number of RFs presented at the beginning of admission (from 2.8% in patients without RF to 100% in patients with 5 RF). Data mining analysis showed relationship between RFs with platelet count as the most important variable in the high-risk group for LTI. CONCLUSIONS: Evaluation of important RFs and judging the severity of patients' condition by studying the importance and relationship between RF at the time of admission can be a useful method for screening LTI in children with FN.