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Pancreatic adenocarcinoma (PAAD) as one of the most aggressive and lethal malignant tumors is correlated with increased morbidity and mortality. Tumorigenesis, growth, and metastasis are affected by various cytokines. Among them, CC chemokines can modulate the infiltration of immune cells and recruit cancer-associated immune cells, which play an important role in the inhibition of tumor immunity and affect the clinical outcome of cancer patients. However, the therapeutic potential and prognostic value of CC chemokines in PAAD have not yet been elucidated. To do this, we comprehensively explore and analyze large amounts of data on the basis of ONCOMINE database, GEPIA, LinkedOmics, cBioPortal, GeneMANIA, UALCAN, jvenn, DAVID 6.8, TRRUST, TIMER, and TISIDB. We found the transcriptional levels of CCL5/7/13/15/18/19/20 in PAAD tissues were remarkably increased, whereas the transcriptional level of CCL17 was decreased. CCL20 expression had significantly been correlated with the tumor stage of PAAD patients. High expressions of CCL5, CCL7, CCL13, CCL18, and CCL20 were notably correlated with the prognosis of patients. Moreover, patients with CCL18 and CCL19 alterations showed a poor prognosis in both overall survival (OS) and disease-specific survival (DSS), and patients with CCL5 and CCL15 alterations also presented a poor prognosis in OS. The functions of the aberrantly expressed CC chemokines were mainly correlated with the cytokine-cytokine receptor interaction, chemokine signaling pathway, inflammatory response, and immune response. Our study shows that the key transcription factors for CC chemokines are RELA and NF-κB1. We also discovered significant associations between the expression levels of CC chemokines and six infiltrating immune cells including CD8+ T cells, CD4+ T cells, B cells, macrophages, neutrophils, and dendritic cells. Taken together, our study indicated the interaction between CC chemokines and PAAD and clarified the value of CC chemokines as potential therapeutic targets as well as prognostic markers for PAAD.

Dental calculus and other preserved microbiome substrates are an attractive target for dietary reconstruction in past populations through a variety of physical, chemical, and molecular means. Recently, studies have attempted to reconstruct diet from archaeological dental calculus using archaeogenetic techniques. While dental calculus may provide a relatively stable environment for DNA preservation, the detection of plants and animals possibly consumed by an individual through DNA analysis is primarily hindered by microbial richness and incomplete reference databases. Moreover, high genomic similarity within eukaryotic groups 1. Introduction 2. Materials and methods 3. Results 3.1. Effects of low read counts on damage patterns 3.2. Identification of dietary reads from synthetic datasets 3.3. Identification of dietary reads from real datasets 4. Discussion and conclusions 4.1. Checklist for authors and reviewers 4.1.1. Field/storage contamination 4.1.2. Is the laboratory methodology suitable for aDNA authentication? 4.1.3. Is the database and pipeline suitable? 4.1.4. Is the taxonomic resolution analyzed sufficient for reliable interpretation? 4.1.5. Have unexpected taxa been reported and evaluated? 4.1.6. Have laboratory controls been evaluated alongside samples? 4.1.7. Has evidence of aDNA authenticity been provided? 4.1.8. Is there other evidence supporting that dietary organisms were consumed?

Background:Cannabis has been cultivated and used for centuries in the north Moroccan Rif (local name is kif). However, its history is poorly known and the date of its first introduction and dispersal in Morocco is still difficult to be precise. Aim: The purpose of the present work is to review the literature on the origin, history, and cultivation of Cannabis in Morocco, as well as data on the morphological, genetic, and phytochemical characteristics of local cultivated varieties. Discussion: Considering the importance of preserving the fragile environment of the Rif and the future development of the Moroccan medical Cannabis market, which will require authentication of the raw material, the use of local strains which are well adapted to the particular environment of the Rif is highly recommended. However, there is no document that summarizes and clarifies the nomenclature and the characteristics of local Moroccan Cannabis. In addition, the recent adoption by Rif growers of improved hybrid cultivars is obliterating the traits and peculiarities of Moroccan Cannabis through genetic introgression. Conclusion: Summarizing and discussing the data from the literature on the characteristics of local Moroccan Cannabis varieties may be useful for their identification and the localization of the areas of the Rif region where their cultivation is still practiced.

The toxicity and associated health risks of typical contaminated groundwater were evaluated using bioassays, the SOS/umu test and the micronucleus assay, with a comparison of identified risks based on bioassay and chemical methods. An analysis of 15 water extracts showed that a lifetime cancer risk (LCR) value of 10−6 was recorded for 47% of water extracts. These results indicated that some water extracts did not exhibit toxicity when analysed using one type of bioassay, yet they indicated high toxicity when analysed using another method. Our results also demonstrated that the LCR values from bioassays were generally greater (2.4-foldmax) than those derived from chemical analysis, a finding indicating that risks can be underestimated or false-negative results can be obtained when only chemical-based methods or even just one bioassay is used. This study suggests that the use of multiple bioassays should be considered to be an efficient method and a comprehensive method should be established for risk assessment. Our findings also suggest that groundwater and freshwater in the studied area might pose significant health risks and exhibit toxicity.

Programmed cell death (PCD) is an important pathologic process after spinal cord injury (SCI), and as a newly type of PCD, ferroptosis is also involved in the secondary SCI, however, the underlying molecular mechanisms remain unclear. Integrating animal experiment and bioinformatics, we validated the ferroptotic phenotype in SCI first, and then bioinformatic analyses, including Gene Ontology enrichment analysis, Kyoto Encyclopedia of Genes and Genomes pathway analysis, gene set enrichment analysis and protein-protein interaction analysis were performed to investigate the ferroptotic genes at 1 day, 3 days, 7 days, 14 days and 56 days post-SCI, finally, the ferroptotic genes in SCI were identified and expression of 5 key genes were validated by western blot. The ferroptotic symbols including iron overload, lipid peroxidation, shrunken mitochondria and ROS accumulation were detected in the acute and sub-acute phase of SCI. The outcomes of bioinformatics suggested that mTOR signaling pathway, HIF-1 signaling pathway, VEGF signaling pathway, Protein processing in endoplasmic reticulum were involved in ferroptotic regulation and ATF-3, XBP-1, HO-1, DDIT-3 and CHAC-1 were selected as the ferroptotic key genes in SCI. Besides, response to oxidative stress, amide metabolic process, cation transport and cytokine production were showed as the essential biological process in ferroptosis after SCI. The ferroptotic phenotype following SCI was validated and the ferroptotic genes and signaling pathways were identified. The results contribute to exploring the ferroptotic mechanism underlying secondary SCI and to providing potential target for clinical treatment.

Background. Esophageal cancer (EC) is the 7th most common neoplasm and the 6th most common cause of cancer-related death worldwide. Immunotherapy is an effective treatment for EC patients. However, there are no dependable markers for predicting prognosis and immunotherapy responses in EC. Our study aims to explore prognostic models and markers in EC as well as predictors for immunotherapy. Methods. The expression profiles of EC were obtained from The Cancer Genome Atlas (TCGA), the Gene Expression Omnibus (GEO), and International Cancer Genome Consortium (ICGC) databases. Cox regression analysis was performed to construct a prognostic model. Overall survival and receiver operating characteristic curve analyses were applied to verify the accuracy of the model. The CIBERSORT algorithm was conducted to quantify the infiltration of different immune cells, and EC was grouped into three immune cell infiltration (ICI) clusters. PD-1 and PD-L1 expressions were compared between the ICI clusters. Overall survival analysis between ICI score and tumor mutation burden was conducted. The immunotherapy response of patients in different ICI score clusters was also compared. The copy number variations, somatic mutations, and single nucleotide polymorphisms were analyzed. Enrichment analyses were also performed. Results. A prognostic model was successfully constructed. Three ICI clusters were identified, and the clusters with high immune and stromal scores tended to have more immune-activated phenotypes and higher expressions of PD-1 and PDL1. The ICI score may be used as a predictor independent of tumor mutation burden. Patients with higher ICI score tended to have better immunotherapeutic responses than those with lower scores. Enrichment analyses showed that the differentially expressed genes were mostly enriched in microvillus and the KRAS and IL6/JAK/STAT3 pathways. The top eight genes with the highest mutation frequencies in EC were identified and all related to the prognosis of EC patients. Conclusions. Our study established an effective prognostic model and identified markers for predicting the prognosis and immunotherapy response of EC patients.

N2-methylguanosine is a post-transcriptional modification of RNA that is found in eukaryotes and archaea. The biological function of m2G modification discovered so far is to control and stabilize the three-dimensional structure of tRNA and the dynamic barrier of reverse transcription. To discover additional biological functions of m2G, it is necessary to develop time-saving and labor-saving calculation tools to identify m2G. In this paper, based on hybrid features and a random forest, a novel predictor, RFhy-m2G, was developed to identify the m2G modification sites for three species. The hybrid feature used by the predictor is used to fuse the three features of ENAC, PseDNC, and NPPS. These three features include primary sequence derivation properties, physicochemical properties, and position-specific properties. Since there are redundant features in hybrid features, MRMD2.0 is used for optimal feature selection. Through feature analysis, it is found that the optimal hybrid features obtained still contain three kinds of properties, and the hybrid features can more accurately identify m2G modification sites and improve prediction performance. Based on five-fold cross-validation and independent testing to evaluate the prediction model, the accuracies obtained were 0.9982 and 0.9417, respectively. The robustness of the predictor is demonstrated by comparisons with other predictors.

Infectious bursal disease virus (IBDV) can cause a highly contagious immunosuppressive disease in young chickens, resulting in considerable economic losses to the poultry industry. MicroRNAs (miRNAs) are crucial regulators of gene expression and are involved in the pathogenesis of IBDV infection. To investigate the roles of miRNA in chicken bursae of Fabricius in response to very virulent IBDV (vvIBDV) infection, RNA sequencing was performed. For this, we established an IBDV infection model as observed using histopathology, transmission electron microscopy (TEM), viral load detection, and cytokine expression levels. In total, 77 differentially expressed (DE) miRNAs were identified, of which 42 were upregulated and 35 were downregulated. A gene ontology analysis showed that genes associated with cellular processes, cells, and binding were enriched, and pathway analyses suggested that axon guidance, tight junctions, and endocytosis may be activated following vvIBDV infection. Moreover, we predicted the target genes of DE miRNAs and constructed an miRNA-mRNA regulatory network. In total, 189 pairs of miRNA-target genes were identified, comprising 67 DE miRNAs and 73 mRNAs. In this network, gga-miR-1684b-3p was identified with the highest fold change, and gga-miR-1788-3p and gga-miR-3530-5p showed a high degree of change, suggesting that they play vital roles in vvIBDV-host interactions. This study is the first to perform a comprehensive analysis of DE miRNAs in the bursa of Fabricius in response to vvIBDV infection, and it provides new insights into the molecular mechanisms underlying vvIBDV infection and pathogenesis.

Purpose This study aimed at exploring the mechanisms underlying nonalcoholic fatty liver disease (NAFLD) and developing new diagnostic biomarkers for nonalcoholic steatohepatitis (NASH). Methods The microarray dataset GES83452 was downloaded from the NCBI-GEO database, and the differentially expressed RNAs (DERs) were screened between the NAFLD and non-NAFLD samples of the baseline and 1-year follow-up time point group based on the Limma package. Results A total of 561 DERs (268 downregulated and 293 upregulated) were screened in the baseline time point group, and 1163 DERs (522 downregulated and 641 upregulated) were screened in the 1-year follow-up time point group. A total of 74 lncRNA–miRNA pairs and 523 miRNA–mRNA pairs were obtained in order to construct a lncRNA–miRNA–mRNA regulatory network. Subsequently, functional enrichment analysis revealed 28 GO and 9 KEGG pathways in the ceRNA regulatory network. LEPR and CXCL10 are involved in the Cytokine–cytokine receptor interaction (P = 1.86E-02), and the FOXO1 is involved in both the insulin signaling pathway (P = 1.79E-02) and the pathways in cancer (P = 2.87E-02). Conclusion LEPR, CXCL10, and FOXO1 were the characteristic target genes for NAFLD.

Diagnosis of LM is limited by low sensitivity of cerebrospinal fluid (CSF) cytopathology. Detecting tumor cells in CSF (CSF-TCs) might be more sensitive. We evaluated if CNSide (CNSide), a novel assay for tumor cell detection in CSF, can detect CSF-TCs better than conventional CSF cytology.We enrolled adults with metastatic breast cancer and clinical suspicion for LM to undergo lumbar puncture (LP) for CSF cytopathology and CNSide. CNSide captured CSF-TCs using a primary 10-antibody mixture, streptavidin-coated microfluidic channel, and biotinylated secondary antibodies. CSF-TCs were assessed for estrogen receptor (ER) expression by fluorescent antibody and HER2 amplification by fluorescent in situ hybridization (FISH). CSF cell-free DNA (cfDNA) was extracted for next-generation sequencing (NGS). Leptomeningeal disease was defined as positive CSF cytology and/or unequivocal MRI findings. We calculated sensitivity and specificity of CSF cytology and CNSide for the diagnosis of LM.Ten patients, median age 51 years (range, 37-64), underwent diagnostic LP with CSF evaluation by cytology and CNSide. CNSide had sensitivity of 100% (95% Confidence Interval [CI], 40%-100%) and specificity of 83% (95% CI, 36%-100%) for LM. Among these patients, concordance of ER and HER2 status between CSF-TCs and metastatic biopsy were 60% and 75%, respectively. NGS of CSF cfDNA identified somatic mutations in three patients, including one with PIK3CA p.H1047L in blood and CSF.CNSide may be a viable platform to detect CSF-TCs, with potential use as a diagnostic tool for LM in patients with metastatic breast cancer. Additional, larger studies are warranted.

The regulatory mechanisms that govern sex differentiation in sturgeon are still poorly understood. The doublesex and Mab-3-related transcription factor (Dmrt) gene family is known for its extensive roles in sex determination and differentiation across vertebrates. This study aimed to identify new members of sturgeon Dmrt family genes and core actors in the gonadal differentiation of Amur sturgeon. A full-length gonad transcriptome database was exploited to identify Dmrt gene orthologs. Analyses of phylogenetic relationships and selection pressure were performed, and tissue expression profiles and spatiotemporal expression patterns in gonads were then analyzed using real-time PCR. In total, five Dmrt family genes were identified from the full-length gonad transcriptome, including Dmrt2, DmrtA1, DmrtA2, DmrtB1a and DmrtB1b. Phylogenetic analysis showed that these genes were clustered into clades corresponding to the doublesex/Mav-3 (DM) genes of vertebrates. Furthermore, the analysis of evolutionary selective pressure indicated that DmrtB1a and DmrtB1b were subject to positive selection, suggesting the existence of adaptive evolution in sturgeon. The extensive tissues expression profiling of each Dmrt family gene revealed typical characteristics. Remarkably, according to a spatiotemporal expression pattern analysis, DmrtA1 and DmrtA2 were predominantly distributed in undifferentiated gonads (UGs) and developing ovaries, whereas DmrtB1b showed the lowest expression in UGs. In later stages, DmrtB1b expression continuously increased in testes and was significantly higher in testes than in ovaries at 24 months after hatching (M) and 36M, which strongly suggests that DmrtB1b is a core regulatory factor involved in sexual differentiation in sturgeon. This study provides a genetic resource of full-length Dmrt family genes and increases the understanding of Dmrt functions in sex differentiation in sturgeon.

The genus Ischnosoma Stephens is reported for the first time in the Korean Peninsula. Four species are recognized [I. convexum (Sharp), I. discoidale discoidale (Sharp), I. fusciventre (Tikhomirova), and I. rosti (Bernhauer)]. Diagnoses, a key, and illustrations of habitus and diagnostic characters are provided to facilitate identification.

This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To evaluate whether digital technology can effectively predict pulmonary exacerbations to allow earlier intervention and improved health outcomes without increasing the burden of treatment in people with cystic fibrosis (CF).

Spatial analysis of microbiomes at single cell resolution with high multiplexity and accuracy has remained challenging. Here we present spatial profiling of a microbiome using sequential error-robust fluorescence in situ hybridization (SEER-FISH), a highly multiplexed and accurate imaging method that allows mapping of microbial communities at micron-scale. We show that multiplexity of RNA profiling in microbiomes can be increased significantly by sequential rounds of probe hybridization and dissociation. Combined with error-correction strategies, we demonstrate that SEER-FISH enables accurate taxonomic identification in complex microbial communities. Using microbial communities composed of diverse bacterial taxa isolated from plant rhizospheres, we apply SEER-FISH to quantify the abundance of each taxon and map microbial biogeography on roots. At micron-scale, we identify clustering of microbial cells from multiple species on the rhizoplane. Under treatment of plant metabolites, we find spatial re-organization of microbial colonization along the root and alterations in spatial association among microbial taxa. Taken together, SEER-FISH provides a useful method for profiling the spatial ecology of complex microbial communities in situ.

The objective of this study is to identify and analyse the main characteristics of areas potentially degraded by desertification and of preserved areas using the Soil Surface Moisture Index (SSMI), alongside the Land Surface Temperature (LST) and Normalized Difference Vegetation Index (NDVI). The study is based on a set of points obtained in the field and from the RGB false colour image for the Environmental Protection Areas (EPA) of the Cariri, in the semi-arid region of Paraíba, using a space-time cross-section covering both rainy and dry periods. The results showed that at all points in Desertified Areas, the main characteristics were a low SSMI, high LST and low NDVI in both periods. The Preserved Areas, on the other hand, presented a high SSMI, moderate LST and high NDVI in the rainy period, with the same characteristics repeated in the dry period for SSMI and NDVI, but with a low LST. Timely identification of these characteristics, both in areas degraded by desertification and in better preserved areas, can provide useful information for future decisions relating to the physical and territorial management of the Conservation Unit. El objetivo de este estudio fue identificar y analizar las principales características de áreas potencialmente degradadas por desertificación y de áreas preservadas. Para ello se utilizaron el Índice de Humedad Superficial del Suelo (IHSS), junto con la Temperatura de la Superficie de la Tierra (TS) y el Índice de Vegetación de Diferencia Normalizada (IVDN). El estudio está basado en un conjunto de puntos obtenidos en el campo y en la composición de la imagen de falso color RGB para el Área de Protección Ambiental (APA) del Carirí, en la región semiárida de Paraíba, utilizando un corte espacio-temporal que abarca la estación lluviosa y seca. Los resultados mostraron que en todos los puntos de las Áreas Desertificadas las principales características fueron el IHSS bajo, TS alto y IVDN bajo en ambos períodos. Las Áreas Preservadas, por su parte, presentaron IHSS alto, TS moderado e IVDN alto en la época de lluvias, con las mismas características repetidas en el periodo seco para IHSS y IVDN, pero con TS bajo. La identificación puntual de estas características, tanto en áreas degradadas por desertificación como en las más conservadas, puede aportar información útil para la toma de decisiones futuras relacionadas con la gestión territorial y física de la Unidad de Conservación.

Rotylenchus is a widely distributed, economically important plant-parasitic nematode group whose species-level identification relies largely on limited morphological characters, including character-based tabular keys and molecular data of ribosomal and mitochondrial genes. In this study, a combined morphological and molecular analysis of three populations of Rotylenchus goodeyi from Belgium, Poland, and the Netherlands revealed important character variations of this species, leading to synonymization of R. rhomboides with R. goodeyi and a high nucleotide variation within cox1 gene sequences in these populations. Additional Illumina sequencing of DNA from individuals of the Dutch population revealed two variants of mitogenomes, each approximately 23 Kb in size, differing by approximately 9% and containing 11 protein-coding genes, 2 ribosomal RNA genes, and as many as 29 transfer RNA genes. In addition to the first representative whole-genome shotgun sequence datasets of the genus Rotylenchus, this study also provides the full-length mitogenome and the ribosomal DNA sequences of R. goodeyi.

Background: Microplastics are found to be one of the major emerging contaminants in the environment. Various environmental occurrences cause the macro plastics to degrade slowly into microplastics. Microplastics present in the water bodies may enter into the fish’s body through ingestion of food and also get adsorbed onto the surface of their gills or skin. Objective: Microplastics of polyethylene were chosen to investigate their sorption capacity on fish scales. The dispersion of polyethylene microplastics was studied by using a Total Dissolved Solids meter. Using this dispersion, the sorption effect was studied, and it revealed that the microplastics had the sorption ability on the fish scales. Method: Polyethylene microplastics were chosen to investigate its sorption capacity on fish scales of Lutjanus gibbus. The sorption effect of microplastics on fish scales were performed by using polyethylene microplastics obtained by bath sonication and the concentration was studied using Total dissolved solids meter. Using polyethylene microplastics dispersion, the sorption effect was carried out on the scales of Lutjanus gibbus for ten days at 8 oC. Sorption of microplastics on fish scales were characterized by FE-SEM, FT-IR, and Raman spectroscopy. Results: Polymer sorption was confirmed by using optical microscopy and FE-SEM. FT-IR and Raman spectroscopy confirmed the existence of polyethylene microplastics on the fish scale. Moreover, polyethylene microplastics sorption studies were also studied in different pH, various concentrations of NaCl and at different time intervals. Conclusions: We have synthesized microplastics from the bulk polyethylene by NaCl solution. This study confirmed the successful sorption of polyethylene microplastics on the fish scale. Our study revealed that marine water may be a suitable medium to facilitate the polymer sorption on aquatic animals/organisms.

Plants have been used as medicines for millennia and are major contributors to developed western pharmacopoeia. The Erythroxylum and Nectaropetalum genera belong to the Erythroxylaceae (coca) family, with select species capable of producing highly valued ‘blockbuster’ medicinal compounds including, amongst others atropine, cocaine, scopolamine, and tigloidine. Erythroxylum delagoense, E. emarginatum, E. pictum, N. capense and N. zuluense are indigenous to the south-east tropical regions of Africa. The morphological similarity between these taxa make identification to species-level troublesome and often unreliable, indicating a need for alternative identification methods. This study aimed to compare gas chromatography-mass spectrometry (GC-MS)- and nuclear magnetic resonance (NMR)-based metabolomics analyses with DNA barcoding to evaluate the identifying characteristics of these coca species. The results emphasise the importance of integrating chemotaxonomy and DNA barcoding techniques in plant identification. In this sample of the Erythroxylaceae, the differentiating identification accuracy was shown to increase from morphology to DNA barcoding to chemotaxonomy. This study further highlights the strengths and weaknesses of various plant identification strategies, as well as providing a developing model for more accurate and reliable species-level identification of plants. The findings from this case study could aid in the identification and classification of other closely related taxa.

Zusammenfassung. Einleitung: Klassische ernährungsepidemiologische Studien (Beobachtungsstudien und randomisierte Interventionsstudien) zeigen, dass die Ernährung ein wichtiger Ansatzpunkt für die Prävention und Therapie psychischer Störungen sein könnte. Diese Studientypen haben allerdings Limitationen, die bei der Ergebnisinterpretation berücksichtigt werden müssen. In dieser narrativen Übersichtsarbeit wird beschrieben, wie genetische Studien ein Bindeglied darstellen können, um einen Zusammenhang zwischen Ernährung und psychischen Störungen herzustellen. Methodik: Im Artikel werden verschiedene Ansätze genetischer phänotypübergreifender Analysen sowie Beispiele für deren Anwendungen in der ernährungspsychiatrischen Forschung beschrieben. Darüber hinaus werden spezifische Voraussetzungen sowie Stärken und Schwächen diskutiert. Ergebnisse: Als Methoden genetischer phänotypübergreifender Analysen sind im Rahmen ernährungspsychiatrischer Forschung bislang genetische Korrelationsanalysen, Look-up-Analysen sowie Mendelsche Randomisierungsstudien (MR-Studien) eingesetzt worden. Genetische Korrelationsanalysen und Look-up-Analysen geben erste Hinweise auf mögliche genetische Überlappungen zwischen einer psychischen Störung und einem Stoffwechselweg und/oder der Versorgung mit einem spezifischen Nährstoff. MR-Studien sind weitergehende Detailanalysen mit dem Ziel, Kausalzusammenhänge zu identifizieren, beinhalten allerdings sehr spezifische Grundvoraussetzungen für ihre Durchführung. Schlussfolgerung: Genetische phänotypübergreifende Analysen sind eine sinnvolle Ergänzung der klassischen Ernährungsepidemiologie. Insbesondere signifikante Ergebnisse von MR-Studien sind eine wichtige Grundlage zur Entwicklung geeigneter Ernährungsinterventionen, die in nachfolgenden randomisiert kontrollierten Interventionsstudien mit deutlich erhöhter Erfolgsaussicht getestet werden können. Sie sind somit wichtige Instrumente einer effizienten ernährungspsychiatrischen Forschung.

Andrographis Herba, the aerial part of Andrographis paniculata (Burm. f.) Wall. ex Nees (Acanthaceae), has a wide geographic distribution and has been used for the treatment of fever, cold, inflammation, and other infectious diseases. In markets, sellers and buyers commonly inadvertently confuse with related species. In addition, most Chinese medicinal herbs are subjected to traditional processing procedures, such as steaming and boiling, before they are sold at dispensaries; therefore, it is very difficult to identify Andrographis Herba when it is processed into Chinese medicines. The identification of species and processed medicinal materials is a growing issue in the marketplace. However, conventional methods of identification have limitations, while DNA barcoding has received considerable attention as a new potential means to identify species and processed medicinal materials. In this study, 17 standard reference materials of A. paniculata, 2 standard decoctions, 27 commercial products and two adulterants were collected. Based on the ITS2 sequence, it could successfully identify A. paniculata and adulterants. Moreover, a nucleotide signature consisting of 71 bp was designed, this sequence is highly conserved and specific within A. paniculata while divergent among other species. Then, we used these new primers to amplify the nucleotide signature region from processed materials. In conclusion, the DNA barcoding method developed in the present study for authenticating A. paniculata is rapid and cost-effective. It can be used in the future to guarantee the quality of Andrographis Herba of each regulatory link for clinical use.

Brassica rapa (AA, 2n = 20) and Raphanus sativus (RR, 2n = 18) are popular vegetables containing multiple secondary metabolites, such as flavonoids and anthocyanins. Nevertheless, few studies on miRNA expression profiles and potential regulatory network of flavonoid metabolism have been reported in the intergeneric hybrid of B. rapa and R. sativus (Brassicacoraphanus, AARR, 2n = 38). Here, the miRNAs of Brassicacoraphanus and its parents were first identified by small RNA sequencing. It was revealed that 315 conserved miRNAs and 193 novel miRNAs were found in Brassicacoraphanus and its parents. Moreover, the miRNA expression profiles were characterized and 204 miRNAs with differential expression were obtained. Further analysis showed that 184 miRNAs were non-additively expressed in Brassicacoraphanus. At last, the potential regulatory network of flavonoid metabolism in Brassicacoraphanus was analyzed by multi-omics data, suggesting possible roles of miR858a and miR157a in regulating flavonoid synthesis pathway in Brassicacoraphanus. Taken together, this study provides useful resources for probing global miRNA expression patterns in Brassicacoraphanus, which facilitates regulatory mechanism research on the biosynthesis pathway of secondary metabolites in Brassicacoraphanus.

Bakır (Cu), bitki büyümesi için gerekli olan temel eser metallerden biridir. Ancak, ortamdaki yüksek miktarda Cu, bitkide toksik etki göstererek büyümeyi olumsuz yönde etkilemektedir. Diğer bir yandan, Cu akümülatörü olan Brassica nigra L., sahip olduğu özel mekanizmalar ile yüksek Cu miktarlarını akümüle edebilmekte ve bu metali farklı hücre bölümlerine taşıyarak sitoplazmadan uzaklaştırabilmektedir. Bu çalışmada, B. nigra’nın düşük Cu seviyesindeki gen anlatım profilinin tespiti amaçlanmıştır. Düşük Cu seviyesinde yetiştirilen B. nigra'nın yapraktaki Cu ile indüklenen gen anlatım profili Arabidopsis ATH1 genom çipi kullanılarak tespit edilmiştir. Elde edilen sonuçlara göre, B. nigra’da 95 gen yukarı regüle ve 72 gen aşağı regüle olarak tanımlanmıştır. Glutatyon S-transferaz, glutatyon redüktaz, ağır metal taşıyıcılar, doğal dirençle ilişkili makrofaj proteinleri, sitokrom p450, MYB-gibi transkripsiyon faktörü, bakır/çinko ve Fe süperoksit dismutazlar gibi Cu ile ilişkili bazı genlerin ve bazı protein kinazların yüksek oranda anlatımının olduğu saptanmıştır. Bu çalışma, fakültatif metalofit olarak tespit edilen B. nigra' nın global gen anlatım profilini sunmakta olup, moleküler bir araç olarak ileriki fitoremediasyon çalışmaları için yardımcı olacaktır., Copper (Cu) is one of the essential trace metals required for plant growth. High amount of Cu in the media inhibits plant growth and is toxic to the plants. Brassica nigra L., a Cu accumulator, can tolerate a high amount of Cu and have specific mechanisms to relocate Cu within the cell compartments and keep the toxic amount of Cu away from the cytoplasm. This study aimed to evaluate the Cu-induced gene expression pattern of B. nigra Diyarbakir ecotype subjected to low Cu treatment. The Arabidopsis ATH1 genome array was used to determine the Cu-induced gene expression in the leaves of B. nigra grown at 25 µM Cu. Ninety-five genes were upregulated, and seventy-two genes were downregulated in the leaves of plants grown under 25 µM Cu. Cu responsive genes, such as glutathione S-transferase, glutathione reductase, heavy metal transporters, natural resistance-associated macrophage proteins, cytochrome p450, MYB-like transcription factor, copper/zinc, and Fe superoxide dismutases, and some protein kinases were highly expressed in the leaves of Cu-treated plants. The present work provides the global gene expression pattern in facultative metallophyte B. nigra, which could serve as a molecular tool for future phytoremediation studies.

Pseudomonas syringae pv. syringae, which causes bacterial canker, is the most polyphagous bacterium in the P. syringae complex because of its broad host range. This pathogen is considered the major bacterial disease in cherry orchards. In this study, several samples were collected from infected sweet cherry (Prunus avium L.) trees in different locations of the Marmara region in Turkey between 2016 and 2018. Sixty-three isolates were identified as P. syringae pv. syringae by pathogenicity, LOPAT, GATTa, and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry tests. Total genomic DNA was extracted to confirm identity, followed by PCR amplification of syrB and cfl genes. Out of 63 isolates, 12 were randomly selected for repetitive element sequence-based PCR and multilocus sequence typing analyses to gain insight into the relationships of those isolates. The cluster analysis of enterobacterial repetitive intergenic consensus-, repetitive extragenic palindromic-, and BOX-A1R-based repetitive extragenic-palindromic-PCR techniques could classify the isolates into two distinct clusters. Phylogenetic analysis was carried out to obtain the relation between isolates and the location. The multilocus sequencing typing analysis of gyrB, rpoDp, rpoDs, and gltA genes allowed a clear allocation of the isolates into two separate main clusters. The relationships among the isolates were also evaluated by constructing a genealogical median-joining network (MJN). The isolates from six locations produced 11 haplotypes that were illustrated in the MJN. The results of this study proved that location could not be an indicator for showing the genetic diversity of P. syringae pv. syringae from cherry orchards. As the genetic variability of Pseudomonads has been demonstrated, this study also showed high diversity among different isolates even within the populations. While more research is recommended, the results of this study contributed to a better understanding of the evolutionary progress of P. syringae pv. syringae and the genetic diversity of sweet cherry isolates.

Onion is among the most consumed vegetables in Uruguay, grown in the northwestern and southern regions of the country. The onion supply presents interannual variations associated with significant postharvest losses, mainly caused by bacterial rots. Besides bulb rotting, onion leaf lesions as well as infections on seed-stalks during seed production may be devastating for some varieties under conducive conditions. This research aimed to identify the causal agents of bulb rots and leaf blight of onion crops in Uruguay. Symptomatic bulbs, seeds-stalks, and leaves were collected from commercial fields from 2015 to 2020. Bacterial colonies were isolated and identified at genera level using physiological tests and 16S rRNA gene sequence analysis. A collection of 59 Pantoea spp. isolates was obtained (11 from bulbs and 48 from leaves and seeds-stalks). Multilocus sequence analysis using four housekeeping genes (rpoB, gyrB, leuS, and fusA) allowed the assignment of the isolates to five Pantoea species: P. ananatis, P. agglomerans, P. allii, P. eucalypti, and P. vagans. The last two species were not previously reported as onion pathogens elsewhere. The ability to cause disease symptoms was tested by leaf inoculation and red onion scale assays. P. ananatis isolates showed the highest aggressiveness in both assays. Specific isolates from P. allii (MAI 6022), P. eucalypti (MAI 6036), P. vagans (MAI 6050), and Pantoea sp. (MAI 6049) ranked second in aggressiveness on onion leaves, whereas only three isolates belonging to P. eucalypti (MAI 6036 and MAI 6058) and P. agglomerans (MAI 6045) exhibited the same scale-clearing phenotype as P. ananatis. Leaf inoculation assays were also performed on a set of eight onion cultivars and breeding lines. Overall, P. ananatis MAI 6032 showed the highest aggressiveness in all tested cultivars, followed by P. eucalypti MAI 6036. The presence of new reported bacterial species leads to complex disease management and highlights the need for further studies on virulence factors and the epidemiology of these pathogens.

Soil erosion is caused due to the dynamic action of erosive agents, mainly water, and is a major threat to the environment. Primary aim of the present study was to study the soil loss dynamics, and identify the environmental hotspots in Madhya Pradesh to aid decision-makers to plan and prioritize appropriate conservation measures. Universal Soil Loss Equation (USLE) and Revised Universal Soil Loss Equation (RUSLE) models were applied for erosion rate estimation by generating thematic maps of R (Rainfall erosivity factor), K (Soil erodibility factor), LS (Topographic factor), C (Cover and management factor), and P (Support practice factor) factors by using several input parameters in QGIS software. Subsequently, the different classes of soil erosion and percentage area under these classes were identified. The average annual soil erosion for the entire state as obtained from the USLE and RUSLE model were 5.80 t.ha-1.yr-1 and 6.64 t.ha-1.yr-1, respectively. The areas under severe risk were 1.09 % and 1.80 %, and very severe risk areas were 1.57 % and 1.83 % as estimated by USLE and RUSLE model, respectively. As compared to RUSLE model, USLE model underestimated rate of soil erosion for most river basins of the state as well as for the entire state.

Intrapartum transperineal ultrasound is considered useful in judging fetal head descent; however, the inability to detect ischial spines on ultrasound images has been a drawback to its legitimacy. The current study aimed to determine the anatomical location of ischial spines, which can be directly applied to intrapartum transperineal ultrasound images. Based on magnetic resonance imaging (MRI) of 67 pregnant women at 33+2 [31+6-34+0] weeks gestation (median [interquartile range: IQR]), we calculated the angle between the pubic symphysis and the midpoint of ischial spines (midline symphysis-ischial spine angle; mSIA), which is theoretically equivalent to the angle of progression at fetal head station 0 on ITU, by determining spatial coordinates of pelvic landmarks and utilizing spatial vector analysis. Furthermore, we measured symphysis-ischial spine distance (SID), defined as the distance between the vertical plane passing the lower edge of the pubic symphysis and the plane that passes the ischial spines. As a result, mSIA was 109.6° [105.1–114.0] and SID 26.4 mm [19.8–30.7] (median, [IQR]). There was no correlation between mSIA or SID and maternal characteristics, including physique. We established a novel method to measure the components of the pelvic anatomy by analyzing the three-dimensional coordinates of MRI data and identified the anatomical location of ischial spines which can be applied to ultrasound images. Our results provide valuable evidence to enhance the reliability of intrapartum transperineal ultrasound in assessing fetal head descent by considering the location of ischial spines.

The study is included isolation and identification of eight species of cyanobacteria from 12 soil samples from Garmat-Ali and Abu-Alkhaseeb in Basrah city. The isolated species have been grown and multiplicated at laboratory condition:Temperature (27±2) ºC and illumination (150-175) Lux for (16:8) hours light : dark cycle. The ability of these species of these species to produce antibiotics against reference strains of the gram positive bacteria, Staphylococcus aureus (NCTC 6571) (gram positive) and the gram negative bacteria, Escherichia coli (NCTC 5933) (gram negative) was tested. Isolate of Nostoc muscorum show inhibition activity with wilde inhibition diameter compared with other isolates. The ability of N.muscorum to secrete antibiotics in the threedifferent fermentation media was tested, the results showed differences in the production of the antibiotiocs between the three different media and the higher productivity was clear in the third medium which showed remarkable activity against bacterial isolates. The antibiotic was purified by using column chromatography technique and assistance the purification of antibiotic was done by using thin layer chromatography (TLC). The produced antibioticswere identified as cryptophycin by determination of: melting point MP), molecular weight and other chemical tests in addition to ultra-violet UV) and infra red spectroscopy (IR). The results of all above tests were showed the similarity between the produced antibiotic aest standard cryptophycin.

BACKGROUND: sBladder urothelial carcinoma is the most prevalent type of bladder cancer, characterized by drug resistance, high recurrence rate, and unfavorable prognosis. Ferroptosis is a newly discovered type of non-apoptotic cell death, which has been reported to be strongly correlated with tumor occurrence and development. OBJECTIVE: In this study, we characterized ferroptosis-specific biomarkers to elucidate the association between ferroptosis-related genes (FRGs) and bladder urothelial carcinoma. METHODS: The TCGA and GEO database were adopted to obtain data and corresponding clinicopathological information. Univariate and multivariate cox regression were performed to establish a ferroptosis-related model. Besides, the KM plot visualized prognosis between high risk and low risk groups. Moreover, cBioportal platform was used to gather information on genetic alteration and DNA methylation of hub FRGs in BLCA patients. Additionally, the GSEA software was used to detect the difference in gene expression between high-risk and low-risk subgroups. RESULTS: Six ferroptosis-related genes were identified to be highly correlated with overall survival. Besides, we explored the genetic variations of these FRGs, as well as the correlation between FRG expression and copy number values. Additionally, the DNA methylation status of these FRGs was determined. Moreover, we constructed a ferroptosis risk model with the six FRGs to predict the prognosis of BLCA. The results demonstrated that a higher risk score indicated an unfavorable prognosis. The ferroptosis signature was associated with clinical and molecular characteristics and could be regarded as an independent prognostic factor for BLCA patients. CONCLUSIONS: In summary, we established and verified a ferroptosis risk model which had the potential to independently predict the prognosis of bladder urothelial carcinoma.

Since the discovery of an oncogenic tropomyosin-receptor kinase (TRK) fusion protein in the early 1980s, our understanding of neurotrophic tropomyosin-receptor kinase (NTRK) fusions, their unique patterns of frequency in different tumor types, and methods to detect them have grown in scope and depth. Identification of these molecular alterations in the management of patients with cancer has become increasingly important with the emergence of histology-agnostic, US Food and Drug Administration-approved, effective TRK protein inhibitors. Herein, we review the biology of TRK in normal and malignant tissues, as well as the prevalence and enrichment patterns of these fusions across tumor types. Testing methods currently used to identify NTRK1-3 fusions will be reviewed in detail, with attention to newer assays including RNA-based next-generation sequencing. Recently proposed algorithms for NTRK fusion testing will be compared, and practical insights provided on how testing can best be implemented and communicated within the multidisciplinary healthcare team.

Tectona grandis L.f is a timber plant that is commonly referred to as teak. Its wide use as a medicine in the various indigenous systems makes it a plant of importance. A wide gamut of phytoconstituents like alkaloids, phenolic glycosides, steroids, etc. has been reported. A renewed interest in this plant has resulted in scientific investigations by various researchers towards the isolation and identification of active constituents along with scientific proof of its biological activities. The different parts of the plant have been scientifically evaluated for their antioxidant, antipyretic, analgesic, hypoglycemic, wound healing, cytotoxic, and many more biological activities. Documentation of this scientific knowledge is of importance to have consolidated precise information encompassing the various aspects of this plant, which could provide a base for future studies. This review is a compilation of the salient reports on these investigations concerning phytochemistry, the methods used to identify and quantify the constituents, the evaluation methods of the biological activity, toxicological studies, allergies and the patent/patent applications. This will further help researchers to find an area of the gap for future studies.

Background: Minodronic acid (MA) is a third-generation nitrogen-containing heterocyclic bisphosphonate used to treat osteoporosis. In the process of starting materials research and preparation, the key intermediate impurities and degradation impurities have a great impact on the quality control of the drug. Objective: A sensitive, reliable, high-performance liquid chromatography (HPLC) method was developed and validated for the quantitative determination of MA and its related impurities (a total of 6 compounds, including 2 new impurities). Methods: The separation was achieved on an InertSustain ODS-4 C18 (250 mm × 4.6 mm, 5 μm) column using the mixture of 0.01 mol/L sodium pyrophosphate and 1 mmol tetrabutylammonium phosphate (the mobile phase pH was adjusted to 7.80 by phosphonic acid). Results: The quantitative analytical method was fully validated with respect to linearity (r > 0.999), sensitivity (limit of detection < 35 ng/mL), precision, accuracy (the recovery was between 98.7% and 104.2%), and robustness. Six process-related impurities in Minodronic Acid (MA) bulk drug were determined by high-performance liquid chromatography (HPLC). Furthermore, except for two starting materials, other four impurities were identified and characterized as 2-(imidazo[1,2-a] pyridin-3-yl) ethyl acetate (Imp-C), 2-(imidazo [1,2-a] pyridin- 3- yl)acetic acid (Imp-D), 3-(2-hydroxy-2,2- diphosphonoethyl)-4H-imidazo [1,2-a] pyridine -4- oxide (Imp-E) and 2,5- Dihydroxy- 3,6-bis(imidazo[1,2-a] pyridine-3-yl methyl) -2,5-dioxo- 1,4,2,5- dioxoDiphosphonium-3,6-diyl) bisphosphonic acid (Imp-F) using liquid chromatograph- mass spectrometer (LC-MS), MS/MS, Infrared Radiation and Nuclear Magnetic Resonance spectroscopy (1H-NMR and 13C-NMR). To the best of our knowledge, two of them (Imp- E and Imp-F) are new compounds and have not been reported previously. Conclusion: The HPLC method was developed and optimized, which could be applied for quantitative detection of the impurities, and further quality evaluation of MA.

Summary Target identification and drug discovery roads have been widely improved over the past decades in onco-hematology. In this review, we summarize recent improvements in the use of physio-pathologically relevant models and innovative screening approaches to accelerate efficient drug development. Using acute myeloid leukemia as an example, we also discuss the main encountered pitfalls and propose alternative roads to improve the drug discovery journey in onco-hematology.

Background: Natural products have been a rich source of compounds for drug discovery. Usually, compounds obtained from natural sources have little or no side effects, thus searching for new lead compounds from traditionally used plant species is still a rational strategy. Introduction: Natural products serve as a useful repository of compounds for new drugs; however, their use has been decreasing, in part because of technical barriers to screening natural products in highthroughput assays against molecular targets. To address this unmet demand, we have developed and validated a high throughput in silico machine learning screening method to identify potential compounds from natural sources. Methods: In the current study, three machine learning approaches, including Support Vector Machine (SVM), Random Forest (RF) and Gradient Boosting Machine (GBM) have been applied to develop the classification model. The model was generated using the cyclooxygenase-2 (COX-2) inhibitors reported in the ChEMBL database. The developed model was validated by evaluating the accuracy, sensitivity, specificity, Matthews correlation coefficient and Cohen’s kappa statistic of the test set. The molecular docking study was conducted on AutoDock vina and the results were analyzed in PyMOL. Results: The accuracy of the model for SVM, RF and GBM was found to be 75.40 %, 74.97 % and 74.60 %, respectively, which indicates the good performance of the developed model. Further, the model has demonstrated good sensitivity (61.25 % - 68.60 %) and excellent specificity (77.72 %- 81.41 %). Application of the model on the NuBBE database, a repository of natural compounds, led us to identify a natural compound, enhydrin possessing analgesic and anti-inflammatory activities. The ML methods and the molecular docking study suggest that enhydrin likely demonstrates its analgesic and anti-inflammatory actions by inhibiting COX-2. Conclusion: Our developed and validated in silico high throughput ML screening methods may assist in identifying drug-like compounds from natural sources.

The majority of DNA-based transposable elements comprise autonomous and nonautonomous copies, or only nonautonomous copies, where the autonomous copy contains an intact gene for a transposase protein and the nonautonomous copy does not. Even if autonomous copies coexist, they are generally less frequent. The Tol2 element of medaka fish is one of the few elements for which a nonautonomous copy has not yet been found. Here, we report the presence of a nonautonomous Tol2 copy that was identified by surveying the medaka genome sequence database. This copy contained three local sequence alterations that affected the deduced amino acid sequence of the transposase: a deletion of 15 nucleotides resulting in a deletion of 5 amino acids, a base substitution causing a single amino acid change, and another base substitution giving rise to a stop codon. Transposition assays using cultured human cells revealed that transposase activity was reduced by the 15-nucleotide deletion and abolished by the nonsense mutation. This is the first example of a nonautonomous Tol2 copy. Thus, Tol2 is in an early stage of decay in the medaka genome, and is therefore a unique element to observe an almost complete decay process that progresses in natural populations.

Nicotiana plumbaginifolia Viviani, commonly known as curl-leaved tobacco, is an annual herbaceous plant belonging to Solanaceae family. This plant is native to Mexico, South America, and parts of the Caribbean and has been reported to be present in Taiwan since 2006. In March 2021, N. plumbaginifolia Viviani, found in Yunlin County, Taiwan, was observed to have phyllody, virescence, and witches’-broom, which is consistent with the disease symptoms caused by phytoplasma infection. Samples of the healthy and symptomatic plants were collected for analysis of the causal agent associated with the diseased N. plumbaginifolia Viviani. Under transmission electron microscopy, the phytoplasma-like pleomorphic bodies were found in the sieve tubes of the diseased plants. The 16S ribosomal RNA (rRNA)-based phylogenetic analysis and the iPhyClassifier-based virtual restriction fragment length polymorphism study demonstrated that the phytoplasma identified in this study can be classified into the 16SrII-V subgroup, which is similar to the peanut witches’-broom phytoplasma, a ‘Candidatus phytoplasma aurantifolia’-related strain. Further identification of SAP54/PHYL1 and SAP11 homologs in the phytoplasma explain the disease symptoms of phyllody, virescence, and witches’-broom observed in diseased N. plumbaginifolia Viviani. The discovery of new phytoplasma plant hosts has gained scientific importance in light of the attempt to unravel an efficient strategy to fight the rapid spread of this disease, which poses a threat to the agricultural sector and food security in Taiwan.

Advancements in next-generation sequencing technology have dramatically reduced the cost and increased the ease of microbial whole genome sequencing. This approach is revolutionizing the identification and analysis of foodborne microbial pathogens, facilitating expedited detection and mitigation of foodborne outbreaks, improving public health outcomes, and limiting costly recalls. However, next-generation sequencing is still anchored in the traditional laboratory practice of the selection and culture of a single isolate. Metagenomic-based approaches, including metabarcoding and shotgun and long-read metagenomics, are part of the next disruptive revolution in food safety diagnostics and offer the potential to directly identify entire microbial communities in a single food, ingredient, or environmental sample. In this review, metagenomic-based approaches are introduced and placed within the context of conventional detection and diagnostic techniques, and essential considerations for undertaking metagenomic assays and data analysis are described. Recent applications of the use of metagenomics for food safety are discussed alongside current limitations and knowledge gaps and new opportunities arising from the use of this technology.

Studies on the impact of ocean acidification on marine organisms involve exposing organisms to future acidification scenarios as projected for open ocean, which has limited relevance for coastal calcifiers. Characterization of reaction norms across a range of pH and identification of tipping points beyond which detrimental effects are observed has been limited and focus on only a few macro-physiological traits. Here we filled this knowledge gap by developing a framework to analyze the broad macro-physiological and molecular responses over a wide pH range of juvenile Pacific oyster, a model species for which the tolerance threshold to acidification remains unknown. We identify low tipping points for physiological traits at pH 7.3-6.9 that coincide with a major reshuffling in membrane lipids and transcriptome. In contrast, shell parameters exhibit effects with pH drop well before tipping points, likely impacting animal fitness. These findings were made possible by the development of an innovative methodology to synthesize and identify the main patterns of variations in large -omic datasets, fit them to pH and identify molecular tipping-points. We propose the application of our framework broadly to the assessment of effects of global change on other organisms.

Most species are extinct, those that are not are often unknown. Sequenced and sampled species are often a minority of known ones. Past evolutionary events involving horizontal gene flow, such as horizontal gene transfer, hybridization, introgression, and admixture, are therefore likely to involve “ghosts,” that is extinct, unknown, or unsampled lineages. The existence of these ghost lineages is widely acknowledged, but their possible impact on the detection of gene flow and on the identification of the species involved is largely overlooked. It is generally considered as a possible source of error that, with reasonable approximation, can be ignored. We explore the possible influence of absent species on an evolutionary study by quantifying the effect of ghost lineages on introgression as detected by the popular D-statistic method. We show from simulated data that under certain frequently encountered conditions, the donors and recipients of horizontal gene flow can be wrongly identified if ghost lineages are not taken into account. In particular, having a distant outgroup, which is usually recommended, leads to an increase in the error probability and to false interpretations in most cases. We conclude that introgression from ghost lineages should be systematically considered as an alternative possible, even probable, scenario. [ABBA–BABA; D-statistic; gene flow; ghost lineage; introgression; simulation.]

Background: Atrial fibrillation (AF) is the most common persistent arrhythmia and an important factor leading to cardiovascular morbidity and mortality. Several key genes and diagnostic markers have been discovered with the development of advanced modern molecular biology techniques, but the etiology and pathogenesis of AF remained unknown. Methods: In this study, three chip-seq data sets and a RNA-seq data set were integrated as a comprehensive network for pathway analysis of the biological functions of related genes in AF, hoping to provide a better understanding on the etiology and pathogenesis of AF. Results: Differential co-expression analysis identified 360 genes with specific expression in AF, and functional enrichment analysis further revealed that these genes were significantly correlated with focal expression (p 0.9) and in different platform data sets (mean AUC>0.75). Conclusion: Finally, a diagnostic model for AF established, thus showing its potential in the early identification and prediction of AF.

Causality assessment for idiosyncratic ADRs mainly relies on epidemiology, signal detection and less often on proven or plausible mechanistic evidence of the drug at a cellular or organ level. Distinct clones of cells can exist within organs of individual patients, some conferring susceptibility to well-recognised Adverse Drug Reactions (ADRs). Recent advances in molecular biology have allowed the development of single-cell clonal techniques, including single-cell RNA sequencing (scRNA-seq) to molecularly fingerprint ADRs and distinguish between distinct clones of cells within organs in individuals, which may confer differing susceptibilities to ADRs. ScRNA- seq permits molecular fingerprinting of some serious ADRs, mainly in the skin, through the identification of Directly Expressed Genes (DEG) of interest within specific clones. Overexpressed DEGs provide an opportunity for targeted treatment strategies to be developed. scRN A-seq could be applied to a number of other ADRs involving tissues that can be biopsied/sampled (including skin, liver, kidney, blood, stem cells) as well as providing a molecular basis for rapid screening of potential therapeutic candidates, which may not otherwise be predictable from a class of toxicity/organ involvement. A framework for putative assessment for ADRs using scRNA-seq is proposed as well as speculating on potential regulatory implications for pharmacovigilance and drug development. Molecular fingerprinting of ADRs using scRNA-seq may allow better targeting for enhanced pharmacovigilance and risk minimisation measures for medicines with appropriate benefit-risk profiles, although cost-effectiveness and other factors, such as frequency/severity of individual ADRs and population differences, will still be relevant.

Background: Serum uric acid (UA) is positively correlated with bone mineral density (BMD). However, the mechanism by which serum UA affects BMD remains unclear. Objective: The aim was carried out to search for the functional proteins related to serum UA and femoral neck BMD to better understand the pathophysiological mechanism of osteoporosis. Materials and Methods: In this study, patients in the UA group (hyperuricaemia combined with femoral neck fracture) and the control group (normal uricaemia combined with femoral neck fracture) were selected according to the inclusion criteria. Total protein was extracted from the femoral neck of each patient. Fluorescence differential gel electrophoresis was used to separate the total proteins, and the differentially expressed protein spots were detected by image analysis. After enzyme digestion, peptide mass fingerprinting and database searches were performed to identify the differentially expressed proteins. DAVID software and Kyoto Encyclopedia of Genes and Genomes (KEGG) data were used for enrichment analysis of the screened differential proteins. Results: After mass spectrometry and database searching, 66 differentially expressed protein spots were identified between the UA group and the control group. Most differentially expressed proteins functioned in cytoskeleton formation, energy metabolism, or signal transduction. They were mainly involved in 50 biological processes, including peroxisome proliferator-activated receptor (PPAR) signalling and fatty acid metabolism. PPARγ and PLIN1 were subject to Western blotting analysis detection; results were consistent with the Label-Free result. Conclusion: Based on an analysis of the biological information, these proteins may be associated with the incidence and progression of the femoral neck bone tissues of hyperuricaemia patients.

Plant parasitic nematodes are a major yield-limiting factor of soybean in the United States and Canada. It has been indicated that soybean cyst nematode (SCN; Heterodera glycines Ichinohe) and reniform nematode (RN; Rotylenchulus reniformis Linford and Oliveira) resistance could be genetically related. For many years, fragmentary data have shown this relationship. This report evaluates RN reproduction on 418 plant introductions (PIs) selected from the U.S. Department of Agriculture Soybean Germplasm Collection with reported SCN resistance. The germplasm was divided into two tests of 214 PIs reported as resistant and 204 PIs reported as moderately resistant to SCN. The defining and reporting of RN resistance changed several times in the last 30 years, causing inconsistencies in RN resistance classification among multiple experiments. Comparison of four RN resistance classification methods was performed: (i) ≤10% as compared with the susceptible check, (ii) using normalized reproduction index (RI) values, and using (iii) transformed data log10(x), and (iv) transformed data log10(x + 1) in an optimal univariate k-means clustering analysis. The method of transformed data log10(x) was selected as the most accurate for classification of RN resistance. Among 418 PIs with reported SCN resistance, the log10(x) method grouped 59 PIs (15%) as resistant and 130 PIs (31%) as moderately resistant to RN. Genotyping of a subset of the most resistant PIs to both nematode species revealed their strong correlation with rhg1-a allele. This research identified genotypes with resistance to two nematode species and potential new sources of RN resistance that could be valuable to breeders in developing resistant cultivars.