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1.
Int J Biol Macromol ; 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32032708

RESUMO

Mitochondrial genome (mitogenome) structure and gene order are generally considered conserved in vertebrates. However, the flatfish (Pleuronectiformes) mitogenomes exhibit the most diversified gene rearrangement patterns. Here, we report a newly sequenced mitogenome of Cynoglossus melampetalus (Pleuronectiformes: Cynoglossidae). The total length of the C. melampetalus mitogenome is 16,651 bp, containing 13 protein-coding genes, two ribosomal RNAs, 22 transfer RNAs, a putative control region, and an L-strand replication origin. Like all previously reported tongue sole (Cynoglossinae) mitogenomes, the C. melampetalus tRNA-Gln gene is inverted from the light to the heavy strand (Q inversion), accompanied by the translocation of CR, which is downstream to the 3'-end of ND1. In addition, we observed a unique tRNA-Ile-Met-Glu (IMQ) gene order that differed from the tRNA-Glu-Ile-Met (QIM) order previously reported for other 14 Cynoglossinae mitogenomes. To our knowledge, it is the first report of two different patterns of mitogenomic gene-arrangement within the same genus in teleost. According to the Q inversion, Met pseudogene (ψMet) and long intergenic gap (186 bp) between M and Q genes, the observed gene rearrangement pattern were presumably supported by mitochondrial recombination and tandem duplication/random loss models. The reduced trend of the intergenic gap between Q and I also suggests that the event of gene rearrangement can be traced back to early Cynoglossinae differentiation.

2.
Artigo em Inglês | MEDLINE | ID: mdl-32059586

RESUMO

Sand-dust environment affects drivers' perceptions of surrounding traffic conditions, resulting in unsafe operations. From an ergonomics perspective, such adverse effects could be alleviated by environment control as well as the assistance of machines. Vehicle-to-vehicle (V2V) communication appears to be an important component of machines in future traffic systems, which could support the driving task. In order to explore what influences V2V communication would generate on traffic systems, this paper proposes a car-following model accounting for V2V communication in a sand-dust environment. The results indicate that V2V communication helps to reduce the fluctuations of acceleration, headway, and velocity, when a small perturbation is added to the traffic flow in sand-dust environment. If a vehicle in the traffic flow stops suddenly, the number of crumped vehicles decreases with V2V communication taken into account. Furthermore, the residual velocities of the crumped vehicles decrease, which means the severity of collision is suppressed. It is concluded that V2V communication can play an active role in the improvement of traffic safety in a sand-dust environment.

3.
Genomics ; 2020 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-32045669

RESUMO

In this study, we determined the complete mitogenome sequence of Calappa bilineata, which is the first mitogenome of Calappidae up to now. The total length is 15,606 bp and includes 13 protein-coding genes, 22 transfer RNAs, two ribosomal RNAs and one control region. The genome composition is highly A + T biased (68.7%), and exhibits a negative AT-skew (-0.010) and GC-skew (-0.267). As with other invertebrate mitogenomes, the PCGs start with the standard ATN and stop with the standard TAN codons or incomplete T. Phylogenetic analysis showed that C. bilineata was most closely related to Matuta planipes (Matutidae), and these two species formed a sister clade, constituting a Calappoidea group and forming a sister clade with part of Eriphioidea. The existence of the polyphyletic families raised doubts over the traditional classification system. These results will help to better understand the features of the C. bilineata mitogenome and lay foundation for further evolutionary relationships within Brachyura.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31982134

RESUMO

Cardiovascular diseases (CVDs) is the first cause of death worldwide, generally exhibiting a high morbidity, high disability rate and high mortality especially in the elderly persons (>50 years old). Previously, extensive studies have demonstrated that cardiac fibrosis plays cardinal roles in the pathogenesis of CVDs. However, due to the unclear underlying mechanisms of cardiac fibrosis, its clinical intervention remains very lacking. Long non-coding RNAs (lncRNAs), a class of non-coding RNA but differing from microRNAs, are generally considered as transcripts with a length ranging 200 to 100 nucleotides. Recently, accumulating evidence showed that lncRNAs involve in the pathogenesis of cardiac fibrosis. Fendrr (FOXF1 adjacent non-coding developmental regulatory RNA), is a spliced long non-coding RNA transcribed bi-directionally with FOXF1 on the opposite strand. Fendrr has been demonstrated to be essential for normal development of the heart and body wall in mouse, and shows a good anti-fibrotic activity in pulmonary fibrosis. In this study, we aimed to explore the effects of Fendrr on cardiac fibrosis. Intriguingly, we first observed that lncRNA Fendrr was up-regulated in the heart tissues of transverse aortic constriction (TAC) induced cardiac fibrosis mouse models, determined by RT-QPCR. Loss-function of Fendrr significantly alleviated the cardiac fibrosis phenotypes induced by TAC, indicating that Fendrr is required for the pathogenesis of cardiac fibrosis. In mechanism, we demonstrated experimentally that Fendrr directly targeting miR-106b, by which the lncRNA promotes cardiac fibrosis (indicated by the elevation of Col1a1, Col3a1, CTGF and ACTA2 expression) in a miR-106b mediated manner. Collectively, our findings highlight the axis of Fendrr/miR-106b/Samd3 in the pathogenesis of cardiac fibrosis, which may be a promising target for clinical intervention target of cardiac fibrosis.

5.
J Alzheimers Dis ; 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31929168

RESUMO

BACKGROUND: Post-stroke cognitive impairment (PSCI) is an important factor causing disabilities after acute ischemic stroke (AIS). Emerging evidence suggested that gut microbiota play an important role in cognitive impairment. OBJECTIVE: This study aimed to explore the association between PSCI and gut microbiota. METHOD: 65 patients with newly diagnostic AIS finished the fecal collection on admission and cognitive assessment 3 months later in the clinic. Fecal samples were subjected to 16SrRNA gene sequencing and gas chromatography-mass spectrometry analysis. Additionally, we enrolled new 18 AIS patients, whose treatment was supplemented by probiotics, to assess the potential of microbial treatment in PSCI. RESULTS: PSCI patients were characterized by the significantly decreased alpha-diversity, disturbed microbial composition, and corresponding metabolites compared with non-PSCI patients. Increased Fusobacterium and deficiency of microbial metabolized short-chain fatty acids (SCFAs) were significantly associated with PSCI. A model based on gut microbiota and SCFAs could predict 3 months or longer PSCI early and accurately after stroke onset. While traditional probiotic administration had little effect on PSCI, it could ameliorate patients' mood, including depression and anxiety in the 3 months after stroke. CONCLUSION: Our study revealed the association between PSCI and gut microbiota and its corresponding metabolites for the first time, suggesting the potential for applying microbiota and its corresponding metabolites to early clinical diagnosis and treatment of PSCI.

6.
Acta Diabetol ; 2020 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-31938886

RESUMO

AIMS: To investigate the correlation of impairment in skeletal muscle and heart in spontaneous type 2 diabetes mellitus (T2DM) rhesus monkeys using magnetic resonance image (MRI). METHODS: Fifteen T2DM monkeys and fourteen healthy control (HC) monkeys were included. The microcirculation of skeletal muscle [skeletal muscle blood flow (SMBF), skeletal muscle oxygen extraction fraction (SMOEF)] and the function and strain of heart were evaluated by MRI. Three regions of interests were chosen on the soleus muscle (SOL), gastrocnemius muscle (GAS) and tibialis anterior muscle (TA) for image analysis. RESULTS: Eight T2DM monkeys and eight HC monkeys were obtained the full data. The SMBF reserves and SMOEF reserves were found significantly decreased in T2DM during inflation in SOL, GAS and TA muscles (all p < 0.05), and the SMBF reserves decreased during hyperemia in GAS and TA muscles (all p < 0.05). In these monkeys, the global peak longitudinal strain (longitudinal PS), peak systolic longitudinal strain rate (longitudinal PSSR) and peak diastolic longitudinal strain rate (longitudinal PDSR) were seen significantly different in T2DM compared to HC monkeys (all p < 0.05). The longitudinal PSSR was found negatively correlated with SMBF reserves in SOL, GAS and TA during inflation in all monkeys. CONCLUSIONS: The impaired microcirculation of skeletal muscle and the myocardial deformation were found in T2DM monkeys with normal ejection fraction. And a negative correlation was existed in the longitudinal PSSR and the SMBF reserves.

7.
Radiol Med ; 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31916105

RESUMO

Lung cancer is pointed as a leading cause of cancer death worldwide. Early lung nodule diagnosis has great significance for treating lung cancer and increasing patient survival. In this paper, we present a novel method to classify the malignant from benign lung nodules based on CT images using squeeze-and-excitation network and aggregated residual transformations (SE-ResNeXt). The state-of-the-art SE-ResNeXt module, which integrates the advantages of SENet for feature recalibration and ResNeXt for feature reuse, has great ability in boosting feature discriminability on imaging pattern recognition. The method is evaluated on the public available LUng Nodule Analysis 2016 (LUNA16) database with 1004 (450 malignant and 554 benign) nodules, achieving an area under the receiver operating characteristic curve (AUC) of 0. 9563 and accuracy of 91.67%. The promising results demonstrate that our method has strong robustness in the classification of nodules. The method has the potential to help radiologists better interpret diagnostic data and differentiate the benign from malignant lung nodules on CT images in clinical practice. To our best knowledge, the effectiveness of SE-ResNeXt on lung nodule classification has not been extensively explored.

8.
Fitoterapia ; 140: 104441, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31778760

RESUMO

In the present work, we reported the triterpenoids isolated from n-butanol fraction of Kadsura heteroclita which is a Tujia ethnomedicine with trivial name "Xuetong". This effort resulted in the isolation of six unpresented triterpenoids xuetongsu A-F (1-6), along with five known triterpenoids (7-11). The structures of the reported compounds were established on the 1D, and 2D NMR and HRESIMS spectra, along with CD spectroscopic analysis. Moreover, the absolute stereochemistry of compound 7 was determined by X-ray diffraction analysis. Antioxidant and cytotoxic activities were evaluated for all isolated compounds, compound 7 shown weak cytotoxic activity against HL-60 with IC50 value of 50.0 µM.


Assuntos
Kadsura/química , Caules de Planta/química , Triterpenos/química , China , Células HL-60 , Humanos , Estrutura Molecular , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação , Triterpenos/isolamento & purificação
9.
Int J Biol Macromol ; 142: 11-17, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31785298

RESUMO

Mitochondrial genomes (mitogenomes) typically contain 13 protein-coding genes, 22 tRNA genes, two rRNA genes, and a single control region (CR). Flatfish mitochondrial genomes (mitogenomes) from three different genera in Bothidae (bothids) contain double CRs that evolved in a concerted manner. How these double CRs maintained identical sequences throughout the evolutionary process is an interesting issue. In the present study, over four hundred arrays of the double CRs of mitogenomes from three bothids (Arnoglossus tenuis, Lophonectes gallus and Psettina iijimae) were performed. Interesting variations between double CRs were observed in P. iijimae mitogenomes, and the networks of CR sequences from P. iijimae indicated a high possibility of genetic information exchange between CRs. No recombination product was detected in our results, indicating that the mechanism of the concerted evolution between the double CRs of P. iijimae was not recombination. We speculate that mismatch repair, a mitochondrial DNA repair mechanism, is a potential explanation for the concerted evolution between these double CRs.

10.
J Food Biochem ; 44(1): e13092, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31721263

RESUMO

Two new polysaccharide fractions (TZP1-1 and TZP2-1) were obtained from the fruiting bodies of Thelephora ganbajun using DEAE-52 cellulose and Superdex 200 columns chromatography. The physiochemical characterization and biological activities of TZP1-1 and TZP2-1 were investigated. The relative molecular weight of TZP1-1 and TZP2-1 were 2.07 × 106 and 4,886 Da, respectively. TZP1-1 included mannose, rhamnose, galactose, and xylose (4:1:83.9:7.5), while TZP2-1 included mannose, glucose, galactose, and xylose (5.4:1:79.0:8.1). The Congo red experiment results confirmed that TZP2-1 had triple helix conformation. Furthermore, both TZP1-1 and TZP2-1 showed a certain cytotoxicity on HeLa and SH-SY5Y cells, while they exhibited a stronger inhibitory effect on HeLa than SH-SY5Y. Besides, the cytotoxicity of TZP1-1 was better than that of TZP2-1. Moreover, both of them exhibited a moderate inhibitory effect on α-amylase and α-glucosidase. These findings could promote the application of polysaccharides from T. ganbajun. PRACTICAL APPLICATIONS: Thelephora ganbajun is an edible fungus widely distributed in Southwestern China. T. ganbajun polysaccharides as important active ingredients have not been reported. In this current study, two polysaccharides fractions (TZP1-1 and TZP2-1) were characterized, and their cytotoxicities and antidiabetic effect were also assayed. These findings could promote polysaccharides from T. ganbajun to be better application.

11.
ChemSusChem ; 13(2): 351-359, 2020 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-31721453

RESUMO

Transition metal phosphides (TMPs) are regarded as highly active electrocatalysts for the hydrogen evolution reaction (HER). However, traditional synthetic routes usually use expensive and dangerous precursors as P donors. The development of a low-cost and ecofriendly method for the synthesis of TMPs is significant for sustainable energy development. Herein, cobalt phosphides anchored on or embedded in a spirulina-derived porous N-doped carbon matrix (Co2 P/NC) was fabricated by two-step hydrothermal treatment and carbonization method, which utilized the intrinsic C, N, and P of biomass cleverly as the sources of C, N, and P, respectively. As a result of the high surface area and porosity that enhance the mass-transfer dynamics, Co2 P/NC shows good electrocatalytic activity at all pH values in the HER. This work not only provides a facile and effective method for the fabrication of TMP nanoparticles loaded onto carbon materials but also opens a new strategy for the utilization of the intrinsic ingredients of biomass for the preparation of other functional electrocatalysts.

12.
J Surg Res ; 246: 170-181, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31590030

RESUMO

BACKGROUND: Electroacupuncture has been reported to protect the body from organ damages, but its mechanisms remain to be explored. This research was designed to investigate the function of electroacupuncture in lung injury resulted from hind limb ischemia-reperfusion (LIR) and whether p38 mitogen-activated protein kinase (p38 MAPK)-mediated nuclear factor erythroid-2-related factor-2 (Nrf2)/heme oxygenase (HO)-1 pathway contributes to the protective effect of electroacupuncture on LIR-originated lung damage. MATERIALS AND METHODS: Rabbits were subjected to occluding femoral artery for 2 h. Then they received reperfusion for 4 h to establish lung injury model. Electroacupuncture stimulation was performed bilaterally at Feishu and Zusanli acupoints for 15 min once a day for 5 d before the experiment and throughout the hind LIR model performing in the experimental day. Blood samples and lung tissues were collected to examine the role of electroacupuncture treatment in inflammatory response, oxidative stress, and lung injury. Both the protein expression and the messenger RNA level of Nrf2 and HO-1 were detected. RESULTS: The results showed that electroacupuncture treatment remarkably alleviated lung injury, decreased inflammatory cytokines secretion, attenuated lung oxidative stress, increased the amount of Nrf2 and HO-1, and increased the ratio of phospho-p38 MAPK to p38 MAPK after LIR. However, the protective effects exerted by electroacupuncture were reversed to some extent by the preconditioning with SB203580, a p38 MAPK-specific inhibitor. CONCLUSIONS: These results suggested that electroacupuncture could attenuate lung injury in rabbits subjected to LIR by inhibition of proinflammatory cytokine response and oxidative stress through activating p38 MAPK-mediated Nrf2/HO-1 pathway.

13.
Org Lett ; 22(1): 150-154, 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31829601

RESUMO

A four-enzyme catalyzed hydroxy regioisomerization of anthracycline was integrated into the biosynthetic pathway of aclacinomycin A (ALM-A), to generate a series of iso-ALMs via directed combinatorial biosynthesis combined with precursor-directed mutasynthesis. Most of the newly acquired iso-ALMs exhibit obviously (1-5-fold) improved antitumor activity. Therefore, we not only developed iso-ALMs with potential as clinical drugs but also demonstrated the utility of this tailoring tool for modification of anthracycline antibiotics in drug discovery and development.

14.
Hepatol Int ; 14(1): 96-104, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31832976

RESUMO

BACKGROUND: The diagnostic and prognostic values of glypican3 (GPC3) and glutamine synthetase (GS) proteins in hepatocellular carcinoma (HCC) have been reported, but their specificity and sensitivity remain low. Here, we applied RNAscope to improve HCC early pathological and differential diagnosis by estimating GPC3 and GS mRNAs. METHODS: We performed RNAscope and immunohistochemistry (IHC) to detect GPC3 and GS biomarkers on the tissue sections of 194 cases, including high- and low-grade liver dysplastic nodules; highly, moderately, and poorly differentiated HCCs; intrahepatic cholangiocarcinomas (ICCs); metastatic HCC; and carcinomas from other organs. RESULTS: The results showed that all the cases that were negative for GPC3 by RNAscope were also negative for this protein by IHC. The use of RNAscope assay improved the GPC3 and GS specificity and sensitivity by 20-30%. Hence, HCC shows early recognition and upgrades the metastatic HCC differentiation by 23% compared with IHC (p = 0.0001, 0.0064). Meanwhile, all liver cirrhosis, cholangiocytes and non-HCC samples were negative for GPC3 and GS except lymphocytes in lymphomas, and 2 (8.3%) out of the 24 ICC samples but not in the cancer cells. CONCLUSION: RNAscope for GPC3 and GS panel was highly specific and sensitive for the pathological identification of dysplastic nodules, early stages of HCCs, and would differentiate them from HCCs and metastatic tumors compared with IHC.

15.
Metab Brain Dis ; 35(1): 201-213, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31834549

RESUMO

Expression of circular RNA (circRNA), a class of noncoding RNAs that regulates gene expression, is altered in Alzheimer's disease. This study profiled differentially expressed circRNAs in peripheral blood mononuclear cells (PBMCs) from five patients with Alzheimer's disease compared to healthy controls using circRNA microarrays. We identified a total of 4060 differentially expressed circRNAs (1990 upregulated and 2070 downregulated) in Alzheimer's disease patients. Among these circRNAs, 10 randomly selected circRNAs were verified using qRT-PCR. The top 10 upregulated and downregulated circRNAs were used to predict their target miRNAs. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed that these differentially expressed circRNAs were strongly associated with inflammation, metabolism, and immune responses, which are all risk factors for Alzheimer's disease. The circRNA-miRNA-mRNA network was most involved in the MAPK, mTOR, AMPK, and WNT signaling pathways in Alzheimer's disease. In conclusion, the current study demonstrated the importance of circRNAs in Alzheimer's disease development. Future studies will evaluate some of these circRNAs as biomarkers for early disease detection and to develop therapeutic strategies to clinically control Alzheimer's disease progression.

16.
Nat Prod Rep ; 37(1): 17-28, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31290896

RESUMO

Covering: 2012 to 2019HemN-like radical S-adenosyl-l-methionine (SAM) enzymes have been recently disclosed to catalyze diverse chemically challenging reactions from primary to secondary metabolic pathways. In this highlight, we summarize the reaction examples catalyzed by HemN-like enzymes to date and the enzymatic mechanisms reported. From the recent mechanistic investigations, we reason that there is a shared initiating mechanism wherein a characteristic SAM methylene radical is proposed to abstract a hydrogen atom from an sp3 carbon or add onto an sp2 carbon center although variations occur thereafter from reaction to reaction, as well as providing a brief insight into some future prospects.

17.
Acta Otolaryngol ; 140(2): 99-104, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31876219

RESUMO

Background: For patients with posterior semicircular canal (PSC) BPPV, Epley re-position maneuver and some improvement methods are the most efficient treatment methods. But there were still 9.43% patients who were not benefit from Epley re-position maneuver.Objective: To measure the angles of semicircular canals and evaluate its effect on Epley maneuver.Methods: Fifteen skull specimens, containing 30 temporal bone specimens were included. After Micro-CT scanning, 3D reconstruction was loaded with the CT image. The angles between each semicircular canal and each standard skull plane were measured. Furthermore, the angles' effect on Epley maneuver was evaluated according to the three-dimension (3D) model.Results: Angles of PSC plane: Frankfurt plane was 71.54 ± 6.51, sagittal plane was 53.77 ± 5.36°, and the coronal plane was 43.33 ± 3.56°. Angles between PSC and the sagittal plane of skulls had an adverse effect on Epley maneuver, when it was less than 45°.Conclusion: 1. Variation could be found in angles between the semicircular canals and the standard planes of skulls, which meant variation of semicircular canals' location existing in skulls. 2. The variation of angles between PSC and sagittal plane could have an adverse effect on the Epley maneuver when the angle was less than 45°, which may cause the Epley maneuver to be invalid.

18.
J Pharm Biomed Anal ; 177: 112848, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31479998

RESUMO

Metabolic syndrome (MetS) is an important risk factor for type 2 diabetes, cardiovascular diseases and all-cause morbidity and mortality. Biomarkers can provide insight into the mechanism, facilitate early detection, and monitor progression of MetS and its response to therapeutic interventions. To identify potential biomarkers, we applied a non-targeted and targeted lipidomics method to characterize plasma metabolic profile in MetS patients. Metabolic profiling was performed on a non-target set (40 cases and 40 controls) on UHPLC-Q-TOF/MS and target set (80 MetS patients and 80 healthy controls) on UHPLC-Q-orbitrap MS. Using comprehensive screening and validation workflow, we identified a panel of three metabolites including PC(18:1/P-16:0), PC(o-22:3/22:3), PC(P-18:1/16:1). Our results indicated that the identified biomarkers may improve the risk prediction and provide a novel tool for monitoring of the progression of disease and response to treatment in MetS patients.

19.
J Environ Sci (China) ; 88: 273-282, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31862068

RESUMO

The effects of disinfection efficiency on microbial communities and the corrosion of cast iron pipes in drinking water distribution systems (DWDSs) were studied. Two annular reactors (ARs) that simulated actual running conditions with UV/Cl2 disinfection and chlorination alone were used. High chlorine consumption and corrosion rate were found in the AR with UV/Cl2. According to functional genes and pyrosequencing tests, a high percentage of iron recycling bacteria was detected within the biofilm of the AR with Cl2 at early running stage, whereas siderophore-producing bacteria were dominant in the biofilm of the AR with UV/Cl2. At the early running stage, the sequential use of UV light and an initial high chlorine dosage suppressed the biomass and iron-recycling bacteria in both bulk water and biofilms, thereby forming less protective scales against further corrosion, which enhanced chlorine consumption. Non-metric multidimensional scaling analysis showed that the bacterial communities in the ARs shaped from within rather than being imported by influents. These results indicate that the initial high disinfection efficiency within the distribution system had not contributed to the accumulation of iron-recycling bacteria at the early running stages. This study offer certain implications for controlling corrosion and water quality in DWDSs.

20.
Pac Symp Biocomput ; 25: 611-622, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31797632

RESUMO

Precision medicine tailors treatment to individuals personal data including differences in their genome. The Pharmacogenomics Knowledgebase (PharmGKB) provides highly curated information on the effect of genetic variation on drug response and side effects for a wide range of drugs. PharmGKB's scientific curators triage, review and annotate a large number of papers each year but the task is challenging. We present the PGxMine resource, a text-mined resource of pharmacogenomic associations from all accessible published literature to assist in the curation of PharmGKB. We developed a supervised machine learning pipeline to extract associations between a variant (DNA and protein changes, star alleles and dbSNP identifiers) and a chemical. PGxMine covers 452 chemicals and 2,426 variants and contains 19,930 mentions of pharmacogenomic associations across 7,170 papers. An evaluation by PharmGKB curators found that 57 of the top 100 associations not found in PharmGKB led to 83 curatable papers and a further 24 associations would likely lead to curatable papers through citations. The results can be viewed at https://pgxmine.pharmgkb.org/ and code can be downloaded at https://github.com/jakelever/pgxmine.

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