Identification of hub genes and potential inhibitory compounds in the process of liver transplantation through transcriptome sequencing by Chujun Duan, Xiaojun Zhao, Xiao Li, Jiangang Xie, Yi Si, Linxiao Wang, Dan Wu, Yifan Wang, Shanshou Liu, Qianmei Wang, Ran Zhuang, Wen Yin, Junjie Li

“…SBVS of the seed molecule PTEN (PDB code: 1D5R) predicted top hits compounds that may serve as potential inhibitors of PTEN, of which the compound ZINC4235331 had the lowest binding affinity of -10 kcal/mol. …”
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Genome-wide association meta-analysis of fish and EPA+DHA consumption in 17 US and European cohorts. by Dariush Mozaffarian, Hassan S Dashti, Mary K Wojczynski, Audrey Y Chu, Jennifer A Nettleton, Satu Männistö, Kati Kristiansson, Mägi Reedik, Jari Lahti, Denise K Houston, Marilyn C Cornelis, Frank J A van Rooij, Maria Dimitriou, Stavroula Kanoni, Vera Mikkilä, Lyn M Steffen, Marcia C de Oliveira Otto, Lu Qi, Bruce Psaty, Luc Djousse, Jerome I Rotter, Kennet Harald, Markus Perola, Harri Rissanen, Antti Jula, Fischer Krista, Evelin Mihailov, Mary F Feitosa, Julius S Ngwa, Luting Xue, Paul F Jacques, Mia-Maria Perälä, Aarno Palotie, Yongmei Liu, Nike A Nalls, Luigi Ferrucci, Dena Hernandez, Ani Manichaikul, Michael Y Tsai, Jessica C Kiefte-de Jong, Albert Hofman, André G Uitterlinden, Loukianos Rallidis, Paul M Ridker, Lynda M Rose, Julie E Buring, Terho Lehtimäki, Mika Kähönen, Jorma Viikari, Rozenn Lemaitre, Veikko Salomaa, Paul Knekt, Andres Metspalu, Ingrid B Borecki, L Adrienne Cupples, Johan G Eriksson, Stephen B Kritchevsky, Stefania Bandinelli, David Siscovick, Oscar H Franco, Panos Deloukas, George Dedoussis, Daniel I Chasman, Olli Raitakari, Toshiko Tanaka

“…No significant association was observed for EPA+DHA, although rs7206790 in the obesity-associated FTO gene was among top hits (P = 8.18x10-7). Post-hoc calculations demonstrated 95% statistical power to detect a genetic variant associated with effect size of 0.05% for fish and 0.08% for EPA+DHA. …”
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Revisiting methotrexate and phototrexate Zinc15 library-based derivatives using deep learning in-silico drug design approach by Farhan Siddique, Farhan Siddique, Ahmar Anwaar, Maryam Bashir, Maryam Bashir, Sumaira Nadeem, Ravi Rawat, Volkan Eyupoglu, Samina Afzal, Mehvish Bibi, Yousef A. Bin Jardan, Mohammed Bourhia

“…The deep learning-based ADMET parameters were employed to generate a 2D QSAR model using the multiple linear regression (MPL) methods with Leave-one-out cross-validated (LOO-CV) Q2 and correlation coefficient R2 values as high as 0.77 and 0.81, respectively.Results: From the QSAR model and virtual screening analysis, the top hits (09, 27, 41, 68, 74, 85, 99, 180) exhibited pIC50 ranging from 5.85 to 7.20 with a minimum binding score of -11.6 to -11.0 kcal/mol and were subjected to further investigation. …”
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CRISPR Screens Identify Toxoplasma Genes That Determine Parasite Fitness in Interferon Gamma-Stimulated Human Cells by Shruthi Krishnamurthy, Parag Maru, Yifan Wang, Mebratu A. Bitew, Debanjan Mukhopadhyay, Yoshiki Yamaryo-Botté, Tatiana C. Paredes-Santos, Lamba O. Sangaré, Christopher Swale, Cyrille Y. Botté, Jeroen P. J. Saeij

“…The gene products of four top hits play a role in preventing early parasite egress in IFNγ-stimulated human cells. …”
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Bioguided Fractionation of Local Plants against Matrix Metalloproteinase9 and Its Cytotoxicity against Breast Cancer Cell Models: In Silico and In Vitro Study by Maywan Hariono, Rollando Rollando, Jasson Karamoy, Pandu Hariyono, M. Atmono, Maria Djohan, Wiwy Wiwy, Rina Nuwarda, Christopher Kurniawan, Nurul Salin, Habibah Wahab

“…Of the 200 compounds screened, 20 compounds that scored the binding affinity −11.2 to −8.1 kcal/mol toward PEX9 were selected as top hits. The binding of these hits were thoroughly investigated and linked to the plants which they were reported to be isolated from. …”
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The Expression of miRNAs Involved in Long-Term Memory Formation in the CNS of the Mollusk <i>Helix lucorum</i> by Gennady V. Vasiliev, Vladimir Y. Ovchinnikov, Pavel D. Lisachev, Natalia P. Bondar, Larisa N. Grinkevich

“…We have shown that in the CNS of <i>Helix lucorum</i> MIR-10 family (26 miRNAs) is the most representative one, including Hlu-Mir-10-S5-5p and Hlu-Mir-10-S9-5p as top hits. Moreover, we have shown the involvement of the MIR-10 family in LTM formation in <i>Helix</i>. …”
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Identification of Additional Anti-Persister Activity against Borrelia burgdorferi from an FDA Drug Library by Jie Feng, Megan Weitner, Wanliang Shi, Shuo Zhang, David Sullivan, Ying Zhang

“…In our previous study, we screened an FDA drug library and reported 27 top hits that showed high activity against Borrelia persisters. …”
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Exploring the medicinal potential of Dark Chemical Matters (DCM) to design promising inhibitors for PLpro of SARS-CoV-2 using molecular screening and simulation approaches by Abbas Khan, Ayesha Liaqat, Adan Masood, Syed Shujait Ali, Liaqat Ali, Abdulrahman Alshammari, Abdullah F. Alasmari, Anwar Mohammad, Yasir Waheed, Dong-Qing Wei

“…Structural-dynamics properties such as dynamic stability, protein packing, and residue flexibility demonstrated the pharmacologically favorable properties of these top hits in contrast to GRL0617. The hydrogen bonding half-life revealed that Asp164, Arg166, Tyr264, and Tyr268 have major contributions to the hydrogen bonding during the simulation. …”
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JIB-04 Has Broad-Spectrum Antiviral Activity and Inhibits SARS-CoV-2 Replication and Coronavirus Pathogenesis by Juhee Son, Shimeng Huang, Qiru Zeng, Traci L. Bricker, James Brett Case, Jinzhu Zhou, Ruochen Zang, Zhuoming Liu, Xinjian Chang, Tamarand L. Darling, Jian Xu, Houda H. Harastani, Lu Chen, Maria Florencia Gomez Castro, Yongxiang Zhao, Hinissan P. Kohio, Gaopeng Hou, Baochao Fan, Beibei Niu, Rongli Guo, Paul W. Rothlauf, Adam L. Bailey, Xin Wang, Pei-Yong Shi, Elisabeth D. Martinez, Steven L. Brody, Sean P. J. Whelan, Michael S. Diamond, Adrianus C. M. Boon, Bin Li, Siyuan Ding

“…By using infectious reporter viruses, we screened small-molecule inhibitors for antiviral activity against SARS-CoV-2. Among the top hits was JIB-04, a compound previously studied for its anticancer activity. …”
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Pharmacoinformatics-Based Approach for Uncovering the Quorum-Quenching Activity of Phytocompounds against the Oral Pathogen, <i>Streptococcus mutans</i> by Shakti Chandra Vadhana Marimuthu, Jayaprabhakaran Murugesan, Ewa Babkiewicz, Piotr Maszczyk, Murugesan Sankaranarayanan, Esakkimuthu Thangamariappan, Joseph Christina Rosy, Sureshbabu Ram Kumar Pandian, Selvaraj Kunjiappan, Vanavil Balakrishnan, Krishnan Sundar

“…However, further in vitro studies are necessary to validate the efficacy of these top hits against <i>S. mutans</i>.…”
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Bias-force guided simulations combined with experimental validations towards GPR17 modulators identification by Sana Kari, Akshaya Murugesan, Ramesh Thiyagarajan, Srivatsan Kidambi, Jamoliddin Razzokov, Chandrabose Selvaraj, Meenakshisundaram Kandhavelu, Parthiban Marimuthu

“…The external bias-potentials were then applied to the screened hits during the MD simulations which enabled to predict a spectrum of rupture peak force values that were used to select four approved drugs –ZINC000003792417 (Sacubitril), ZINC000014210457 (Victrelis), ZINC000001536109 (Pralatrexate) and ZINC000003925861 (Vorapaxar)– as top hits. The hits selected turns out to demonstrate unique dissociation pathways, interaction pattern, and change in polar network over time. …”
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The Effect of Genetic Variation on the Placental Transcriptome in Humans by Triin Kikas, Kristiina Rull, Kristiina Rull, Kristiina Rull, Robin N. Beaumont, Rachel M. Freathy, Maris Laan

“…However, this study was not able to confirm a significant overrepresentation of genome-wide association studies top hits among the placental eSNP and eGenes, reported by Peng et al. (2017). …”
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Growth inhibition of plasmodium falciparum by Nano-molar concentrations of 1-(4‑hydroxy-3-methoxyphenyl) decan-3-one (6-paradol); is a cure at hand? by Vikky Awasthi, Yash Gupta, Rubika Chauhan, Prakasha Kempaiah, Jyoti Das

“…The antimalarial targetablity of CS was confirmed with the phylogenetic conservancy, protein modeling, validation and subjected to High throughput virtual screening (HTVS) with a complete secondary metabolite library of Z.o. Among the top hits, the second hit 6-paradol (1-(4‑hydroxy-3-methoxyphenyl)decan-3-one) was available as a nature-identical synthetic compound. …”
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De novo assembly and comparative transcriptome analysis of Monilinia fructicola, Monilinia laxa and Monilinia fructigena, the causal agents of brown rot on stone fruits by Rita M. De Miccolis Angelini, Domenico Abate, Caterina Rotolo, Donato Gerin, Stefania Pollastro, Francesco Faretra

“…Approximately, 50% of the assembled contigs had significant hits when blasted against the NCBI non-redundant protein database and top-hits results were represented by Botrytis cinerea, Sclerotinia sclerotiorum and Sclerotinia borealis proteins. …”
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Mutational analysis of SARS-CoV-2 ORF6-KPNA2 binding interface and identification of potent small molecule inhibitors to recuse the host immune system by Muhammad Suleman, Muhammad Suleman, Afsheen Said, Haji Khan, Shoaib Ur Rehman, Shoaib Ur Rehman, Abdulrahman Alshammari, Sergio Crovella, Hadi M. Yassine, Hadi M. Yassine

“…Subsequent all-atoms simulations of these top hits revealed consistent dynamics, indicating their stability and their potential to interact effectively with the interface residues. …”
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Single-cell RNA-seq analysis of the brainstem of mutant SOD1 mice reveals perturbed cell types and pathways of amyotrophic lateral sclerosis by Wenting Liu, Sharmila Venugopal, Sana Majid, In Sook Ahn, Graciel Diamante, Jason Hong, Xia Yang, Scott H. Chandler

“…Importantly, DEGs from various cell types overlapped with known ALS genes from the literature and with top hits from an existing human ALS genome-wide association study (GWAS), implicating the potential cell types in which the ALS genes function with ALS pathogenesis. …”
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Small molecule glucagon release inhibitors with activity in human islets by Michael A. Kalwat, Michael A. Kalwat, Karina Rodrigues-dos-Santos, Derk D. Binns, Shuguang Wei, Anwu Zhou, Matthew R. Evans, Bruce A. Posner, Michael G. Roth, Melanie H. Cobb

“…ConclusionGiven the set of tested candidates were all top hits from the primary screen in rodent α-cells, this suggests some conservation of mechanism of action between human and rodents, at least for SW088799. …”
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Genome-Wide DNA Methylation Patterns in Persistent Attention-Deficit/Hyperactivity Disorder and in Association With Impulsive and Callous Traits by Mandy Meijer, Marieke Klein, Marieke Klein, Eilis Hannon, Dennis van der Meer, Dennis van der Meer, Catharina Hartman, Jaap Oosterlaan, Jaap Oosterlaan, Dirk Heslenfeld, Pieter J. Hoekstra, Jan Buitelaar, Jan Buitelaar, Jan Buitelaar, Jonathan Mill, Barbara Franke, Barbara Franke

“…We found neither significant epigenome-wide single CpG sites nor regions associated with impulsive and callous traits; the top-hits from these analyses were annotated to genes involved in neurotransmitter release and the regulation of the biological clock. …”
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Compound NSC84167 selectively targets NRF2-activated pancreatic cancer by inhibiting asparagine synthesis pathway by Bingbing Dai, Jithesh J. Augustine, Ya’an Kang, David Roife, Xinqun Li, Jenying Deng, Lin Tan, Leona A. Rusling, John N. Weinstein, Philip L. Lorenzi, Michael P. Kim, Jason B. Fleming

“…Among the >100,000 compounds analyzed, NSC84167, termed herein as NRF2 synthetic lethality compound-01 (NSLC01), was one of the top hits (r = 0.71, P < 0.001) and selected for functional characterization. …”
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Protocol for the EMPHASIS study; epigenetic mechanisms linking maternal pre-conceptional nutrition and children’s health in India and Sub-Saharan Africa by Giriraj R. Chandak, Matt J. Silver, Ayden Saffari, Karen A. Lillycrop, Smeeta Shrestha, Sirazul Ameen Sahariah, Chiara Di Gravio, Gail Goldberg, Ashutosh Singh Tomar, Modupeh Betts, Sara Sajjadi, Lena Acolatse, Philip James, Prachand Issarapu, Kalyanaraman Kumaran, Ramesh D. Potdar, Andrew M. Prentice, Caroline H. D. Fall, the EMPHASIS study group, Lena Acolatse, Meraj Ahmed, Modupeh Betts, Giriraj R. Chandak, Harsha Chopra, Cyrus Cooper, Momodou K. Darboe, Chiara Di Gravio, Caroline H. D. Fall, Meera Gandhi, Gail R. Goldberg, Prachand Issarapu, Philip James, Ramatoulie Janha, Landing M. A. Jarjou, Lovejeet Kaur, Sarah H. Kehoe, Kalyanaraman Kumaran, Karen A. Lillycrop, Mohammed Ngum, Suraj S. Nongmaithem, Stephen Owens, Ramesh D. Potdar, Andrew M. Prentice, Ann Prentice, Tallapragada Divya Sri Priyanka, Ayden Saffari, Sirazul Ameen Sahariah, Sara Sajjadi, Harshad Sane, Smeeta Shrestha, Matt J. Silver, Ashutosh Singh Tomar, Kate A. Ward, Dilip Kumar Yadav, Chittaranjan S. Yajnik

“…Differences in DNA methylation between allocation groups will be identified using the Illumina Infinium MethylationEPIC array, and by pyrosequencing top hits and selected candidate loci. Associations will be analysed between DNA methylation and health-related phenotypic outcomes, including size at birth, and children’s post-natal growth, body composition, skeletal development, cardio-metabolic risk markers (blood pressure, serum lipids, plasma glucose and insulin) and cognitive function. …”
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