cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.26021209
title: Identification of mitophagy and ferroptosis-related hub genes associated with intracerebral haemorrhage through bioinformatics analysis

description: Mitophagy and ferroptosis occur in intracerebral haemorrhage (ICH) but our understanding of mitophagy and ferroptosis-related genes remains incomplete. This study aims to identify shared ICH genes for both processes. ICH differentially expressed mitophagy and ferroptosis-related genes (DEMFRGs) were sourced from the GEO database and literature. Enrichment analysis elucidated functions. Hub genes were selected via STRING, MCODE, and MCC algorithms in Cytoscape. miRNAs targeting hubs were predicted using miRWalk 3.0, forming a miRNA-hub gene network. Immune microenvironment variances were assessed with MCP and TIMER. Potential small molecules for ICH were forecasted <i>via</i> CMap database. 64 DEMFRGs and ten hub genes potentially involved in various processes like ferroptosis, TNF signalling pathway, MAPK signalling pathway, and NF-kappa B signalling pathway were discovered. Several miRNAs were identified as shared targets of hub genes. The ICH group showed increased infiltration of monocytic lineage and myeloid dendritic cells compared to the Healthy group. Ten potential small molecule drugs (e.g. Zebularine, TWS-119, CG-930) were predicted <i>via</i> CMap. Several shared genes between mitophagy and ferroptosis potentially drive ICH progression <i>via</i> TNF, MAPK, and NF-kappa B pathways. These results offer valuable insights for further exploring the connection between mitophagy, ferroptosis, and ICH.
DOI: 10.6084/m9.figshare.26311252
title: Worldwide distribution of genetic factors related to severity of COVID-19 infection

description: Genome-wide association studies of COVID-19 severity have been carried out mostly on European or East Asian populations with small representation of other world regions. Here we explore the worldwide distribution and linkage disequilibrium (LD) patterns of genetic variants previously associated with COVID-19 severity. We followed up the results of a large Spanish genome-wide meta-analysis on 26 populations from the 1000 Genomes Project by calculating allele frequencies and LD scores of the nine most significant SNPs. We also used the entire set of summary statistics to compute polygenic risk scores (PRSs) and carried out comparisons at the population and continental level. We observed the strongest differences among continental regions for the five top SNPs in chromosome 3. European, American, and South Asian populations showed similar LD patterns. Average PRSs in South Asian and American populations were consistently higher than those observed in Europeans. While PRS distributions were similar among South Asians, the American populations showed striking differences among them. Considering the caveats of PRS transferability across ethnicities, our analysis showed that American populations present the highest genetic risk score, hence potentially higher propensity, for COVID-19 severity. Independent validation is warranted with additional summary statistics and phenotype data.
DOI: 10.6084/m9.figshare.26311252.v1
title: Worldwide distribution of genetic factors related to severity of COVID-19 infection

description: Genome-wide association studies of COVID-19 severity have been carried out mostly on European or East Asian populations with small representation of other world regions. Here we explore the worldwide distribution and linkage disequilibrium (LD) patterns of genetic variants previously associated with COVID-19 severity. We followed up the results of a large Spanish genome-wide meta-analysis on 26 populations from the 1000 Genomes Project by calculating allele frequencies and LD scores of the nine most significant SNPs. We also used the entire set of summary statistics to compute polygenic risk scores (PRSs) and carried out comparisons at the population and continental level. We observed the strongest differences among continental regions for the five top SNPs in chromosome 3. European, American, and South Asian populations showed similar LD patterns. Average PRSs in South Asian and American populations were consistently higher than those observed in Europeans. While PRS distributions were similar among South Asians, the American populations showed striking differences among them. Considering the caveats of PRS transferability across ethnicities, our analysis showed that American populations present the highest genetic risk score, hence potentially higher propensity, for COVID-19 severity. Independent validation is warranted with additional summary statistics and phenotype data.
DOI: 10.6084/m9.figshare.26021209.v1
title: Identification of mitophagy and ferroptosis-related hub genes associated with intracerebral haemorrhage through bioinformatics analysis

description: Mitophagy and ferroptosis occur in intracerebral haemorrhage (ICH) but our understanding of mitophagy and ferroptosis-related genes remains incomplete. This study aims to identify shared ICH genes for both processes. ICH differentially expressed mitophagy and ferroptosis-related genes (DEMFRGs) were sourced from the GEO database and literature. Enrichment analysis elucidated functions. Hub genes were selected via STRING, MCODE, and MCC algorithms in Cytoscape. miRNAs targeting hubs were predicted using miRWalk 3.0, forming a miRNA-hub gene network. Immune microenvironment variances were assessed with MCP and TIMER. Potential small molecules for ICH were forecasted <i>via</i> CMap database. 64 DEMFRGs and ten hub genes potentially involved in various processes like ferroptosis, TNF signalling pathway, MAPK signalling pathway, and NF-kappa B signalling pathway were discovered. Several miRNAs were identified as shared targets of hub genes. The ICH group showed increased infiltration of monocytic lineage and myeloid dendritic cells compared to the Healthy group. Ten potential small molecule drugs (e.g. Zebularine, TWS-119, CG-930) were predicted <i>via</i> CMap. Several shared genes between mitophagy and ferroptosis potentially drive ICH progression <i>via</i> TNF, MAPK, and NF-kappa B pathways. These results offer valuable insights for further exploring the connection between mitophagy, ferroptosis, and ICH.
DOI: 10.6084/m9.figshare.27604664
title: Phylogeographic analysis of Y-chromosomal haplogroup C2a-M48-F8472, a minor paternal lineage of Han populations with possible ancestry of Xiongnu

description: Y-chromosome haplogroup C2a-M48-F8472, a unique paternal line in the ancient Xiongnu population, is concentrated in the modern Han people. The most closely related lineage of this paternal lineage is mainly distributed in Tungusic-, Mongolic-, and Turkic-speaking populations. To investigate the formation process of this unique distribution state. In total, 36 sequences of haplogroup C2a-M48-F8472 were analysed to generate a revised phylogenetic tree with age estimation and to explore the geographic distribution pattern. The results suggested that northern China is likely the diffusion centre of this paternal haplogroup. This lineage is concentrated in the Liu clan (刘姓) of Han populations and may have originated in the Tuge tribe (屠各) of Xiongnu populations. The initial expansion (∼2,600 years ago) and the second phase of expansion (∼1,570 years ago) of haplogroup C2a-M48-F8472 coincide with the earlier appearance and later disappearance of the Tuge tribe. As a sub-clade of M48, the history of F8472 suggested that ancient peoples related to Tungusic-speaking populations were intricately connected with the demographic history of populations in the Mongolian Plateau. The appearance of this paternal line in the Han population is helpful for understanding the mixed history of ancient and modern people in the Mongolian Plateau and Central China.
DOI: 10.15468/dl.3kqcqx
title: Occurrence Download

description: A dataset containing 444 species occurrences available in GBIF matching the query:
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 "TaxonKey is one of (Sparidae, 209454778, Sparidae, Sparidae, Sparidae, Sparidae, 205993695, Sparidae, Sparidae, Sparidae, 205986161, Sparidae, Sparidae, Sparidae, 209346469, Sparidae, Sparidae, Sparidae, Sparidae, Sparidae, Sparidae, Sparidae, 205973273, 204357656, 209667199, Sparidae, Sparidae, Sparidae, Sparidae, Sparidae, Sparidae, Sparidae, Sparidae, Sparidae, Sparidae, Sparidae, 209459667, Sparidae, Sparidae, Sparidae, Sparidae, Sparidae, Sparidae, Sparidae, Sparidae, Sparidae, Sparidae, 205939152, Sparidae, Sparidae, Sparidae, 212108397, Sparidae, Sparidae, Sparidae, 157073718, Sparidae, 204227584, Sparidae, Sparidae, 208592787, Sparidae, Sparidae, Sparidae, 197286779, 209286643, 212282735, 205227323, Sparidae, Sparidae, Sparidae, Sparidae, Sparidae, Sparidae, Sparidae, 197875183, Sparidae, 204865177, 205889059, Sparidae, Sparidae, Sparidae, 158144640, 210656586, Sparidae, 212386582, Sparidae, Sparidae, Sparidae, Sparidae, 209458958, 204985412, 210655459, Sparidae, 211762849, 212360712, Sparidae, 206013982, Sparidae, Sparidae, Sparidae, Sparidae, Sparidae, 205982173, Sparidae, Sparidae, Sparidae, 205986158, 212101300, Sparidae, Sparidae, Sparidae, Sparidae, Sparidae, Sparidae, Sparidae, Sparidae, Sparidae, SPARIDAE, Sparidae, Sparidae, Sparidae, 187337877, 210218628, Sparidae, Sparidae, Sparidae, Sparidae, Sparidae, Sparidae, Sparidae, 212276927, Sparidae, Sparidae, Sparidae, Sparidae, Sparidae, Sparidae, Sparidae, Sparidae, Sparidae, Sparidae , Sparidae, Sparidae, Sparidae, Sparidae, Sparidae Bonaparte, 161427290, Sparidae Rafinesque 1818, Sparidae Rafinesque, 1810, Sparidae Cuvier, 1817, Sparidae Rafinesque, 1818, Sparidae Bonaparte, 1832, Sparidae Rafinesque, 1818, Sparidae Rafinesque, 1818, Sparidae Rafinesque, 1818, Sparidae Bonaparte 1851, Sparidae Rafinesque, 1818, Sparidae Rafinesque, 1810, Sparidae Rafinesque 1818, Sparidae Rafinesque, 1818, Characidae Latreille 1825, Lethrinidae Bonaparte, 1838, Nemipteridae Regan, 1913, Eunicidae Berthold, 1827, Haemulidae, Centracanthidae Gill, 1893, 161428090, Maenidae, Centracanthidae, Centracanthidae Gill, 1893)",
 "BasisOfRecord is one of (Specimen, Human Observation, Observation, Living Specimen, Machine Observation, Literature Occurrence)",
 "Geometry POLYGON((109.5 20.15,117.25 20.15,117.25 24,109.5 24,109.5 20.15))",
 "HasCoordinate is true",
 "HasGeospatialIssue is false"
 ]
}

 The dataset includes 444 records from 9 constituent datasets; see https://api.gbif.org/v1/occurrence/download/0049101-241126133413365/datasets/export for details.
 
Data from some individual datasets included in this download may be licensed under less restrictive terms.
DOI: 10.6084/m9.figshare.26396373
title: Design, synthesis, and evaluation of novel stilbene derivatives that degrade acidic nucleoplasmic DNA-binding protein 1 (And1) and synergize with PARP1 inhibitor in NSCLC cells

description: Specifically inducing the degradation of acidic nucleoplasmic DNA-binding protein 1 (And1) is a promising antitumor strategy. Our previous study identified Bazedoxifene (BZA) and CH3 as specific And1 degraders and validated their activity in reversing radiotherapy resistance <i>in vitro</i> and <i>in vivo</i>. However, unelucidated structure-activity relationships and moderate activity have limited their application. In this study, 27 novel CH3 derivatives were designed and synthesised based on the cavity topology of the WD40 domain of And1. Among them, <b>A15</b> with a “V” conformation significantly induced And1 degradation in NSCLC cells. In addition, this study demonstrated a potential synthetic lethal effect of And1 degraders and PARP1 inhibitors. 1 µM of Olaparib in combination with 5 µM of <b>A15</b> significantly inhibited the proliferation of A549 and H460 cells. Overall, these compounds are valuable tools for elucidating And1 biology, and their special spatial conformation make them promising candidates for future optimisation studies.
DOI: 10.6084/m9.figshare.26396373.v1
title: Design, synthesis, and evaluation of novel stilbene derivatives that degrade acidic nucleoplasmic DNA-binding protein 1 (And1) and synergize with PARP1 inhibitor in NSCLC cells

description: Specifically inducing the degradation of acidic nucleoplasmic DNA-binding protein 1 (And1) is a promising antitumor strategy. Our previous study identified Bazedoxifene (BZA) and CH3 as specific And1 degraders and validated their activity in reversing radiotherapy resistance <i>in vitro</i> and <i>in vivo</i>. However, unelucidated structure-activity relationships and moderate activity have limited their application. In this study, 27 novel CH3 derivatives were designed and synthesised based on the cavity topology of the WD40 domain of And1. Among them, <b>A15</b> with a “V” conformation significantly induced And1 degradation in NSCLC cells. In addition, this study demonstrated a potential synthetic lethal effect of And1 degraders and PARP1 inhibitors. 1 µM of Olaparib in combination with 5 µM of <b>A15</b> significantly inhibited the proliferation of A549 and H460 cells. Overall, these compounds are valuable tools for elucidating And1 biology, and their special spatial conformation make them promising candidates for future optimisation studies.
DOI: 10.6084/m9.figshare.25039392
title: Computational fragment-based drug design of potential Glo-I inhibitors

description: In this study, a fragment-based drug design approach, particularly <i>de novo</i> drug design, was implemented utilising three different crystal structures in order to discover new privileged scaffolds against glyoxalase-I enzyme as anticancer agents. The fragments were evoluted to indicate potential inhibitors with high receptor affinities. The resulting compounds were served as a benchmark for choosing similar compounds from the ASINEX® database by applying different computational ligand-based drug design techniques. Afterwards, the selection of potential hits was further aided by various structure-based approaches. Then, 14 compounds were purchased, and tested <i>in vitro</i> against Glo-I enzyme. Of the tested 14 hits, the biological screening results showed humble activities where the percentage of Glo-I inhibition ranged from 0–18.70 %. Compound <b>19</b> and compound <b>28</b>, whose percentage of inhibitions are 18.70 and 15.80%, respectively, can be considered as hits that need further optimisation in order to be converted into lead-like compounds.
DOI: 10.6084/m9.figshare.25039392.v1
title: Computational fragment-based drug design of potential Glo-I inhibitors

description: In this study, a fragment-based drug design approach, particularly <i>de novo</i> drug design, was implemented utilising three different crystal structures in order to discover new privileged scaffolds against glyoxalase-I enzyme as anticancer agents. The fragments were evoluted to indicate potential inhibitors with high receptor affinities. The resulting compounds were served as a benchmark for choosing similar compounds from the ASINEX® database by applying different computational ligand-based drug design techniques. Afterwards, the selection of potential hits was further aided by various structure-based approaches. Then, 14 compounds were purchased, and tested <i>in vitro</i> against Glo-I enzyme. Of the tested 14 hits, the biological screening results showed humble activities where the percentage of Glo-I inhibition ranged from 0–18.70 %. Compound <b>19</b> and compound <b>28</b>, whose percentage of inhibitions are 18.70 and 15.80%, respectively, can be considered as hits that need further optimisation in order to be converted into lead-like compounds.
DOI: 10.6084/m9.figshare.27605770
title: Discovering a novel dual specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A) inhibitor and its impact on tau phosphorylation and amyloid-β formation

description: Dual-specificity tyrosine-regulated kinase 1 A (DYRK1A) is crucial in neurogenesis, synaptogenesis, and neuronal functions. Its dysregulation is linked to neurodegenerative disorders like Down syndrome and Alzheimer’s disease. Although the development of DYRK1A inhibitors has significantly advanced in recent years, the selectivity of these drugs remains a critical challenge, potentially impeding further progress. In this study, we utilised structure-based virtual screening (SBVS) from NCI library to discover novel DYRK1A inhibitors. The top-ranked compounds were then validated through enzymatic assays to assess their efficacy towards DYRK1A. Among them, NSC361563 emerged as a potent and selective DYRK1A inhibitor. It was shown to decrease tau phosphorylation at multiple sites, thereby enhancing tubulin stability. Moreover, NSC361563 diminished the formation of amyloid β and offered neuroprotective benefits against amyloid β-induced toxicity. Our research highlights the critical role of selective DYRK1A inhibitors in treating neurodegenerative diseases and presents a promising starting point for the development of targeted therapies.
DOI: 10.6084/m9.figshare.27605770.v1
title: Discovering a novel dual specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A) inhibitor and its impact on tau phosphorylation and amyloid-β formation

description: Dual-specificity tyrosine-regulated kinase 1 A (DYRK1A) is crucial in neurogenesis, synaptogenesis, and neuronal functions. Its dysregulation is linked to neurodegenerative disorders like Down syndrome and Alzheimer’s disease. Although the development of DYRK1A inhibitors has significantly advanced in recent years, the selectivity of these drugs remains a critical challenge, potentially impeding further progress. In this study, we utilised structure-based virtual screening (SBVS) from NCI library to discover novel DYRK1A inhibitors. The top-ranked compounds were then validated through enzymatic assays to assess their efficacy towards DYRK1A. Among them, NSC361563 emerged as a potent and selective DYRK1A inhibitor. It was shown to decrease tau phosphorylation at multiple sites, thereby enhancing tubulin stability. Moreover, NSC361563 diminished the formation of amyloid β and offered neuroprotective benefits against amyloid β-induced toxicity. Our research highlights the critical role of selective DYRK1A inhibitors in treating neurodegenerative diseases and presents a promising starting point for the development of targeted therapies.
DOI: 10.6084/m9.figshare.26790510
title: In-cell bioluminescence resonance energy transfer (BRET)-based assay uncovers ceritinib and CA-074 as SARS-CoV-2 papain-like protease inhibitors

description: Papain-like protease (PLpro) is an attractive anti-coronavirus target. The development of PLpro inhibitors, however, is hampered by the limitations of the existing PLpro assay and the scarcity of validated active compounds. We developed a novel in-cell PLpro assay based on BRET and used it to evaluate and discover SARS-CoV-2 PLpro inhibitors. The developed assay demonstrated remarkable sensitivity for detecting the reduction of intracellular PLpro activity while presenting high reliability and performance for inhibitor evaluation and high-throughput screening. Using this assay, three protease inhibitors were identified as novel PLpro inhibitors that are structurally disparate from those previously known. Subsequent enzymatic assays and ligand-protein interaction analysis based on molecular docking revealed that ceritinib directly inhibited PLpro, showing high geometric complementarity with the substrate-binding pocket in PLpro, whereas CA-074 methyl ester underwent intracellular hydrolysis, exposing a free carboxyhydroxyl group essential for hydrogen bonding with G266 in the BL2 groove, resulting in PLpro inhibition.
DOI: 10.6084/m9.figshare.26790510.v1
title: In-cell bioluminescence resonance energy transfer (BRET)-based assay uncovers ceritinib and CA-074 as SARS-CoV-2 papain-like protease inhibitors

description: Papain-like protease (PLpro) is an attractive anti-coronavirus target. The development of PLpro inhibitors, however, is hampered by the limitations of the existing PLpro assay and the scarcity of validated active compounds. We developed a novel in-cell PLpro assay based on BRET and used it to evaluate and discover SARS-CoV-2 PLpro inhibitors. The developed assay demonstrated remarkable sensitivity for detecting the reduction of intracellular PLpro activity while presenting high reliability and performance for inhibitor evaluation and high-throughput screening. Using this assay, three protease inhibitors were identified as novel PLpro inhibitors that are structurally disparate from those previously known. Subsequent enzymatic assays and ligand-protein interaction analysis based on molecular docking revealed that ceritinib directly inhibited PLpro, showing high geometric complementarity with the substrate-binding pocket in PLpro, whereas CA-074 methyl ester underwent intracellular hydrolysis, exposing a free carboxyhydroxyl group essential for hydrogen bonding with G266 in the BL2 groove, resulting in PLpro inhibition.
DOI: 10.6084/m9.figshare.27268468
title: Synthesis and biological evaluation of quinoxaline derivatives as ASK1 inhibitors

description: Inhibiting apoptosis signal regulated kinase 1 (ASK1) is an attractive strategy for treating diseases such as non-alcoholic steatohepatitis and multiple sclerosis. Here, we report the discovery of a dibromo substituted quinoxaline fragment containing <b>26e</b> as an effective small-molecule inhibitor of ASK1, with an IC<sub>50</sub> value of 30.17 nM. In addition, the cell survival rate of <b>26e</b> at different concentrations was greater than 80%, especially at 0.4 μM. Its cell survival rate was significantly higher than <b>GS-4997</b>, indicating its good safety in normal human liver LO2 cells. The Oil Red O staining experiment showed that <b>26e</b> decreased the lipid droplets in a dose-dependent manner. Further biochemical analyses revealed that <b>26e</b> could reduce the content of T-CHO, LDL, and TG in FFA-induced LO2 cells, and had the potential to treat non-alcoholic fatty disease. These findings provide a good choice for the future development of ASK1 inhibitors.
DOI: 10.6084/m9.figshare.27268468.v1
title: Synthesis and biological evaluation of quinoxaline derivatives as ASK1 inhibitors

description: Inhibiting apoptosis signal regulated kinase 1 (ASK1) is an attractive strategy for treating diseases such as non-alcoholic steatohepatitis and multiple sclerosis. Here, we report the discovery of a dibromo substituted quinoxaline fragment containing <b>26e</b> as an effective small-molecule inhibitor of ASK1, with an IC<sub>50</sub> value of 30.17 nM. In addition, the cell survival rate of <b>26e</b> at different concentrations was greater than 80%, especially at 0.4 μM. Its cell survival rate was significantly higher than <b>GS-4997</b>, indicating its good safety in normal human liver LO2 cells. The Oil Red O staining experiment showed that <b>26e</b> decreased the lipid droplets in a dose-dependent manner. Further biochemical analyses revealed that <b>26e</b> could reduce the content of T-CHO, LDL, and TG in FFA-induced LO2 cells, and had the potential to treat non-alcoholic fatty disease. These findings provide a good choice for the future development of ASK1 inhibitors.