cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.5281/zenodo.10865995
title: 04 PerformDevelop_F_long_final for LMM
DOI: 10.6084/m9.figshare.1623206
title: Role of AMPK signaling in mediating the anticancer effects of silibinin in esophageal squamous cell carcinoma

description: <b><i>Objective</i></b>: Emerging evidence suggests that activation of adenosine monophosphate-activated protein kinase (AMPK) may suppress cancer growth. Identification of novel AMPK activators is therefore crucial to exploit AMPK as a potential target for cancer prevention and treatment.<b><i>Research design and methods</i></b>: We determined the expression status and role of AMPK in esophageal squamous cell carcinoma (ESCC) and investigated whether silibinin, a nontoxic natural product, could activate AMPK to inhibit ESCC development.<b><i>Results</i></b>: Our results from 49 pairs of human ESCC and normal tissues showed that AMPK was constitutively inactive in the majority (69.4%) of ESCC. We found that silibinin induced apoptosis, and inhibited ESCC cell proliferation <i>in vitro</i> and tumorigenicity <i>in vivo</i> without any adverse effects. Silibinin also markedly suppressed the invasive potential of ESCC cells <i>in vitro</i> and their ability to form lung metastasis in nude mice. The anticancer effects of silibinin were abrogated by the presence of compound C or shRNA against AMPK. More importantly, silibinin enhanced the sensitivity of ESCC cells and tumors to the chemotherapeutic drugs, 5-fluorouracil and cisplatin.<b><i>Conclusions</i></b>: This preclinical study supports that AMPK is a valid therapeutic target and suggests that silibinin may be a potentially useful therapeutic agent and chemosensitizer for esophageal cancer.
DOI: 10.6084/m9.figshare.1623206.v1
title: Role of AMPK signaling in mediating the anticancer effects of silibinin in esophageal squamous cell carcinoma

description: <b><i>Objective</i></b>: Emerging evidence suggests that activation of adenosine monophosphate-activated protein kinase (AMPK) may suppress cancer growth. Identification of novel AMPK activators is therefore crucial to exploit AMPK as a potential target for cancer prevention and treatment.<b><i>Research design and methods</i></b>: We determined the expression status and role of AMPK in esophageal squamous cell carcinoma (ESCC) and investigated whether silibinin, a nontoxic natural product, could activate AMPK to inhibit ESCC development.<b><i>Results</i></b>: Our results from 49 pairs of human ESCC and normal tissues showed that AMPK was constitutively inactive in the majority (69.4%) of ESCC. We found that silibinin induced apoptosis, and inhibited ESCC cell proliferation <i>in vitro</i> and tumorigenicity <i>in vivo</i> without any adverse effects. Silibinin also markedly suppressed the invasive potential of ESCC cells <i>in vitro</i> and their ability to form lung metastasis in nude mice. The anticancer effects of silibinin were abrogated by the presence of compound C or shRNA against AMPK. More importantly, silibinin enhanced the sensitivity of ESCC cells and tumors to the chemotherapeutic drugs, 5-fluorouracil and cisplatin.<b><i>Conclusions</i></b>: This preclinical study supports that AMPK is a valid therapeutic target and suggests that silibinin may be a potentially useful therapeutic agent and chemosensitizer for esophageal cancer.
DOI: 10.6084/m9.figshare.1625309
title: A second hadrosauroid dinosaur from the early Late Cretaceous of Zuoyun, Shanxi Province, China

description: A second basal hadrosauroid dinosaur, <i>Zuoyunlong huangi</i> gen. et sp. nov., is reported from the early Late Cretaceous Zhumapu Formation in Zuoyun County, Shanxi Province, northern China. <i>Zuoyunlong</i> preserves a partial right ilium and ischium and is unique in having a very short postacetabular process 50% as long as the iliac central plate. Our cladistic analysis recovers <i>Zuoyunlong</i> as the most basal Late Cretaceous hadrosauroid, with a sister taxon relationship with <i>Probactrosaurus</i> from the late Early Cretaceous of Inner Mongolia. Including <i>Zuoyunlong</i>, four Cenomanian basal hadrosauroids have been recorded, and the two taxa in North America (<i>Eolambia</i> and <i>Protohadros</i>) represent the earliest known hadrosauroids outside of Asia. In the light of the proposed phylogenetic topology and biogeographic data, the discovery of <i>Zuoyunlong</i> indicates that the first dispersal of hadrosauroids from Asia to North America probably happened around the boundary between the Early and Late Cretaceous.
DOI: 10.6084/m9.figshare.1625309.v1
title: A second hadrosauroid dinosaur from the early Late Cretaceous of Zuoyun, Shanxi Province, China

description: A second basal hadrosauroid dinosaur, <i>Zuoyunlong huangi</i> gen. et sp. nov., is reported from the early Late Cretaceous Zhumapu Formation in Zuoyun County, Shanxi Province, northern China. <i>Zuoyunlong</i> preserves a partial right ilium and ischium and is unique in having a very short postacetabular process 50% as long as the iliac central plate. Our cladistic analysis recovers <i>Zuoyunlong</i> as the most basal Late Cretaceous hadrosauroid, with a sister taxon relationship with <i>Probactrosaurus</i> from the late Early Cretaceous of Inner Mongolia. Including <i>Zuoyunlong</i>, four Cenomanian basal hadrosauroids have been recorded, and the two taxa in North America (<i>Eolambia</i> and <i>Protohadros</i>) represent the earliest known hadrosauroids outside of Asia. In the light of the proposed phylogenetic topology and biogeographic data, the discovery of <i>Zuoyunlong</i> indicates that the first dispersal of hadrosauroids from Asia to North America probably happened around the boundary between the Early and Late Cretaceous.
DOI: 10.6084/m9.figshare.1626630
title: Radiopharmaceutical evaluation of <sup>131</sup>I-protohypericin as a necrosis avid compound

description: Hypericin is a necrosis avid agent useful for nuclear imaging and tumor therapy. Protohypericin, with a similar structure to hypericin except poorer planarity, is the precursor of hypericin. In this study, we aimed to investigate the impact of this structural difference on self-assembly, and evaluate the necrosis affinity and metabolism in the rat model of reperfused hepatic infarction. Protohypericin appeared less aggregative in solution compared with hypericin by fluorescence analysis. Biodistribution data of <sup>131</sup>I-protohypericin showed the percentage of injected dose per gram of tissues (%ID/g) increased with time and reached to the maximum of 7.03 at 24 h in necrotic liver by gamma counting. The maximum ratio of target/non-target tissues was 11.7-fold in necrotic liver at 72 h. Pharmacokinetic parameters revealed that the half-life of <sup>131</sup>I-protohypericin was 14.9 h, enabling a long blood circulation and constant retention in necrotic regions. SPECT-CT, autoradiography, and histological staining showed high uptake of <sup>131</sup>I-protohypericin in necrotic tissues. These results suggest that <sup>131</sup>I-protohypericin is a promising necrosis avid compound with a weaker aggregation tendency compared with hypericin and it may have a broad application in imaging and oncotherapy.
DOI: 10.6084/m9.figshare.1626630.v1
title: Radiopharmaceutical evaluation of <sup>131</sup>I-protohypericin as a necrosis avid compound

description: Hypericin is a necrosis avid agent useful for nuclear imaging and tumor therapy. Protohypericin, with a similar structure to hypericin except poorer planarity, is the precursor of hypericin. In this study, we aimed to investigate the impact of this structural difference on self-assembly, and evaluate the necrosis affinity and metabolism in the rat model of reperfused hepatic infarction. Protohypericin appeared less aggregative in solution compared with hypericin by fluorescence analysis. Biodistribution data of <sup>131</sup>I-protohypericin showed the percentage of injected dose per gram of tissues (%ID/g) increased with time and reached to the maximum of 7.03 at 24 h in necrotic liver by gamma counting. The maximum ratio of target/non-target tissues was 11.7-fold in necrotic liver at 72 h. Pharmacokinetic parameters revealed that the half-life of <sup>131</sup>I-protohypericin was 14.9 h, enabling a long blood circulation and constant retention in necrotic regions. SPECT-CT, autoradiography, and histological staining showed high uptake of <sup>131</sup>I-protohypericin in necrotic tissues. These results suggest that <sup>131</sup>I-protohypericin is a promising necrosis avid compound with a weaker aggregation tendency compared with hypericin and it may have a broad application in imaging and oncotherapy.
DOI: 10.6084/m9.figshare.1626631
title: Fabrication of poly(<b>γ</b>-glutamic acid)-based biopolymer as the targeted drug delivery system with enhanced cytotoxicity to APN/CD13 over-expressed cells

description: Poly(γ-glutamic acid)-based targeted drug delivery system (PAMCN) targeting transmembrane metalloprotease aminopeptidase-N (APN/CD13) was fabricated and evaluated for the enhancement of targeting efficiency and cytotoxicity. The cisplatin (CDDP) loading content of PAMCN was about 36 ± 5% and PAMCN showed a sustainable release profile with a half-maximal release time (<i>t</i><sub>1/2</sub>) of 23 h. The average size of PAMCN was 132 ± 18 nm determined by light scattering (LS) and 158 ± 67 nm by atomic force microscopy (AFM). Flow cytometry and fluorescence microscope analysis showed that the drug carrier (PAMN) could specifically bind to human umbilical vein endothelial cells (HUVEC). PAMCN enhanced the efficacy of CDDP to HUVEC cells with the half maximal inhibitory concentration (IC<sub>50</sub>) value decreased to 90.83 ± 33.00 μg/ml comparing with free CDDP treatment and showed less tube formation amounts (<i>p</i> &lt; 0.01) than free CDDP in matrigel angiogenesis inhibition assay <i>in vitro. In vivo</i> toxicity experiment indicated that the survival rate of KM mice in PAMCN group was 100% and PAMCN reduced the hepatic and renal toxicity significantly compared to free CDDP group. Therefore, this novel drug delivery system presents a promising potential for antiangiogenic chemotherapy.
DOI: 10.6084/m9.figshare.1626631.v1
title: Fabrication of poly(<b>γ</b>-glutamic acid)-based biopolymer as the targeted drug delivery system with enhanced cytotoxicity to APN/CD13 over-expressed cells

description: Poly(γ-glutamic acid)-based targeted drug delivery system (PAMCN) targeting transmembrane metalloprotease aminopeptidase-N (APN/CD13) was fabricated and evaluated for the enhancement of targeting efficiency and cytotoxicity. The cisplatin (CDDP) loading content of PAMCN was about 36 ± 5% and PAMCN showed a sustainable release profile with a half-maximal release time (<i>t</i><sub>1/2</sub>) of 23 h. The average size of PAMCN was 132 ± 18 nm determined by light scattering (LS) and 158 ± 67 nm by atomic force microscopy (AFM). Flow cytometry and fluorescence microscope analysis showed that the drug carrier (PAMN) could specifically bind to human umbilical vein endothelial cells (HUVEC). PAMCN enhanced the efficacy of CDDP to HUVEC cells with the half maximal inhibitory concentration (IC<sub>50</sub>) value decreased to 90.83 ± 33.00 μg/ml comparing with free CDDP treatment and showed less tube formation amounts (<i>p</i> &lt; 0.01) than free CDDP in matrigel angiogenesis inhibition assay <i>in vitro. In vivo</i> toxicity experiment indicated that the survival rate of KM mice in PAMCN group was 100% and PAMCN reduced the hepatic and renal toxicity significantly compared to free CDDP group. Therefore, this novel drug delivery system presents a promising potential for antiangiogenic chemotherapy.
DOI: 10.6084/m9.figshare.1626637
title: A low-molecular-weight heparin-coated doxorubicin-liposome for the prevention of melanoma metastasis

description: Tumor metastasis is the biggest challenge in cancer therapy. During the metastasis process, metastatic cells could acquire stealth ability toward immune system through the formation of a protection cloak by hijacking platelets (PTs). Heparins, a heterogeneous mixture of glycosaminoglycans, can inhibit metastatic cascades by blocking P-selectin-mediated intercellular adhesion between tumor cells and PTs. In this study, low-molecular-weight heparin-coated doxorubicin-loaded liposome (LMWH-DOX-Lip) was developed for metastasis preventative therapy. The formation of LMWH-DOX-Lip was based on electrostatic interactions between the negatively charged heparins and cationic lipids. LMWH-DOX-Lip prepared at the optimum prescription possessed high entrapment efficiency, ideal particle size and zeta potential. Morphology of LMWH-DOX-Lip was characterized by atomic force microscopy and transmission electron microscopy. The results of confocal microscopic observations and flow cytometry analysis indicated that LMWH-DOX-Lip mediated an efficient cellular uptake in B16F10 melanoma cell line. Besides, LMWH-DOX-Lip displayed an increased cytotoxic over their unmodified counterparts. Furthermore, the inhibition effect of LMWH-DOX-Lip on adhesion between tumor cells and PTs/P-selectin was observed. <i>In vivo</i> study performed on a pulmonary melanoma mouse model revealed a substantially tumor metastasis prevention by LMWH-DOX-Lip. All these results suggested that LMWH-DOX-Lip could significantly inhibit metastasis through preventing the tumor cell–platelet interactions and in the meantime suppressed tumor growth.
DOI: 10.6084/m9.figshare.1626637.v1
title: A low-molecular-weight heparin-coated doxorubicin-liposome for the prevention of melanoma metastasis

description: Tumor metastasis is the biggest challenge in cancer therapy. During the metastasis process, metastatic cells could acquire stealth ability toward immune system through the formation of a protection cloak by hijacking platelets (PTs). Heparins, a heterogeneous mixture of glycosaminoglycans, can inhibit metastatic cascades by blocking P-selectin-mediated intercellular adhesion between tumor cells and PTs. In this study, low-molecular-weight heparin-coated doxorubicin-loaded liposome (LMWH-DOX-Lip) was developed for metastasis preventative therapy. The formation of LMWH-DOX-Lip was based on electrostatic interactions between the negatively charged heparins and cationic lipids. LMWH-DOX-Lip prepared at the optimum prescription possessed high entrapment efficiency, ideal particle size and zeta potential. Morphology of LMWH-DOX-Lip was characterized by atomic force microscopy and transmission electron microscopy. The results of confocal microscopic observations and flow cytometry analysis indicated that LMWH-DOX-Lip mediated an efficient cellular uptake in B16F10 melanoma cell line. Besides, LMWH-DOX-Lip displayed an increased cytotoxic over their unmodified counterparts. Furthermore, the inhibition effect of LMWH-DOX-Lip on adhesion between tumor cells and PTs/P-selectin was observed. <i>In vivo</i> study performed on a pulmonary melanoma mouse model revealed a substantially tumor metastasis prevention by LMWH-DOX-Lip. All these results suggested that LMWH-DOX-Lip could significantly inhibit metastasis through preventing the tumor cell–platelet interactions and in the meantime suppressed tumor growth.
DOI: 10.6084/m9.figshare.1627841
title: Cumulates of arc magmas incorporated into the Sulu UHP metamorphic belt, eastern China

description: ABSTRACTThe Hujialin ultramafic complex in the central region of the Sulu ultra-high pressure (UHP) metamorphic belt consists of discontinuous lenses of garnet-bearing clinopyroxenite and dunite surrounded by marginal serpentinite. The clinopyroxenite shows relatively low concentrations of compatible elements, such as Cr (≤1670 ppm) and Ni (≤514 ppm) and Ir-group platinum group elements (IPGE; Ir, Os, and Ru; ≤4.8 ppb in total). They show varying ratios (0.02–2.50) of IPGE to Pd-group PGE (PPGE). Their chondrite-normalized rare earth elements (REE) patterns are convex and the total REE concentrations range from 18 to 63 times that of Cl chondrite. The bulk rocks show a ‘subduction-related’ geochemical signature, with high concentrations of fluid-mobile elements (i.e. Sr, Ba) relative to high-field strength elements (i.e. Nb, Y, Zr). Clinopyroxene is diopside and contains low Al<sub>2</sub>O<sub>3</sub> (&lt;2.76 wt.%) and high SiO<sub>2</sub> (54.6–56.9 wt.%). Olivine grains enclosed by clinopyroxene and in the matrix show relatively low Fo (76.6–80.7) and NiO contents (0.18–0.29 wt.%). The bulk rock compositions and mineral chemistry of olivine and clinopyroxene suggest that the unit was a cumulate of a subduction-related melt. On the other hand, dunite and its hydration product, serpentinite, have a different origin. The bulk rock and mineral chemistry suggest that dunite represents a mantle wedge peridotite in a spinel-stable field. Both clinopyroxenite and spinel-bearing dunite were once located in the mantle wedge below the southern margin of the North China craton (NCC), and were dragged by a mantle flow into the continental subduction channel along the interface between the subducting Yangtze craton (YZC) and the overlying NCC. Although clinopyroxenite and dunite are dense (2.8–3.2 g/cm<sup>3</sup>), the buoyancy-driven exhumation of voluminous granitic rocks of the YZC likely brought clinopyroxenite and dunite to shallow crustal depths. The lack of the evidence for high pressure to ultra-high pressure (HP-UHP) metamorphism in spinel-bearing dunite may be explained by overall low Al and Ca in the bulk rocks. Alternatively, dunite was not subducted to deep levels, but exhumed together with the deeply subducted clinopyroxenites and granite during their exhumation.
DOI: 10.6084/m9.figshare.1627841.v2
title: Cumulates of arc magmas incorporated into the Sulu UHP metamorphic belt, eastern China

description: ABSTRACTThe Hujialin ultramafic complex in the central region of the Sulu ultra-high pressure (UHP) metamorphic belt consists of discontinuous lenses of garnet-bearing clinopyroxenite and dunite surrounded by marginal serpentinite. The clinopyroxenite shows relatively low concentrations of compatible elements, such as Cr (≤1670 ppm) and Ni (≤514 ppm) and Ir-group platinum group elements (IPGE; Ir, Os, and Ru; ≤4.8 ppb in total). They show varying ratios (0.02–2.50) of IPGE to Pd-group PGE (PPGE). Their chondrite-normalized rare earth elements (REE) patterns are convex and the total REE concentrations range from 18 to 63 times that of Cl chondrite. The bulk rocks show a ‘subduction-related’ geochemical signature, with high concentrations of fluid-mobile elements (i.e. Sr, Ba) relative to high-field strength elements (i.e. Nb, Y, Zr). Clinopyroxene is diopside and contains low Al<sub>2</sub>O<sub>3</sub> (&lt;2.76 wt.%) and high SiO<sub>2</sub> (54.6–56.9 wt.%). Olivine grains enclosed by clinopyroxene and in the matrix show relatively low Fo (76.6–80.7) and NiO contents (0.18–0.29 wt.%). The bulk rock compositions and mineral chemistry of olivine and clinopyroxene suggest that the unit was a cumulate of a subduction-related melt. On the other hand, dunite and its hydration product, serpentinite, have a different origin. The bulk rock and mineral chemistry suggest that dunite represents a mantle wedge peridotite in a spinel-stable field. Both clinopyroxenite and spinel-bearing dunite were once located in the mantle wedge below the southern margin of the North China craton (NCC), and were dragged by a mantle flow into the continental subduction channel along the interface between the subducting Yangtze craton (YZC) and the overlying NCC. Although clinopyroxenite and dunite are dense (2.8–3.2 g/cm<sup>3</sup>), the buoyancy-driven exhumation of voluminous granitic rocks of the YZC likely brought clinopyroxenite and dunite to shallow crustal depths. The lack of the evidence for high pressure to ultra-high pressure (HP-UHP) metamorphism in spinel-bearing dunite may be explained by overall low Al and Ca in the bulk rocks. Alternatively, dunite was not subducted to deep levels, but exhumed together with the deeply subducted clinopyroxenites and granite during their exhumation.
DOI: 10.6084/m9.figshare.1627841.v1
title: Cumulates of arc magmas incorporated into the Sulu UHP metamorphic belt, eastern China

description: ABSTRACTThe Hujialin ultramafic complex in the central region of the Sulu ultra-high pressure (UHP) metamorphic belt consists of discontinuous lenses of garnet-bearing clinopyroxenite and dunite surrounded by marginal serpentinite. The clinopyroxenite shows relatively low concentrations of compatible elements, such as Cr (≤1670 ppm) and Ni (≤514 ppm) and Ir-group platinum group elements (IPGE; Ir, Os, and Ru; ≤4.8 ppb in total). They show varying ratios (0.02–2.50) of IPGE to Pd-group PGE (PPGE). Their chondrite-normalized rare earth elements (REE) patterns are convex and the total REE concentrations range from 18 to 63 times that of Cl chondrite. The bulk rocks show a ‘subduction-related’ geochemical signature, with high concentrations of fluid-mobile elements (i.e. Sr, Ba) relative to high-field strength elements (i.e. Nb, Y, Zr). Clinopyroxene is diopside and contains low Al<sub>2</sub>O<sub>3</sub> (&lt;2.76 wt.%) and high SiO<sub>2</sub> (54.6–56.9 wt.%). Olivine grains enclosed by clinopyroxene and in the matrix show relatively low Fo (76.6–80.7) and NiO contents (0.18–0.29 wt.%). The bulk rock compositions and mineral chemistry of olivine and clinopyroxene suggest that the unit was a cumulate of a subduction-related melt. On the other hand, dunite and its hydration product, serpentinite, have a different origin. The bulk rock and mineral chemistry suggest that dunite represents a mantle wedge peridotite in a spinel-stable field. Both clinopyroxenite and spinel-bearing dunite were once located in the mantle wedge below the southern margin of the North China craton (NCC), and were dragged by a mantle flow into the continental subduction channel along the interface between the subducting Yangtze craton (YZC) and the overlying NCC. Although clinopyroxenite and dunite are dense (2.8–3.2 g/cm<sup>3</sup>), the buoyancy-driven exhumation of voluminous granitic rocks of the YZC likely brought clinopyroxenite and dunite to shallow crustal depths. The lack of the evidence for high pressure to ultra-high pressure (HP-UHP) metamorphism in spinel-bearing dunite may be explained by overall low Al and Ca in the bulk rocks. Alternatively, dunite was not subducted to deep levels, but exhumed together with the deeply subducted clinopyroxenites and granite during their exhumation.