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  • 1
    Online Resource
    Online Resource
    Effect of Rivaroxaban vs Enoxaparin on Major Cardiac Adverse Events and Bleeding Risk in the Acute Phase of Acute Coronary Syndrome : The H-REPLACE Randomized Equivalence and Noninferiority Trial
    American Medical Association (AMA) ; 2023
    In:  JAMA Network Open Vol. 6, No. 2 ( 2023-02-10), p. e2255709-
    Details
    In: JAMA Network Open, American Medical Association (AMA), Vol. 6, No. 2 ( 2023-02-10), p. e2255709-
    Abstract: Parenteral enoxaparin is a preferred anticoagulant used in the acute phase for patients with acute coronary syndrome (ACS). The safety and efficacy of short-term low-dose rivaroxaban in this clinical setting remain unknown. Objective To compare the safety and efficacy of rivaroxaban vs enoxaparin in the acute phase of ACS. Design, Setting, and Participants This multicenter, prospective, open-label, active-controlled, equivalence and noninferiority trial was conducted from January 2017 through May 2021 with a 6-month follow-up at 21 hospitals in China. Participants included patients with ACS missing the primary reperfusion window or before selective revascularization. Data were analyzed from November 2021 to November 2022. Interventions Participants were randomized 1:1:1 to oral rivaroxaban 2.5 mg or 5 mg or 1 mg/kg subcutaneous enoxaparin twice daily in addition to dual antiplatelet therapy (DAPT; aspirin 100 mg and clopidogrel 75 mg once daily) for a mean of 3.7 days. Main Outcomes and Measures The primary safety end point was bleeding events, as defined by the International Society on Thrombosis and Haemostasis, and the primary efficacy end point was major adverse cardiovascular events (MACEs), including cardiac death, myocardial infarction, rerevascularization, or stroke during the 6-month follow-up. Results Of 2055 enrolled patients, 2046 (99.6%) completed the trial (mean [SD] age 65.8 [8.2] years, 1443 [70.5%] male) and were randomized to enoxaparin (680 patients), rivaroxaban 2.5 mg (683 patients), or rivaroxaban 5 mg (683 patients). Bleeding rates were 46 patients (6.8%) in the enoxaparin group, 32 patients (4.7%) in the rivaroxaban 2.5 mg group, and 36 patients (5.3%)in the rivaroxaban 5 mg group (rivaroxaban 2.5 mg vs enoxaparin: noninferiority hazard ratio [HR] , 0.68; 95% CI, 0.43 to 1.07; P  = .005; rivaroxaban 5 mg vs enoxaparin: noninferiority HR, 0.88; 95% CI, 0.70 to 1.09; P  = .001). The incidence of MACEs was similar among groups, and noninferiority was reached in the rivaroxaban 5 mg group (HR, 0.60; 95% CI, 0.31 to 1.16, P  = .02) but not in the rivaroxaban 2.5 mg group (HR, 0.68; 95% CI, 0.36 to 1.30; P  = .05) compared with the enoxaparin group. Conclusions and Relevance In this equivalence and noninferiority trial, oral rivaroxaban 5 mg showed noninferiority to subcutaneous enoxaparin (1 mg/kg) for patients with ACS treated with DAPT during the acute phase. Results of this feasibility study provide useful information for designing future randomized clinical trials with sufficient sample sizes. Trial Registration ClinicalTrials.gov Identifier: NCT03363035
    Type of Medium: Online Resource
    ISSN: 2574-3805
    URL: Article
    DOI: 10.1001/jamanetworkopen.2022.55709
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2023
    detail.hit.zdb_id: 2931249-8
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  • 2
    Online Resource
    Online Resource
    Abstract 494: BPI-452080: A potent and selective HIF-2α inhibitor for the treatment of clear cell renal cell carcinoma, von Hippel-Lindau disease, and other solid tumors
    American Association for Cancer Research (AACR) ; 2023
    In:  Cancer Research Vol. 83, No. 7_Supplement ( 2023-04-04), p. 494-494
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 83, No. 7_Supplement ( 2023-04-04), p. 494-494
    Abstract: The most observed alteration in clear cell renal cell carcinoma (ccRCC) is the inactivation of the tumor suppressor von Hippel-Lindau (VHL) E3 ligase due to genetic predisposition, somatic mutations, or methylation. Loss of VHL can lead to hypoxia-inducible factor 2α (HIF-2α) accumulation and elevated expression of HIF target genes, such as VEGFA, many of which facilitate angiogenesis, proliferation, and metastasis of ccRCC. Therefore, inhibiting HIF-2α has become a new strategy for the treatment of ccRCC. Here, we present the discovery of BPI-452080, a selective small molecule HIF-2α inhibitor. In VHL defective ccRCC cell lines, BPI-452080 potently and selectively blocked the heterodimerization of HIF-2α with HIF-1β, but not that of HIF-1α with HIF-1β. It inhibited the downstream hypoxia-responsive gene transcription and VEGFA protein secretion. In multiple xenograft mouse models, oral administration of BPI-452080 significantly inhibited tumor growth in a dose-dependent manner. BPI-452080 demonstrated good PK/PD correlation in the 786-O xenograft model after a single dosing, as shown by a concentration-dependent inhibition of VEGFA secretion in plasma and a reduction of the mRNA levels of VEGFA, CXCR4, CCND1, and GLUT1 genes in tumor tissue. Moreover, BPI-452080 exhibited good bioavailability in multiple pre-clinical species, favorable ADME properties, and good tolerance in toxicology studies. In conclusion, BPI-452080 is a potent, selective, and orally bioavailable HIF-2α inhibitor which presents a novel therapeutic option for ccRCC, von Hippel-Lindau disease, and other solid tumors. BPI-452080 is planned to enter Phase I clinical trial in China in early 2023. Citation Format: Pingping Wang, Rongwen Yang, Yun Sun, Xuepeng Ju, Jiayu Zhao, Yanju Liu, Xiaoyun Liu, Zhengyao Zou, Jialin Ren, Min Wang, Haibo Chen, Xuegang Yi, Jian Zhang, Teng Ma, Gaoliang Cheng, Lijia Liu, Jing Guo, Xiangyong Liu, Hong Lan, Lieming Ding, Jiabing Wang. BPI-452080: A potent and selective HIF-2α inhibitor for the treatment of clear cell renal cell carcinoma, von Hippel-Lindau disease, and other solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 494.
    Type of Medium: Online Resource
    ISSN: 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2023-494
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2023
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 3
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    Online Resource
    Photothermal Regulated Nanozyme of CuFeS2 Nanoparticles for Efficiently Promoting Wound Healing Infected by Multidrug Resistant Bacteria
    MDPI AG ; 2022
    In:  Nanomaterials Vol. 12, No. 14 ( 2022-07-19), p. 2469-
    Details
    In: Nanomaterials, MDPI AG, Vol. 12, No. 14 ( 2022-07-19), p. 2469-
    Abstract: Peroxidase-mediated chemokinetic therapy (CDT) can effectively resist bacteria; however, factors such as the high dosage of drugs seriously limit the antibacterial effect. Herein, CuFeS2 nanoparticles (NPs) nanozyme antibacterial system with the photothermal effect and peroxidase-like catalytic activity are proposed as a combined antibacterial agent with biosafety, high-efficiency, and broad-spectrum antibacterial ability. In addition, the as-obtained CuFeS2 NPs with a low doses of Cu+ and Fe3+ can change the permeability of bacterial cell membranes and break the antioxidant balance by consuming intracellular glutathione (GSH), which results in more conducive ROS production. Meanwhile, the photothermal heating can regulate the CuFeS2 NPs close to their optimal reaction temperature (60 °C) to release more hydroxyl radical in low concentrations of H2O2 (100 µM). The proposed CuFeS2 NPs-based antibacterial system achieve more than 99% inactivation efficiency of methicillin-resistant Staphylococcus aureus (106 CFU mL−1 MRSA), hyperspectral bacteria β-Escherichia coli (106 CFU mL−1 ESBL) and Pseudomonas aeruginosa (106 CFU mL−1 PA), even at low concentration (2 μg mL−1), which is superior to those of the conventional CuO NPs at 4 mg mL−1 reported in the literature. In vivo experiments further confirm that CuFeS2 NPs can effectively treat wounds infected by MRSA and promote the wound healing. This study demonstrates that excellent antibacterial ability and good biocompatibility make CuFeS2 NPs a potential anti-infection nanozyme with broad application prospects.
    Type of Medium: Online Resource
    ISSN: 2079-4991
    URL: Article
    DOI: 10.3390/nano12142469
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2662255-5
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  • 4
    Online Resource
    Online Resource
    Abstract 495: Discovery of BPI-221351, a potent, selective, orally available, and brain penetrating dual inhibitor of mutant IDH1/2
    American Association for Cancer Research (AACR) ; 2023
    In:  Cancer Research Vol. 83, No. 7_Supplement ( 2023-04-04), p. 495-495
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 83, No. 7_Supplement ( 2023-04-04), p. 495-495
    Abstract: Isocitrate dehydrogenases 1 and 2 (IDH1 and IDH2) are critical enzymes of the tricarboxylic acid cycle, which convert isocitrate into α-ketoglutarate (α-KG). IDH1 or IDH2 mutations are observed in more than 80% of low- to mid-grade gliomas and in ~20% of acute myeloid leukemia (AML). Tumor-related IDH1/2 mutants acquire a novel function of using α-KG as a substrate to produce R-2-hydroxyglutarate (2-HG). 2-HG is an oncogenic metabolite, and reducing it by inhibiting mutant IDH1 or IDH2 has been shown to be an effective treatment approach. Although agents targeting IDH1 or IDH2 have been approved to treat IDH-mutant cancers, existing IDH1 inhibitors do not cross the blood-brain barrier, a feature needed for treating glioma. Furthermore, resistant mutations do occur, including cross-isoform mutations, which call for the development of dual IDH1/2 inhibitors with good brain penetration. However, IDH1/2 dual inhibitors are rarely discovered. Here we report the discovery of BPI-221351, a potent inhibitor of mutant IDH1 and mutant IDH2. BPI-221351 shows excellent inhibitory activities against both IDH1 and IDH2 enzymes, and potently suppresses 2-HG levels in tumor cells harboring IDH1 or IDH2 mutants. In an IDH-mutant xenograft model, BPI-221351 reduced 2-HG to baseline level up to 24 h after a single oral dose administration. In addition, BPI-221351 possesses excellent blood-brain-barrier penetration with a higher drug concentration in the brain than that in plasma. In conclusion, BPI-221351 exhibits strong activity towards both IDH1 and IDH2 mutants in vitro and in vivo with favorable pharmacological properties, presenting a new therapeutic opportunity for treating glioma and other relevant cancers. Citation Format: Hongling Shen, Xiaofeng Xu, Yabin Li, Xizhen Song, Jie Chen, Yunting Bi, Jing Guo, Tong Xu, Huijuan Zhang, Lijia Liu, Zhengyao Zou, Jialin Ren, Jun Tong, Xiaoyun Liu, Hongfei Rong, Teng Ma, Chao Wang, Xiangyong Liu, Hong Chen, Jiayu Zhao, Xuepeng Ju, Haibo Chen, Haidi Shen, Hong Lan, Lieming Ding, Jiabing Wang. Discovery of BPI-221351, a potent, selective, orally available, and brain penetrating dual inhibitor of mutant IDH1/2 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 495.
    Type of Medium: Online Resource
    ISSN: 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2023-495
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2023
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 5
    Online Resource
    Online Resource
    Abstract 501: Discovery of BPI-460372, a potent and selective inhibitor of TEAD for the treatment of solid tumors harboring Hippo pathway aberrations
    American Association for Cancer Research (AACR) ; 2023
    In:  Cancer Research Vol. 83, No. 7_Supplement ( 2023-04-04), p. 501-501
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 83, No. 7_Supplement ( 2023-04-04), p. 501-501
    Abstract: The Hippo signaling pathway is critical for the regulation of organ development, tissue homeostasis, and tumorigenesis by controlling the activation status of yes-associated protein (YAP) or its homolog PDZ-binding motif (TAZ). As a major downstream effector, the transcription factor TEAD is activated by forming a complex with YAP/TAZ. Hippo pathway aberrations, such as NF2-deficiency or LATS1/2 mutations leading to hyperactivation of YAP/TAZ and subsequent activation of TEAD, have been reported in many cancers, including mesothelioma, meningioma, soft tissue sarcoma and non-small cell lung cancer. Inhibiting TEAD auto-palmitoylation by directly blocking the palmitoylation pocket of TEAD is a potential therapeutic approach for cancer treatment. Here we present BPI-460372, a novel small molecule that directly blocks the TEAD auto-palmitoylation. BPI-460372 covalently and irreversibly binds to the cysteine residue in the TEAD palmitoylation pocket, preventing TEAD palmitoylation and inhibiting its biological function. BPI-460372 significantly inhibits the expression of a TEAD-responsive element reporter, as well as the mRNA of downstream target genes such as CTGF and CYR61 in NF2-deficient cells. At the cellular level, BPI-460372 strongly inhibited the proliferation of tumor cells harboring Hippo pathway aberrations. BPI-460372 also significantly suppressed tumor growth in NF2-deficient or LATS1/2 mutation xenograft models. In addition, BPI-460372 exhibited excellent oral bioavailability, high exposure across multiple species, and adequate ADME properties. In conclusion, BPI-460372 is a potent and selective TEAD palmitoylation inhibitor for the treatment of solid tumors harboring Hippo pathway aberrations. It is planned to enter Phase I clinical trial in China in early 2023. Citation Format: Hongling Shen, Xiaofeng Xu, Hongfei Rong, Xizhen Song, Jinheng Gao, Jie Chen, Di Zhu, Xiangdong Zhao, Jun Tong, Zhengyao Zou, Xiaoyun Liu, Jin Guo, Yan Xu, Yabin Li, Xiangyong Liu, Hong Chen, Jiayu Zhao, Yanju Liu, Xuepeng Ju, Haibo Chen, Hong Lan, Lieming Ding, Jiabing Wang. Discovery of BPI-460372, a potent and selective inhibitor of TEAD for the treatment of solid tumors harboring Hippo pathway aberrations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 501.
    Type of Medium: Online Resource
    ISSN: 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2023-501
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2023
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 6
    Online Resource
    Online Resource
    Discovering influential factors in variational autoencoders
    Elsevier BV ; 2020
    In:  Pattern Recognition Vol. 100 ( 2020-04), p. 107166-
    Details
    In: Pattern Recognition, Elsevier BV, Vol. 100 ( 2020-04), p. 107166-
    Type of Medium: Online Resource
    ISSN: 0031-3203
    URL: Article
    DOI: 10.1016/j.patcog.2019.107166
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2020
    detail.hit.zdb_id: 1466343-0
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  • 7
    Online Resource
    Online Resource
    Comparison of performance, fatty acid composition, enzymes and gene expression between overfed Xupu geese with large and small liver
    Informa UK Limited ; 2021
    In:  Italian Journal of Animal Science Vol. 20, No. 1 ( 2021-01-01), p. 102-111
    Details
    In: Italian Journal of Animal Science, Informa UK Limited, Vol. 20, No. 1 ( 2021-01-01), p. 102-111
    Type of Medium: Online Resource
    ISSN: 1828-051X
    URL: Article
    DOI: 10.1080/1828051X.2021.1872423
    Language: English
    Publisher: Informa UK Limited
    Publication Date: 2021
    detail.hit.zdb_id: 2408994-1
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  • 8
    Online Resource
    Online Resource
    Environmental and economic sustainability in pricing strategy of carbon tax: application of environmental Kuznets curve and real options approach
    IOP Publishing ; 2021
    In:  IOP Conference Series: Earth and Environmental Science Vol. 865, No. 1 ( 2021-10-01), p. 012041-
    Details
    In: IOP Conference Series: Earth and Environmental Science, IOP Publishing, Vol. 865, No. 1 ( 2021-10-01), p. 012041-
    Type of Medium: Online Resource
    ISSN: 1755-1307 , 1755-1315
    URL: Article
    DOI: 10.1088/1755-1315/865/1/012041
    Language: Unknown
    Publisher: IOP Publishing
    Publication Date: 2021
    detail.hit.zdb_id: 2434538-6
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  • 9
    Online Resource
    Online Resource
    P‐21: Effects of Low Hydrogen Dielectric Film on a‐IGZO TFT Properties
    Wiley ; 2015
    In:  SID Symposium Digest of Technical Papers Vol. 46, No. 1 ( 2015-06), p. 1195-1197
    Details
    In: SID Symposium Digest of Technical Papers, Wiley, Vol. 46, No. 1 ( 2015-06), p. 1195-1197
    Abstract: Low hydrogen dielectric film deposition method was used in PECVD. The properties of amorphous IGZO (a‐IGZO) bottom‐gate thin film transistor using this method were investigated and compared. The PBTS (Positive Bias Temperature Stress) and NBTS (Negative Bias Temperature Stress) reduced to 0.481V, and ‐0.269V, respectively. The overall properties of a‐IGZO TFT using low hydrogen dielectric recipe meet the demand of oxide backplane in both LCD and OLED field.
    Type of Medium: Online Resource
    ISSN: 0097-966X , 2168-0159
    URL: Issue
    URL: Article
    DOI: 10.1002/sdtp.2015.46.issue-1
    DOI: 10.1002/sdtp.10055
    Language: English
    Publisher: Wiley
    Publication Date: 2015
    detail.hit.zdb_id: 2526337-7
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  • 10
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    Reduced-Order Observer-Based Preassigned Finite-Time Control of Nonlinear Systems and Its Applications
    Institute of Electrical and Electronics Engineers (IEEE) ; 2023
    In:  IEEE Transactions on Systems, Man, and Cybernetics: Systems Vol. 53, No. 7 ( 2023-7), p. 4205-4215
    Details
    In: IEEE Transactions on Systems, Man, and Cybernetics: Systems, Institute of Electrical and Electronics Engineers (IEEE), Vol. 53, No. 7 ( 2023-7), p. 4205-4215
    Type of Medium: Online Resource
    ISSN: 2168-2216 , 2168-2232
    URL: Article
    DOI: 10.1109/TSMC.2023.3241365
    Language: Unknown
    Publisher: Institute of Electrical and Electronics Engineers (IEEE)
    Publication Date: 2023
    detail.hit.zdb_id: 2696557-4
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