Publications by authors named "Z Y Zhang"

65,648 Publications

Design, synthesis and biological evaluation of novel benzofuran derivatives as potent LSD1 inhibitors.

Eur J Med Chem 2021 Apr 24;220:113501. Epub 2021 Apr 24.

Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang, 110016, Liaoning, China.

Lysine-specific demethylase 1 (LSD1) is a FAD-dependent enzyme, which has been proposed as a promising target for therapeutic cancer. Herein, a series of benzofuran derivatives were designed, synthesized and biochemical evaluated as novel LSD1 inhibitors based on scaffold hopping and conformational restriction strategy. Most of the compounds potently suppressed the enzymatic activities of LSD1 and potently inhibited tumor cells proliferation. In particular, the representative compound 17i exhibited excellent LSD1 inhibition at the molecular levels with IC = 0.065 μM, as well as anti-proliferation against MCF-7, MGC-803, H460, A549 and THP-1 tumor cells with IC values of 2.90 ± 0.32, 5.85 ± 0.35, 2.06 ± 0.27, 5.74 ± 1.03 and 6.15 ± 0.49 μM, respectively. The binding modes of these compounds were rationalized by molecular docking. Meanwhile, a preliminary druggability evaluation showed that compound 17i displayed favorable liver microsomal stability and weak inhibitory activity against CYPs at 10 μM. Remarkably, H460 xenograft tumors studies revealed that 17i demonstrated robust in vivo antitumor efficacy without significant side effects. All the results demonstrated that compound 17i could represent a promising lead for further development.
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http://dx.doi.org/10.1016/j.ejmech.2021.113501DOI Listing
April 2021

Electrospun cobalt Prussian blue analogue-derived nanofibers for oxygen reduction reaction and lithium-ion batteries.

J Colloid Interface Sci 2021 Apr 21;599:280-290. Epub 2021 Apr 21.

School of Applied Physics and Materials, Wuyi University, Jiangmen, China; Key Laboratory for Liquid-Solid Structural Evolution and Processing of Materials (Ministry of Education), School of Materials Science and Engineering, Shandong University, Jinan, China. Electronic address:

Electrospinning is an effective technique to fabricate one-dimensional materials. In this study, cobalt-embedded carbon nanofibers (Co@CNFs) are obtained via carbonization of electrospun cobalt Prussian blue analogue (Co-Co PBA) under nitrogen atmosphere. The Co@CNFs have metallic cobalt surrounded by graphitic carbon shells and possess high specific surface area, rich porosity, high graphitic degree, and rational nitrogen doping. The structure merits endow them with excellent electrocatalytic performances for oxygen reduction reaction (ORR): an onset potential of 0.867 V vs. RHE and 0.784 V vs. RHE at j =  - 3 mA cm with a four-electron transfer process. Through a further mild oxidation process, we obtain CoO nanoparticles-embedded nitrogen-doped carbon (CoO@CNFs) with spindle-like morphology. When working as the anode materials for lithium-ion batteries (LIBs), CoO@CNFs show high specific capacity, good stability, and excellent rate capability. The CoO@CNFs anode delivers a discharge specific capacity of 1404 mA h g after 100 cycles at a current density of 100 mA g and about 500 mA h g after 500 cycles at 2000 mA g. The diffusion- and capacitive-controlled processes both contribute to the charge storage of the CoO@CNFs electrode. This study provides a new strategy to fabricate the excellent electrocatalysts for ORR and anode materials for LIBs via facile electrospinning.
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http://dx.doi.org/10.1016/j.jcis.2021.04.102DOI Listing
April 2021

Perineuronal net abnormalities in Slc13a4 mice are rescued by postnatal administration of N-acetylcysteine.

Exp Neurol 2021 May 1:113734. Epub 2021 May 1.

The School of Biomedical Sciences, The University of Queensland, Brisbane, QLD 4072, Australia; Queensland Brain Institute, The University of Queensland, Brisbane, QLD 4072, Australia. Electronic address:

Disruptions to either sulfate supply or sulfation enzymes can affect brain development and have long-lasting effects on brain function, yet our understanding of the molecular mechanisms governing this are incomplete. Perineuronal nets (PNNs) are highly sulfated, specialized extracellular matrix structures that regulate the maturation of synaptic connections and neuronal plasticity. We have previously shown that mice heterozygous for the brain sulfate transporter Slc13a4 have abnormal social interactions, memory, exploratory behaviors, stress and anxiety of postnatal origin, pointing to potential deficits in PNN biology, and implicate SLC13A4 as a critical factor required for regulating normal synaptic connectivity and function. Here, we sought to investigate aberrant PNN formation as a potential mechanism contributing to the functional deficits displayed by Slc13a4 mice. Following social interactions, we reveal reduced neuronal activation in the somatosensory cortex of Slc13a4 mice, and altered inhibitory and excitatory postsynaptic currents. In line with this, we found a reduction in parvalbumin-expressing neurons decorated with PNNs, as well as reduced expression of markers for PNN maturation. Finally, we reveal that postnatal administration of N-acetylcysteine prevented PNN abnormalities from manifesting in Slc13a4 adult animals. Collectively, these data highlight a central role for postnatal SLC13A4 in normal PNN formation, circuit function and subsequent animal behavior.
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http://dx.doi.org/10.1016/j.expneurol.2021.113734DOI Listing
May 2021

Activation of TOR signaling by diverse nitrogen signals in plants.

Dev Cell 2021 May;56(9):1213-1214

Department of Plant Biology, Carnegie Institution for Science, Stanford, CA 94305, USA. Electronic address:

Growth control in eukaryotes depends on the TOR kinase, which integrates energy and nutrient signals. In this issue of Developmental Cell, Liu et al. demonstrate that, in plants, inorganic nitrogen and amino acids activate TOR via the GTPase ROP2 to promote cell proliferation and leaf growth in the shoot.
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http://dx.doi.org/10.1016/j.devcel.2021.04.014DOI Listing
May 2021

Sex differences in the longitudinal relationship of low-grade inflammation and echocardiographic measures in the Hoorn and FLEMENGHO Study.

PLoS One 2021 4;16(5):e0251148. Epub 2021 May 4.

Department of Epidemiology & Data Science, Amsterdam UMC, Amsterdam Cardiovascular Sciences, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.

Background: This study aimed to determine the within-person and between-persons associations of low-grade inflammation (LGI) and endothelial dysfunction (ED) with echocardiographic measures related to diastolic dysfunction (DD) in two general populations and whether these associations differed by sex.

Methods: Biomarkers and echocardiographic measures were measured at both baseline and follow-up in the Hoorn Study (n = 383) and FLEMENGHO (n = 491). Individual biomarker levels were combined into either a Z-score of LGI (CRP, SAA, IL-6, IL-8, TNF-α and sICAM-1) or ED (sICAM-1, sVCAM-1, sE-selectin and sTM). Mixed models were used to determine within-person and between-persons associations of biomarker Z-scores with left ventricular ejection fraction (LVEF), left ventricular mass index (LVMI) and left atrial volume index (LAVI). These associations were adjusted for a-priori selected confounders.

Results: Overall Z-scores for LGI or ED were not associated with echocardiographic measures. Effect modification by sex was apparent for ED with LVEF in both cohorts (P-for interaction = 0.08 and 0.06), but stratified results were not consistent. Effect modification by sex was apparent for TNF-α in the Hoorn Study and E-selectin in FLEMENGHO with LVEF (P-for interaction≤0.05). In the Hoorn Study, women whose TNF-α levels increased with 1-SD over time had a decrease in LVEF of 2.2 (-4.5;0.01) %. In FLEMENGHO, men whose E-selectin levels increased with 1-SD over time had a decrease in LVEF of 1.6 (-2.7;-0.5) %.

Conclusion: Our study did not show consistent associations of LGI and ED with echocardiographic measures. Some evidence of effect modification by sex was present for ED and specific biomarkers.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0251148PLOS
May 2021