Publications by authors named "X Liu"

81,829 Publications

Design, synthesis, and biological evaluation of furosemide analogs as therapeutics for the proteopathy and immunopathy of Alzheimer's disease.

Eur J Med Chem 2021 Jun 2;222:113565. Epub 2021 Jun 2.

Krembil Research Institute, University Health Network, Toronto, Canada; Faculty of Pharmacy, University of Toronto, Ontario, Canada; Faculty of Medicine, University of Toronto, Ontario, Canada; Department of Chemistry, University of Toronto, Ontario, Canada. Electronic address:

β-Amyloid (Aβ) triggered proteopathic and immunopathic processes are a postulated cause of Alzheimer's disease (AD). Monomeric Aβ is derived from amyloid precursor protein, whereupon it aggregates into various assemblies, including oligomers and fibrils, which disrupt neuronal membrane integrity and induce cellular damage. Aβ is directly neurotoxic/synaptotoxic, but may also induce neuroinflammation through the concomitant activation of microglia. Previously, we have shown that furosemide is a known anthranilate-based drug with the capacity to downregulate the proinflammatory microglial M1 phenotype and upregulate the anti-inflammatory M2 phenotype. To further explore the pharmacologic effects of furosemide, this study reports a series of furosemide analogs that target both Aβ aggregation and neuroinflammation, thereby addressing the combined proteopathic-immunopathic pathogenesis of AD. Forty compounds were synthesized and evaluated. Compounds 3c, 3g, and 20 inhibited Aβ oligomerization; 33 and 34 inhibited Aβ fibrillization. 3g and 34 inhibited the production of TNF-α, IL-6, and nitric oxide, downregulated the expression of COX-2 and iNOS, and promoted microglial phagocytotic activity, suggesting dual activity against Aβ aggregation and neuroinflammation. Our data demonstrate the potential therapeutic utility of the furosemide-like anthranilate platform in the development of drug-like molecules targeting both the proteopathy and immunopathy of AD.
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http://dx.doi.org/10.1016/j.ejmech.2021.113565DOI Listing
June 2021

Identifying key areas of imbalanced supply and demand of ecosystem services at the urban agglomeration scale: A case study of the Fujian Delta in China.

Sci Total Environ 2021 Jun 5;791:148173. Epub 2021 Jun 5.

School of Architecture, Tianjin University, Tianjin 300072, China.

The coordinated supply and demand of ecosystem services (ESs) is important for ensuring regional sustainable development. However, research identifying key areas of imbalanced supply and demand of ESs at the urban agglomeration scale is limited. Therefore, in this study, using the Fujian Delta urban agglomeration of China as the research area, based on multi-source data, and analysis tools, such as ArcGIS, ENVI, and GeoDa, we constructed a research framework and indicator system for ESs supply and demand to determine the spatial change law, matching degree, and coupling coordination degree (CCD) of the ESs. On this basis, the key areas of imbalanced supply and demand of ESs were identified, and optimization strategies were proposed. The results showed that (1) there is obvious spatial heterogeneity between ESs supply and demand in the study area, and different degrees of spatial changes occurred with urbanization. Specifically, areas with large changes were concentrated in urban core areas and economic development zones. (2) The matching degree between ESs supply and demand is quite diverse and shows a trend of polarization. Under the influence of urbanization, some cities began facing ESs supply shortages. (3) Overall, the CCD between ESs supply and demand in the study area is in a state of mild incoordination, but with increasing urbanization, some cities have turned into a state of extreme incoordination. Our results indicate that the ESs supply and demand status in some cities at the urban agglomeration scale has become increasingly severe. Therefore, it is necessary to focus on certain "key areas" to formulate optimization strategies. For key areas with "low supply-high demand" and extreme incoordination, the population and land use intensity should be controlled to reduce the ESs demand level. Meanwhile, for key areas with "high supply-low demand" and extreme incoordination, the utilization efficiency of ecological resources should be improved to enhance the ESs supply capacity. The results of this study will help decision-makers optimize the relationship between ESs supply and demand in order to achieve the sustainable development of urban agglomeration.
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http://dx.doi.org/10.1016/j.scitotenv.2021.148173DOI Listing
June 2021

HIF-1α-activated TM4SF1-AS1 promotes the proliferation, migration, and invasion of hepatocellular carcinoma cells by enhancing TM4SF1 expression.

Biochem Biophys Res Commun 2021 Jun 9;566:80-86. Epub 2021 Jun 9.

The Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, 310014, China. Electronic address:

Long non-coding RNAs (lncRNAs) are essential drivers or suppressors in human hepatocellular carcinoma (HCC) by participating in controlling transcription, translation, mRNA stability, and protein degradation protein-protein interaction. TM4SF1-AS1 is recently identified as a tumor-promoting factor in lung cancer. Nevertheless, its function in HCC and related molecular mechanisms remain unknown. Here, our data indicated that either hypoxia or hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitor (DMOG) induced the upregulation of TM4SF1-AS1 in HCC cells. HIF-1α knockdown rather than HIF-2α silencing remarkably abrogated hypoxia-upregulated TM4SF1-AS1 expression. Furthermore, we confirmed the elevated expression of TM4SF1-AS1 in HCC tissue samples and cell lines. The silencing of TM4SF1-AS1 prominently inhibited the proliferative, migratory, and invasive abilities of HCC cells. TM4SF1-AS1 depletion significantly blocked hypoxia-enhanced Hep3B cell proliferation and mobility. Interfering TM4SF1-AS1 remarkably reduced TM4SF1 mRNA and protein levels in HCC cells. But TM4SF1-AS1 knockdown did not impact the stability of TM4SF1 mRNA. Hypoxia enhanced the expression of TM4SF1 mRNA, which was subsequently decreased by TM4SF1-AS1 knockdown in HCC cells. We confirmed the positive correlation between TM4SF1 mRNA and TM4SF1-AS1 expression in HCC specimens. Finally, TM4SF1 prominently reversed the inhibitory role of TM4SF1-AS1 depletion in Hep3B cells. In summary, hypoxia-responsive TM4SF1-AS1 was overexpressed in human HCC and contributed to the malignant behaviors of tumor cells by enhancing TM4SF1-AS1 expression.
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http://dx.doi.org/10.1016/j.bbrc.2021.06.011DOI Listing
June 2021

Microwave-enhanced reductive immobilization of high concentrations of chromium in a field soil using iron polysulfide.

J Hazard Mater 2021 Jun 3;418:126293. Epub 2021 Jun 3.

School of Environment and Energy, Guangdong Provincial Key Laboratory of Solid Wastes Pollution Control and Resource Recycling, South China University of Technology, Guangzhou 510006, China; School of Metallurgy and Environment, Central South University, Changsha 410083, China.

High concentrations of Cr(VI) are often detected in contaminated soil. Yet, cost-effective remediation technologies have been lacking. In this study, we prepared a type of FeS based on commercial FeSO.7HO and CaS and tested a microwave-assisted technology based on FeS for reductive immobilization of high concentrations of Cr(VI) in a field contaminated soil. The as-prepared FeS particles appeared as a honeycomb-like and highly porous structure. The microwave-assisted FeS reduction process was able to rapidly reduce the TCLP-based reachability of Cr(VI) from 391.8 to 2.6 mg·L. The dosage of FeS, S/Fe molar ratio, initial moisture content, microwave power, and irradiation time can all affect the treatment effectiveness. After 500 days curing under atmospheric conditions, the TCLP-leached concentration of Cr remained below the regulatory limit of 5 mg·L, while other treatments failed to meet the goal. S or S served as the primary electron donors, whereas Fe facilitated the microwave absorption and the formation of the stable final product of FeCrO. S and Fe are mostly precipitated in soil. The microwave-assisted FeS reduction was shown to be an effective approach to rapidly reduce the leachability of Cr(VI) in contaminated soil, especially in heavily contaminated soil.
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http://dx.doi.org/10.1016/j.jhazmat.2021.126293DOI Listing
June 2021

Co-benefits of biochar-supported nanoscale zero-valent iron in simultaneously stabilizing soil heavy metals and reducing their bioaccessibility.

J Hazard Mater 2021 Jun 6;418:126292. Epub 2021 Jun 6.

College of Environmental & Resource Sciences, Zhejiang Provincial Key Laboratory of Agricultural Resources and Environment, Zhejiang University, Hangzhou 310058, China. Electronic address:

We investigated the performance and encapsulation mechanisms of novel biochar-supported nanoscale zero-valent iron (nZVI-BC) used for the remediation of soil co-contaminated with arsenic (As), cadmium (Cd), and lead (Pb) via incubation and column experiments. Compared with the control, 0.50% of nZVI-BC significantly decreased the leakage of As, Cd, and Pb by 97.94-98.45%, 42.86-81.12%, and 82.14-92.49%, respectively. In addition, 0.50% of nZVI-BC could transform the fraction of unstable heavy metals into a stable form, which substantially decreased the availability, leachability, and bioaccessibility of the heavy metals and hence greatly reduced the human health exposure risk. Column experiments showed that 0.50% of nZVI-BC effectively restrained the leaching of As, Cd, and Pb by 95.60-99.84%, 70.82-84.18%, and 91.68-99.81%, respectively. The predominant encapsulation mechanisms of nZVI-BC included complexation, precipitation/co-precipitation, reduction, and the formation of ternary surface complexes. Based on these insights, we can devise new strategies for the remediation of soil co-contaminated with As, Cd, and Pb.
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http://dx.doi.org/10.1016/j.jhazmat.2021.126292DOI Listing
June 2021