Publications by authors named "Wei Ai"

51 Publications

A stable and ultrafast K ion storage anode based on phase-engineered MoSe.

Chem Commun (Camb) 2021 Apr 22;57(32):3885-3888. Epub 2021 Mar 22.

Frontiers Science Center for Flexible Electronics, Xi'an Institute of Flexible Electronics (IFE) and Xi'an Institute of Biomedical Materials & Engineering, Northwestern Polytechnical University, 127 West Youyi Road, Xi'an 710072, China. and Key Laboratory of Flexible Electronics (KLOFE) & Institute of Advanced Materials (IAM), Jiangsu National Synergetic Innovation Center for Advanced Materials (SICAM), Nanjing Tech University (NanjingTech), 30 South Puzhu Road, Nanjing 211816, China and Key Laboratory for Organic Electronics & Information Displays (KLOEID) and Institute of Advanced Materials (IAM), SICAM, Nanjing University of Posts & Telecommunications, Nanjing 210023, China.

Potassium-ion batteries (PIBs) are attracting increasing attention due to the abundance of K resources, but the sluggish kinetics and inferior cycling stability of anodes still hinder their application. Herein, we present a hybrid 1T/2H phase MoSe anode, which shows noticeable pseudocapacitive response and fast kinetics for K storage. Correspondingly, superior electrochemical performances including a high reversible capacity of 440 mA h g after 100 cycles at 0.1 A g and superb rate capacity of 211 mA h g at 20.0 A g are achieved. We believe this work may shed light on the phase engineering of transition metal compounds for rapid charging PIBs.
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http://dx.doi.org/10.1039/d1cc00341kDOI Listing
April 2021

Nrf2 epigenetic derepression induced by running exercise protects against osteoporosis.

Bone Res 2021 Feb 26;9(1):15. Epub 2021 Feb 26.

Center for Organ Fibrosis and Remodeling Research, Jiangsu Key Lab of Molecular Medicine, Nanjing University Medical School, Nanjing, 210093, China.

Osteoporosis (OP) is a common skeletal disease involving low bone mineral density (BMD) that often leads to fragility fracture, and its development is affected by multiple cellular pathologies and associated with marked epigenetic alterations of osteogenic genes. Proper physical exercise is beneficial for bone health and OP and reportedly possesses epigenetic modulating capacities; however, whether the protective effects of exercise on OP involve epigenetic mechanisms is unclear. Here, we report that epigenetic derepression of nuclear factor erythroid derived 2-related factor-2 (Nrf2), a master regulator of oxidative stress critically involved in the pathogenesis of OP, mediates the significant osteoprotective effects of running exercise (RE) in a mouse model of OP induced by ovariectomy. We showed that Nrf2 gene knockout (Nfe2l2) ovariectomized mice displayed a worse BMD reduction than the controls, identifying Nrf2 as a critical antiosteoporotic factor. Further, femoral Nrf2 was markedly repressed with concomitant DNA methyltransferase (Dnmt) 1/Dnmt3a/Dnmt3b elevations and Nrf2 promoter hypermethylation in both patients with OP and ovariectomized mice. However, daily 1-h treadmill RE significantly corrected epigenetic alterations, recovered Nrf2 loss and improved the femur bone mass and trabecular microstructure. Consistently, RE also normalized the adverse expression of major osteogenic factors, including osteoblast/osteoclast markers, Nrf2 downstream antioxidant enzymes and proinflammatory cytokines. More importantly, the RE-conferred osteoprotective effects observed in the wild-type control mice were largely abolished in the Nfe2l2 mice. Thus, Nrf2 repression due to aberrant Dnmt elevation and subsequent Nrf2 promoter hypermethylation is likely an important epigenetic feature of the pathogenesis of OP, and Nrf2 derepression is essential for the antiosteoporotic effects of RE.
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http://dx.doi.org/10.1038/s41413-020-00128-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7910611PMC
February 2021

Kinetically Controlled, Scalable Synthesis of γ-FeOOH Nanosheet Arrays on Nickel Foam toward Efficient Oxygen Evolution: The Key Role of In-Situ-Generated γ-NiOOH.

Adv Mater 2021 Mar 10;33(11):e2005587. Epub 2021 Feb 10.

Frontiers Science Center for Flexible Electronics, Xi'an Institute of Flexible Electronics (IFE) and Xi'an Institute of Biomedical Materials & Engineering, Northwestern Polytechnical University, 127 West Youyi Road, Xi'an, 710072, China.

Layered γ-type iron oxyhydroxide (γ-FeOOH) is a promising material for various applications; however, its sheet-shaped structure often suffers from instability that results in aggregation and leads to inferior performance. Herein, a kinetically controlled hydrolysis strategy is proposed for the scalable synthesis of γ-FeOOH nanosheets arrays (NAs) with enhanced structural stability on diverse substrates at ambient conditions. The underlying mechanisms for the growth of γ-FeOOH NAs associated with their structural evolution are systematically elucidated by alkalinity-controlled synthesis and time-dependent experiments. As a proof-of-concept application, γ-FeOOH NAs are developed as electrocatalysts for the oxygen evolution reaction (OER), where the sample grown on nickel foam (NF) exhibits superior performance of high catalytic current density, small Tafel slope, and exceptional durability, which is among the top level of FeOOH-based electrocatalysts. Density functional theory calculations suggest that γ-NiOOH in situ generated from the electrooxidation of NF would induce charge accumulation on the Fe sites of γ-FeOOH NAs, leading to enhanced OER intermediates adsorption for water splitting. This work affords a new technique to rationally design and synthesize γ-FeOOH NAs for various applications.
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http://dx.doi.org/10.1002/adma.202005587DOI Listing
March 2021

State-Of-The-Art and Future Challenges in High Energy Lithium-Selenium Batteries.

Adv Mater 2021 Mar 25;33(10):e2003845. Epub 2021 Jan 25.

Frontiers Science Center for Flexible Electronics, Xi'an Institute of Flexible Electronics (IFE) and Xi'an Institute of Biomedical Materials & Engineering, Northwestern Polytechnical University (NPU), 127 West Youyi Road, Xi'an, 710072, China.

Li-chalcogen batteries, especially the Li-S batteries (LSBs), have received paramount interests as next generation energy storage techniques because of their high theoretical energy densities. However, the associated challenges need to be overcome prior to their commercialization. Elemental selenium, another chalcogen member, would be an attractive alternative to sulfur owing to its higher electronic conductivity, comparable capacity density, and moreover, excellent compatibility with carbonate electrolytes. Unlike LSBs, the research and development of Li-Se batteries (LSeBs) have garnered burgeoning attention but are still in their infant stage, where a comprehensive yet in-depth overview is highly imperative to guide future research. Herein, a critical review of LSeBs, in terms of the underlying mechanisms, cathode design, blocking layer engineering, and emerging solid-state electrolytes is provided. First, the electrolyte-dependent electrochemistry of LSeBs is discussed. Second, the advances in Se-based cathodes are comprehensively summarized, especially highlighting the state-of-the-art Se S cathodes, and mainly focusing on their structures, compositions, and synthetic strategies. Third, the versatile separators/interlayers optimization and interface regulation are outlined, with a particular focus on the emerging solid-state electrolytes for advanced LSeBs. Last, the remaining challenges and research orientations in this booming field are proposed, which are expected to motivate more insightful works.
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http://dx.doi.org/10.1002/adma.202003845DOI Listing
March 2021

Discovery of highly potent and selective influenza virus neuraminidase inhibitors targeting 150-cavity.

Eur J Med Chem 2021 Feb 13;212:113097. Epub 2020 Dec 13.

Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 44 West Culture Road, 250012, Jinan, Shandong, PR China; China-Belgium Collaborative Research Center for Innovative Antiviral Drugs of Shandong Province, 44 West Culture Road, 250012, Jinan, Shandong, PR China. Electronic address:

Encouraged by our earlier discovery of N1-selective inhibitors, the 150-cavity of influenza virus neuraminidases (NAs) could be further exploited to yield more potent oseltamivir derivatives. Herein, we report the design, synthesis and biological evaluation of a series of novel oseltamivir derivatives via the structural modifications at C-NH of oseltamivir targeting 150-cavity. Among them, compound 5c bearing 4-(3-methoxybenzyloxy)benzyl group exhibited the most potent activity, which was lower or modestly improved activities than oseltamivir carboxylate (OSC) against N1 (H1N1), N1 (H5N1) and N1 (H5N1-H274Y). Specifically, there was 30-fold loss of activity against the wild-type strain H1N1. However, 5c displayed 4.85-fold more potent activity than OSC against H5N1-H274Y NA. Also, 5c demonstrated low cytotoxicity in vitro and no acute toxicity in mice. Molecular docking studies provided insights into the high potency of 5c against N1 and N1-H274Y mutant NAs. Besides, the in silico prediction of physicochemical properties and CYP enzymatic inhibitory ability of representative compounds were conducted to evaluate their drug-like properties.
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http://dx.doi.org/10.1016/j.ejmech.2020.113097DOI Listing
February 2021

Optimization of the pre-tension and separation distance for measurement of the dynamic elastic modulus and macromolecular orientation of a polypropylene monofilament via the sonic velocity method.

Rev Sci Instrum 2020 Dec;91(12):123906

State Key Laboratory of New Textile Materials and Advanced Processing Technologies, Wuhan Textile University, Wuhan, Hubei 430200, People's Republic of China.

Using a fiber orientation degree measurement instrument (i.e., a dynamic modulus tester), 28 groups of averaged sonic pulse travel times in a polypropylene monofilament were measured and recorded under five pre-tensions across eight separation distances. The zero-time (or delay time) T, sonic velocity C, sonic modulus E, Hermans orientation factor F, and orientation angle θ were calculated via two- and multi-point methods. The good agreement observed between the scatter plots of calculated data and the regression lines shows that the multi-point method provides reliable, accurate determination of the sonic modulus (or the dynamic elastic modulus) and the orientation parameters. Surprisingly, the zero-time for sonic pulse propagation depends significantly on the separation distance in practice, although it does not in theory. For easy and rapid measurement or relative comparisons using the two-point method, the optimal range of pre-tension is 0.1 gf/den-0.2 gf/den, and the optimal separation distances are 200 mm and 400 mm. The two-point method is appropriate for industrial applications, while because of its greater accuracy, the multi-point method is preferred for scientific research.
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http://dx.doi.org/10.1063/5.0006731DOI Listing
December 2020

Histone deacetylase 3 aberration inhibits Klotho transcription and promotes renal fibrosis.

Cell Death Differ 2021 Mar 6;28(3):1001-1012. Epub 2020 Oct 6.

Center of Organ Fibrosis and Remodeling, Jiangsu Key Lab of Molecular Medicine, Nanjing University School of Medicine, Nanjing, China.

Development of renal fibrosis is a hallmark of renal aging and chronic kidney disease of all etiologies and characterized by extensive renal cell injuries and subsequent myofibroblast transdifferentiations (MTDs), which are significantly influenced by aberrant histone deacetylase (HDAC) activities. However, the key HDAC isoforms and effectors that are causally involved in the processes remain poorly understood. Here, we report that aberrant HDAC3 induction and its inhibition of Klotho, a renal epithelium-enriched aging suppressor, contribute significantly to renal fibrogenesis. HDAC3 was preferentially elevated with concomitant Klotho suppression in fibrotic kidneys incurred by unilateral ureter obstruction (UUO) and aristolochic acid nephropathy (AAN), whereas Hdac3 knockout resisted the fibrotic pathologies. The HDAC3 elevation is substantially blocked by the inhibitors of TGFβ receptor and Smad3 phosphorylation, suggesting that TGFβ/Smad signal activates Hdac3 transcription. Consistently, an HDAC3-selective inhibitor RGFP966 derepressed Klotho and mitigated the renal fibrotic injuries in both UUO and AAN mice. Further, HDAC3 overexpression or inhibition in renal epithelia inversely affected Klotho abundances and HDAC3 was inducibly associated with transcription regulators NCoR and NF-kB and bound to Klotho promoter in fibrotic kidney, supporting that aberrant HDAC3 targets and transcriptionally inhibits Klotho under renal fibrotic conditions. More importantly, the antirenal fibrosis effects of RGFP966 were largely compromised in mice with siRNA-mediated Klotho knockdown. Hence, HDAC3 aberration and the subsequent Klotho suppression constitute an important regulatory loop that promotes MTD and renal fibrosis and uses of HDAC3-selective inhibitors are potentially effective in treating renal fibrotic disorders.
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http://dx.doi.org/10.1038/s41418-020-00631-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937860PMC
March 2021

Assessment of the Contrast-Enhanced Ultrasound in Percutaneous Nephrolithotomy for the Treatment of Patients with Nondilated Collecting System.

J Endourol 2021 Apr 30;35(4):436-443. Epub 2020 Oct 30.

Department of Urology, The Second People's Hospital of China Three Gorges University, The Second People's Hospital of Yichang, Yichang, China.

To investigate the clinical value of contrast-enhanced ultrasound (CEUS) in percutaneous nephrolithotomy (PCNL) for kidney stone patients without hydronephrosis. Patients with nondilated collecting system kidney stones who underwent PCNL between October 2018 and December 2019 at our hospital were enrolled in this study. Patients who met the inclusion criteria were randomized into two groups: a CEUS-guided PCNL group and a conventional ultrasound (US)-guided PCNL group. The operation results of the two groups were compared, including the number of attempts for effective puncture, duration to effective puncture, stone clearance rate, blood loss, postoperative complications, and hospital stay. Fifty-six patients with a nondilated collecting system who underwent PCNL for 60 kidneys were included in this study, including 4 patients who underwent bilateral PCNL due to bilateral renal stones. There were 30 kidneys in each group. All patients successfully underwent PCNL. The CEUS-guided PCNL group had more accurate punctures, with a higher effective rate of one puncture and shorter puncture time. There was no statistically significant difference in stone clearance rate between the two groups. Four cases of double channels were established in the conventional US-guided PCNL group, while there was only one case in the CEUS-guided PCNL group. In the CEUS-guided PCNL group, most cases (96.7%, 29/30) had no or only mild complications, which were significantly better than the conventional US-guided PCNL group (76.7%, 23/30). The mean postoperative hemoglobin loss in the CEUS-guided PCNL group was 9.5 (range 1-25) g/L, which was significantly lower than 15.5 (range 5-52) g/L in the conventional US-guided PCNL group. The CEUS technique can improve visibility of the nondilated renal collecting system, facilitate selection of suitable calix, and identify renal calix fornix. It also benefits needle placement in patients with a nondilated collecting system.
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http://dx.doi.org/10.1089/end.2020.0564DOI Listing
April 2021

Novel Human Urate Transporter 1 Inhibitors as Hypouricemic Drug Candidates with Favorable Druggability.

J Med Chem 2020 10 21;63(19):10829-10854. Epub 2020 Sep 21.

Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 44 West Culture Road, 250012 Jinan, Shandong, PR China.

Lesinurad, a human urate transporter 1 (URAT1) inhibitor approved as a medication for the treatment of hyperuricemia associated with gout in 2015, can cause liver and renal toxicity. Here, we modified all three structural components of lesinurad by applying scaffold hopping, bioisosterism, and substituent-decorating strategies. In a mouse model of acute hyperuricemia, 21 of the synthesized compounds showed increased serum uric acid (SUA)-reducing activity; SUA was about 4-fold lower in animals treated with , , and compared with lesinurad or benzbromarone. In the URAT1 inhibition assay, was over 8-fold more potent than lesinurad (IC: 1.57 μM 13.21 μM). Notably, also displayed potent inhibitory activity (IC = 31.73 μM) against GLUT9. Furthermore, we also preliminarily explored the effect of chirality on the potency of the promising derivatives and . Compounds , , and showed favorable drug-like pharmacokinetics and appear to be promising candidates for the treatment of hyperuricemia and gout.
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http://dx.doi.org/10.1021/acs.jmedchem.0c00223DOI Listing
October 2020

High-performance sodium-ion anodes enabled by a low-temperature molten salt approach.

Chem Commun (Camb) 2020 Sep;56(77):11422-11425

Frontiers Science Center for Flexible Electronics (FSCFE), Shaanxi Institute of Flexible Electronics (SIFE) & Shaanxi Institute of Biomedical Materials and Engineering (SIBME), Northwestern Polytechnical University (NPU), 127 West Youyi Road, Xi'an 710072, China.

A low-temperature doping approach has been developed for fabricating nitrogen and sulfur co-doped few-layer graphene (NS-FLG) by annealing graphene oxide in KSCN molten salt at 175 °C. The as-prepared NS-FLG with a high doping level and unique few-layer structure delivers remarkable performance for sodium-ion batteries (SIBs) in terms of a high reversible capacity of 325.4 mA h g-1 at 0.5 A g-1, a superb rate capacity of 203.6 mA h g-1 at 10 A g-1, and ultra-long cyclability over 5100 cycles. This work provides a new avenue for exploring advanced graphene-based materials towards SIBs and even other electrochemical fields.
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http://dx.doi.org/10.1039/d0cc04112bDOI Listing
September 2020

Lychee seed polyphenol inhibits Aβ-induced activation of NLRP3 inflammasome via the LRP1/AMPK mediated autophagy induction.

Biomed Pharmacother 2020 Oct 5;130:110575. Epub 2020 Aug 5.

Sichuan Key Medical Laboratory of New Drug Discovery and Druggability Evaluation, Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia Medica, School of Pharmacy, Ministry of Education & Medical Electrophysiological Key Laboratory of Sichuan Province, Southwest Medical University, Luzhou, 646000, China; Education Ministry Key Laboratory of Medical Electrophysiology, Southwest Medical University, Luzhou, 646000, China. Electronic address:

Emerging evidence indicates that the enhancement of microglial autophagy inhibits the NLRP3 inflammasome mediated neuroinflammation in Alzheimer's disease (AD). Meanwhile, low density lipoprotein receptor-related protein 1 (LRP1) highly expressed in microglia is able to negatively regulate neuroinflammation and positively regulate autophagy. In addition, we have previously reported that an active lychee seed fraction enriching polyphenol (LSP) exhibits anti-neuroinflammation in Aβ-induced BV-2 cells. However, its molecular mechanism of action is still unclear. In this study, we aim to investigate whether LSP inhibits the NLRP3 inflammasome mediated neuroinflammation and clarify its molecular mechanism in Aβ-induced BV-2 cells and APP/PS1 mice. The results showed that LSP dose- and time-dependently activated autophagy by increasing the expression of Beclin 1 and LC3II in BV-2 cells, which was regulated by the upregulation of LRP1 and its mediated AMPK signaling pathway. In addition, both the Western blotting and fluorescence microscopic results demonstrated that LSP could significantly suppress the activation of NLRP3 inflammasome by inhibiting the expression of NLRP3, ASC, the cleavage of caspase-1, and the release of IL-1β in Aβ(1-42)-induced BV-2 cells. In addition, the siRNA LRP1 successfully abolished the effect of LSP on the activation of AMPK and its mediated autophagy, as well as the inhibition of NLRP3 inflammasome. Furthermore, LSP rescued PC-12 cells which were induced by the conditioned medium from Aβ(1-42)-treated BV-2 cells. Moreover, LSP improved the cognitive function and inhibited the NLRP3 inflammasome in APP/PS1 mice. Taken together, LSP inhibited the NLRP3 inflammasome-mediated neuroinflammation in the in vitro and in vivo models of AD, which was closely associated with the LRP1/AMPK-mediated autophagy. Thus, the findings from this study further provide evidences for LSP serving as a potential drug for the treatment of AD in the future.
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http://dx.doi.org/10.1016/j.biopha.2020.110575DOI Listing
October 2020

Enhancing PPARγ by HDAC inhibition reduces foam cell formation and atherosclerosis in ApoE deficient mice.

Pharmacol Res 2020 10 1;160:105059. Epub 2020 Jul 1.

Center for Organ Fibrosis and Remodeling, Jiangsu Key Lab of Molecular Medicine, Nanjing University Medical School, Nanjing, 210093, China. Electronic address:

Atherosclerosis (AS) is a risky cardiovascular disease with limited treatment options. Various pan or type-selective histone deacetylase (HDAC) inhibitors are reportedly atheroprotective against atherosclerosis (AS); however, the key effectors and the main cellular processes that mediate the protective effects remain poorly defined. Here, we report that PPARγ (Peroxisome proliferator-activated receptor gamma), a transcription factor actively involved in lipid metabolism with strong tissue protective and anti-inflammation properties, is a critical mediator of the anti-AS effects by HDAC inhibition. We showed that a well-known pan-HDAC inhibitor TSA (Trichostatin A) reduced foam cell formation of macrophages that is accompanied by a marked elevation of PPARγ and its downstream cholesterol efflux transporter ABCA1 (ATP-binding membrane cassette transport protein A1) and ABCG1. In an AS model of ApoE mice fed on high-fat diet, TSA treatment alleviated AS lesions, similarly increased PPARγ and the downstream cholesterol transporters and mitigated the induction of inflammatory cytokine TNFα and IL-1β. Exploring the potential cause of PPARγ elevation revealed that TSA induced the acetylation of C/EBPα (CCAAT enhancer binding protein alpha), the upstream regulator of PPARγ, through which it increased PPARγ transactivation. More importantly, we generated a strain of PPARγ/ApoE double knockout mice and demonstrated that lack of PPARγ abrogated the protective effects of TSA on foam cell formation of peritoneal macrophages and the AS pathogenesis. Taken together, these results unravel that C/EBPα and PPARγ are the HDAC-sensitive components of an epigenetic signaling pathway mediating foam cell formation and AS development, and suggest that targeting C/EBPα/PPARγ axis by HDAC inhibitors possesses therapeutic potentials in retarding the progression of AS and the related cardiovascular diseases.
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http://dx.doi.org/10.1016/j.phrs.2020.105059DOI Listing
October 2020

Ceftazidime-related urinary calculi in a young boy: a case report.

J Int Med Res 2020 Apr;48(4):300060520921667

Department of Urology, Second People's Hospital of Yichang, Second People's Hospital of China Three Gorges University, Yichang, Hubei, China.

Certain drugs can cause kidney stones but as far as we are aware, ceftazidime-related urinary calculi have not been previously reported. We report here a case of an 8-year-old boy who developed hydronephrosis secondary to urinary calculi after receiving ceftazidime 2.0 g by intravenous infusion daily for two weeks. Previously, his left kidney showed no signs of disease. A retrograde double J ureteral stent was inserted, ceftazidime terminated, fluids increased and urine alkalised. On day 25, the patient showed no signs of kidney stones or hydronephrosis. Clinicians should be aware of the possibility of ceftazidime-related urinary calculi particularly if patients are receiving long-term treatment.
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http://dx.doi.org/10.1177/0300060520921667DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7223203PMC
April 2020

Low-temperature molten salt synthesis of MoS@CoS heterostructures for efficient hydrogen evolution reaction.

Chem Commun (Camb) 2020 May;56(41):5548-5551

Frontiers Science Center for Flexible Electronics (FSCFE), Shaanxi Institute of Flexible Electronics (SIFE) & Shaanxi Institute of Biomedical Materials and Engineering (SIBME), Northwestern Polytechnical University (NPU), 127 West Youyi Road, Xi'an 710072, China. and Key Laboratory for Organic Electronics & Information Displays (KLOEID) and Institute of Advanced Materials (IAM), SICAM, Nanjing University of Posts & Telecommunications, Nanjing 210023, Jiangsu, China and Key Laboratory of Flexible Electronics (KLOFE) & Institute of Advanced Materials (IAM), Jiangsu National Synergetic Innovation Center for Advanced Materials (SICAM), Nanjing Tech University (NanjingTech), 30 South Puzhu Road, Nanjing 211816, China.

A versatile low-temperature molten salt approach has been developed for fabricating a MoS2@CoS2 heterostructure electrocatalyst, where low-cost molten KSCN serves as both the reaction medium and sulfur source. The as-obtained electrocatalyst with a defect-rich structure is highly efficient for the hydrogen evolution reaction (HER), delivering a low overpotential of 96 mV at an HER current density of 10 mA cm-2, a small Tafel slope of 60 mV dec-1, and outstanding durability. Density functional theory (DFT) calculations suggest that the heterostructures present an optimized Gibbs free energy of hydrogen adsorption (ΔGH*) close to zero, which is responsible for the excellent HER performance.
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http://dx.doi.org/10.1039/d0cc01726dDOI Listing
May 2020

Discovery of novel "Dual-site" binding oseltamivir derivatives as potent influenza virus neuraminidase inhibitors.

Eur J Med Chem 2020 Apr 15;191:112147. Epub 2020 Feb 15.

Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, 250012, Jinan, Shandong, PR China. Electronic address:

From our research group, it was noticed that oseltamivir derivatives targeting 150-cavity of neuraminidase enzyme (NA) could significantly increase antiviral activity. Thus, we further enriched the C5-NH position of oseltamivir structure to obtain more potent oseltamivir derivatives. In this article a series of oseltamivir derivatives were synthesized by modifying C5-NH position of oseltamivir. All the compounds were evaluated for in vitro antiviral activity against H5N1 and H5N8. Encouragingly, compounds 9a and 11e were exhibited prominent activity, which is similar to oseltamivir carboxylate (OSC) and in NAs inhibitory assay, 11e showed remarkable potency against N1 (H5N1), N2 (H5N2), N6 (H5N6) and N8 (H5N8). In addition, 11e demonstrated low cytotoxicity and no obvious toxicity at the dose of 1500 mg/kg in mice. Molecular docking studies of 9a and 11e provided a plausible rationale for the high potency against group-1 NAs. This work provided new insights to design further neuraminidase inhibitors, which can help to investigate new potent inhibitors for group-1 and group-2 shortly.
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http://dx.doi.org/10.1016/j.ejmech.2020.112147DOI Listing
April 2020

Novel urate transporter 1 (URAT1) inhibitors: a review of recent patent literature (2016-2019).

Expert Opin Ther Pat 2019 Nov 14;29(11):871-879. Epub 2019 Oct 14.

Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University , Jinan , Shandong , PR China.

: Human urate transporter 1 (URAT1), which is an influx transporter protein, is located at the apical surface of renal tubular cells and presumed to be the major transporter responsible for the reabsorption of urate from blood. About 90% of patients develop hyperuricemia due to insufficient urate excretion; thus, it is important to develop URAT1 inhibitors that could enhance renal urate excretion by blocking the reabsorption of urate anion. : In this review, the authors addressed the patent applications (2016-2019) about URAT1 inhibitors and some medicinal chemistry strategies employed in these patents. : Substituent decorating, bioisosterism, and scaffold hopping are three common medicinal chemistry strategies used in the discovery of URAT1 inhibitors. Meanwhile, the introduction of sulfonyl group into small molecules has become one of the important strategies for structural optimization of URAT1 inhibitors. Furthermore, developing drug candidates targeting both URAT1 and xanthine oxidase (XOD) has attracted lots of interest and attention.
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http://dx.doi.org/10.1080/13543776.2019.1676727DOI Listing
November 2019

Robust depth estimation for multi-occlusion in light-field images.

Opt Express 2019 Aug;27(17):24793-24807

Occlusion is one of the most important issues in light-field depth estimation. In this paper, we propose a light-field multi-occlusion model with the analysis of light transmission. By the model, occlusions in different views are discussed separately. An adaptive algorithm of anti-occlusion in the central view is proposed to obtain more precise consistency regions (unoccluded views) in the angular domain and a subpatch approach of anti-occlusion in other views is presented to optimize the initial depth maps, where depth boundaries are better preserved. Then we propose a curvature confidence analysis approach to make depth evaluation more accurate and it is designed in an energy model to regularize the depth maps. Experimental results demonstrate that the proposed algorithm achieves better subjective and objective quality in depth maps compared with state-of-the-art algorithms.
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http://dx.doi.org/10.1364/OE.27.024793DOI Listing
August 2019

A long-cycling anode based on a coral-like Sn nanostructure with a binary binder.

Chem Commun (Camb) 2019 Aug;55(70):10460-10463

Institute of Flexible Electronics (IFE), Northwestern Polytechnical University (NPU), 127 West Youyi Road, Xi'an 710072, China.

A coral-like metallic Sn nanostructure was synthesized towards an advanced Li-ion battery anode via a facile one-pot displacement reaction. In the presence of 5 wt% sodium carboxymethyl cellulose and 5 wt% graphene oxide as a binary binder, the electrode demonstrates extraordinary Li storage behaviors in terms of high initial coulombic efficiency (68.7%), long-cycling life (800 cycles with a retention capacity of 422 mA h g-1 at 500 mA g-1), and superb rate capability. The fascinating electrochemical performance could be attributed to the 3D interconnected nanostructure together with the binary binder to ease the volume expansion of Sn.
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http://dx.doi.org/10.1039/c9cc04477aDOI Listing
August 2019

PPARγ preservation via promoter demethylation alleviates osteoarthritis in mice.

Ann Rheum Dis 2019 10 25;78(10):1420-1429. Epub 2019 Jun 25.

Jiangsu Key Laboratory of Molecular Medicine, Nanjing University School of Medicine, Nanjing, China

Objectives: Osteoarthritis (OA) is the most common degenerative joint disease in aged population and its development is significantly influenced by aberrant epigenetic modifications of numerous OA susceptible genes; however, the precise mechanisms that DNA methylation alterations affect OA pathogenesis remain undefined. This study investigates the critical role of epigenetic PPARγ (peroxisome proliferator-activated receptor-gamma) suppression in OA development.

Methods: Articular cartilage expressions of PPARγ and bioactive DNA methyltransferases (DNMTs) from OA patients and mice incurred by DMM (destabilisation of medial meniscus) were examined. DNA methylation status of both human and mouse PPARγ promoters were assessed by methylated specific PCR and/or bisulfite-sequencing PCR. OA protections by a pharmacological DNA demethylating agent 5Aza (5-Aza-2'-deoxycytidine) were compared between wild type and PPARγ knockout mice.

Results: Articular cartilages from both OA patients and DMM mice display substantial PPARγ suppressions likely due to aberrant elevations of DNMT1 and DNMT3a and consequential PPARγ promoter hypermethylation. 5Aza known to inhibit both DNMT1 and DNMT3a reversed the PPARγ promoter hypermethylation, recovered the PPARγ loss and effectively attenuated the cartilage damage in OA mice. 5Aza also inhibited the OA-associated excessive inflammatory cytokines and deficit anti-oxidant enzymes, which were blocked by a specific PPARγ inhibitor in cultured chondrocytes. Further, 5Aza-confered protections against the cartilage damage and the associated abnormalities of OA-susceptible factors were significantly abrogated in PPARγ knockout mice.

Conclusion: Epigenetic PPARγ suppression plays a key role in OA development and PPARγ preservation via promoter demethylation possesses promising therapeutic potentials in clinical treatment of OA and the related joint diseases.
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http://dx.doi.org/10.1136/annrheumdis-2018-214940DOI Listing
October 2019

Design, synthesis and biological evaluation of "Multi-Site"-binding influenza virus neuraminidase inhibitors.

Eur J Med Chem 2019 Sep 30;178:64-80. Epub 2019 May 30.

Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, 250012, Jinan, Shandong, PR China. Electronic address:

Encouraged by our earlier discovery of neuraminidase inhibitors targeting 150-cavity or 430-cavity, herein, to yield more potent inhibitors, we designed, synthesized, and biologically evaluated a series of novel oseltamivir derivatives via modification of C-1 and C5-NH of oseltamivir by exploiting 150-cavity and/or 430-cavity. Among the synthesized compounds, compound 15e, the most potent N1-selective inhibitor targeting 150-cavity, showed 1.5 and 1.8 times greater activity than oseltamivir carboxylate (OSC) against N1 (H5N1) and N1 (H5N1-H274Y). In cellular assays, 15e also exhibited greater potency than OSC against H5N1 with EC of 0.66 μM. In addition, 15e demonstrated low cytotoxicity in vitro and low acute toxicity in mice. Molecular docking studies provided insights into the high potency of 15e against N1 and N1-H274Y mutant NA. Overall, we envisioned that the significant breakthrough in the discovery of potent group-1-specific neuraminidase inhibitors may lead to further investigation of more potent anti-influenza agents.
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http://dx.doi.org/10.1016/j.ejmech.2019.05.076DOI Listing
September 2019

Investigation of expression and effects of TGF-β1 and MMP-9 in lens epithelial cells of diabetic cataract rats.

Authors:
Ke Li Wei Ai

Exp Ther Med 2019 Jun 8;17(6):4522-4526. Epub 2019 Apr 8.

Department of ENT, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430014, P.R. China.

Expressions and effects of transforming growth factor- 1 (TGF-β1) and matrix metalloproteinase-9 (MMP-9) in lens epithelial cells (LECs) of diabetic cataract rats were investigated. A total of 40 female Sprague-Dawley rats were randomly divided into study and control group. Rats in study group were successfully modeled diabetic cataract rats, and rats in control group were normal rats. Immunohistochemical staining was used to determine positive and negative granules in cytoplasm, and image proplus image analysis system to calculate the integral optical density of the average positive area. Quantitative analysis was performed on TGF-β1 and MMP-9 in LECs of rats in study and control groups at the 2nd and 4th weekends. There were no statistically significant differences in length and age between the two groups of rats (P>0.05). Glucose concentration in the blood of rats in study group after modeling was significantly higher than that before modeling (P<0.001), and that after modeling was significantly higher in study group than that in control group (P<0.001). The expression of TGF-β1 protein in LECs of rats in study group at T2 (the 4th weekend) was significantly higher than that at T1 (the 2nd weekend) (P<0.001), and that of TGF-β1 protein was significantly higher in study group than that in control group at T1 and T2 (P<0.001). The expression of MMP-9 protein in LECs of rats in study group at T2 was significantly higher than that at T1 (P<0.001), and that of MMP-9 protein was significantly higher in study group than that in control group at T1 and T2 (P<0.001). The TGF-β1 expression was positively correlated with the MMP-9 expression in LECs of diabetic cataract rats (r=0.825, P<001). The increased expression of MMP-9 and TGF-β1 may play an important role in the occurrence and development of diabetic cataract.
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http://dx.doi.org/10.3892/etm.2019.7471DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6488997PMC
June 2019

Progressively Exposing Active Facets of 2D Nanosheets toward Enhanced Pseudocapacitive Response and High-Rate Sodium Storage.

Adv Mater 2019 Apr 11;31(17):e1900526. Epub 2019 Mar 11.

Division of Physics and Applied Physics, School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore, 637371, Singapore.

Sodium-ion batteries are gradually regarded as a prospective alternative to lithium-ion batteries due to the cost consideration. Here, three kinds of tin (IV) sulfide nanosheets are controllably designed with progressively exposed active facets, leading to beneficial influences on the Na storage kinetics, resulting in gradient improvements of pseudocapacitive response and rate performance. Interestingly, different forms of kinetics results are generated accompanying with the morphology and structure evolution of the three nanosheets. Finally, detailed density functional theory simulations are also applied to analyze the above experimental achievements, proving that different exposed facets of crystalline anodes possess dissimilar Na storage kinetics. The investigation experiences and conclusions shown in this work are meaningful to explore many other proper structure design routes toward the high-rate and stable metal-ions storage.
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http://dx.doi.org/10.1002/adma.201900526DOI Listing
April 2019

Klotho recovery by genistein via promoter histone acetylation and DNA demethylation mitigates renal fibrosis in mice.

J Mol Med (Berl) 2019 04 26;97(4):541-552. Epub 2019 Feb 26.

Jiangsu Key Laboratory of Molecular Medicine, Nanjing University School of Medicine, 22 Hankou Road, Nanjing, 210093, China.

Renal fibrosis is a common histomorphological feature of renal aging and chronic kidney diseases of all etiologies, and its initiation and progression are substantially influenced by aberrant epigenetic modifications of fibrosis-susceptible genes, yet without effective therapy. "Epigenetic diets" exhibit tissue-protective and epigenetic-modulating properties; however, their anti-renal fibrosis functions and the underlying mechanisms are less understood. In this study, we show that genistein, a phytoestrogenic isoflavone enriched in dietary soy products, exhibits impressive anti-renal fibrosis activities by recovering epigenetic loss of Klotho, a kidney-enriched anti-aging and fibrosis-suppressing protein. Mouse fibrotic kidneys induced by UUO (unilateral ureteral occlusion) displayed severer Klotho suppression and adverse expression of renal fibrosis-associated proteins, but genistein administration markedly recovered the Klotho loss and attenuated renal fibrosis and the protein expression abnormalities. The examination of possible causes of the Klotho recovery revealed that genistein simultaneously inhibited histone 3 deacetylation of Klotho promoter and normalized the promoter DNA hypermethylation by suppressing elevated DNA methyltransferase DNMT1 and DNMT3a. More importantly, genistein's anti-renal fibrosis effects on the renal fibrotic lesions and the abnormal expressions of fibrosis-associated proteins were abrogated when Klotho is knockdown by RNA interferences in UUO mice. Thus, our results identify Klotho restoration via epigenetic histone acetylation and DNA demethylation as a critical mechanism of genistein's anti-fibrosis function and shed new lights on the potentials of epigenetic diets in preventing or treating aging or renal fibrosis-associated kidney diseases. KEY MESSAGES: Genistein prevents renal fibrosis and the associated Klotho suppression in UUO mice. Genistein upregulates Klotho in part by reversing the promoter histone 3 hypoacetylation. Genistein also preserves Klotho via relieving Klotho promoter hypermethylation. Genistein demethylates Klotho promoter by inhibiting aberrant DNMT1/3a expression. Genistein restoration of Klotho is essential for its anti-renal fibrosis function.
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http://dx.doi.org/10.1007/s00109-019-01759-zDOI Listing
April 2019

Calcium Supplementation Enhanced Adipogenesis and Improved Glucose Homeostasis Through Activation of Camkii and PI3K/Akt Signaling Pathway in Porcine Bone Marrow Mesenchymal Stem Cells (pBMSCs) and Mice Fed High Fat Diet (HFD).

Cell Physiol Biochem 2018 15;51(1):154-172. Epub 2018 Nov 15.

Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou,

Background/aims: It has been implicated that calcium supplementation is involved in reducing body weight/fat and improving glucose homeostasis. However, the underlying mechanisms are still not fully understood. Here, we investigated the effects of calcium supplementation on adipogenesis and glucose homeostasis in porcine bone marrow mesenchymal stem cells (pBMSCs) and high fat diet (HFD)-fed mice and explored the involved signaling pathways.

Methods: In vitro, pBMSCs were treated with 4 mM extracellular calcium ([Ca2+]o) and/or 1 μM nifedipine, 0.1 μM BAPTA-AM, 1 μM KN-93, 50 nM wortmannin for 10 days. The intracellular calcium ([Ca2+]i) levels were measured using Fluo 3-AM by flow cytometry. The adipogenic differentiation of pBMSCs was determined by Oil Red-O staining and triglyceride assay. The expression of marker genes involved in adipogenesis (peroxisome proliferator activated receptor γ (PPARγ) and CCAAT/enhancer binding protein α (C/EBPα)) and glucose uptake (glucose transporter 4 (GLUT4)), as well as the activation of Ca2+/calmodulin-dependent protein kinase II (CaMKII) and PI3K/Akt-FoxO1/AS160 signaling pathways were determined by Western blotting. Glucose uptake and utilization were examined using 2-NBDG assay and glucose content assay, respectively. In vivo, C57BL/6J male mice were fed a HFD (containing 1.2% calcium) without or with 0.6% (w/w) calcium chloride in drinking water for 13 weeks. The adipogenesis, glucose homeostasis and the involvement of CaMKII and PI3K/Akt signaling pathway were also assessed.

Results: In vitro, [Ca2+]o stimulated pBMSCs adipogenesis by increasing [Ca2+]i level and activating CaMKII and PI3K/Akt-FoxO1 pathways. In addition, [Ca2+]o promoted glucose uptake/utilization by enhancing AS160 phosphorylation, GLUT4 expression and translocation. However, the stimulating effects of [Ca2+]o on pBMSCs adipogenesis and glucose uptake/utilization were abolished by L-VGCC blocker Nifedipine, [Ca2+]i chelator BAPTA-AM, CaMKII inhibitor KN-93, or PI3K inhibitor Wortmannin. In vivo, calcium supplementation decreased body weight and fat content, increased adipocyte number, and improved glucose homeostasis, with elevated PPARγ and GLUT4 expression and PI3K/Akt activation in iWAT.

Conclusion: calcium supplementation enhanced adipogenesis and glucose uptake in pBMSCs, which was coincident with the increased adipocyte number and improved glucose homeostasis in HFD-fed mice, and was associated with activation of CaMKII and PI3K/Akt-FoxO1/AS160 pathways. These data provided a broader understanding of the mechanisms underlying calcium-induced body weight/fat loss and glycemic control.
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http://dx.doi.org/10.1159/000495171DOI Listing
December 2018

Engineering Morphologies of Cobalt Pyrophosphates Nanostructures toward Greatly Enhanced Electrocatalytic Performance of Oxygen Evolution Reaction.

Small 2018 Jul 2:e1801068. Epub 2018 Jul 2.

Institute for Clean Energy and Advanced Materials, Faculty of Materials and Energy, Southwest University, Chongqing, 400715, China.

Herein, a surfactant- and additive-free strategy is developed for morphology-controllable synthesis of cobalt pyrophosphate (CoPPi) nanostructures by tuning the concentration and ratio of the precursor solutions of Na P O and Co(CH COO) . A series of CoPPi nanostructures including nanowires, nanobelts, nanoleaves, and nanorhombuses are prepared and exhibit very promising electrocatalytic properties toward the oxygen evolution reaction (OER). Acting as both reactant and pseudo-surfactant, the existence of excess Na P O is essential to synthesize CoPPi nanostructures for unique morphologies. Among all CoPPi nanostructures, the CoPPi nanowires catalyst renders the best catalytic performance for OER in alkaline media, achieving a low Tafel slope of 54.1 mV dec , a small overpotential of 359 mV at 10 mA cm , and superior stability. The electrocatalytic activities of CoPPi nanowires outperform the most reported non-noble metal based catalysts, even better than the benchmark Ir/C (20%) catalyst. The reported synthesis of CoPPi gives guidance for morphology control of transition metal pyrophosphate based nanostructures for a high-performance inexpensive material to replace the noble metal-based OER catalysts.
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http://dx.doi.org/10.1002/smll.201801068DOI Listing
July 2018

Controllable Design of MoS Nanosheets Anchored on Nitrogen-Doped Graphene: Toward Fast Sodium Storage by Tunable Pseudocapacitance.

Adv Mater 2018 Jul 23;30(27):e1800658. Epub 2018 May 23.

Division of Physics and Applied Physics, School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore, 637371, Singapore.

Transition-metal disulfide with its layered structure is regarded as a kind of promising host material for sodium insertion, and intensely investigated for sodium-ion batteries. In this work, a simple solvothermal method to synthesize a series of MoS nanosheets@nitrogen-doped graphene composites is developed. This newly designed recipe of raw materials and solvents leads the success of tuning size, number of layers, and interplanar spacing of the as-prepared MoS nanosheets. Under cut-off voltage and based on an intercalation mechanism, the ultrasmall MoS nanosheets@nitrogen-doped graphene composite exhibits more preferable cycling and rate performance compared to few-/dozens-layered MoS nanosheets@nitrogen-doped graphene, as well as many other reported insertion-type anode materials. Last, detailed kinetics analysis and density functional theory calculation are also employed to explain the Na - storage behavior, thus proving the significance in surface-controlled pseudocapacitance contribution at the high rate. Furthermore, this work offers some meaningful preparation and investigation experiences for designing electrode materials for commercial sodium-ion batteries with favorable performance.
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http://dx.doi.org/10.1002/adma.201800658DOI Listing
July 2018

Klotho preservation by Rhein promotes toll-like receptor 4 proteolysis and attenuates lipopolysaccharide-induced acute kidney injury.

J Mol Med (Berl) 2018 09 5;96(9):915-927. Epub 2018 May 5.

Nanjing University School of Medicine, Jiangsu Key Lab of Molecular Medicine, 22 Hankou Road, Nanjing, 210093, China.

Renal anti-aging protein Klotho exhibits impressive properties of anti-inflammation and renal protection, however is suppressed early after renal injury, making Klotho restoration an attractive strategy of treating renal inflammatory disorders. Here, we reported that Klotho is enriched in macrophages and Klotho preservation by Rhein, an anthraquinone derived from medicinal plant rhubarb, attenuates lipopolysaccharide (LPS)-induced acute inflammation essentially via promoting toll-like receptor 4 (TLR4) degradation. LPS-induced pro-inflammatory NF-κB signaling and cytokine expressions coincided with Klotho repression and toll-like receptor 4 (TLR4) elevation in macrophages, renal epithelial cells, and acutely- inflamed kidney. Intriguingly, Rhein treatment effectively corrected the inverted alterations of Klotho and TLR4 and mitigated the TLR4 downstream inflammatory response in a Klotho restoration and TLR4 repression-dependent manner. Klotho inducibly associated with TLR4 after LPS stimulation and suppressed TLR4 protein abundance mainly via a proteolytic process sensitive to the inhibition of Klotho's putative β-glucuronidase activity. Consistently, Klotho knockdown by RNA interferences largely diminished the anti-inflammatory and renal protective effects of Rhein in a mouse model of acute kidney injury incurred by LPS. Thus, Klotho suppression of TLR4 via deglycosylation negatively controls TLR-associated inflammatory signaling and the endogenous Klotho preservation by Rhein or possibly other natural or synthetic compounds possesses promising potentials in the clinical treatment of renal inflammatory disorders.

Key Messages: • Klotho is highly expressed in macrophages and repressed by LPS in vitro and in vivo. • Klotho inhibits LPS-induced TLR4 accumulation and the downstream signaling. • Klotho decreases TLR4 via a deglycosylation-associated proteolytic process. • Rhein effectively prevents acute inflammation-incurred Klotho suppression. • Rhein reversal of Klotho attenuates LPS-induced acute inflammation and kidney injury.
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http://dx.doi.org/10.1007/s00109-018-1644-7DOI Listing
September 2018

Phytol stimulates the browning of white adipocytes through the activation of AMP-activated protein kinase (AMPK) α in mice fed high-fat diet.

Food Funct 2018 Apr;9(4):2043-2050

Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou 510642, P. R. China and ALLTECH-SCAU Animal Nutrition Control Research Alliance and National Engineering Research Center for Breeding Swine Industry, South China Agricultural University, Guangzhou 510642, P. R. China.

Stimulating the browning of white adipocytes contributes to the restriction of obesity and related metabolic disorders. This study aimed to investigate the browning effects of phytol on mice inguinal subcutaneous white adipose tissue (iWAT) and explore the underlying mechanisms. Our results demonstrated that phytol administration decreased body weight gain and iWAT index, and stimulated the browning of mice iWAT, with the increased expression of brown adipocyte marker genes (UCP1, PRDM16, PGC1α, PDH, and Cyto C). In addition, phytol treatment activated the AMPKα signaling pathway in mice iWAT. In good agreement with the in vivo findings, the in vitro results showed that 100 μM phytol stimulated brown adipogenic differentiation and formation of brown-like adipocytes in the differentiated 3T3-L1 by increasing the mitochondria content and oxygen consumption, and promoting mRNA and/or protein expression of brown adipocyte markers (UCP1, PRDM16, PGC1α, PDH, Cyto C, Cidea and Elovl3) and beige adipocyte markers (CD137 and TMEM26). Meanwhile, phytol activated the AMPKα signaling pathway in the differentiated 3T3-L1. However, the inhibition of AMPKα with Compound C totally abolished phytol-stimulated brown adipogenic differentiation and formation of brown-like adipocytes. In conclusion, these results showed that phytol stimulated the browning of mice iWAT, which was coincident with the increased formation of brown-like adipocytes in the differentiated 3T3-L1, and appeared to be primarily mediated by the AMPKα signaling pathway. These data provided new insight into the role of phytol in regulating the browning of WAT and suggested the potential application of phytol as a nutritional intervention for the restriction of obesity and related metabolic disorders.
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http://dx.doi.org/10.1039/C7FO01817GDOI Listing
April 2018

Phytol increases adipocyte number and glucose tolerance through activation of PI3K/Akt signaling pathway in mice fed high-fat and high-fructose diet.

Biochem Biophys Res Commun 2017 08 29;489(4):432-438. Epub 2017 May 29.

Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou 510642, PR China; National Engineering Research Center for Breeding Swine Industry, South China Agricultural University, Guangzhou 510642, PR China. Electronic address:

It has been shown that adipose tissue hyperplasia (increased adipocyte number or adipogenesis) has beneficial effects on metabolic health. The aim of the present study was to determine whether phytol could modulate hyperplasia/adipogenesis and glucose homeostasis, and to explore the underlying mechanisms in mice fed high-fat and high fructose diet (HFFD). Our results demonstrated that phytol administration decreased body weight gain and inguinal subcutaneous white adipose tissue (iWAT) weight. However, phytol significantly increased the adipocyte number in iWAT, with the smaller average adipocyte diameter. Meanwhile, OGTT result showed that phytol improved glucose tolerance. In accord, phytol administration markedly increased expression of marker genes associated with adipogenesis (PPARγ and C/EBPα) and glucose uptake (AS160 and GLUT4) and activated PI3K/Akt signaling pathway in mice iWAT. In agreement with the in vivo findings, the in vitro results indicated that 100 μM phytol significantly enhanced 3T3-L1 adipogenesis and glucose uptake, and activated PI3K/Akt signaling pathway. However, phytol-induced enhancement of 3T3-L1 adipognesis and glucose uptake, activation of PI3K/Akt signaling pathway, elevation of marker genes involved in adipogensis and glucose uptake, as well as translocation of GLUT4 from cytoplasm to membrane were abolished by Wortmannin, a specific PI3K/Akt inhibitor. Taken together, phytol increased adipocyte number in iWAT and improved glucose tolerance in mice fed HFFD, which was coincident with the enhanced adipogenesis and glucose uptake in 3T3-L1, and was associated with activation of PI3K/Akt signaling pathway. These data suggested the application of phytol as a potential nutritional agent to combat obesity and type 2 diabetes.
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http://dx.doi.org/10.1016/j.bbrc.2017.05.160DOI Listing
August 2017

Lauric Acid Stimulates Mammary Gland Development of Pubertal Mice through Activation of GPR84 and PI3K/Akt Signaling Pathway.

J Agric Food Chem 2017 Jan 22;65(1):95-103. Epub 2016 Dec 22.

College of Animal Science and National Engineering Research Center for Breeding Swine Industry, South China Agricultural University , Guangzhou 510642, P. R. China.

It has been demonstrated that dietary fat affects pubertal mammary gland development. However, the role of lauric acid (LA) in this process remains unclear. Thus, this study aimed to investigate the effects of LA on mammary gland development in pubertal mice and to explore the underlying mechanism. In vitro, 100 μM LA significantly promoted proliferation of mouse mammary epithelial cell line HC11 by regulating expression of proliferative markers (cyclin D1/3, p21, PCNA). Meanwhile, LA activated the G protein-coupled receptor 84 (GPR84) and PI3K/Akt signaling pathway. In agreement, dietary 1% LA enhanced mammary duct development, increased the expression of GPR84 and cyclin D1, and activated PI3K/Akt in mammary gland of pubertal mice. Furthermore, knockdown of GPR84 or inhibition of PI3K/Akt totally abolished the promotion of HC11 proliferation induced by LA. These results showed that LA stimulated mammary gland development of pubertal mice through activation of GPR84 and PI3K/Akt signaling pathway.
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http://dx.doi.org/10.1021/acs.jafc.6b04878DOI Listing
January 2017