Publications by authors named "Xiaotong Gu"

10 Publications

  • Page 1 of 1

Design, synthesis and evaluation of novel 9-arylalkyl-10-methylacridinium derivatives as highly potent FtsZ-targeting antibacterial agents.

Eur J Med Chem 2021 Oct 28;221:113480. Epub 2021 Apr 28.

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

With the increasing incidence of antibiotic resistance, new antibacterial agents having novel mechanisms of action hence are in an urgent need to combat infectious diseases caused by multidrug-resistant (MDR) pathogens. Four novel series of substituted 9-arylalkyl-10-methylacridinium derivatives as FtsZ inhibitors were designed, synthesized and evaluated for their antibacterial activities against various Gram-positive and Gram-negative bacteria. The results demonstrated that they exhibited broad-spectrum activities with substantial efficacy against MRSA and VRE, which were superior or comparable to the berberine, sanguinarine, linezolid, ciprofloxacin and vancomycin. In particular, the most promising compound 15f showed rapid bactericidal properties, which avoid the emergence of drug resistance. However, 15f showed no inhibitory effect on Gram-negative bacteria but biofilm formation study gave possible answers. Further target identification and mechanistic studies revealed that 15f functioned as an effective FtsZ inhibitor to alter the dynamics of FtsZ self-polymerization, which resulted in termination of the cell division and caused cell death. Further cytotoxicity and animal studies demonstrated that 15f not only displayed efficacy in a murine model of bacteremia in vivo, but also no significant hemolysis to mammalian cells. Overall, this compound with novel skeleton could serve as an antibacterial lead of FtsZ inhibitor for further evaluation of drug-likeness.
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http://dx.doi.org/10.1016/j.ejmech.2021.113480DOI Listing
October 2021

EEG-based Brain-Computer Interfaces (BCIs): A Survey of Recent Studies on Signal Sensing Technologies and Computational Intelligence Approaches and Their Applications.

IEEE/ACM Trans Comput Biol Bioinform 2021 Jan 19;PP. Epub 2021 Jan 19.

Brain-Computer interfaces (BCIs) enhance the capability of human brain activities to interact with the environment. Recent advancements in technology and machine learning algorithms have increased interest in electroencephalographic (EEG)-based BCI applications. EEG-based intelligent BCI systems can facilitate continuous monitoring of fluctuations in human cognitive states under monotonous tasks, which is both beneficial for people in need of healthcare support and general researchers in different domain areas. In this review, we survey the recent literature on EEG signal sensing technologies and computational intelligence approaches in BCI applications, compensating for the gaps in the systematic summary of the past five years. Specifically, we first review the current status of BCI and signal sensing technologies for collecting reliable EEG signals. Then, we demonstrate state-of-the-art computational intelligence techniques, including fuzzy models and transfer learning in machine learning and deep learning algorithms, to detect, monitor, and maintain human cognitive states and task performance in prevalent applications. Finally, we present a couple of innovative BCI-inspired healthcare applications and discuss future research directions in EEG-based BCI research.
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http://dx.doi.org/10.1109/TCBB.2021.3052811DOI Listing
January 2021

Photobiomodulation suppresses JNK3 by activation of ERK/MKP7 to attenuate AMPA receptor endocytosis in Alzheimer's disease.

Aging Cell 2021 01 18;20(1):e13289. Epub 2020 Dec 18.

MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, South China Normal University, Guangzhou, China.

Alzheimer's disease (AD), a severe age-related neurodegenerative disorder, lacks effective therapeutic methods at present. Physical approaches such as gamma frequency light flicker that can effectively reduce amyloid load have been reported recently. Our previous research showed that a physical method named photobiomodulation (PBM) therapy rescues Aβ-induced dendritic atrophy in vitro. However, it remains to be further investigated the mechanism by which PBM affects AD-related multiple pathological features to improve learning and memory deficits. Here, we found that PBM attenuated Aβ-induced synaptic dysfunction and neuronal death through MKP7-dependent suppression of JNK3, a brain-specific JNK isoform related to neurodegeneration. The results showed PBM-attenuated amyloid load, AMPA receptor endocytosis, dendrite injury, and inflammatory responses, thereby rescuing memory deficits in APP/PS1 mice. We noted JNK3 phosphorylation was dramatically decreased after PBM treatment in vivo and in vitro. Mechanistically, PBM activated ERK, which subsequently phosphorylated and stabilized MKP7, resulting in JNK3 inactivation. Furthermore, activation of ERK/MKP7 signaling by PBM increased the level of AMPA receptor subunit GluR 1 phosphorylation and attenuated AMPA receptor endocytosis in an AD pathological model. Collectively, these data demonstrated that PBM has potential therapeutic value in reducing multiple pathological features associated with AD, which is achieved by regulating JNK3, thus providing a noninvasive, and drug-free therapeutic strategy to impede AD progression.
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http://dx.doi.org/10.1111/acel.13289DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7811840PMC
January 2021

Efficient photocatalytic removal of phthalates easily implemented over a bi-functional {001}TiO surface.

Chemosphere 2021 Jan 4;263:128257. Epub 2020 Sep 4.

School of Chemical Science and Engineering, Shanghai Key Lab of Chemical Assessment and Sustainability, Key Laboratory of Yangtze River Water Environment, Tongji University, Shanghai, 200092, People's Republic of China. Electronic address:

It is stubborn to remove the lowly concentrated phthalic acid esters (PAEs) that usually coexist with other highly concentrated but low-toxic pollutants in municipal sewage. Herein, we report a novel strategy for completely removing the PAEs over a bi-functional {001}TiO surface (with highly exposed {001} facet), which not only serve as functional sites to specifically adsorb the target PAEs pollutants, but also contribute to an enhanced oxidation ability. The adsorption behavior of PAEs on {001}TiO is analyzed deeply through kinetic experiments combining with in situ ATR-FTIR spectroscopy and theoretical calculations. The results reveal that the adsorption capacities of PAEs on {001}TiO are about 4-5 times higher than that on TiO, both of which follow the pseudo-second-order and Langmuir model. This is mainly attributed to the interfacial Lewis Acid-Base Pair between {001} facet Ti sites and CO of PAEs. Benefitting from the specific adsorption capability toward target pollutant and enhanced oxidation ability of {001} facets, nearly 100% of DMP or DEP in simulated wastewater can be eliminated by {001}TiO within 2 h illumination, and the relevant degradation rate constants (k) (3.67 h for DMP and 2.19 h for DEP) are 5.73 and 3.08 folds higher than that of pure TiO, respectively. In the application of municipal wastewater, nearly 76% of DMP and 85% DEP can be eliminated by {001}TiO within 2 h illumination, which are nearly 3-6 fold higher than that of pure TiO.
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http://dx.doi.org/10.1016/j.chemosphere.2020.128257DOI Listing
January 2021

Total Synthesis of Semaglutide Based on a Soluble Hydrophobic-Support-Assisted Liquid-Phase Synthetic Method.

ACS Comb Sci 2020 12 15;22(12):821-825. Epub 2020 Oct 15.

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

Considering the high cost of the production of semaglutide, which is currently the most promising antidiabetic drug especially for the treatment of type 2 diabetes mellitus, a new synthetic route of semaglutide production that possesses excellent yield and high purity is of vital importance. Herein, we reported a newly developed synthetic route of semaglutide that is simple and efficient, based on a soluble hydrophobic-support-assisted liquid-phase synthetic method by applying Alloc-chemistry to the synthesis of the main chain peptide and side chain peptide of semaglutide. With careful optimization of the reaction conditions and innovative strategy of post-synthetic treatments, the total yield and purity of the crude semaglutide was improved satisfactorily.
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http://dx.doi.org/10.1021/acscombsci.0c00134DOI Listing
December 2020

In situ growth of M-{001}TiO/Ti photoelectrodes: synergetic dominant {001} facets and ratio-optimal surface junctions for the effective oxidation of environmental pollutants.

Chem Commun (Camb) 2020 Jan 8;56(9):1337-1340. Epub 2020 Jan 8.

School of Chemical Science and Engineering, Shanghai Key Lab of Chemical Assessment and Sustainability, Key Laboratory of Yangtze River Water Environment, Tongji University, Shanghai 200092, People's Republic of China.

We report a novel {001}TiO/Ti photoelectrode by directly constructing "mirror-like" TiO microspheres on a Ti foil substrate (M-{001}TiO/Ti). It presents highly enhanced PEC oxidation capability of DMP wastewater, which is mainly attributed to the significant synergetic effects of high exposure of {001} facets and equivalent {001}/{101} facet junctions.
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http://dx.doi.org/10.1039/c9cc09296jDOI Listing
January 2020

Direct Conversion of Human Urine Cells to Neurons by Small Molecules.

Sci Rep 2019 11 13;9(1):16707. Epub 2019 Nov 13.

Institute of Public Health, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.

Transdifferentiation of other cell type into human neuronal cells (hNCs) provides a platform for neural disease modeling, drug screening and potential cell-based therapies. Among all of the cell donor sources, human urine cells (hUCs) are convenient to obtain without invasive harvest procedure. Here, we report a novel approach for the transdifferentiation of hUCs into hNCs. Our study demonstrated that a combination of seven small molecules (CAYTFVB) cocktail induced transdifferentiation of hUCs into hNCs. These chemical-induced neuronal cells (CiNCs) exhibited typical neuron-like morphology and expressed mature neuronal markers. The neuronal-like morphology revealed in day 1, and the Tuj1-positive CiNCs reached to about 58% in day 5 and 38.36% Tuj1+/MAP2+ double positive cells in day 12. Partial electrophysiological properties of CiNCs was obtained using patch clamp. Most of the CiNCs generated using our protocol were glutamatergic neuron populations, whereas motor neurons, GABAergic or dopaminergic neurons were merely detected. hUCs derived from different donors were converted into CiNCs in this work. This method may provide a feasible and noninvasive approach for reprogramming hNCs from hUCs for disease models and drug screening.
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http://dx.doi.org/10.1038/s41598-019-53007-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6854089PMC
November 2019

Recent progress on carbon nanomaterials for the electrochemical detection and removal of environmental pollutants.

Nanoscale 2019 Jul 29;11(25):11992-12014. Epub 2019 May 29.

School of Chemical Science and Engineering, Shanghai Key Lab of Chemical Assessment and Sustainability, Key Laboratory of Yangtze River Water Environment, Tongji University, Shanghai 200092, People's Republic of China.

Rapid global industrialization and explosive population growth have resulted in an increase in the discharge of harmful and toxic compounds. These toxic inorganic gases, volatile organic compounds, heavy metals, personal care products, endocrine-disrupting chemicals, dyes, and pharmaceuticals are destroying the balance in the Earth and increasing environmental toxicity at an alarming rate. Thus, their detection, adsorption and removal are of great significance. Various carbon nanomaterials including carbon nanotubes, graphene, mesoporous carbon, carbon dots, and boron-doped diamond have been extensively utilized and further proven to be ideal candidates for resolving environmental problems, emerging as adsorbents, electrochemical sensors and electrodes. Herein, we review the recent advances, progress and achievements in the design and properties of carbon nanomaterials and their applications for the electrochemical detection and removal of environmental pollutants.
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http://dx.doi.org/10.1039/c9nr02935dDOI Listing
July 2019

Noninvasive estimation of assist pressure for direct mechanical ventricular actuation.

Rev Sci Instrum 2018 Feb;89(2):025108

School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, Shanghai 200240, China.

Direct mechanical ventricular actuation is effective to reestablish the ventricular function with non-blood contact. Due to the energy loss within the driveline of the direct cardiac compression device, it is necessary to acquire the accurate value of assist pressure acting on the heart surface. To avoid myocardial trauma induced by invasive sensors, the noninvasive estimation method is developed and the experimental device is designed to measure the sample data for fitting the estimation models. By examining the goodness of fit numerically and graphically, the polynomial model presents the best behavior among the four alternative models. Meanwhile, to verify the effect of the noninvasive estimation, the simplified lumped parameter model is utilized to calculate the pre-support and the post-support left ventricular pressure. Furthermore, by adjusting the driving pressure beyond the range of the sample data, the assist pressure is estimated with the similar waveform and the post-support left ventricular pressure approaches the value of the adult healthy heart, indicating the good generalization ability of the noninvasive estimation method.
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http://dx.doi.org/10.1063/1.5005043DOI Listing
February 2018

Photoactivation of ERK/CREB/VMAT2 pathway attenuates MPP-induced neuronal injury in a cellular model of Parkinson's disease.

Cell Signal 2017 09 13;37:103-114. Epub 2017 Jun 13.

MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631, China. Electronic address:

The vesicular monoamine transporter 2 (VMAT2) pumps dopamine from cytoplasm into synaptic vesicles for subsequent release, and the deficits of VMAT2 has been implicated in the dopaminergic neuronal cell loss which is considered as a typical pathological feature of Parkinson's disease (PD). Low-power laser irradiation (LPLI), a potent noninvasive physiotherapy approach, is capable of penetrating into nerve tissue to exert beneficial effects such as promoting nerve regeneration and ATP production. In the present study, we demonstrated that LPLI protects against MPP-induced neurotoxicity via upregulation of VMAT2 in SH-SY5Y human dopaminergic neuroblastoma cells. The photoactivation of ERK phosphorylated cAMP-response element binding protein (CREB) at Ser133, and thus increased the ability of CREB binding to the promoter region of VMAT2, leading to elevated VMAT2 expression, which contributes to dopamine release and cell survival. Taken together, for the first time to our knowledge, the results showed that LPLI attenuates MPP-induced neurotoxicity through activation of ERK/CREB/VMAT2 pathway, suggesting that the manipulation of VMAT2 by LPLI may provide a potential therapeutic strategy for PD.
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http://dx.doi.org/10.1016/j.cellsig.2017.06.007DOI Listing
September 2017