Publications by authors named "Kai Zhong"

152 Publications

Remediation of Soil in a Deserted Arsenic Plant Site Using Synthesised MgAlFe-LDHs.

Authors:
Kai Zhong Chaolan Zhang Siwei Ren He Huang Qun Rong Yongxin Zhou

Bull Environ Contam Toxicol 2021 Mar 28. Epub 2021 Mar 28.

Guangxi Bossco Environmental Protection Technology Co., Ltd, Nanning, 530007, People's Republic of China.

Layered double hydroxides (LDHs) are promising soil contamination amendment agents for its efficient absorbing abilities. However, the application of LDHs in remediation of heavy metal contaminated soil are to be developed. In this study, we synthesized MgAlFe-LDHs by introducing Fe into interlayer of the MgAl-LDHs using co-precipitation method. X-ray diffraction (XRD), Fourier transform infrared spectrometer (FT-IR) and scanning electron microscope (SEM) were employed to characterized the micro structure of MgAlFe-LDHs. And then pot incubation and pilot experiments were conducted to investigate the heavy metal removal efficiencies of MgAlFe-LDHs and its potential being applicated in As contaminated soil amendment from a deserted arsenic plant site. Incubation experiments showed that the MgAlFe-LDHs had a higher removal efficiency on arsenic contaminated soil compared to other agents. And the results of pilot experiments indicated that the MgAlFe-LDHs can immobilize up to 90% of the As in soil with 5% (w/w) addition. Based on the results above, MgAlFe-LDHs are promising materials amending the heavy metal contaminated soil with practical application value.
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http://dx.doi.org/10.1007/s00128-021-03189-5DOI Listing
March 2021

Electrophysiological characterization of photoreceptor-like cells in human inducible pluripotent stem cell-derived retinal organoids during in vitro maturation.

Authors:
Lingyun Li Huan Zhao Haohuan Xie Tasneem Akhtar Yichuan Yao Yuan Cai Kai Dong Yonghao Gu Jin Bao Jutao Chen Mei Zhang Kai Zhong Weiping Xu Tian Xue

Stem Cells 2021 Mar 4. Epub 2021 Mar 4.

Eye Center, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, People's Republic of China.

Retinal organoids (ROs) derived from human inducible pluripotent stem cells (hiPSCs) exhibit considerable therapeutic potential. However, current quality control of ROs during in vitro differentiation is largely limited to the detection of molecular markers, often by immunostaining, polymerase chain reaction (PCR) assays and sequencing, often without proper functional assessments. As such, in the current study, we systemically characterized the physiological maturation of photoreceptor-like cells in hiPSC-derived ROs. By performing patch-clamp recordings from photoreceptor-like cells in ROs at distinct differentiation stages (ie, Differentiation Day [D]90, D150, and D200), we determined the electrophysiological properties of the plasma membrane and several characteristic ion channels closely associated with the physiological functions of the photoreceptors. Ionic hallmarks, such as hyperpolarization-activated cyclic nucleotide-gated (HCN) channels and cyclic nucleotide-gated (CNG) channels, matured progressively during differentiation. After D200 in culture, these characteristic currents closely resembled those in macaque or human native photoreceptors. Furthermore, we demonstrated that the hyperpolarization-activated inward current/depolarization-activated outward current ratio (I /I ), termed as the inward-outward current (IOC) ratio hereon, accurately represented the maturity of photoreceptors and could serve as a sensitive indicator of pathological state. Thus, this study provides a comprehensive dataset describing the electrophysiological maturation of photoreceptor-like cells in hiPSC-derived ROs for precise and sensitive quality control during RO differentiation.
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http://dx.doi.org/10.1002/stem.3363DOI Listing
March 2021

Discovery of A031 as effective proteolysis targeting chimera (PROTAC) androgen receptor (AR) degrader for the treatment of prostate cancer.

Authors:
Linrong Chen Liuquan Han Shujun Mao Ping Xu Xinxin Xu Ruibo Zhao Zhihua Wu Kai Zhong Guangliang Yu Xiaolei Wang

Eur J Med Chem 2021 Apr 23;216:113307. Epub 2021 Feb 23.

State Key Laboratory of Applied Organic Chemistry, Department of Chemistry, Lanzhou University, 222 S. Tianshui Rd, Lanzhou, 730000, PR China. Electronic address:

Androgen receptor (AR) is an effective therapeutic target for the treatment of prostate cancer. We report herein the design, synthesis, and biological evaluation of highly effective proteolysis targeting chimeras (PROTAC) androgen receptor (AR) degraders, such as compound A031. It could induce the degradation of AR protein in VCaP cell lines in a time-dependent manner, achieving the IC 50 value of less than 0.25 μM. The A031 is 5 times less toxic than EZLA and works with an appropriate half-life (t 1/2) or clearance rate (Cl). Also, it has a significant inhibitory effect on tumor growth in zebrafish transplanted with human prostate cancer (VCaP). Therefore, A031 provides a further idea of developing novel drugs for prostate cancer.
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http://dx.doi.org/10.1016/j.ejmech.2021.113307DOI Listing
April 2021

Effects of Bacillus megaterium L222 on quality and bacterial diversity of Sichuan paocai.

Authors:
Fangping Luo Zhenying Yang Kai Zhong Chi Huang Zhiyi Yu Ziyue Peng Yanping Wu Qian Bu Hong Gao

Food Res Int 2021 Feb 15;140:109994. Epub 2020 Dec 15.

College of Biomass Science and Engineering and Healthy Food Evaluation Research Center, Sichuan University, Chengdu 610065, China; Key Laboratory of Food Science and Technology of Ministry of Education of Sichuan Province, Sichuan University, Chengdu 610065, China. Electronic address:

Bacillus sp. was found in the Sichuan paocai, but their possible effects on Sichuan paocai fermentation are still elusive. In this study, the effect of Bacillus megaterium L222 isolated from high-quality homemade Sichuan paocai on the flavor characteristics and bacterial diversity was investigated. Overall, 7 organic acids, 16 free amino acids, and 48 volatile substances were detected in the B. megaterium L222-inoculated paocai (BMP) and spontaneously fermented paocai (SP) within 7 days. The metabolites produced in BMP were significantly different from that in SP, and 13 main flavor-related metabolites were the discriminant markers. The contents of free amino acids in BMP were much higher than that in SP. Compared to the SP group, the BMP group could better maintain the high level of alcohols, which improved the synthesis of esters, and controlled the increase of the content of sulfides. The representative bacteria in BMP were Weissella, Lactococcus, Bacillus, Leuconostoc, and the inoculation of B. megaterium L222 could significantly increase the amount of Weissella and inhibit the growth of opportunistic pathogen and other bacteria during the fermentation process of paocai. This study presents an important basis for the development of B. megaterium L222 as a starter for paocai fermentation.
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http://dx.doi.org/10.1016/j.foodres.2020.109994DOI Listing
February 2021

Generation of an NANS homozygous knockout human induced pluripotent stem cell line by the insertion of GFP-P2A-Puro via CRISPR/Cas9 editing.

Authors:
Qian Bu Huaqin Zhang Qian Liu Yanping Dai Qian Wei Aiqin Xue Yan Huang Kai Zhong Yina Huang Hong Gao Xiaobo Cen

Stem Cell Res 2020 12 20;49:102052. Epub 2020 Oct 20.

National Chengdu Center for Safety Evaluation of Drugs, State Key Lab of Biotherapy/Collaborative Innovation Center of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China.

N-acetylneuraminic acid synthase (NANS), the gene encoding the synthase for N-acetylneuraminic acid (NeuNAc; sialic acid), is closely associated with infantile-onset severe developmental delay and skeletal dysplasia. However, the role and the involved mechanisms of NANS functioning have not been fully understood to date. Here, we generated a homozygous NANS-knockout human induced pluripotent stem cell (iPSC) line, NCCSEDi001-A-1, via the CRISPR/Cas9-based gene editing method. The NCCSEDi001-A-1 cell line does not express NANS protein, but maintains a normal karyotype, pluripotency, and trilineage differentiation potential.
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http://dx.doi.org/10.1016/j.scr.2020.102052DOI Listing
December 2020

Metal-induced G-quadruplex polymorphism for ratiometric and label-free detection of lead pollution in tea.

Authors:
Yanping Wu Yachen Shi Sha Deng Chengyong Wu Ruijie Deng Guiping He Mi Zhou Kai Zhong Hong Gao

Food Chem 2021 May 20;343:128425. Epub 2020 Oct 20.

College of Biomass Science and Engineering, Healthy Food Evaluation Research Center and Key Laboratory of Food Science and Technology of Ministry of Education of Sichuan Province, Sichuan University, Chengdu 610065, China. Electronic address:

Lead pollution are critical concerns for food safety and human health. Herein, a ratiometric metal-induced G-quadruplex polymorphism was introduced to construct aptamer probes, enabling label-free and ratiometric detection of lead in tea, thus is promising for on-site detection of lead pollution. The key feature of the aptamer probe is the synergistic utilization of the dual-wavelength fluorescent signal outputs from a G-quadruplex specific dye and a DNA intercalation dye under a single-wavelength excitation, leading to a more stable and reliable recognition of Pb than that of analyses based on single fluorescent reporter. The aptamer probe allowed to a mix-and-read, rapid, cost-effective detection of Pb with high specificity and accuracy. Pb analysis in tap water and tea exhibited good performance with recovery rates of 92.3%-109.0%. The adoption of ratiometric metal-induced G-quadruplex polymorphism would be a compelling design strategy for constructing robust aptasensor, facilitating the translation of aptamer for food safety control.
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http://dx.doi.org/10.1016/j.foodchem.2020.128425DOI Listing
May 2021

A Machine Learning Protocol for Predicting Protein Infrared Spectra.

Authors:
Sheng Ye Kai Zhong Jinxiao Zhang Wei Hu Jonathan D Hirst Guozhen Zhang Shaul Mukamel Jun Jiang

J Am Chem Soc 2020 11 30;142(45):19071-19077. Epub 2020 Oct 30.

Hefei National Laboratory for Physical Sciences at the Microscale, CAS Center for Excellence in Nanoscience, School of Chemistry and Materials Science, University of Science and Technology of China, Hefei, Anhui 230026, People's Republic of China.

Infrared (IR) absorption provides important chemical fingerprints of biomolecules. Protein secondary structure determination from IR spectra is tedious since its theoretical interpretation requires repeated expensive quantum-mechanical calculations in a fluctuating environment. Herein we present a novel machine learning protocol that uses a few key structural descriptors to rapidly predict amide I IR spectra of various proteins and agrees well with experiment. Its transferability enabled us to distinguish protein secondary structures, probe atomic structure variations with temperature, and monitor protein folding. This approach offers a cost-effective tool to model the relationship between protein spectra and their biological/chemical properties.
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http://dx.doi.org/10.1021/jacs.0c06530DOI Listing
November 2020

Ratiometric-enhanced G-Quadruplex Probes for Amplified and Mix-to-Read Detection of Mercury Pollution in Aquatic Products.

Authors:
Yanping Wu Yuxi Yue Sha Deng Guiping He Hong Gao Mi Zhou Kai Zhong Ruijie Deng

J Agric Food Chem 2020 Oct 15;68(43):12124-12131. Epub 2020 Oct 15.

College of Biomass Science and Engineering, Healthy Food Evaluation Research Center, Sichuan University, Chengdu 610065, China.

Mercury, as a global toxic pollutant, is easy to be accumulated in aquatic products and poses a great threat to human health. In this work, we proposed a mix-to-read, label-free, and robust assay for detecting mercury pollution in aquatic products by engineering a ratiometric-enhanced G-quadruplex probe. The transformation from the G-quadruplex to a hairpin-like structure allows us to confer a ratiometric and leveraged response to Hg, amplifying the signal-to-background ratio for Hg detection. Hg response was further improved by screening parallel- and antiparallel-, single-, and multiple-stranded G-quadruplex structures. Compared to the common aptamer probes, the ratiometric-enhanced G-quadruplex probe increased the sensitivity for Hg detection by 4.7 times. This proposed sensing system allowed a simple and one-tube homogenous detection of Hg at room temperature using a single unlabeled DNA sequence. Its application for Hg detection in fish and shrimp conferred satisfactory recovery rates ranging from 98.5 to 105.9%. The label-free and mix-to-read assay is promising for the onsite detection of mercury pollution and facilitating food safety of aquatic products.
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http://dx.doi.org/10.1021/acs.jafc.0c05658DOI Listing
October 2020

Ultra-High-Resolution MRI Study of Age-Related Brain Subcortical Susceptibility Alteration in Rhesus Monkeys at 9.4 T.

Authors:
Qingqing Wen Hongyi Yang Jiali Li Jin Zhang Haiyang Tong Qiong Ye Kai Zhong

Front Aging Neurosci 2020 14;12:259. Epub 2020 Aug 14.

High Magnetic Field Laboratory, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, China.

Iron concentration in the brain has been suggested as a biomarker of pathologic neurodegeneration. However, the iron concentration changes in healthy aging as well. This study aimed to quantify the age-related changes in iron concentration in the gray matter of healthy rhesus monkeys using quantitative susceptibility mapping (QSM). Three-dimensional gradient-echo images of 16 female rhesus monkey brains aged between 2 and 26 years were acquired . The susceptibilities in the brain regions of the caudate nucleus (Cd), putamen (Pt), globus pallidus (Gp), and substantia nigra (Sn) were analyzed. The susceptibility varied across different brain regions, with higher levels in the Gp and Sn. Susceptibilities in all analyzed brain regions were linearly correlated with age, yet the plateau period as observed in human brains was absent. This is the first report of the age-related variability of susceptibility in the deep gray matter of rhesus monkey brains at 9.4 T, with an isotropic resolution of 150 μm. Awareness of age-related changes in susceptibility is vital for the establishment of a baseline to facilitate the differentiation of pathologic neurodegeneration from healthy aging in non-human primate studies.
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http://dx.doi.org/10.3389/fnagi.2020.00259DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7461968PMC
August 2020

High-energy, tunable, long-wave mid-infrared optical parametric oscillator based on BaGaSe crystal.

Authors:
Degang Xu Jiaxin Zhang Yixin He Yuye Wang Jiyong Yao Yangwu Guo Chao Yan Longhuang Tang Jining Li Kai Zhong Yicheng Wu Jianquan Yao

Opt Lett 2020 Sep;45(18):5287-5290

A high-energy, tunable, long-wave mid-infrared optical parametric oscillator (OPO) based on the crystal was demonstrated in this Letter with 1064 nm laser pumping. The mid-infrared OPO was designed as a double-pass single resonant oscillator (DP-SRO) to reduce the threshold and improve the outputs. Further optimization on the cavity length was theoretically and experimentally studied. With a short cavity length of 30 mm, the output energy of over 1 mJ/pulse at 11 µm was obtained with the pump energy of 39.5 mJ/pulse. In addition, a wide tuning range of 8-14 µm was experimentally achieved by rotating the crystal.
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http://dx.doi.org/10.1364/OL.401956DOI Listing
September 2020

Dynamic changes in vascular size and density in transgenic mice with Alzheimer's disease.

Authors:
Xiaowen Xu Tong Meng Qingqing Wen Mengling Tao Peijun Wang Kai Zhong Yong Shen

Aging (Albany NY) 2020 Sep 9;12(17):17224-17234. Epub 2020 Sep 9.

Institute on Aging and Brain Disorders, First University Affiliated Hospital, Neurodegenerative Disorder Research Center, Division of Life and Medical Sciences, University of Science and Technology of China, Hefei Material Science National Laboratory at Microscale, CAS-Key Laboratory of Brain Functions and Brain Disorders, Center for Excellent in Brain Science and Intelligence Technology, Hefei, China.

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases. Here, we used vessel size imaging to investigate the specific microvascular changes and most susceptible brain regions during AD progression in an amyloid precursor protein 23 (APP23) transgenic AD mouse model. Using 9.4 Tesla magnetic resonance imaging (MRI), the values of microvascular density (Density), mean vessel diameter (mVD), and vessel size index (VSI) were compared between APP23 and wild-type (WT) mice at 3, 6, 9, 14, and 20 months of age. Our results demonstrate that in 20-month old APP23 and WT mice, the Density values were significantly decreased, while the vascular dilatation and diameter had increased. However, a transient increase in the cortex Density at 14-months was observed in APP23 mice. Additionally, our results suggest that the hippocampus is the susceptible brain region affected by the abnormal microvascular angiogenesis during the early stages of AD. Together, our findings indicate that vessel size imaging using MRI can provide novel biomarkers for the early detection of AD, and for monitoring the effects of vascular-targeted therapeutics in AD.
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http://dx.doi.org/10.18632/aging.103672DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7521516PMC
September 2020

Acrylamide exposure represses neuronal differentiation, induces cell apoptosis and promotes tau hyperphosphorylation in hESC-derived 3D cerebral organoids.

Authors:
Qian Bu Yan Huang Meng Li Yanping Dai Xin Fang Ke Chen Qian Liu Aiqin Xue Kai Zhong Yina Huang Hong Gao Xiaobo Cen

Food Chem Toxicol 2020 Oct 5;144:111643. Epub 2020 Aug 5.

West China School of Public Health and Heathy Food Evaluation Research Center and West China Fourth Hospital, Sichuan University, Chengdu 610041, China; National Chengdu Center for Safety Evaluation of Drugs, State Key Lab of Biotherapy/Collaborative Innovation Center of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, 610041, China. Electronic address:

Acrylamide (ACR) is a common food contaminant with neurotoxic effects that are formed in the Maillard browning reaction during the heat processing of food. Importantly, pregnant women are also exposed to ACR in food during pregnancy and thus, the fetus is likely affected. However, the mechanisms of ACR-caused neurotoxicity on human brain development are still unclear. Many recent studies employed cerebral organoids based on human embryonic stem cells (hESC) for investigating human neurodevelopmental disorders and toxicity. Here, we generated hESC-derived cerebral organoids to evaluate the neurodevelopmental toxicity of ACR. The results indicated that exposure to ACR significantly altered the transcriptional profile, increased nuclear factor erythroid 2-related factor 2 (NRF2)-mediated gene expression, induced cell apoptosis, repressed neuronal differentiation, and promoted tau hyperphosphorylation in cerebral organoids, which may contribute to ACR-induced neurodevelopmental toxicity. These results indicate that the risk of transplacental exposure of the fetus to ACR should be evaluated and pregnant mothers should limit their exposure to ACR.
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http://dx.doi.org/10.1016/j.fct.2020.111643DOI Listing
October 2020

Modified BBO-Based Multivariate Time-Series Prediction System With Feature Subset Selection and Model Parameter Optimization.

Authors:
Xiaodong Na Min Han Weijie Ren Kai Zhong

IEEE Trans Cybern 2020 Jul 8;PP. Epub 2020 Jul 8.

Multivariate time-series prediction is a challenging research topic in the field of time-series analysis and modeling, and is continually under research. The echo state network (ESN), a type of efficient recurrent neural network, has been widely used in time-series prediction, but when using ESN, two crucial problems have to be confronted: 1) how to select the optimal subset of input features and 2) how to set the suitable parameters of the model. To solve this problem, the modified biogeography-based optimization ESN (MBBO-ESN) system is proposed for system modeling and multivariate time-series prediction, which can simultaneously achieve feature subset selection and model parameter optimization. The proposed MBBO algorithm is an improved evolutionary algorithm based on biogeography-based optimization (BBO), which utilizes an S-type population migration rate model, a covariance matrix migration strategy, and a Lévy distribution mutation strategy to enhance the rotation invariance and exploration ability. Furthermore, the MBBO algorithm cannot only optimize the key parameters of the ESN model but also uses a hybrid-metric feature selection method to remove the redundancies and distinguish the importance of the input features. Compared with the traditional methods, the proposed MBBO-ESN system can discover the relationship between the input features and the model parameters automatically and make the prediction more accurate. The experimental results on the benchmark and real-world datasets demonstrate that MBBO outperforms the other traditional evolutionary algorithms, and the MBBO-ESN system is more competitive in multivariate time-series prediction than other classic machine-learning models.
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http://dx.doi.org/10.1109/TCYB.2020.2977375DOI Listing
July 2020

Vibrational mode frequency correction of liquid water in density functional theory molecular dynamics simulations with van der Waals correction.

Authors:
Kai Zhong Chun-Chieh Yu Mayank Dodia Mischa Bonn Yuki Nagata Tatsuhiko Ohto

Phys Chem Chem Phys 2020 Jun;22(22):12785-12793

Graduate School of Engineering Science, Osaka University, 1-3 Machikaneyama, Toyonaka, Osaka 560-8531, Japan.

The frequencies and spectral lineshapes of the stretch and bending modes of water provide invaluable information on the microscopic structures of water in aqueous solutions and at the water/solid interfaces. Density functional theory molecular dynamics (DFT-MD) simulation has been used not only for predicting the properties of water but also for interpreting the vibrational spectra of water. Since the accuracy of the DFT-MD simulations relies on the choice of the exchange-correlation functionals and dispersion correction schemes employed, the predicted vibrational spectra at different levels of DFT theory differ significantly, prohibiting precise comparison of simulated spectra with experimental data. Here, we simulate the vibrational density of states for liquid heavy water based on various DFT-MD trajectories. We find that DFT-MD simulations tend to predict excessive inhomogeneous broadening for the stretch mode of water. Furthermore, we develop a frequency correction scheme for the stretch and bending modes of liquid water, which substantially improves the prediction of the vibrational spectra.
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http://dx.doi.org/10.1039/c9cp06335hDOI Listing
June 2020

Application of 9.4T MRI in Wilson Disease Model TX Mice With Quantitative Susceptibility Mapping to Assess Copper Distribution.

Authors:
Yongsheng Han Jianjian Dong Chenchen Xu Rao Rao Shan Shu Guangda Li Nan Cheng Yun Wu Hongyi Yang Yongzhu Han Kai Zhong

Front Behav Neurosci 2020 22;14:59. Epub 2020 Apr 22.

High Magnetic Field Laboratory, Hefei Institutes of Physical Science, Chinese Academy of Sciences (CAS), Hefei, China.

In the current study, we used 9.4-tesla magnetic resonance imaging (9.4T MRI) and inductively coupled plasma mass spectrometry (ICP-MS) to investigate the distribution of copper in the brain samples of a murine model of Wilson's disease (WD) following penicillamine (PCA) treatment. We also evaluated if the distribution of copper in the brain samples of mice was correlated with behavioral symptoms. Results from the behavioral experiments showed that 7 days of PCA treatment decreased the total distance traveled in the open field and the number of rearing and climbing instances among the toxic milk (TX) mice as compared with model group. We also observed that the open arm ratio in the elevated plus-maze (EPM) was reduced, escape latency in the Barnes maze test was increased, and avoidance in the open field was enhanced in TX mice following 14 days of PCA treatment as compared with those in untreated TX mice. We found that PCA treatment for 21-28 days improved the cognitive abilities, exploratory behavior, and movement behavior of TX mice. The PCA-treated mice also exhibited varying degrees of magnetic susceptibilities in the cortex, corpus striatum, hippocampus, and amygdaloid nucleus across the treatment period. Low copper concentrations were found in all of the analyzed brain regions of PCA-treated mice after 21-28 days as compared with the model group ( < 0.05). However, copper concentrations were increased in the primary motor cortex and cerebellum at 7 days post-PCA treatment as compared with those in the model group ( < 0.05). After 14 days of PCA treatment, the copper concentrations in the sensorimotor cortex, corpus striatum, hippocampus, and amygdaloid nucleus were higher than those detected without treatment. The results from a Pearson's correlation analysis revealed that there was a significant ( < 0.05) correlation between copper concentrations and magnetic susceptibility in all of the brain regions that were analyzed. Therefore, our results indicate that copper concentration and magnetic susceptibility are associated with alterations in mood-related behavior, recognition memory, and movement behaviors in TX mice that are treated with PCA. The redistribution of copper in the TX mouse brain during PCA treatment may aggravate changes in behavioral performance.
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http://dx.doi.org/10.3389/fnbeh.2020.00059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7189732PMC
April 2020

Two new cadmium(II) coordination polymers based on imidazole-containing ligands: synthesis, structural characterization and fluorescence properties.

Authors:
Bing Feng Li Xi Ting Xu Tong Min Dong Wan Ying Zhou Yang Gu Lei Gong Kai Long Zhong

Acta Crystallogr C Struct Chem 2020 Apr 5;76(Pt 4):314-321. Epub 2020 Mar 5.

School of Biology and Environment, Nanjing Polytechnic Institute, Nanjing 210048, People's Republic of China.

The judicious selection of suitable ligands is vitally important in the construction of novel metal-organic frameworks (MOFs) with fascinating structures and interesting properties. Recently, imidazole-containing multidentate ligands have received much attention. Two new Cd coordination frameworks, namely, poly[tris{μ-1,4-bis[(1H-imidazol-1-yl)methyl]benzene-κN:N}tetrakis(nitrato-κO,O')dicadmium], [Cd(NO)(CHN)], (I), and poly[[bis{μ-1,3,5-tris[(1H-imidazol-1-yl)methyl]benzene-κN:N:N}cadmium] hexafluorosilicate], {[Cd(CHN)](SiF)}, (II), have been synthesized and characterized by elemental analysis, IR spectroscopy and single-crystal X-ray diffraction. In polymer (I), the 1,4-bis[(1H-imidazol-1-yl)methyl]benzene ligand bridges Cd ions with a distorted seven-coordinated pentagonal bipyramidal geometry, forming a one-dimensional ladder chain, and the nitrate anions coordinate to the Cd ions in a terminal bidentate fashion. In the crystal, adjacent chains are further connected by C-H...O hydrogen bonds to generate a two-dimensional (2D) supramolecular structure. Polymer (II) exhibits a 2D layered structure in which 1,3,5-tris[(1H-imidazol-1-yl)methyl] benzene ligands join Cd centres having a six-coordinated octahedral structure. The layers are connected by hexafluorosilicate anions via C-H...F hydrogen-bond interactions, giving rise to a three-dimensional supramolecular network structure in the solid state. In addition, powder X-ray diffraction (PXRD) patterns were recorded, thermogravimetric analyses (TGA) carried out and fluorescence properties investigated.
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http://dx.doi.org/10.1107/S2053229620002594DOI Listing
April 2020

Zeolitic Metal Cluster Carboxylic Framework for Selective Carbon Dioxide Chemical Fixation through the Superlarge Cage.

Authors:
Kai Zhong Rui-Feng Yang Wen-Yan Zhang Yang-Tian Yan Xiao-Jie Gou Wen-Huan Huang Yao-Yu Wang

Inorg Chem 2020 Mar 5;59(6):3912-3918. Epub 2020 Mar 5.

Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of the Ministry of Education, Shaanxi Key Laboratory of Physico-Inorganic Chemistry, College of Chemistry & Materials Science, Northwest University, Xi'an 710127, P. R. China.

Metal-organic frameworks (MOFs) with zeolitic structure process fantastic structural metrics and display excellent applications in many aspects; however, they are difficult to assemble. Herein, on the basis of a tetrahedral ZnO cluster and a 3,5-bis(2,4-dicarboxylphenyl)nitrobenzene (HL) ligand, a novel sodalite (SOD) zeolitic cluster framework (ZCF), {[Zn(O)(L)]·4DMF·6HO} (; DMF = ,-dimethylformamide), has been hydrothermally synthesized. Compared with the traditional SOD zeolitic framework of ZIF-8, the cage size of is dramatically improved from 16.9 to 29.2 Å by the introduction of longer tetradentate carboxylic ligands. Moreover, because of the functional nitryl group in the ligand, exhibits a high CO/CH selectivity. Hence, further research on the chemical fixation of CO is implemented, which reveals excellent heterogeneous catalytic activity and durability. Especially, a unique selective catalytic performance with a high yield of 88.3% on a larger molecular size reactant (glycidyl phenyl ether) is observed, which is attributed to the stereoselection effect of the superlarge cage and abundant ZnO catalytic clusters in .
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http://dx.doi.org/10.1021/acs.inorgchem.9b03581DOI Listing
March 2020

Neuroprotective effects of saffron on the late cerebral ischemia injury through inhibiting astrogliosis and glial scar formation in rats.

Authors:
Kai Zhong Rou-Xin Wang Xiao-Dong Qian Ping Yu Xin-Ying Zhu Qi Zhang Yi-Lu Ye

Biomed Pharmacother 2020 Jun 26;126:110041. Epub 2020 Feb 26.

School of Basic Medical Sciences & Forensic Medicine, Hangzhou Medical College, Hangzhou, Zhejiang, China. Electronic address:

This study is to explore the neuroprotective effects and involved glial scar of saffron (Crocus sativus L.) on the late cerebral ischemia in rats. Focal cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) in Sprague Dawley rats that were randomly divided into sham group, MCAO group, edaravone group (as a positive control) and saffron groups (saffron extract 30, 100, 300 mg/kg). Saffron was administered orally at 2 h at the first day and once daily from day 2 to 42 after ischemia. Behavioral changes were detected from day 43 to 46 after ischemia to evaluate the effects of saffron. Infarct volume, survival neuron density, activated astrocyte, and the thickness of glial scar were also detected. GFAP, neurocan, phosphocan, neurofilament expressions and inflammatory cytokine contents were detected by Western-blotting and ELISA methods, respectively. Saffron improved the body weight loss, neurological deficit and spontaneous activity. It also ameliorated anxiety-like state and cognitive dysfunction, which were detected by elevated plus maze (EPM), marble burying test (MBT) and novel object recognition test (NORT). Toluidine blue staining found that saffron treatment decreased the infarct volume and increased the neuron density in cortex in the ischemic boundary zone. The activated astrocyte number and the thickness of glial scar in the penumbra zone reduced after saffron treatment. Additionally, saffron decreased the contents of IL-6 and IL-1β, increased the content of IL-10 in the ischemic boundary zone. GFAP, neurocan, and phosphocan expressions in ischemic boundary zone and ischemic core zone all decreased after saffron treatment. Saffron exerted neuroprotective effects on late cerebral ischemia, associating with attenuating astrogliosis and glial scar formation after ischemic injury.
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http://dx.doi.org/10.1016/j.biopha.2020.110041DOI Listing
June 2020

Untargeted lipidomic analysis of human hippocampus for temporal lobe epilepsy with hippocampal sclerosis.

Authors:
Heng Zhang Peng Ren Yan Huang Weiying Zeng Kai Zhong Hong Gao Xiaobo Cen Qian Bu

Epilepsy Res 2020 03 19;161:106299. Epub 2020 Feb 19.

Department of Food Science and Technology, College of Biomass and Engineering and Healthy Food Evaluation Research Center, Sichuan University, Chengdu, 610065, China; National Chengdu Center for Safety Evaluation of Drugs, State Key Lab of Biotherapy/Collaborative Innovation Center of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, 610041, China. Electronic address:

Mesial temporal lobe epilepsy (mTLE), a very common chronic neurological disorder, is frequently accompanied by neurodegeneration in the hippocampus, resulting in hippocampal sclerosis (HS); HS is the most common morphological correlate of drug resistance in mTLE patients. Incomplete knowledge of pathological changes in mTLE with HS complicates its therapy. Growing evidence indicates a role of lipid signaling pathways in epileptogenesis; thus, lipid signals emerge as potential biomarkers for the onset and evolving course of this epileptic disorder, and are potential therapeutic agents and targets. Therefore, in this study, we recruited 23 patients with medically intractable mTLE-HS and 24 non-mTLE-HS controls. We applied lipidomic analysis to identify the lipidomic profiles in the hippocampal samples of both groups. The lipidomic profiles of the hippocampus were distinctive between mTLE-HS patients and controls. We also observed that the abundance of total triglycerides showed a striking reduction in the hippocampus of mTLE-HS patients. We identified that 33 lipids were significantly differentially expressed in the hippocampus of mTLE-HS patients compared with those in the hippocampus of the controls; this might contribute to target some molecular mechanisms involved in epileptogenesis. The present study therefore reports that lipidomic changes in mTLE-HS patients may contribute to the molecular architecture of an epileptic brain.
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http://dx.doi.org/10.1016/j.eplepsyres.2020.106299DOI Listing
March 2020

Extracellular production of recombinant trefoil factor 3 by .

Authors:
He-Ping Li Chun-Mei Xu Bing-Yan Wen An-Qi Li Guang-Ming Zha Xiang-Yang Jin Yun-Ze Zhao Lu-Ping Feng Ye-Dong Cao Guo-Yu Yang Yue-Ying Wang Kai Zhong

Exp Ther Med 2020 Mar 28;19(3):2149-2154. Epub 2020 Jan 28.

Key Laboratory of Animal Biochemistry and Nutrition, Ministry of Agriculture, Henan Agricultural University, Zhengzhou, Henan 450002, P.R. China.

Trefoil factor 3 (TFF3) is involved in cell adhesion, motility and apoptosis, regulates mucosal immunity and maintains the functional integrity of intestinal epithelia. The upregulation of TFF3 expression in the weaning rat intestine attracted our interest. The present study hypothesized that TFF3 may serve a role in preventing diarrhea in weaning piglets, which is an important consideration in the pig farming industry. Previous recombinant TFF3 protein expression yields obtained from were too low and the bioactivity of the protein was poor. Hence, this expression system was unsuitable for industrial applications. The present study explored the production of recombinant TFF3 in a expression system, aiming to enhance the expression level of bioactive protein. To achieve this, the TFF3-encoding gene fragment was fused into an shuttle vector pNCMO2. High levels of TFF3 (30 mg/l) were produced and secreted into the culture medium in soluble form with a molecular mass of 13.6 kDa and high immunoreactivity in western blotting. Thus, may be used to produce useful mucosal factors for biochemical analyses and mucosal protection, and in industrial applications to produce novel inhibitors of diarrhea.
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http://dx.doi.org/10.3892/etm.2020.8477DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7027283PMC
March 2020

Insight into effects of isolated Eurotium cristatum from Pingwu Fuzhuan brick tea on the fermentation process and quality characteristics of Fuzhuan brick tea.

Authors:
Yue Xiao Kai Zhong Jin-Rong Bai Yan-Ping Wu Hong Gao

J Sci Food Agric 2020 Jul 20;100(9):3598-3607. Epub 2020 Apr 20.

College of Biomass Science and Engineering and Healthy Food Evaluation Research Center, Sichuan University, Chengdu, China.

Background: Pingwu Fuzhuan brick tea is a type of post-fermented tea manufactured from leaves of the tea plant, Camellia sinensis var. sinensis, the quality of which is influenced by numerous factors, especially microorganisms. Currently, there is little research on the effect of microorganisms on the fermentation and quality characteristics of Pingwu Fuzhuan brick tea. Investigation of the main fungus in this tea and its effect on the fermentation process and tea quality can provide insights into the manufacturing of 'western road' border-selling tea and could lay the foundation for the popularization of Pingwu Fuzhuan brick tea.

Results: The main 'golden flower fungus' in Pingwu Fuzhuan brick tea was isolated and identified as Eurotium cristatum (GenBank accession number: MF800948.1; strain PW-1). Compared with natural fermentation, PW-1 inoculated fermentation accelerated biotransformation of phenolic compounds, which provided tea samples with better taste and tea infusion color. The proportions of velvety and sweet-tasting amino acids increased after 16-day fermentation with PW-1. Alcohols were the most abundant volatiles, with 40.13% and 39.43% content in NF16d and IF16d tea samples, respectively. Orthogonal partial least-squares discriminant analysis (OPLS-DA) and hierarchical clustering analysis (HCA) further revealed that naturally fermented and PW-1 fermented teas were significantly different.

Conclusion: Strain PW-1 plays an important role in the fermentation process of Fuzhuan brick tea. Considering fermentation efficiency and tea quality, fermentation inoculated with E. cristatum PW-1 can be applied in the manufacturing of 'western road' border-selling tea. © 2020 Society of Chemical Industry.
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http://dx.doi.org/10.1002/jsfa.10353DOI Listing
July 2020

What makes smartphone games successful in food information communication?

Authors:
Liran Christine Shan Julie L Schiro Kai Zhong Patrick Wall

NPJ Sci Food 2020 30;4. Epub 2020 Jan 30.

1Institute of Food and Health, University College Dublin, Belfield, Dublin, 4 Republic of Ireland.

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http://dx.doi.org/10.1038/s41538-020-0062-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6992668PMC
January 2020

Structural Characteristics and Hypolipidemic Activity of Theabrownins from Dark Tea Fermented by Single Species PW-1.

Authors:
Yue Xiao Maoyun Li Yanping Wu Kai Zhong Hong Gao

Biomolecules 2020 01 30;10(2). Epub 2020 Jan 30.

College of Biomass Science and Engineering and Healthy Food Evaluation Research Center, Sichuan University, Chengdu 610065, China.

Recently, studies on theabrownins (TBs), the main bioactive polymeric pigments found in dark tea, have received increasing attention for its health effects. Thus far, information on their structural characteristics is unclear. In the present study, theabrownins were isolated from single species PW-1-fermented loose tea and their structural and hypolipidemic characteristics were studied for the first time. The theabrownins were fractionated by their molecular weights and were then analyzed. Ultraviolet-visible spectrophotometry (UV-Vis) and Flourier transformation infrared spectroscopy (FT-IR) showed that they were polymerized phenolic substances containing abundant hydroxy and carboxyl groups. All theabrownin samples exhibited hypolipidemic activity in high-fat zebrafish; among which TBs-10-30k sample, decreased lipid level in high-fat zebrafish to 51.57% at 1000 μg/mL, was most effective. It was found that TBs-10-30k was a type of amorphous and thermostable polymer with slice shape and smooth surface under scanning electron microscope (SEM). Atomic force microscope (AFM) analysis showed that it had island-like structure because of aggregation of theabrownin molecules. Pyrolysis-gas chromatography-mass spectrometry (Py-GC-MS) analysis further showed that the main pyrolytic products of TBs-10-30k were hexadecanoic acid (33.72%), phenol (14.90%), and eicosane (12.95%), indicating TBs-10-30k was mainly composed of phenols, lipids, saccharides, and proteins. These results not only facilitate subsequent identification of theabrownins, but also provide insights into the applications of theabrownins in functional foods.
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http://dx.doi.org/10.3390/biom10020204DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072556PMC
January 2020

Defect Engineering of MoS for Room-Temperature Terahertz Photodetection.

Authors:
Ying Xie Fei Liang Shumeng Chi Dong Wang Kai Zhong Haohai Yu Huaijin Zhang Yanxue Chen Jiyang Wang

ACS Appl Mater Interfaces 2020 Feb 28;12(6):7351-7357. Epub 2020 Jan 28.

State Key Laboratory of Crystal Materials and Institute of Crystal Materials , Shandong University , Jinan 250100 , China.

Two-dimensional (2D) materials have exotic intrinsic electronic band structures and are considered as revolutionary foundations for novel nanodevices. Band engineering of 2D materials may pave a new avenue to overcome numerous challenges in modern technologies, such as room temperature (RT) photodetection of light with photon energy below their band gaps. Here, we reported the pioneering RT MoS-based photodetection in the terahertz (THz) region via introducing Mo and S vacancies for rational band gap engineering. Both the generation and transport of extra carriers, driven by THz electromagnetic radiations, were regulated by the vacancy concentration as well as the resistivity of MoS samples. Utilizing the balance between the carrier concentration fluctuation and carrier-scattering probability, a high RT photoresponsivity of 10 mA/W at 2.52 THz was realized in an Mo-vacancy-rich MoS sample. This work overcomes the challenge in the excessive dark current of RT THz detection and offers a convenient way for further optoelectronic and photonic devices based on band gap-engineered 2D materials.
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http://dx.doi.org/10.1021/acsami.9b21671DOI Listing
February 2020

Preliminary study on fine structures of subcortical nuclei in rhesus monkeys by 9.4 T MRI.

Authors:
Huan-Zhi Chen Hong-Yi Yang Kai Zhong Jia-Li Li

Zool Res 2020 Mar;41(2):199-202

Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China.

Changes in fine structures of the brain over a life span can have robust effects on neural activity and brain function, which both play crucial roles in neurodegenerative diseases. Clinically, however, low-resolution MRI only provides limited information about fine brain structures. Here, using high-resolution 9.4 T MRI, we established a set of structural images and explored the fine structures of the claustrum, hippocampus, amygdala complex, and subregions of the amygdala complex (BLA, including lateral, basal, and accessory basal subnuclei) in rhesus macaque () brains. Based on these high-resolution images, we were able to discriminate the subregional boundaries accurately and, at the same time, obtain the volume of each brain nuclei. Thus, advanced high-resolution 9.4 T MRI not only provides a new strategy for early diagnosis of neurodegenerative diseases, but also provides the ability to observe fine structural changes in the brain across a life span.
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http://dx.doi.org/10.24272/j.issn.2095-8137.2020.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7109013PMC
March 2020

Spatial Distribution and Formation Mechanism of Water-soluble Inorganic Ions in PM During a Typical Winter Haze Episode in Guilin, China.

Authors:
Tengfa Long Bin Peng Zhihui Yang Cynthia Sabrine Ishimwe Chongjian Tang Ning Zhao Hong Lin Kai Zhong Shan Zhong

Arch Environ Contam Toxicol 2020 Apr 1;78(3):367-376. Epub 2020 Jan 1.

Key Laboratory of Ecology of Rare and Endangered Species and Environmental Protection (Guangxi Normal University), Ministry of Education, Guilin, China.

A 5-day PM sampling campaign was conducted during a typical haze episode from December 16 to 20, 2016, at five urban sites and one background site in Guilin, a famous tourist city in Southern China. A total of 30 PM samples were collected, and water-soluble inorganic ions (WSII) (SO, NO, NH, Ca, K Cl, Na, and Mg) were determined using ion chromatography. Correlation analysis, principal component analysis, and coefficient of divergence were applied to identify the formation mechanisms of secondary inorganic ions, potential sources, and spatial distribution of WSII. The average mass concentrations of PM at each sampling site were 71.6-127.85 μg m, which were more than the National Ambient Air Quality Standard (GB3095-2012, GradeII (35 μg m)) in China. SO NO, and NH were the major WSII, accounting for 34.43-40.59% of PM mass. NO/SO ratio revealed that stationary sources-induced PM was still remarkable. Cl/Na ratio and their strong correlation (r = 0.824) indicated that atmospheric transport from outside urban region played an effective role during the haze episode. Spatial variations of WSII are not pronounced at five urban sites except the background site. High relative humidity and O contributed to evidently influence the transformation of SO to SO but not obvious to NO oxidation. Finally, the major sources of WSII are identified as the mixture of sea salt, coal combustion, biomass burning, vehicle exhaust and agricultural emissions (66.892%), and fugitive sources (19.7%).
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http://dx.doi.org/10.1007/s00244-019-00699-6DOI Listing
April 2020

HS mediates apoptosis in response to inflammation through PI3K/Akt/NFκB signaling pathway.

Authors:
Yueying Wang Chengyu Zhang Chunmei Xu Luping Feng Anqi Li Xiangyang Jin Shuang Guo Xianqin Jiao Jingsong Liu Yujie Guo Heshui Zhu Liqiang Han Guoyu Yang Kai Zhong Heping Li

Biotechnol Lett 2020 Mar 23;42(3):375-387. Epub 2019 Dec 23.

Key Laboratory of Animal Biochemistry and Nutrition, Ministry of Agriculture, Henan Agricultural University, Zhengzhou, 450046, Henan, People's Republic of China.

Objectives: Hydrogen sulfide (HS) is involved in regulating cell apoptosis and proliferation. However, The effects and mechanism of HS on the apoptosis of mammary epithelial cells that suffer from an inflammatory response remain unknown.

Results: An inflammatory cell model was used to explore whether exogenous HS regulates lipopolysaccharides (LPS)-induced cell proliferation and apoptosis. We found that HS affected cell viability, the inflammatory response and apoptosis in LPS-treated cells in a concentration-dependent manner. Moreover, exogenous HS rescued LPS-induced cystathionine γ-lyase (CSE) inhibition and cystathionine β-synthase (CBS) synthesis. Interestingly, in cells undergoing inflammation-induced apoptosis, HS activated the PI3K/Akt and NFκB signal pathways both tested concentrations. Akt appeared to be a key crosstalk molecule that played a "bridge" role.

Conclusions: HS regulates LPS-induced inflammation and apoptosis by activating the PI3K/Akt/NFκB signaling pathway. Hence, NaHS may be clinically useful for preventing or treating mastitis.
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http://dx.doi.org/10.1007/s10529-019-02782-3DOI Listing
March 2020

UNC5C‑knockdown enhances the growth and metastasis of breast cancer cells by potentiating the integrin α6/β4 signaling pathway.

Authors:
Mingjing Yuan Fuan Xie Xianyuan Xia Kai Zhong Lanlan Lian Shihui Zhang Li Yuan Jun Ye

Int J Oncol 2020 Jan 2;56(1):139-150. Epub 2019 Dec 2.

State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, P.R. China.

Unc‑5 Netrin Receptor C (UNC5C) is a netrin‑1 dependence receptor that mediates the induction of apoptosis in the absence of netrin‑1. The present study found that UNC5C is heterogeneously expressed in breast cancer cell lines. By knocking down UNC5C in SK‑BR‑3 and ZR‑75‑30 cells and overexpressing UNC5c in MDA‑MB‑231 cells, it was demonstrated that UNC5C exerts an inhibitory effect on the growth and metastasis of breast cancer cells. The mechanism involved a UNC5C‑knockdown‑induced enhancement of matrix metalloproteinase (MMP)3, MMP7, MMP9 and MMP10 expression via activation of the PI3K/AKT, ERK and p38 MAPK signaling pathways. Notably, UNC5C directly interacted with integrin α6, which is involved in the growth and metastasis of breast cancer cells. Additionally, UNC5C‑knockdown enhanced the phosphorylation of FAK and SRC, which are key kinases in the netrin‑1/Unc5C and netrin‑1/integrin α6/β4 signaling pathways. This suggests that netrin‑1 functions as an integrator for both the netrin‑1/Unc5C and netrin‑1/integrin α6/β4 signaling pathways. UNC5C‑knockdown potentiated netrin‑1/integrin α6/β4 signaling. Given that UNC5C‑knockdown inhibited integrin‑liked protein kinase phosphorylation at Thr‑173, at least in SK‑BR‑3 cells, this may be an inhibitory phosphorylation site rather than activating phosphorylation site for relaying integrin signaling.
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http://dx.doi.org/10.3892/ijo.2019.4931DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6910211PMC
January 2020

Tunable dual-color terahertz wave parametric oscillator based on KTP crystal.

Authors:
Longhuang Tang Degang Xu Yuye Wang Chao Yan Yixin He Jining Li Kai Zhong Jianquan Yao

Opt Lett 2019 Dec;44(23):5675-5678

A tunable dual-color KTP terahertz (THz) wave parametric oscillator (TPO) pumped by a dual-wavelength laser was proposed in this Letter. Theoretical analysis denotes that the emission of a tunable dual-color THz wave can be achieved by the simultaneous stimulated polariton scattering processes from multiple A1-symmetry phonon modes of the KTP crystal. The tunable dual-color THz wave emitted from KTP TPO was demonstrated in our experiment, where the THz frequencies simultaneously tuned from 3.15 THz to 11.63 THz and from 1.47 THz to 6.03 THz with some gaps. The maximum dual-color THz output energy of 1.31 μJ was obtained under the THz frequencies of 5.94 THz and 4.42 THz. Moreover, at a certain phase-matching angle, the THz output energies for the two frequencies were independent, which means that the dual-color THz wave emission with any energy ratio can be achieved by adjusting the pump energy ratio between a dual-wavelength laser.
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http://dx.doi.org/10.1364/OL.44.005675DOI Listing
December 2019

Tetramethylpyrazine Reduces Epileptogenesis Progression in Electrical Kindling Models by Modulating Hippocampal Excitatory Neurotransmission.

Authors:
Yan Jin Song Cai Yuepeng Jiang Kai Zhong Chengping Wen Yeping Ruan Lindsey A Chew Rajesh Khanna Zhenghao Xu Jie Yu

ACS Chem Neurosci 2019 12 6;10(12):4854-4863. Epub 2019 Dec 6.

Department of Pharmacology , University of Arizona College of Medicine and College of Pharmacy , Tucson , Arizona 85724 , United States.

Antiepileptic drugs (AEDs) are the primary agents prescribed for clinical management of limbic epilepsy. However, high incidence of pharmacoresistance and a limited armory of drugs for inhibiting the pathological progression of epilepsy pose major obstacles to managing epilepsy. Here, we investigated the effect of tetramethylpyrazine (TMP), the main bioactive alkaloid isolated from the oriental medicine , against the epileptogenesis progression of acute hippocampal and corneal (6 Hz) electrical kindling models of TLE. TMP dose-dependently limited the progression of seizures and reduced the after-discharge duration (ADDs) in a hippocampal mouse kindling model. Mice treated with TMP (20, 50 mg/kg, i.p.) remained in stage 1 of epileptic progression for a protracted period, requiring additional stimulation to induce stages 2-5 epileptic phenotypes. TMP (50 mg/kg) also inhibited 6 Hz corneal kindling progression. In contrast, TMP did not reverse the phenotypes induced in a generalized seizures (GS) model, or the maximal electroshock (MES) or pentylenetetrazole (PTZ)-induced models of epilepsy. Furthermore, patch clamp recordings revealed no effect of TMP (10 μM) on CA1 hippocampal neurons' intrinsic properties but suppressed the (i) frequency of spontaneous excitatory post synaptic currents (sEPSCs), (ii) paired pulse ratio (PPR), and (iii) long-term potentiation (LTP) induction in the Schaffer collateral-CA1 pathway. TMP suppressed the activity of calcium, but not sodium, channels. Taken together, these results suggest that TMP has an antiepileptogenic effect, likely through suppression of excitatory synaptic transmission by its effects on inhibition of calcium channels; these traits distinguish TMP from currently available AEDs. As mice administered TMP did not show any neurologic impairment in the object recognition and open field tests, the data support further development of TMP as a promising treatment for epilepsy.
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http://dx.doi.org/10.1021/acschemneuro.9b00575DOI Listing
December 2019