Synthesis and structure–activity relationship of N-(piperidin-4-yl)benzamide derivatives as activators of hypoxia-inducible factor 1 pathways

Zhi-Ning Huang,Han Liang,Hong Qiao,Bao-Rui Wang,Ning Qu,Hua Li,Run-Run Zhou,Li-Juan Wang,Shan-Hua Li,Fu-Nan Li 대한약학회 2018 Archives of Pharmacal Research Vol.41 No.12

Guided by bioisosterism and pharmacokinetic parameters, we designed and synthesized a series of novel benzamide derivatives. Preliminary in vitro studies indicated that compounds 10b and 10j show significant inhibitory bioactivity in HepG2 cells (IC50 values of 0.12 and 0.13 μM, respectively). Compounds 10b and 10j induced the expression of HIF-1α protein and downstream target gene p21, and upregulated the expression of cleaved caspase-3 to promote tumor cells apoptosis.

Portable Low-Cost MRI System Based on Permanent Magnets/Magnet Arrays

Huang, Shaoying,Ren, Zhi Hua,Obruchkov, Sergei,Gong, JIa,Dykstra, Robin,Yu, Wenwei Korean Society of Magnetic Resonance in Medicine 2019 Investigative Magnetic Resonance Imaging Vol.23 No.3

Portable low-cost magnetic resonance imaging (MRI) systems have the potential to enable "point-of-care" and timely MRI diagnosis, and to make this imaging modality available to routine scans and to people in underdeveloped countries and areas. With simplicity, no maintenance, no power consumption, and low cost, permanent magnets/magnet arrays/magnet assemblies are attractive to be used as a source of static magnetic field to realize the portability and to lower the cost for an MRI scanner. However, when taking the canonical Fourier imaging approach and using linear gradient fields, homogeneous fields are required in a scanner, resulting in the facts that either a bulky magnet/magnet array is needed, or the imaging volume is too small to image an organ if the magnet/magnet array is scaled down to a portable size. Recently, with the progress on image reconstruction based on non-linear gradient field, static field patterns without spatial linearity can be used as spatial encoding magnetic fields (SEMs) to encode MRI signals for imaging. As a result, the requirements for the homogeneity of the static field can be relaxed, which allows permanent magnets/magnet arrays with reduced sizes, reduced weight to image a bigger volume covering organs such as a head. It offers opportunities of constructing a truly portable low-cost MRI scanner. For this exciting potential application, permanent magnets/magnet arrays have attracted increased attention recently. A magnet/magnet array is strongly associated with the imaging volume of an MRI scanner, image reconstruction methods, and RF excitation and RF coils, etc. through field patterns and field homogeneity. This paper offers a review of permanent magnets and magnet arrays of different kinds, especially those that can be used for spatial encoding towards the development of a portable and low-cost MRI system. It is aimed to familiarize the readers with relevant knowledge, literature, and the latest updates of the development on permanent magnets and magnet arrays for MRI. Perspectives on and challenges of using a permanent magnet/magnet array to supply a patterned static magnetic field, which does not have spatial linearity nor high field homogeneity, for image reconstruction in a portable setup are discussed.

Numerical investigation of the three-dimensional dynamic process of sabot discard

HUANG Zhen-gui,WESSAM Mahfouz Elnaggar,CHEN Zhi-hua 대한기계학회 2014 JOURNAL OF MECHANICAL SCIENCE AND TECHNOLOGY Vol.28 No.7

The sabot discard process of an armor-piercing, fin-stabilized discarding sabot (APFSDS) is crucial for the flight stability of the projectile. In this paper, the sabot discard behavior after projectile ejection from the muzzle is investigated at Mach number 4.0 and angle ofattack of 0°. 3D compressible equations implemented with a dynamic unstructured tetrahedral mesh are numerically solved with a commercialcomputational fluid dynamics (CFD) code (FLUENT 12.0). Six-degrees-of-freedom (6DOF) rigid-body motion equations issolved with the CFD results through a user-defined function to update the sabot trajectory at every time step. A combination of springbasedsmoothing and local re-meshing is employed to regenerate the meshes around the sabot and describe its movement at each timestep. Computational results show three different separation processes during the sabot discard process. Furthermore, the aerodynamicforces of APFSDS are calculated, and the trajectories of the three sabots are illustrated through the numerical solution of 6DOF equations. The results of the present study agree well with typical experimental results and provide detailed parameters that are important for analyzingthe stability of the projectile. The present computations confirm that the numerical solution of the governing equations of aerodynamicsand 6DOF rigid-body equations are a feasible method to study the sabot discard processes of APFSDS.

Remarkable impact of amino acids on ginsenoside transformation from fresh ginseng to red ginseng

Zhi Liu,Xin Wen,Chong-Zhi Wang,Wei Li,Wei-Hua Huang,Juan Xia,Chang-Chun Ruan,Chun-Su Yuan 고려인삼학회 2020 Journal of Ginseng Research Vol.44 No.3

Background: Amino acids are one of the major constituents in Panax ginseng, including neutral aminoacid, acidic amino acid, and basic amino acid. However, whether these amino acids play a role in ginsenosideconversion during the steaming process has not yet been elucidated. Methods: In the present study, to elucidate the role of amino acids in ginsenoside transformation fromfresh ginseng to red ginseng, an amino acids impregnation pretreatment was applied during thesteaming process at 120 C. Acidic glutamic acid and basic arginine were used for the acid impregnationtreatment during the root steaming. The ginsenosides contents, pH, browning intensity, and free aminoacids contents in untreated and amino acidetreated P. ginseng samples were determined. Results: After 2 h of steaming, the concentration of less polar ginsenosides in glutamic acidetreatedP. ginseng was significantly higher than that in untreated P. ginseng during the steaming process. However,the less polar ginsenosides in arginine-treated P. ginseng increased slightly. Meanwhile, free aminoacids contents in fresh P. ginseng, glutamic acid-treated P. ginseng, and arginine-treated P. ginsengsignificantly decreased during steaming from 0 to 2h. The pH also decreased in P. ginseng samples at hightemperatures. The pH decrease in red ginseng was closely related to the decrease in basic amino acidslevels during the steaming process. Conclusion: Amino acids can remarkably affect the acidity of P. ginseng sample by altering the pH value. Theywere the main influential factors for the ginsenoside transformation. These results are useful in elucidatingwhy andhowsteaming induces the structural change of ginsenoside in P. ginseng and also provides an effectiveand green approach to regulate the ginsenoside conversion using amino acids during the steaming process.

Cloning, Expression, and Characterization of Endoglucanase Gene egIV from Trichoderma viride AS 3.3711

( Huang Xiao Mei ),( Jin Xia Fan ),( Qian Yang ),( Xiu Ling Chen ),( Zhi Hua Liu ),( Yun Wang ),( Da Qing Wang ) 한국미생물 · 생명공학회 2012 Journal of microbiology and biotechnology Vol.22 No.3

Endoglucanase gene egIV was cloned from Trichoderma viride AS 3.3711, an important cellulose-producing fungus, by using an RT-PCR protocol. The egIV cDNA is 1,297 bp in length and contains a 1,035 bp open reading frame encoding a 344 amino acid protein with an estimated molecular mass of 35.5 kDa and isoelectronic point (pI) of 5.29. The expression of gene egIV in T. viride AS 3.3711 could be induced by sucrose, corn straw, carboxymethylcellulose (CMC), or microcrystalline cellulose, but especially by CMC. The transcripts of egIV were regulated under these substrates, but the expression level of the egIV gene could be inhibited by glucose and fructose. Three recombinant vectors, pYES2-xegIV, pYES2Mα-egIV, and pYES2Mα-xegIV, were constructed to express the egIV gene in Saccharomyces cerevisiae H158. The CMCase activity of yeast transformants IpYES2Mα-xegIV was higher than that of transformant IpYES2-xegIV or IpYES2Mα-egIV, with the highest activity of 0.13 U/ml at induction for 48 h, illustrating that the modified egIV gene could enhance CMCase activity and that MFα signal peptide from S. cerevisiae could regulate exogenous gene expression more effectively in S. cerevisiae. The recombinant EGIV enzyme was stable at pH 3.5 to 7.5 and temperature of 35oC to 65oC. The optimal reaction condition for EGIV enzyme activity was at the temperature of 55oC, pH of 5.0, 0.75 mM Ba2+, and using CMC as substrate. Under these conditions, the highest activity of EGIV enzyme in transformant IpYES2Mα-xegIV was 0.18 U/ml. These properties would provide technical parameters for utilizing cellulose in industrial bioethanol production.

Endophytic Fungal strains Specifically Modified the Biochemical Status of Grape Cells

Li-Hua Huang,Ming-Zhi Yang,Xiu-Jin Ao,An-Yun Ren,Ming-Quan Yuan,Han-Bo Zhang 한국식물학회 2018 Journal of Plant Biology Vol.61 No.4

Previously, specific interactions in morphologywere observed between grape cells and endophytic fungalstrains during a dual culture experiment. However, thebiochemical impacts of these fungal endophytes on grapecells is also expected due to their potential application in grapequality management. After assessed multiple physiochemicaltraits to those grape cells which have co-cultured with differentendophytic fungal strains in this study, and found the presenceof fungal endophytes obviously triggered ROS stress responsesin grape cells, and the biochemical status in grape cells weredifferentially modified by different fungal strains. In thosetested endophytic fungal strains, RH37 (Epicoccum sp.),RH6 (Alternaria sp.), RH32 (Alternaria sp.) and RH34(Trichothecium sp.) conferred greater metabolic impacts ongrape cells. And soluble protein (SPr), total flavonoids (TF),total phenols (TPh) and malondialdehyde (MDA) on the otherhand, were sensitive biochemical parameters which can beinfluenced in greater ranges than other detected parameters. Most interestedly, fungal endophytes shaped metabolitespatterns in grape cells during the dual culture appeared fungalgenus/species/strain-specificity. The work confirmed thesignificance of fungal endophytes in grape metabolic regulationand elucidated the possibility to purposely manage grapequality using tool of fungal endophytes.

Cordycepin protects against β–amyloid and ibotenic acid– induced hippocampal CA1 pyramidal neuronal hyperactivity

Li-Hua Yao,Jinxiu Wang,Chao Liu,Shanshan Wei,Guoyin Li,Songhua Wang,Wei Meng,Zhi-Bin Liu,Li-Ping Huang 대한약리학회 2019 The Korean Journal of Physiology & Pharmacology Vol.23 No.6

Cordycepin exerts neuroprotective effects against excitotoxic neuronal death. However, its direct electrophysiological evidence in Alzheimer’s disease (AD) remains unclear. This study aimed to explore the electrophysiological mechanisms underlying the protective effect of cordycepin against the excitotoxic neuronal insult in AD using whole-cell patch clamp techniques. β-Amyloid (Aβ) and ibotenic acid (IBO)–induced injury model in cultured hippocampal neurons was used for the purpose. The results revealed that cordycepin significantly delayed Aβ + IBO–induced excessive neuronal membrane depolarization. It increased the onset time/latency, extended the duration, and reduced the slope in both slow and rapid depolarization. Additionally, cordycepin reversed the neuronal hyperactivity in Aβ + IBO–induced evoked action potential (AP) firing, including increase in repetitive firing frequency, shortening of evoked AP latency, decrease in the amplitude of fast afterhyperpolarization, and increase in membrane depolarization. Further, the suppressive effect of cordycepin against Aβ + IBO–induced excessive neuronal membrane depolarization and neuronal hyperactivity was blocked by DPCPX (8-cyclopentyl-1,3-dipropylxanthine, an adenosine A1 receptor–specific blocker). Collectively, these results revealed the suppressive effect of cordycepin against the Aβ + IBO–induced excitotoxic neuronal insult by attenuating excessive neuronal activity and membrane depolarization, and the mechanism through the activation of A1R is strongly recommended, thus highlighting the therapeutic potential of cordycepin in AD.

Rapid preparation and characterization of chitosan nanoparticles for oligonucleotide

Mu-hua Cheng,Yao-xiong Huang,Han-jian Zhou,Zhi Liu,Jian-fang Li 한국물리학회 2010 Current Applied Physics Vol.10 No.3

Chitosan is regarded as one of the potential candidates as a gene carrier. However, the poor solubility of chitosan is the major limiting factor in its utilization as a gene carrier. The purpose of this study was to simplify the method of preparing the nanoparticles of chitosan linked with antisense oligonucleotide (asON). The main step was preparing the derivatives of chitosan phosphate (CSP) in order to easily dissolve in aqueous solution. The nanoparticles were formed using a simple mixed method for CSP and asON, and the nanoparticle’s forming condition was optimized so that the nanoparticle’s characterization could be examined. Results showed that it was simple to make the nanoparticles under the optimal condition of 2:1 M proportion of CSP and asON. The size of the nanoparticles was 102.6 ± 12.0 nm, its zeta potential was 1.45 ± 1.75, and the encapsulated ratio of the chitosan crosslinked the asON was 87.6 ± 3.5%. The infrared spectra and electron microscope displayed that chitosan may combine with the asON to form equirotal nanoparticles. In conclusion, it was simple and feasible to form chitosan nanoparticles for asON using the CSP, and the CSP can efficiently encapsulate asON.

Current Evidence on the Relationship Between Two Polymorphisms in the NBS1 Gene and Breast Cancer Risk: a Meta-analysis

Zhang, Zhi-Hua,Yang, Lin-Sheng,Huang, Fen,Hao, Jia-Hu,Su, Pu-Yu,Sun, Ye-Huan Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.11

Introduction: Published studies on the association between Nijmegen breakage syndrome 1(NBS1) gene polymorphisms and breast cancer risk have been inconclusive, and a meta-analysis was therefore performed for clarification. Methods: Eligible articles were identified by a search of MEDLINE and EMBASE bibliographic databases for the period up to March 2012. The presence of between-study heterogeneity was investigated using the chi-square-based Cochran's Q statistic test. When there was statistical heterogeneity, the random effects model was chosen; otherwise, fixed effects estimates were reported as an alternative approach. Results: A total of 11 eligible articles (14 case-control studies) were identified, nine case-control studies were for the 657del5 mutation (7,534 breast cancer cases, 14,034 controls) and five case-control studies were for the I171V mutation (3,273 breast cancer cases, 4,004 controls). Our analysis results indicated that the 657del5 mutation was associated with breast cancer risk (carriers vs. non-carriers: pooled OR =2.63, 95% CI: 1.76-3.93), whereas the I171V mutation was not (carriers vs. non-carriers: pooled OR =1.52, 95% CI: 0.70-3.28). Conclusion: The present meta-analysis suggests that the 657del5 gene mutation in the NBS1 gene plays a role in breast cancer risk, while the I171V mutation does not exert a significant influence.

Remarkable impact of amino acids on ginsenoside transformation from fresh ginseng to red ginseng

Liu, Zhi,Wen, Xin,Wang, Chong-Zhi,Li, Wei,Huang, Wei-Hua,Xia, Juan,Ruan, Chang-Chun,Yuan, Chun-Su The Korean Society of Ginseng 2020 Journal of Ginseng Research Vol.44 No.3

Background: Amino acids are one of the major constituents in Panax ginseng, including neutral amino acid, acidic amino acid, and basic amino acid. However, whether these amino acids play a role in ginsenoside conversion during the steaming process has not yet been elucidated. Methods: In the present study, to elucidate the role of amino acids in ginsenoside transformation from fresh ginseng to red ginseng, an amino acids impregnation pretreatment was applied during the steaming process at 120℃. Acidic glutamic acid and basic arginine were used for the acid impregnation treatment during the root steaming. The ginsenosides contents, pH, browning intensity, and free amino acids contents in untreated and amino acid-treated P. ginseng samples were determined. Results: After 2 h of steaming, the concentration of less polar ginsenosides in glutamic acid-treated P. ginseng was significantly higher than that in untreated P. ginseng during the steaming process. However, the less polar ginsenosides in arginine-treated P. ginseng increased slightly. Meanwhile, free amino acids contents in fresh P. ginseng, glutamic acid-treated P. ginseng, and arginine-treated P. ginseng significantly decreased during steaming from 0 to 2h. The pH also decreased in P. ginseng samples at high temperatures. The pH decrease in red ginseng was closely related to the decrease in basic amino acids levels during the steaming process. Conclusion: Amino acids can remarkably affect the acidity of P. ginseng sample by altering the pH value. They were the main influential factors for the ginsenoside transformation. These results are useful in elucidating why and how steaming induces the structural change of ginsenoside inP. ginseng and also provides an effective and green approach to regulate the ginsenoside conversion using amino acids during the steaming process.