Structure-Activity Relationship and Evaluation of Phenethylamine and Tryptamine Derivatives for Affinity towards 5-Hydroxytryptamine Type 2A Receptor

( Shujie Wang ),( Anlin Zhu ),( Suresh Paudel ),( Choon-gon Jang ),( Yong Sup Lee ),( Kyeong-man Kim ) 한국응용약물학회 2023 Biomolecules & Therapeutics(구 응용약물학회지) Vol.31 No.2

Among 14 subtypes of serotonin receptors (5-HTRs), 5-HT_2AR plays important roles in drug addiction and various psychiatric disorders. Agonists for 5-HT_2AR have been classified into three structural groups: phenethylamines, tryptamines, and ergolines. In this study, the structure-activity relationship (SAR) of phenethylamine and tryptamine derivatives for binding 5-HT_2AR was determined. In addition, functional and regulatory evaluation of selected compounds was conducted for extracellular signal-regulated kinases (ERKs) and receptor endocytosis. SAR studies showed that phenethylamines possessed higher affinity to 5-HT_2AR than tryptamines. In phenethylamines, two phenyl groups were attached to the carbon and nitrogen (R³) atoms of ethylamine, the backbone of phenethylamines. Alkyl or halogen groups on the phenyl ring attached to the β carbon exerted positive effects on the binding affinity when they were at para positions. Oxygen-containing groups attached to R³ exerted mixed influences depending on the position of their attachment. In tryptamine derivatives, tryptamine group was attached to the β carbon of ethylamine, and ally groups were attached to the nitrogen atom. Oxygen-containing substituents on large ring and alkyl substituents on the small ring of tryptamine groups exerted positive and negative influence on the affinity for 5-HT_2AR, respectively. Ally groups attached to the nitrogen atom of ethylamine exerted negative influences. Functional and regulatory activities of the tested compounds correlated with their affinity for 5-HT_2AR, suggesting their agonistic nature. In conclusion, this study provides information for designing novel ligands for 5-HT_2AR, which can be used to control psychiatric disorders and drug abuse.

Biased Dopamine D₂ Receptors Exhibit Distinct Intracellular Trafficking Properties and ERK Activation in Different Subcellular Domains

( Shujie Wang ),( Lulu Peng ),( Kyeong-man Kim ) 한국응용약물학회 2024 Biomolecules & Therapeutics(구 응용약물학회지) Vol.32 No.1

Biased signaling or functional selectivity refers to the ability of an agonist or receptor to selectively activate a subset of transducers such as G protein and arrestin in the case of G protein-coupled receptors (GPCRs). Although signaling through arrestin has been reported from various GPCRs, only a few studies have examined side-by-side how it differs from signaling via G protein. In this study, two signaling pathways were compared using dopamine D₂ receptor (D₂R) mutants engineered via the evolutionary tracer method to selectively transduce signals through G protein or arrestin (D₂G and D₂Arr, respectively). D₂G mediated the inhibition of cAMP production and ERK activation in the cytoplasm. D₂Arr, in contrast, mediated receptor endocytosis accompanied by arrestin ubiquitination and ERK activation in the nucleus as well as in the cytoplasm. D₂Arr-mediated ERK activation occurred in a manner dependent on arrestin3 but not arrestin2, accompanied by the nuclear translocation of arrestin3 via importin1. D₂R-mediated ERK activation, which occurred in both the cytosol and nucleus, was limited to the cytosol when cellular arrestin3 was depleted. This finding supports the results obtained with D₂Arr and D₂G. Taken together, these observations indicate that biased signal transduction pathways activate distinct downstream mechanisms and that the subcellular regions in which they occur could be different when the same effectors are involved. These findings broaden our understanding on the relation between biased receptors and the corresponding downstream signaling, which is critical for elucidating the functional roles of biased pathways.

Effect of Annealing on Lattice Strain and Near-Band-Edge Emission of ZnO Nanorods

Musbah Babikier,Jinzhong Wang,Dunbo Wang,Qian Li,Jianming Sun,Yuan Yan,Wenqi Wang,Qingjiang Yu,Shujie Jiao,Shiyong Gao,Hongtao Li 대한금속·재료학회 2014 ELECTRONIC MATERIALS LETTERS Vol.10 No.4

The effect of air and oxygen annealing on the structural and the optical properties of hydrothermally synthesized ZnO nanorods was investigated. After hydrothermal synthesis, the resulting ZnO nanorods were annealed in air and under an oxygen atmosphere at 370°C for 1 h. X-ray diffraction results revealed that the oxygen-annealed nanorods possessed high crystallinity with a hexagonal-wurtzite crystal structure in the (002) plane. Evaluation of strain showed a tensile lattice strain of 0.426% resulting from oxygen annealing. The photoluminescence measurements showed that the relative intensity ratio of the near-band-edge emission (NBE) to the green emission (INBE/IGE) increased from ~2.6 for the as-grown ZnO nanorods to ~68.7 when the nanorods were annealed under oxygen. After annealing, a red shift of ~30 and ~44 meV in the NBE was observed for the nanorods that were annealed in air and under oxygen, respectively. This shift is attributed to the interaction between the neutral acceptors and the adsorbed oxygen atoms.

Principals’ perceptions of effective teaching: A survey of Chinese school principals

Shujie Liu,Jian Wang,Hongmei Liang 한국교육개발원 2015 KEDI Journal of Educational Policy Vol.12 No.2

Principals’ beliefs of effective teaching presumably shape their efforts to recruit teachers, evaluate teaching quality, support teachers to develop their teaching practices, and nurture the professional environment that promotes high the teaching quality in their schools. Drawing on survey data from 314 Chinese principals, this study examines principals’ perceptions of effective teaching and compares them with those of Chinese teachers and U.S. school principals in the literature. The study found that Chinese principals believed effective teaching practices to be those that align lesson plans with student learning styles, engage students actively in the learning process, offer clear, specific, and timely feedback, treat all students with respect, and maintain a physical and emotional safe environment for learning. These ideas are consistent with Chinese teachers’ perceptions about effective teaching but are clearly differentiated from those of U.S. principals. These perceptions were varied as participants had different years of administrative experiences, worked in urban or rural schools, and in schools with different levels of student performance.

Response Surface Methodology for Optimizing the Preparation Process of Cellulose Acetate/Polylactic Acid Nonwoven Surgical Gown Material

Shujie Zhang,Lisong Fu,Zhaowei Yang,Mengke Jing,Ziwei Zhang,Shijian Xiang,Rui Wang 한국섬유공학회 2021 Fibers and polymers Vol.22 No.4

In view of the problems that traditional woven surgical gowns are prone to cross infection in blocking blood andliquid spillage, cellulose acetate (CA)/polylactic acid (PLA) nonwoven materials were prepared to improve the functionalrequirements of surgical materials in combination with the rapidly developing green fibers. Fiber mixing ratio, fiber webareal weight and water jet pressure were selected to optimize the preparation process of cellulose acetate/polylactic acid (CA/PLA) nonwoven materials with moisture permeability and filtration efficiency. The results showed that the fiber mixing ratiowas 49:51, and the fiber web areal weight was 130 g/m2, and the water jet pressure was 7 MPa. Under this process, moisturepermeability is 5240.86 g/(m2·h), and the filtration efficiency is 38.12 %, which is close to the theoretical value. It shows thatthe response surface method has practical application value, indicating that the response surface method has practicalapplication value, and can provide a theoretical basis for the preparation process parameters of barrier and comfort nonwovensurgical gowns at the same time.

Design, Synthesis, and Functional Evaluation of 1, 5-Disubstituted Tetrazoles as Monoamine Neurotransmitter Reuptake Inhibitors

Paudel Suresh,Wang Shuji,Kim Eunae,Kundu Dooti,Min Xiao,Shin Chan Young,Kim Kyeong-Man 한국응용약물학회 2022 Biomolecules & Therapeutics(구 응용약물학회지) Vol.30 No.2

Tetrazoles were designed and synthesized as potential inhibitors of triple monoamine neurotransmitters (dopamine, norepinephrine, serotonin) reuptake based on the functional and docking simulation of compound 6 which were performed in a previous study. The compound structure consisted of a tetrazole-linker (n)-piperidine/piperazine-spacer (m)-phenyl ring, with tetrazole attached to two phenyl rings (R1 and R2). Altering the carbon number in the linker (n) from 3 to 4 and in the spacer (m) from 0 to 1 increased the potency of serotonin reuptake inhibition. Depending on the nature of piperidine/piperazine, the substituents at R1 and R2 exerted various effects in determining their inhibitory effects on monoamine reuptake. Docking study showed that the selectivity of tetrazole for different transporters was determined based on multiple interactions with various residues on transporters, including hydrophobic residues on transmembrane domains 1, 3, 6, and 8. Co-expression of dopamine transporter, which lowers dopamine concentration in the biophase by uptaking dopamine into the cells, inhibited the dopamine-induced endoctytosis of dopamine D2 receptor. When tested for compound 40 and 56, compound 40 which has more potent inhibitory activity on dopamine reuptake more strongly disinhibited the inhibitory activity of dopamine transporter on the endocytosis of dopamine D2 receptor. Overall, we identified candidate inhibitors of triple monoamine neurotransmitter reuptake and provided a theoretical background for identifying such neurotransmitter modifiers for developing novel therapeutic agents of various neuropsychiatric disorders.

Screening and Molecular Cloning of a Protective Antigen from the Midgut of Haemaphysalis longicornis

Yonghong Hu,Jincheng Zhang,Shujie Yang,Hui Wang,Hua Zeng,Tiantian Zhang,Jingze Liu 대한기생충학열대의학회 2013 The Korean Journal of Parasitology Vol.51 No.3

Study on the performance of different discharging devices of a continuous production system

Zhenya Duan,Jie Wang,Shujie Sun,Wenchen Li,Haodong Zhang,Guoyue Qiao,Junmei Zhang,Jingtao Wang 한국화학공학회 2022 Korean Journal of Chemical Engineering Vol.39 No.4

Based on the developed continuous production system of sodium phenol carboxylation reaction, severaltypes of discharging devices are proposed, which are suitable for the case where the transported particles are not easyto maintain a stable state in the transported fluid. Numerical simulations of the gas-solid two-phase flow characteristicsand particle distribution were performed with DPM, and the particle retention ratio and fluid loss degree were proposedto investigate the performance of the discharging devices. The results of simulations and industrial experimentsshowed that a guide plate installed in the “B” discharging device can solve the accumulation problem, realize the efficientand continuous delivery of the particles, and maintain a uniform distribution of particles. This study can providea reference for the design of a gas-solid two-phase discharging device, and guide the industrial experimental operationand modification of continuous production systems for sodium phenol carboxylation.

Whole-genome sequence association study identifies cyclin dependent kinase 8 as a key gene for the number of mummified piglets

Wu Pingxian,Chen Dejuan,Wang Kai,Wang Shujie,Liu Yihui,Jiang Anan,Xiao Weihang,Jiang Yanzhi,Zhu Li,Xu Xu,Qiu Xiaotian,Li Xuewei,Tang Guoqing 아세아·태평양축산학회 2023 Animal Bioscience Vol.36 No.1

Objective: Pigs, an ideal biomedical model for human diseases, suffer from about 50% early embryonic and fetal death, a major cause of fertility loss worldwide. However, identifying the causal variant remains a huge challenge. This study aimed to detect single nucleotide polymorphisms (SNPs) and candidate genes for the number of mummified (NM) piglets using the imputed whole-genome sequence (WGS) and validate the potential candidate genes. Methods: The imputed WGS was introduced from genotyping-by-sequencing (GBS) using a multi-breed reference population. We performed genome-wide association studies (GWAS) for NM piglets at birth from a Landrace pig populatiGWAS peak located on SSC11: 0.10 to 7.11 Mbp (Top SNP, SSC11:1,889,658 bp; p = 9.98E-13) was identified in cyclin dependent kinase on. A total of 300 Landrace pigs were genotyped by GBS. The whole-genome variants were imputed, and 4,252,858 SNPs were obtained. Various molecular experiments were conducted to determine how the genes affected NM in pigs. Results: A strong GWAS peak located on SSC11: 0.10 to 7.11 Mbp (Top SNP, SSC11:1,889,658 bp; p = 9.98E-13) was identified in cyclin dependent kinase 8 (CDK8) gene, which plays a crucial role in embryonic retardation and lethality. Based on the molecular experiments, we found that Y-box binding protein 1 (YBX1) was a crucial transcription factor for CDK8, which mediated the effect of CDK8 in the proliferation of porcine ovarian granulosa cells via transforming growth factor beta/small mother against decapentaplegic signaling pathway, and, as a consequence, affected embryo quality, indicating that this pathway may be contributing to mummified fetal in pigs. Conclusion: A powerful imputation-based association study was performed to identify genes associated with NM in pigs. CDK8 was suggested as a functional gene for the proliferation of porcine ovarian granulosa cells, but further studies are required to determine causative mutations and the effect of loci on NM in pigs.

Dynamics of a High‑voltage Switchgear System Excited by Earthquake

Tao Sun,Wei Wang,Shuji Yang,Ling Li 대한전기학회 2020 Journal of Electrical Engineering & Technology Vol.15 No.2

Mechanical failure of the high-voltage switchgear induced by vibration will cause the fault of electric system. It is necessary to evaluate the dynamic characteristics of switchgear in advance. In this paper, a numerical dynamic model of the whole switchgear system excited by earthquake is developed in Finite Element Method. Vibration characteristics are acquired by modal analysis. Structural deformation, under the seismic load, is also obtained in response spectrum analysis. Modal analysis indicates that resonance of system is not serious. While, results from response spectrum analysis show a largest deformation in rear cabinet wall, which is consistent with the deformation trend shown in modal shapes. The experiment data in the fnished Shaking Table Test show an agreement with simulation results as well. Analysis results show that the switchgear has a good aseismic performance