Structures, biomimetic synthesis, and anti-SARS-CoV-2 activity of two pairs of enantiomeric phenylpropanoid-conjugated protoberberine alkaloids from the rhizomes of Corydalis decumbens

Jing-Guang Lu,Yingwei Wang,Ming-Rong Yang,Cai-Yun Wang,Jieru Meng,Jiazheng Liu,Zifeng Yang,Kongsong Wu,Li-Ping Bai,Guo-Yuan Zhu,Zhi-Hong Jiang 대한약학회 2022 Archives of Pharmacal Research Vol.45 No.9

(±)-Decumicorine A ( 1 ) and (±)- epi -decumicorine A ( 2 ), two pairs of enantiomeric isoquinoline alkaloids featuring a novel phenylpropanoid-conjugated protoberberine skeleton, were isolated and purifi ed from the rhizomes of Corydalis decumbens . The separation of (±)- 1 and (±)- 2 was achieved by chiral HPLC to produce four optically pure enantiomers. The structures and absolute confi gurations of compounds (−)- 1 , (+)- 1 , (−)- 2 , and (+)- 2 were elucidated by spectroscopic analysis, ECD calculations, and X-ray crystallographic analyses. The two racemates were generated from a Diels-Alder [4 + 2] cycloaddition between jatrorrhizine and ferulic acid in the proposed biosynthetic pathways, which were fully verifi ed by a biomimetic synthesis. Moreover, compound (+)- 1 exhibited an antiviral entry eff ect on SARS-CoV-2 pseudovirus by blocking spike binding to the ACE2 receptor on HEK-293T-ACE2 h host cells.

Simultaneous treatment with sorafenib and glucose restriction inhibits hepatocellular carcinoma in vitro and in vivo by impairing SIAH1-mediated mitophagy

Zhou Jing,Feng Ji,Wu Yong,Dai Hui-Qi,Zhu Guang-Zhi,Chen Pan-Hong,Wang Li-Ming,Lu Guang,Liao Xi-Wen,Lu Pei-Zhi,Su Wen-Jing,Hooi Shing Chuan,Ye Xin-Pin,Shen Han-Ming,Peng Tao,Lu Guo-Dong 생화학분자생물학회 2022 Experimental and molecular medicine Vol.54 No.-

Transarterial chemoembolization (TACE) is the first-line treatment for unresectable intermediate-stage hepatocellular carcinoma (HCC). It is of high clinical significance to explore the synergistic effect of TACE with antiangiogenic inhibitors and the molecular mechanisms involved. This study determined that glucose, but not other analyzed nutrients, offered significant protection against cell death induced by sorafenib, as indicated by glucose deprivation sensitizing cells to sorafenib-induced cell death. Next, this synergistic effect was found to be specific to sorafenib, not to lenvatinib or the chemotherapeutic drugs cisplatin and doxorubicin. Mechanistically, sorafenib-induced mitophagy, as indicated by PINK1 accumulation, increased the phospho-poly-ubiquitination modification, accelerated mitochondrial membrane protein and mitochondrial DNA degradation, and increased the amount of mitochondrion-localized mKeima-Red engulfed by lysosomes. Among several E3 ubiquitin ligases tested, SIAH1 was found to be essential for inducing mitophagy; that is, SIAH1 silencing markedly repressed mitophagy and sensitized cells to sorafenib-induced death. Notably, the combined treatment of glucose restriction and sorafenib abolished ATP generation and mitophagy, which led to a high cell death rate. Oligomycin and antimycin, inhibitors of electron transport chain complexes, mimicked the synergistic effect of sorafenib with glucose restriction to promote cell death mediated via mitophagy inhibition. Finally, inhibition of the glucose transporter by canagliflozin (a clinically available drug used for type-II diabetes) effectively synergized with sorafenib to induce HCC cell death in vitro and to inhibit xenograft tumor growth in vivo. This study demonstrates that simultaneous treatment with sorafenib and glucose restriction is an effective approach to treat HCC, suggesting a promising combination strategy such as transarterial sorafenib-embolization (TASE) for the treatment of unresectable HCC.

Numerical simulation of tip clearance impact on a pumpjet propulsor

Lu, Lin,Pan, Guang,Wei, Jing,Pan, Yipeng The Society of Naval Architects of Korea 2016 International Journal of Naval Architecture and Oc Vol.8 No.3

Numerical simulation based on the Reynolds Averaged Naviere-Stokes (RANS) Computational Fluid Dynamics (CFD) method had been carried out with the commercial code ANSYS CFX. The structured grid and SST $k-{\omega}$ turbulence model had been adopted. The impact of non-condensable gas (NCG) on cavitation performance had been introduced into the Schnerr and Sauer cavitation model. The numerical investigation of cavitating flow of marine propeller E779A was carried out with different advance ratios and cavitation numbers to verify the numerical simulation method. Tip clearance effects on the performance of pumpjet propulsor had been investigated. Results showed that the structure and characteristics of the tip leakage vortex and the efficiency of the propulsor dropped more sharply with the increase of the tip clearance size. Furthermore, the numerical simulation of tip clearance cavitation of pumpjet propulsor had been presented with different rotational speed and tip clearance size. The mechanism of tip clearance cavitation causing a further loss of the efficiency had been studied. The influence of rotational speed and tip clearance size on tip clearance cavitation had been investigated.

Numerical simulation of tip clearance impact on a pumpjet propulsor

Lin Lu,Guang Pan,Jing Wei,Yipeng Pan 대한조선학회 2016 International Journal of Naval Architecture and Oc Vol.8 No.3

Numerical simulation based on the Reynolds Averaged NaviereStokes (RANS) Computational Fluid Dynamics (CFD) method had been carried out with the commercial code ANSYS CFX. The structured grid and SST keu turbulence model had been adopted. The impact of noncondensable gas (NCG) on cavitation performance had been introduced into the Schnerr and Sauer cavitation model. The numerical investigation of cavitating flow of marine propeller E779A was carried out with different advance ratios and cavitation numbers to verify the numerical simulation method. Tip clearance effects on the performance of pumpjet propulsor had been investigated. Results showed that the structure and characteristics of the tip leakage vortex and the efficiency of the propulsor dropped more sharply with the increase of the tip clearance size. Furthermore, the numerical simulation of tip clearance cavitation of pumpjet propulsor had been presented with different rotational speed and tip clearance size. The mechanism of tip clearance cavitation causing a further loss of the efficiency had been studied. The influence of rotational speed and tip clearance size on tip clearance cavitation had been investigated.

Ginsenoside Rh2 reduces depression in offspring of mice with maternal toxoplasma infection during pregnancy by inhibiting microglial activation via the HMGB1/TLR4/NF-kB signaling pathway

Xiang Xu,Yu-Nan Lu,Jia-Hui Cheng,Hui-Wen Lan,Jing-Mei Lu,Guang-Nan Jin,Guang-Hua Xu,Cheng-Hua Jin,Juan Ma,Hu-Nan Piao,Xuejun Jin,Lian-Xun Piao 고려인삼학회 2022 Journal of Ginseng Research Vol.46 No.1

Background: Maternal Toxoplasma gondii (T. gondii) infection during pregnancy has been associated with various mental illnesses in the offspring. Ginsenoside Rh2 (GRh2) is a major bioactive compound obtained from ginseng that has an anti-T. gondii effect and attenuates microglial activation through toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-kB) signaling pathway. GRh2 also alleviated tumor-associated or lipopolysaccharide-induced depression. However, the effects and potential mechanisms of GRh2 on depression-like behavior in mouse offspring caused by maternal T. gondii infection during pregnancy have not been investigated. Methods: We examined GRh2 effects on the depression-like behavior in mouse offspring, caused by maternal T. gondii infection during pregnancy, by measuring depression-like behaviors and assaying parameters at the neuronal and molecular level. Results: We showed that GRh2 significantly improved behavioral measures: sucrose consumption, forced swim time and tail suspended immobility time of their offspring. These corresponded with increased tissue concentrations of 5-hydroxytryptamine and dopamine, and attenuated indoleamine 2,3-dioxygenase or enhanced tyrosine hydroxylase expression in the prefrontal cortex. GRh2 ameliorated neuronal damage in the prefrontal cortex. Molecular docking results revealed that GRh2 binds strongly to both TLR4 and high mobility group box 1 (HMGB1). Conclusion: This study demonstrated that GRh2 ameliorated the depression-like behavior in mouse offspring of maternal T. gondii infection during pregnancy by attenuating the excessive activation of microglia and neuroinflammation through the HMGB1/TLR4/NF-kB signaling pathway. It suggests that GRh2 could be considered a potential therapy in preventing and treating psychiatric disorders in the offspring mice of mothers with prenatal exposure to T. gondii infection.

High-j Proton h11/2 and g7/2 Intruder Bands in 113In

Ma Ke Yan,Lu Jing Bin,Ma Ying Jun,Li Jian,Yang Dong,Sun Wu Ji,Wang Hao,Pan Hao Nan,Wang Jia Qi,Yang Qing Yu,Zhang Da Ming,Zhu Li Hua,Wu Xiao Guang,Zheng Yun,Li Cong Bo 한국물리학회 2020 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.76 No.12

Excited states of 113In have been populated through the heavy-ion fusion evaporation reaction 110Pd(7Li, 4n)113In. A new band with the configuration of a proton d5/2 orbital is identified. Two ΔI = 2 intruder bands, built on the πh11/2 and the πg7/2 orbitals, have been extended to spins (63/2-)ħ and (55/2+)ħ, respectively. The negative-parity πh11/2 intruder band shows a smooth increase in aligned spin, which is attributed to a strong proton-neutron interaction. The properties of the positive-parity πg7/2 band are discussed based on tilted axis cranking model calculations, and the features of the antimagnetic rotation for this band are shown after backbend. Furthermore, the contributions of the two-shears-like mechanism, the neutron (gd)ν shell and the core rotation are investigated for the positive-parity πg7/2 band.

Photo-induced antifouling polyvinylidene fluoride ultrafiltration membrane driven by weak visible light

Ting Wang,Ling-li Jiang,Lu-lu Huang,Li-guang Wu,Chun-juan Li,Jing Cai 한국공업화학회 2020 Journal of Industrial and Engineering Chemistry Vol.89 No.-

To enhance the performance of ultrafiltration membranes, a polyvinylidenefluoride (PVDF) blendingmembrane with photo-induced antifouling performance was fabricated. La3+- and Yb3+-doped titaniumdioxide-reduced graphene oxide (TiO2-RGO) composites were initially prepared by adsorption-phasesynthesis coupled with solvothermal reduction. The doped TiO2-RGO composites were then blendedwith the PVDF materials. The results showed that adding well-distributed, doped, and hydrophilic TiO2-RGO improved the pore structures and surface polarity of the blending membranes, thus improving theirpermeation and antifouling performance. After addition of doped TiO2-RGO with photocatalytic activity,the antifouling performance of the resulting blending membranes increased under weak visible-lightirradiation. The agglomerated doped TiO2-RGO in the polymeric matrix reduced the hydrophilicity andporosity of the resulting membranes, thereby decreasing their water permeability and antifoulingperformance. Solvothermal reduction through ethylene glycol also improved the photocatalytic activityof Yb-doped TiO2-RGO and enhanced the affinity between doped TiO2-RGO and PVDF. These two effectssimultaneously increased the water permeability and photo-induced antifouling performance of theblending membranes. Theflux recovery rate of the blending membranes containing Yb-doped TiO2-RGOtreated by ethylene glycol exceeded 69% after illumination. In particular, theflux recovery rate ofmembranes reached about 96% after illumination coupling with washing.

Phenolic acids in Panax ginseng inhibit melanin production through bidirectional regulation of melanin synthase transcription via different signaling pathways

Jianzeng Liu,Xiaohao Xu,Jingyuan Zhou,Guang Sun,Zhenzhuo Li,Lu Zhai,Jing Wang,Rui Ma,Daqing Zhao,Rui Jiang,Liwei Sun 고려인삼학회 2023 Journal of Ginseng Research Vol.47 No.6

Background: Our previous investigation indicated that the preparation of Panax ginseng Meyer(P. ginseng) inhibited melanogenesis. It comprised salicylic acid (SA), protocatechuic acid (PA), p-coumaricacid (p-CA), vanillic acid (VA), and caffeic acid (CA). In this investigation, the regulatory effects ofP. ginseng phenolic acid monomers on melanin production were assessed. Methods: In vitro and in vivo impact of phenolic acid monomers were assessed. Results: SA, PA, p-CA and VA inhibited tyrosinase (TYR) to reduce melanin production, whereas CA hadthe opposite effects. SA, PA, p-CA and VA significantly downregulated the melanocortin 1 receptor(MC1R), cycle AMP (cAMP), protein kinase A (PKA), cycle AMP-response element-binding protein (CREB),microphthalmia-associated transcription factor (MITF) pathway, reducing mRNA and protein levels ofTYR, tyrosinase-related protein 1 (TYRP1), and TYRP2. Moreover, CA treatment enhanced the cAMP, PKA,and CREB pathways to promote MITF mRNA level and phosphorylation. It also alleviated MITF proteinlevel in a-MSH-stimulated B16F10 cells, comparable to untreated B16F10, increasing the expression ofphosphorylation glycogen synthase kinase 3b (p-GSK3b), b-catenin, p-ERK/ERK, and p-p38/p38. Furthermore, the GSK3b inhibitor promoted p-GSK3b and p-MITF expression, as observed in CA-treatedcells. Moreover, p38 and ERK inhibitors inhibited CA-stimulated p-p38/p38, p-ERK/ERK, and p-MITFincrease, which had negative binding energies with MC1R, as depicted by molecular docking. Conclusion: P. ginseng roots' phenolic acid monomers can safely inhibit melanin production by bidirectionallyregulating melanin synthase transcription. Furthermore, they reduced MITF expression viaMC1R/cAMP/PKA signaling pathway and enhanced MITF post-translational modification via Wnt/mitogen-activated protein kinase signaling pathway.

Discovery of Chitin Deacetylase Inhibitors through Structure-Based Virtual Screening and Biological Assays

( Yaodong Liu ),( Sibtain Ahmed ),( Yaowei Fang ),( Meng Chen ),( Jia An ),( Guang Yang ),( Xiaoyue Hou ),( Jing Lu ),( Qinwen Ye ),( Rongjun Zhu ),( Qitong Liu ),( Shu Liu ) 한국미생물생명공학회 2022 Journal of microbiology and biotechnology Vol.32 No.4

Chitin deacetylase (CDA) inhibitors were developed as novel antifungal agents because CDA participates in critical fungal physiological and metabolic processes and increases virulence in soil-borne fungal pathogens. However, few CDA inhibitors have been reported. In this study, 150 candidate CDA inhibitors were selected from the commercial Chemdiv compound library through structure-based virtual screening. The top-ranked 25 compounds were further evaluated for biological activity. The compound J075-4187 had an IC50 of 4.24 ± 0.16 μM for AnCDA. Molecular docking calculations predicted that compound J075-4187 binds to the amino acid residues, including active sites (H101, D48). Furthermore, compound J075-4187 inhibited food spoilage fungi and plant pathogenic fungi, with minimum inhibitory concentration (MIC) at 260 μg/ml and minimum fungicidal concentration (MFC) at 520 μg/ml. Therefore, compound J075-4187 is a good candidate for use in developing antifungal agents for fungi control.