RSC Chemical Biology
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2026
·
IF 3.9
Zheng Chu,Liting Xu,Honglin Chen,Tianyun Fan,Xueqian Hu,Yin Kwan Wong,Qiaoli Shi,Junzhe Zhang,Chengchao Xu,Jigang Wang,Huan Tang
Treatment of acute promyelocytic leukemia (APL) remains challenged by toxicities associated with current regimens, highlighting the need for novel and safer therapeutic agents. Here, we identify Eupalinolide B (EB), a natural sesquiterpene lactone isolated from Eupatorium lindleyanum DC., as a potent anti-leukemic compound targeting the human APL-derived HL-60 cell line. Through integrated chemoproteomic profiling and functional validation, we demonstrate that EB covalently binds and inhibits 26S proteasome non-ATPase regulatory subunit 14 (PSMD14), a deubiquitinase enzyme (DUB) within the 19S proteasome regulatory particle. This inhibition disrupts PSMD14-mediated stabilization of key oncoproteins RAC-alpha serine/threonine-protein kinase 1 (AKT1) and cyclin-dependent kinase 4 (CDK4), promoting their proteasomal degradation. As a result, EB induces G2/M cell cycle arrest and apoptosis in leukemia cells. Both genetic knockdown and pharmacological inhibition of PSMD14 recapitulate EB's effects, confirming its essential role in leukemia cell survival and proliferation. Collectively, these findings uncover a previously unrecognized PSMD14–AKT1/CDK4 regulatory axis in leukemia and position EB as a promising chemical probe and lead compound for the development of targeted covalent inhibitors against oncogenic DUBs.
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Journal of Materials Chemistry A
·
2023
·Vol. 11
·期 11
·5615-5626
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IF 11.9
Xiaohui Li,Xianyi Wei,Xiaoge Wang,Chenjie Lou,Wenda Zhang,Jungu Xu,Zhaoji Luo,Mingxue Tang,Sihao Deng,Lunhua He,Xianran Xing,Junliang Sun,Xiaojun Kuang
Melilite-type oxide ion conductors usually were observed in pure gallate compounds. Here a new mellite interstitial oxide ion conductor Ca2−xLaxGa2GeO7+x/2 (0 ≤ x ≤ 0.15) was developed by the substitution of La3+ for Ca2+ in Ca2Ga2GeO7 containing mixed GaO4/GeO4 tetrahedral layers. Neutron powder diffraction data indicated that the introduced interstitial oxide ions were accommodated in the distorted pentagonal rings, close to the coordination environment of (Ga2/Ge)O4 containing terminal oxygen. Defect formation energy calculations further reveal that the interstitial oxygen not only favors to approach the GaO4 tetrahedra, in agreement with studies of other pure gallate systems, but also is confined to the GeO4 tetrahedra. Bond-valence-energy landscape calculations and molecular dynamics simulations revealed that the interstitial oxide ions were transported among the pentagonal rings within the tetrahedral layers through a cooperative mechanism involving the synergistic knock-on motion between interstitial and framework oxygens. In Ca2Ga2GeO7, the La3+ substitution for Ca2+ only extended up to x = 0.15, which is much lower than those in the La–(Ca/Sr/Ba) based gallate mellites. The x = 0.15 composition resulted in oxide ion conductivities ∼2.79 × 10−5 S cm−1 to 1.68 × 10−3 S cm−1, with oxygen transport numbers of ∼92.65%, two orders of magnitude higher than that of the parent material. However, compared with pure gallate melilite interstitial oxide ion conductors with the same interstitial oxide ion concentrations, Ca1.85La0.15Ga2GeO7.075 has about one order of magnitude lower conductivity. The lower interstitial oxide ion concentration and conductivity in Ca2−xLaxGa2GeO7+x/2 reveal that although Ge4+ has similar chemical properties to the adjacent Ga3+, the subtle differences in size and the resultant covalent bonding ability make the mixed GaO4 and GeO4 tetrahedral layers in mellite unfavorable for accommodation and transportation of interstitial oxygens.
研究领域:
材料科学
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固体离子学
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能源材料
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晶体化学
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离子传输
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POLYMER
·
2020
·
IF 4.231
Tiantian Guo,Yi Wang,Yaping Qiao,Xiaoyan Yuan,Yunhui Zhao,Lixia Ren
One-dimensional photonic crystals (1D PCs) prepared by solvent annealing self-assembly of bottlebrush block copolymers have attracted much attention due to their low cost and convenient preparation. However, such 1D PCs are usually unstable as the reflectance will red shift at high temperature. Herein, we study the thermal stability of 1D PCs by post-thermal self-assembly. In general, the 1D PCs with lamellar structures are prepared by solvent annealing self-assembly of bottlebrush block copolymers with hard main chain, polystyrene- block -poly( tert -butyl acrylate) (H(PS- b -P t BA)). At temperatures higher than the glass transition temperature of side chains and main chain, the 1D PCs start to post self-assembly, which reaches equilibrium state when treated at high temperature for 8 h. Correspondingly, the reflectance of the 1D PCs red shifts from purple to blue gradually with temperature increase. Scanning electron microscope characterization shows that after thermal treatment, the domain spacing of the lamellar phases is increased from 108 nm to 160 nm, which results in the red shift of the reflectance wavelength. The red shift of the 1D PCs is related to the metastable self-assembly of bottlebrush block copolymers, which will further self-assemble at high temperatures to increase the domain spacing. After reaching equilibrium, the 1D PCs are thermal stable, which shows potential in high temperature resistance.
研究领域:
材料科学
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聚合物化学
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光子学
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纳米技术
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热性能
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BIOORGANIC CHEMISTRY
·
2026
·
IF 5.1
Xu-Mei Gan,Wei-Jie Chen,Yu-Hang Xie,Cui-Xia Wang,Yan-Qiu Deng,Zhen-Wei Zhang
A series of new dihydropyrano[2,3- b ]indoles were designed, synthesized, and meticulously evaluated for their antiproliferative activities against multiple human tumor cell lines, including A549, MCF-7, DU145, HeLa, and HepG2 cells. Among these derivatives, compound 4k exhibited the most potent antitumor activity against non-small cell lung cancer (NSCLC) A549 cells. Further mechanistic investigations showed that 4k arrested the A549 cell cycle at the S phase but triggered only weak apoptosis. Instead, 4k eliminated cells through non-apoptotic mechanisms involving the simultaneous inhibition of autophagy and induction of ferroptosis in NSCLC by elevating reactive oxygen species (ROS) levels, reducing mitochondrial membrane potential (MMP), and downregulating glutathione peroxidase 4 (GPX4) expression. Moreover, 4k also showed potent in vivo antitumor activity in a fluorescent zebrafish xenograft model. Additionally, the potential target proteins were predicted and preliminarily validated using network pharmacology and molecular docking. Collectively, our findings identified 4k as a dual modulator that blocks autophagy and sequentially triggers ferroptosis, offering a promising therapeutic strategy to overcome apoptosis resistance.
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JOURNAL OF HAZARDOUS MATERIALS
·
2022
·
IF 14.224
Shulin Zuo,Lilin Wang,Yan Liu,Yanzong Zhang
In recent years, researchers have devoted themselves to developing composites containing cobalt as highly active heterogeneous catalysts of persulfate. Most of them reported that the catalytic degradation processes of organic pollutants were accompanied by the leaching of cobalt ions, but only a few studies considered the contribution of the dissolved cobalt ion to the degradation of organic compounds. A research paper in Journal of Hazardous Materials reported a study on synthesis, application and catalytic mechanisms of cobalt doped hydroxyapatite (Co-HAP) for Rhodamine B (RhB) degradation. We find that non-main catalytic mechanisms were listed and that the effect of Co-HAP was overestimated.
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FOOD CHEMISTRY
·
2023
·
IF 8.8
Xianlong Zhang,Yiheng Shi,Panpan Wang,Di Wu,Jianghua Liu,Rui Huang,Yongning Wu,Guoliang Li
Inspired by a biomineralization behavior, we prepared a nanoflower-like artificial clickase (namely LCN clickase) for portable and sensitive click SERS immunoassay of foodborne bacterial pathogen. Encouraged by its high click catalytic activity to trigger Cu(I)-catalyzed azide-alkyne cycloaddition reaction, LCN clickase was successfully used for establishing a novel click SERS immunoassay by combining the clickase-mediated SERS signal variation at Raman-silent region. The developed method not only effectively eliminated the interferences between Raman reporter and biological species, but also reduced the complex sample matrix interference. Compared with traditional CuAAC-based immunoassays, the established method avoided the superfluous dissolution process of nanocatalysts and eliminated the requirement of reducing agent during detection, thereby shortening detection time and improving detection reliability. Impressively, the proposed method showed high selectivity and sensitivity for detection of Salmonella enterica serovar Paratyphi B with a low LOD of 20 CFU/mL, exhibiting a great potential in detection of foodborne bacterial pathogen in food samples.
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POLYMERS FOR ADVANCED TECHNOLOGIES
·
2023
·Vol. 34
·期 5
·1739-1751
·
IF 3.4
Na Ni,Tiantang Fan,Wuyou Ye,Qi Xia,Dongyang Liu,Jingwen Qin,Zhongyong Fan,Qing Liu
Poly( L -lactic acid) (PLLA) is a biocompatible material and has found its application in bioresorbable vascular stents (BVS). However, the crystallization of pure PLLA makes it brittle as a medical implant device. In this work, the biodegradable poly(1,3-trimethylene carbonate- b -( L -lactide- ran -glycolide acid)) (PTLG) terpolymers with improved mechanical performance were developed and processed into peripheral vascular stents by a novel 3D 4-axial printing technology. The PTLG terpolymers were successfully synthesized by ring-opening copolymerization of L -lactic acid (LLA), 1,3-trimethylene carbonate (PTMC) and glycolide acid (GA) units. The crystallinity and mechanical properties of the PTLG terpolymers with various degradation rate depends on the chain sequence structure and the component contents. Compared with the stent prepared by laser engraving, the peripheral vascular stent prepared by the 3D 4-axial printing technology exhibit a finer structure and smoother strut surface. It was found that both the strut diameters and the molecular weight of PTMC affect the radial force of the stents and that the apparent activation energy of thermal decomposition of the stents is mainly influenced by the molecular weight of PTMC and the component ratio. Therefore, the addition of the PTMC segment can effectively improve the flexibility of the PTLG terpolymer stent and the 3D printed PTLG terpolymer-based stent. Furthermore, CCK-8 and live/dead staining suggested that the stents have good biocompatibility.
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INVESTIGATIONAL NEW DRUGS
·
2023
·Vol. 41
·期 1
·134-141
·
IF 3.4
Yan Gaobo,Zhang Hongyan,Li Yan,Miao Guoqiang,Liu Xiaolei,Lv Qifan
Lysine-specific demethylase 1 (LSD1) has been a promising target to treat prostate cancer, and discovery of novel LSD1 inhibitors would have great clinical significance. In this work, viscosalactone B was first identified as a novel LSD1 inhibitor. Viscosalactone B isolated from Withania Somnifera displayed antiproliferative activity against PC3, DU145, C42B, PC3/MDVR, DU145/MDVR, and C42B/MDVR cells with IC 50 values of 1.17, 0.72, 3.86, 2.06, 0.96 and 1.15 μM, respectively. In comparison, it was a selective LSD1 inhibitor with an IC 50 value of 970.27 nM and could induce a significant accumulation of LSD1 substrates H3K9me1, H3K9me2, and H3K4me1 in a concentration-dependent manner in DU145 cells. According to docking studies, it formed hydrogen bonds with the Thr11, Lys14, and Arg8 residues of LSD1. Importantly, while it displayed potent antitumor efficacy in vivo, it did not show obvious cytotoxicity on the major organs of nude mice. Therefore, viscosalactone B, as a novel LSD1 inhibitor, is a potential candidate that can be used for the treatment of prostate cancer in clinics.
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OPTICAL MATERIALS
·
2023
·
IF 3.9
Han Kang,Ze Zhang,Wei Zhou
Rhodamine B(RhB) was encapsulated in Tb(btc) (btc = 1,2,4-benzene tricarboxylic acid) frameworks by “one-pot” method, and the complex RhB@Tb(btc) with host-guest dual fluorescence emissions was synthesized. Compared with the stability of Tb 3+ emission, the characteristic emission of RhB at 620 nm showed a more sensitive response to ambient temperature. By integrating the different temperature dependence of Tb 3+ and RhB emissions, the temperature sensing of RhB@Tb(btc) was determined with relative sensitivity ranging from 0.43 to 0.59% K −1 (temperature range 298–353 K). Among several common antibiotics, RhB@Tb(btc) showed fluorescence quenching response to metronidazole (MDZ) and color transition to levofloxacin (LOFX) respectively with stable reusability. The combination of photoinduced electron transfer and internal filtration effect was confirmed as the contributor to MDZ induced fluorescence quenching. Furthermore, hydrogels and milk, which were added antibiotics on purpose for simulating unsafe foods, were detected at in situ temperature by RhB@Tb(btc) test paper, which achieved highly sensitive and highly selective detection to MDZ and LOFX with limit of detection reaching 10 −6 M.
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PHARMACEUTICAL DEVELOPMENT AND TECHNOLOGY
·
2022
·
IF 3.915
Ziyi Li,Zhenghua Li,Jianhua He,Jianping Liu
Salvianolic acid B (SAB) is a widely used cardioprotective agent, while its clinical application was limited by poor intestinal absorption and low oral bioavailability. In this study, SAB phospholipid (SP) complex was first prepared to improve the lipophilicity of SAB and then combined with d-glucose to further enhance intestinal absorption. Compared with free SAB, SP or the mixture of SAB and d-glucose, combination of SP and d-glucose showed higher intestinal absorption evidenced by increased effective permeation coefficient (Peff) in the in situ single-pass intestinal perfusion (SPIP) assay. Subsequently, SP and d-glucose at mass ratio of 1:6, with the highest Peff of SAB, were chosen for the preparation of complexed pellets to improve oral absorption efficiency of SAB. As expected, the obtained pellets significantly enhanced oral bioavailability of SAB in the pharmacokinetic study characterized by increasing Cmax and AUC0–t of SAB by 14.88-fold and 5.02-fold than free SAB, respectively. In conclusion, combination of d-glucose in SP pellets can effectively improve the intestinal absorption and oral bioavailability of SAB.
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BIOPROCESS AND BIOSYSTEMS ENGINEERING
·
2022
·Vol. 45
·期 4
·749-759
·
IF 3.434
Zhang Xiao-guang,Xue Yu,Lu Ze-ping,Xu Hua-jin,Hu Yi
In this study, a series of proline ionic liquids with different lengths of hydrophobic alkyl on the side chain were used to modify the Candida Antarctic lipase B (CALB). The catalytic activity, thermal stability and tolerance to methanol and DMSO of the modified enzyme were all improved simultaneously. The optimum temperature changed from 55 to 60 ℃. The hydrophobicity and anion type of the modifier have important influence on the catalytic performance of CALB. CALB modified by [ProC 12 ][H 2 PO 4 ] has a better effect. Under the optimal conditions, its hydrolysis activity was 3.0 times than that of the native enzyme, the catalytic efficiency Kcat/Km improved 2.8 times in aqueous phase, and the tolerance to organic solvent with strong polarity (50% methanol 2 h) was increased by 6.8 times. Fluorescence spectra and circular dichroism (CD) spectroscopy showed that the introduction of ionic liquids changed the microenvironment near the fluorophores of the enzyme protein, the α-helix decreased and β-sheet increased in the secondary structure of the modified enzymes. The root mean square deviation (RMSD), residue root mean square fluctuation (RMSF), radius of gyration (Rg), and solution accessible surface area (SASA) of [ProC 2 ][Br]-CALB, [ProC 12 ][Br]-CALB and native CALB were obtained for comparison by molecular dynamics simulation. The results of dynamics simulation were in good agreement with enzymology experiment. The introduction of ionic liquids can keep CALB in a better active conformation, and proline ionic liquids with long hydrophobic chains can significantly improve the surface hydrophobicity and overall rigidity of CALB. This research offers a new idea for rapid screening of efficient modifiers and provision of enzymes with high stability and activity for industrial application.
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Frontiers in Bioengineering and Biotechnology
·
2022
·
IF 6.064
Xue Yu,Zhang Xiao-Guang,Lu Ze-Ping,Xu Chao,Xu Hua-Jin,Hu Yi
Various betaine ionic liquids composed of different chain lengths and different anions were designed and synthesized to modify Candida antarctica lipase B (CALB). The results showed that the catalytic activity of all modified lipases improved under different temperature and pH conditions, while also exhibiting enhanced thermostability and tolerance to organic solvents. With an increase in ionic liquid chain length, the modification effect was greater. Overall, CALB modified by [BetaineC16][H2PO4] performed best, with the modified CALB enzyme activity increased 3-fold, thermal stability increased 1.5-fold when stored at 70°C for 30 min, with tolerance increased 2.9-fold in 50% DMSO and 2.3-fold in 30% mercaptoethanol. Fluorescence and circular dichroism (CD) spectroscopic analysis showed that the introduction of an ionic liquid caused changes in the microenvironment surrounding some fluorescent groups and the secondary structure of the CALB enzyme protein. In order to establish the enzyme activity and stability change mechanisms of the modified CALB, the structures of CALB modified with [BetaineC4][Cl] and [BetaineC16][Cl] were constructed, while the reaction mechanisms were studied by molecular dynamics simulations. Results showed that the root mean square deviation (RMSD) and total energy of modified CALB were less than those of native CALB, indicating that modified CALB has a more stable structure. Root mean square fluctuation (RMSF) calculations showed that the rigidity of modified CALB was enhanced. Solvent accessibility area (SASA) calculations exhibited that both the hydrophilicity and hydrophobicity of the modified enzyme-proteins were improved. The increase in radial distribution function (RDF) of water molecules confirmed that the number of water molecules around the active sites also increased. Therefore, modified CALB has enhanced structural stability and higher hydrolytic activity.
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