CARBOHYDRATE POLYMERS
·
2020
·
IF 7.182
Dongmei Wu,Jiaqi Zheng,Weiwei Hu,Xiaoliang Zheng,Qiaojun He,Robert J. Linhardt,Xingqian Ye,Shiguo Chen
Rhamnogalacturonan I (RG-I) pectin are regarded as strong galectin-3 (Gal-3) antagonist because of galactan sidechains. The present study focused on discussing the effects of more structural regions in pectin on the anti-Gal-3 activity. The water-soluble pectin (WSP) recovered from citrus canning processing water was categorized as RG-I pectin. The controlled enzymatic hydrolysis was employed to sequentially remove the α-1,5-arabinan, homogalaturonan and β-1,4-galactan in WSP. The Gal-3-binding affinity KD (kd/ka) of WSP and debranched pectins were calculated to be 0.32 μM, 0.48 μM, 0.56 μM and 1.93 μM. Moreover, based on the more sensitive cell line (MCF-7) model, the IC 30 value of WSP was lower than these of modified pectins, indicating decreased anti-Gal-3 activity. Our results suggested that the total amount of neutral sugar sidechains, the length of arabinan and cooperation between HG and RG-I played important roles in the anti-Gal-3 activity of WSP, not the Gal/Ara ratio or RG-I/HG ratio. These results provided a new insight into structure-activity relationship of citrus segment membrane RG-I as a galectin-3 antagonist and a new functional food.
研究领域:
食品科学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF MEDICINAL CHEMISTRY
·
2023
·
IF 7.3
Zhiyuan Cheng,Yijie Wang,Yao Zhang,Chan Zhang,Mengru Wang,Wei Wang,Jiacheng He,Yang Wang,Hankun Zhang,Qiansen Zhang,Chunyong Ding,Deyan Wu,Linlin Yang,Mingyao Liu,Weiqiang Lu
Nowadays, small-molecule drugs have become an indispensable part of tumor immunotherapy. Accumulating evidence has indicated that specifically blocking PGE2/EP4 signaling to induce robust antitumor immune response represents an attractive immunotherapy strategy. Herein, a 2H-indazole-3-carboxamide containing compound 1 was identified as a EP4 antagonist hit by screening our in-house small-molecule library. Systematic structure–activity relationship exploration leads to the discovery of compound 14, which displayed single-nanomolar EP4 antagonistic activity in a panel of cell functional assays, high subtype selectivity, and favorable drug-like profiles. Moreover, compound 14 profoundly inhibited the up-regulation of multiple immunosuppression-related genes in macrophages. Oral administration of compound 14, either as monotherapy or in combination with an anti-PD-1 antibody, significantly impaired tumor growth via enhancing cytotoxic CD8+ T cell-mediated antitumor immunity in a syngeneic colon cancer model. Thus, these results demonstrate the potential of compound 14 as a candidate for developing novel EP4 antagonists for tumor immunotherapy.
研究领域:
肿瘤学
·
免疫学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
Science Advances
·
2025
·Vol. 11
·期 30
·
IF 12.5
Caifeng Deng,Liukang Yu,Xuan Zhao,Yuxiao Chen,Jiabin Mei,Jie Wei,Xiaoyuan Chen,Guanghua Lei,Chao Zeng
Osteoarthritis (OA) is a multifactorial disease characterized by joint inflammation and cartilage degeneration, with no disease-modifying drugs available. The vicious cycle between the inflammatory microenvironment (inflamed soil) and dysfunctional chondrocytes (degeneration-related seeds) drives the chronic progressive deterioration of OA. Here, we report a genetically engineered chondrocyte-mimetic nanoplatform (termed HKL-GECM@MPNPs) comprising a honokiol (HKL)–loaded mitochondrion-targeting nanoparticle core coated with an interleukin-1 receptor type 2 (IL-1R2)–overexpressing chondrocyte membrane. HKL-GECM@MPNPs fuse with OA chondrocytes, transferring IL-1R2 onto the plasma membrane and reprogramming the inflamed microenvironment through IL-1β blockade. Mitochondrion-targeting cores then directly deliver HKL to restore mitochondrial sirtuin-3 in OA chondrocytes, reprogramming the cells’ pathological phenotype. Intra-articular injection of HKL-GECM@MPNPs in OA mice reduces inflammation, alleviates joint pain, and mitigates cartilage damage through a synergistic effect. Moreover, HKL-GECM@MPNPs effectively reverse cartilage degeneration in human OA cartilage explants. This approach highlights the potential of HKL-GECM@MPNPs to combine IL-1β blockade and mitochondrial sirtuin-3 restoration as a promising strategy for OA treatment.
研究领域:
纳米医学
·
生物工程
·
免疫学
·
分子生物学
·
药理学
·
风湿病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Plant Science
·
2022
·
IF 6.627
Lei Wenli,Song Yuyang,Long Ai,Que Yanyan,He Shuzhong,Zhong Hang,Chen Yang
The medicinal plants were wildly library of natural products in drug discovery. The most active molecules with seven-membered rings skeleton represent a challenge for construction. A stereoselectivity (4 + 3) cycloadditions between allenyl ethers and substituted furans induced by chiral auxiliaries has been investigated. And the results showed significant stereoselectivities and regioselectivities. The optical cycloadducts with an oxygen-substituted seven-membered ring framework were generated by removing chiral auxiliaries under acidic conditions. The antiproliferative activity of the novel compounds displayed moderate antiproliferative effects toward T47D cells.
研究领域:
有机化学
·
药物化学
·
癌症研究
✓ 已验证
DOI
PubMed
高影响因子
Polymers
·
2022
·Vol. 14
·期 21
·4655
·
IF 4.967
Hongyan Wu,Xinying Ao,Jianan Liu,Junya Zhu,Jingran Bi,Hongman Hou,Hongshun Hao,Gongliang Zhang
The 3-(Methylthio) propyl isothiocyanate (MTPITC)-loaded inclusion complex prepared by α-cyclodextrin (α-CD) was incorporated into chitosan (CS) film to fabricate a packaging material for fresh chicken meat preservation. Scanning electron microscope images indicated homogenous dispersion of the MTPITC-α-CD in CS polymer. Fourier-transform infrared and X-ray diffraction techniques revealed that MTPITC-α-CD was incorporated into the CS film matrix by the physical interactions. The introduction of MTPITC-α-CD improved the UV-vis light-blocking ability, with a slight loss of transparency. Although the water solubility and water vapor barrier capacity were not significantly influenced by the addition of MTPITC-α-CD, the antioxidant attribute was significantly enhanced. The CS-MTPITC-α-CD film displayed obvious and sustained suppressive effects againstSalmonella typhimurium, with the inhibition zone diameters of 14.7 mm at 12 h and 7.3 mm at 24 h, respectively. Moreover, the quality index analysis indicated that the CS-MTPITC-α-CD film-wrapped fresh chicken, during refrigerated storage, exhibited better preservative efficacy than the control groups, with the total viable counts of 6.5 Log CFU/g, total volatile base nitrogen of 8.4 mg/100 g, pH of 6.6, thiobarbituric acid-reactive substances of 0.2 mg/kg, and the sensory score of 5 at day 16. Collectively, these results suggest that CS-MTPITC-α-CD film is a prospective packaging candidate for delaying the quality deterioration of chicken meat.
研究领域:
食品科学
·
材料科学
·
生物技术
✓ 已验证
DOI
高影响因子
JOURNAL OF MOLECULAR STRUCTURE
·
2024
·
IF 4
Anthony Roucou,Xiujuan Wang,Jonas Bruckhuisen,Manuel Roca,Colwyn Bracquart,Robin Blanchart,Luyao Zou,Qian Gou,Arnaud Cuisset,Guillaume Dhont
3-methylcatechol (3MC) is a molecule of environmental interest due to its presence in the atmosphere during biomass burning events, leading to the formation of secondary organic aerosols. This paper goes one step further than the paper from A.S. Hazrah et al. (2022) [10] . A three-dimensional torsional potential energy surface was determined, confirming the existence of three rotamers for 3MC. One dimensional potential energy curves along the rotation of the methyl group were computed and fitted to estimate the barrier height in each conformer . Experiments were performed at low temperature in the microwave domain ( 2 − 20 GHz range) and, for the first time, in the millimeter-wave domain ( 70 − 110 GHz range) at T = 323 K with a specially designed heated absorption cell. The rotational linelist was fitted to provide updated spectroscopic parameters for the two 3MC conformers of lowest energies. In particular, the A − E splitting is observed in the microwave region for both conformers while in the millimeter-wave region, it is only seen for the conformer of the lowest energy.
研究领域:
环境科学
·
量子化学
·
大气科学
✓ 已验证
产品关联
DOI
高影响因子
Biomaterials Science
·
2022
·Vol. 10
·期 23
·6804-6817
·
IF 7.59
Guiyin Li,Wenzhan Li,Shengnan Li,Xinhao Li,Xiaoqing Yao,Wen Xue,Jintao Liang,Jiejing Chen,Zhide Zhou
Glypican-3 (GPC3) is a membrane-associated proteoglycan that is specifically upregulated in hepatocellular carcinoma (HCC) and has become one of the most promising biomarkers closely related to the occurrence and development of HCC. In this work, platinum@palladium nanoparticles decorated with hemin-reduced graphene oxide (H-rGO-Pt@Pd NPs) were used not only as a support for GPC3 aptamer (GPC3Apt) immobilization, but also as a new redox nanoprobe in electrochemical analysis for the determination of GPC3. The electrochemical aptasensor involved a reaction cell with a three-electrode system, and the differential pulse voltammetry (DPV) technique was adopted. In the presence of GPC3, the formed GPC3Apt–GPC3 complexes had stable structures and were cleaved from the electrode surface, leading to more electroactive H-rGO-Pt@Pd NPs repelling freely from the GPC3Apt/H-rGO-Pt@Pd NPs and thus to the increase of the oxidation peak current of hemin in H-rGO-Pt@Pd NPs. Under optimal conditions and a working voltage of +700 mV (vs. Ag/AgCl), the label-free electrochemical GPC3 aptasensor showed superior performance with a wider concentration linear range (0.001–10.0 μg mL−1), a lower limit of detection (LOD) (0.181 ng mL−1, S/N = 3), a higher sensitivity (0.0446 μA μM−1 cm−2) and good selectivity. Furthermore, the fabricated aptasensor was applied to GPC3 determination in human serum samples with satisfactory recoveries of 94.3%–119% and RSDs of 0.15%–5.78%. The current work provides a flexible approach for the rapid and sensitive analysis of GPC3 and has a broad application prospect in the diagnosis of HCC.
研究领域:
生物医学工程
·
分析化学
·
肿瘤学
✓ 已验证
DOI
PubMed
高影响因子
Nanoscale
·
2019
·Vol. 11
·期 13
·6182-6191
·
IF 6.97
Jinjin Ma,Qianting Yao,John A. McLeod,Lo-Yueh Chang,Chih-Wen Pao,Jiatang Chen,Tsun-Kong Sham,Lijia Liu
Inorganic lead halide perovskite CsPbX3 (X = Cl, Br, or I) nanocrystals are promising candidate materials for light-emitting devices and optoelectronics. Mn-Doped CsPbX3 is of particular interest, as the Mn-doping introduces an additional emission band, making this material a promising white-light emitter. In this study, Mn-doped CsPb(Br/Cl)3 nanocrystals are prepared at room-temperature and ambient pressure. The chemical environment of Mn, and the luminescence of these nanocrystals are analyzed in detail using X-ray diffraction (XRD), extended X-ray absorption fine structure (EXAFS), X-ray absorption near-edge structure (XANES) and X-ray excited optical luminescence (XEOL). Although the introduction of Mn does not alter the long-range order of the CsPbX3 crystal, it leads to a local lattice contraction with the bond length of Mn–X much shorter than Pb–X. We also find excitation energy-dependence in both the intensity and wavelength of the perovskite excitonic emission band, while only in intensity of the Mn emission band. Detailed fitting of the XEOL reveals that the perovskite emission band is dual-channel, and it is the excitation energy-dependent intensity variation of these two channels that drives the observed red-shift of the combined emission band. Our findings also confirm that the Mn emission band is driven by exciton-Mn energy transfer and clarify the Mn chemical environment and the luminescence mechanism in Mn-doped CsPb(Br/Cl)3 nanocrystals.
研究领域:
材料科学
·
光电子学
·
纳米技术
·
固体物理
✓ 已验证
DOI
高影响因子
JOURNAL OF ALLOYS AND COMPOUNDS
·
2022
·
IF 6.371
Xiangchao Zhao,Yuansong Luo,Xiujian Zhao
NASICON-type solid electrolyte Li 1.3 Al 0.3 Ti 1.7 (PO 4 ) 3 (LATP) has become an excellent substitute for organic liquid electrolytes due to its high ionic conductivity and exceptional air stability. However, its application is limited by its poor sintering characteristics and high grain boundary resistance. In this study, TeO 2 was introduced into LATP as a sintering aid to promote its sintering, and its properties were measured by XRD , SEM, XPS, EIS and dilatometry . The results show that the addition of TeO 2 can form eutectic liquid phase in LATP ceramic pellets during sintering, thus effectively promoting particle sintering. Not only the grain size was greatly increased, but also grain boundary and pore defects were reduced. With the help of TeO 2 , the performance of LATP is greatly improved when sintered at only 750 °C, the relative density and total ionic conductivity reached 90.64% and 0.207 mS/cm, respectively. The highest total ionic conductivity of 0.279 mS/cm and the highest relative density of 93.81% were obtained when sintered at 800 ℃ and 950 ℃, respectively. However, due to the volatilization of Li and Te at high temperature, the relative density and total ionic conductivity of LATP with TeO 2 added sintered at high temperature have only a small increase compared to that without addition. In conclusion, this study provides a feasible scheme for improving LATP performance.
研究领域:
材料科学
·
电化学
·
固体物理
✓ 已验证
DOI
高影响因子
ORGANIC PROCESS RESEARCH & DEVELOPMENT
·
2020
·
IF 3.023
Zeyu Yang,Wenjie Ye,Youyu Xie,Qinghai Liu,Rong Chen,Hualei Wang,Dongzhi Wei
Bioreductions catalyzed by alcohol dehydrogenases (ADHs) play an important role in the synthesis of chiral alcohols. However, the synthesis of ethyl (S)-4-chloro-3-hydroxybutyrate [(S)-CHBE], an important drug intermediate, has significant challenges concerning high substrate or product inhibition toward ADHs, which complicates its production. Herein, we evaluated a novel ADH, SmADH31, obtained from the Stenotrophomonas maltophilia genome, which can tolerate extremely high concentrations (6 M) of both substrate and product. The coexpression of SmADH31 and glucose dehydrogenase from Bacillus subtilis in Escherichia coli meant that as much as 660 g L–1 (4.0 M) ethyl 4-chloroacetoacetate was completely converted into (S)-CHBE in a monophasic aqueous system with a >99.9% ee value and a high space-time yield (2664 g L–1 d–1). Molecular dynamics simulation shed light on the high activity and stereoselectivity of SmADH31. Moreover, five other optically pure chiral alcohols were synthesized at high concentrations (100–462 g L–1) as a result of the broad substrate spectrum of SmADH31. All these compounds act as important drug intermediates, demonstrating the industrial potential of SmADH31-mediated bioreductions.
研究领域:
生物化学
·
药物化学
·
酶工程
✓ 已验证
DOI
高影响因子
JOURNAL OF THE ELECTROCHEMICAL SOCIETY
·
2019
·Vol. 166
·期 15
·B1426
·
IF 3.12
Haiyun Zhai,Shiqiao Wang,Jianfeng Zhou,Jianbin Pan,Yanli Tong,Qinghua Mei,Qing Zhou
A sensitive and facile electrochemical sensor based on glassy carbon electrode (GCE) receiving electrochemical anodic pretreatment for signal amplification was developed for the determination of 3-nitrotyrosine (3-NT) (an oxidative stress biomarker). Adding sodium hexadecyl sulfate (SDS) to 0.1 M HNO3 solution was conducive to adsorption onto the surface of modified electrode, which promoted electron exchange and enhanced electrochemical behaviors by significantly increasing the hydrophobicity of electrode surface. Scanning electron microscopy showed that the surface of modified GCE had a remarkably thin layer composed of dense nanoparticles owing to surface layer oxidation, growth of graphite oxide thin layer and microscopic mechanical destruction of electrode surface during cyclic voltammetry by anodization oxidation. Under optimal conditions, the current change of 3-NT in square wave stripping voltammetry (SWV) was linearly related to its concentration in the range of 0.05∼30.0 μM, with a detection limit (S/N = 3) of 17.0 nM, acceptable stability and reproducibility. Additionally, this sensor was successfully applied to detect 3-NT in human serum samples.
研究领域:
分析化学
·
生物医学工程
·
电化学
✓ 已验证
DOI
高影响因子
MACROMOLECULES
·
2020
·
IF 5.918
Dalong Zhai,Mingjing Zhu,Shuwen Chen,Yue Yin,Xin Shang,Lixin Li,Gang Zhou,Juan Peng
Despite recent impressive advances in synthesis of all-conjugated diblock copolymers via facile quasi-living Grignard metathesis (GRIM) polymerization, it remains challenging to achieve well-defined all-conjugated triblock copolymers of interest. Herein, we report the judicious design and synthesis of a series of all-conjugated triblock copoly(3-alkylthiophene)s consisting of poly(3-butylthiophene) (P3BT), poly(3-hexylthiophene) (P3HT), poly(3-octylthiophene) (P3OT), or poly(3-dodecylthiophene) (P3DDT) in all 12 possible combinations. The effects of block sequences and the length of alkyl side chains on their cocrystallization and microphase-separated structures are investigated. Moreover, the correlation between different crystalline structures and charge mobilities in organic field-effect transistors (OFETs) is scrutinized. These rationally synthesized triblock copoly(3-alkylthiophene)s self-assemble into cocrystals with an edge-on orientation in as-cast and 150 °C-annealed samples. Remarkably, the combinations with the shortest alkyl side chains placed as the central block (i.e., P3HT-b-P3BT-b-P3OT, P3HT-b-P3BT-b-P3DDT, P3OT-b-P3BT-b-P3DDT, and P3OT-b-P3HT-b-P3DDT) exhibit higher film crystallinity and charge mobilities than the other two combinations where the blocks with shortest alkyl side chains are located at two terminals. Intriguingly, upon thermal annealing near the melting temperature of these combinations, P3BT-b-P3OT-b-P3HT, P3BT-b-P3DDT-b-P3OT, and P3HT-b-P3DDT-b-P3OT can retain their cocrystalline structure while the other combinations are found to microphase separate. Finally, the all-conjugated triblock copoly(3-alkylthiophene)s with proper block sequence demonstrate stable charge mobilities at high temperatures and good flexibility in OFET devices. Taken together, this study elucidates that the block sequence is of key importance on control of the crystallization and charge transport behavior of poly(3-alkylthiophene)-based triblock copolymers.
研究领域:
材料科学
·
有机电子学
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）