MOLECULES
·
2022
·Vol. 27
·期 4
·1209
·
IF 4.927
Jiacheng He,Xianhua Lin,Fanhui Meng,Yumiao Zhao,Wei Wang,Yao Zhang,Xiaolei Chai,Ying Zhang,Weiwei Yu,Junjie Yang,Guichao Li,Xuekui Du,Hankun Zhang,Mingyao Liu,Weiqiang Lu
Metastatic pancreatic cancer remains a major clinical challenge, emphasizing the urgent need for the exploitation of novel therapeutic approaches with superior response. In this study, we demonstrate that the aberrant activation of prostaglandin E2(PGE2) receptor 4 (EP4) is a pro-metastatic signal in pancreatic cancer. To explore the therapeutic role of EP4 signaling, we developed a potent and selective EP4 antagonist L001 with single-nanomolar activity using a panel of cell functional assays. EP4 antagonism by L001 effectively repressed PGE2-elicited cell migration and the invasion of pancreatic cancer cells in a dose-dependent manner. Importantly, L001 alone or combined with the chemotherapy drug gemcitabine exhibited remarkably anti-metastasis activity in a pancreatic cancer hepatic metastasis model with excellent tolerability and safety. Mechanistically, EP4 blockade by L001 abrogated Yes-associated protein 1 (YAP)-driven pro-metastatic factor expression in pancreatic cancer cells. The suppression of YAP’s activity was also observed upon L001 treatment in vivo. Together, these findings support the notions that EP4–YAP signaling axis is a vital pro-metastatic pathway in pancreatic cancer and that EP4 inhibition with L001 may deliver a therapeutic benefit for patients with metastatic pancreatic cancer.Keywords:pancreatic cancer;metastasis;EP4;small molecule;YAP
研究领域:
肿瘤学
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药理学
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分子生物学
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DOI
PubMed
高影响因子
FOOD CHEMISTRY
·
2024
·
IF 8.5
Jilei Wang,Qu Li,Yun Sun,Jingwen Liu,Zhao Jiang,Zhuoping Zheng,Li Liu,Xinhui Min,Yougui Yu,Qing Zheng
Elucidating the mechanisms underlying Baijiu production is a shared aspiration among academic groups specializing in the field of Baijiu research. This study comprehensively examined the mechanisms underlying the yellowish coloration of Baijiu through a synergistic application of chromatographic, spectroscopic, and physical methodologies. Aging of Baijiu in earthenware pots involves the infiltration of mineral ions such as iron, aluminum, and calcium; however, these ions are detected at extremely low concentrations and are therefore not linked to the development of Baijiu's yellowish color. Instead, the yellowish coloration is attributed to the diverse colorants generated during the high-temperature fermentation of small-molecule sugars derived from the saccharification of grain materials. Although these colorants exist in minimal quantities and exhibit spectral absorption peaks ranging from 300 to 450 nm, their overlapping spectra collectively contribute to the light-absorbing properties of Baijiu across a broad wavelength range, ultimately accounting for its characteristic yellowish color.
研究领域:
食品科学
·
化学
✓ 已验证
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2023
·
IF 9.5
Haichao Cao,Yue Chen,Zhigang Qian,Tingjie Huang,Nan Zou,Daxia Zhang,Wei Mu,Beixing Li,Feng Liu
The foliar loss of pesticides causes serious utilization decline and environmental risk. On the basis of biomimetics, pesticide-loaded microcapsules (MCs) with spontaneous deformation on foliar micro/nanostructures, like the snail suction cup, are prepared by interfacial polymerization. By controlling the usage or types of small alcohols in the MC preparation system, the flexibility of MCs is tunable. Through the investigation of emulsions and MC structures, we discover that the migration and distribution of small alcohols driven by amphiphilicity affect the process of interfacial polymerization between polyethylene glycol and 4,4-methylenediphenyl diisocyanate. By hydrophobic modification of the polymer and competition for oil monomers of small alcohols, the thickness and compactness of shells are reduced, whereas the density of the core is increased. As a result of the regulation in structures, the flexibility of MCs is improved significantly. In particularly, the MCs-N-pentanol (0.1 mol kg–1) with the best flexibility show strong scouring resistance on varied foliar structures, sustained release property on the air/solid interface, and persistent control effect against foliar diseases. The pesticide-loaded soft MCs provide an effective way to improve pesticide foliar utilization.
研究领域:
农学
·
材料科学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2025
·
IF 3.1
Yu-Qing Zhu,Jing-Wen Liu,Jing Zhou,Cheng-Ying Wu,Fang Long,Jin-Di Xu,Shan-Shan Zhou,Qian Mao,Ming Kong,Song-Lin Li,Hong Shen
Atractylodis Macrocephalae Rhizoma (AMR) is one of the commonly used medicinal and edible herbs in China. To prevent infestation of moths and mildew, chemical-fumigation is applied during post-harvest processing, which would produce harmful substances. Ultralow oxygen (ULO) storage, as a potential controlled atmosphere preservation method for Traditional Chinese Medicines (TCMs), has no residue of chemical hazards, but its impact on chemical composition of TCMs is unclear. Here, to evaluate the impact of ULO preservation on the quality of AMR, a UPLC-QTOF-MS/MS-based non-targeted metabolomics approach was employed to screen out the differential components after AMR had been stored under ULO conditions for 18 months. The differential components were identified, and further semi-quantified with peak areas. Additionally, the differential components with known activity were quantified using HPLC-DAD and GC-TQ-MS/MS analysis. The molecular weight distribution and monosaccharide composition of polysaccharides were analyzed using HPGPC-ELSD and HPLC-DAD to assess the impact of ULO on the carbohydrates. As it showed, 20 differential components of AMR under ULO were screened and identified when compared to normal atmosphere (NA) with 21 % oxygen concentration. As storage duration increased, the levels of atractylenolides I, II, and III in both ULO and NA storage conditions increased, with significant differences in their total content (16.06 mg/g in ULO vs. 47.57 mg/g in NA). Confirmatory experiments revealed that atractylone is the precursor compound of atractylenolides and the total content of atractylenolides I, II, and III produced from atractylone in ULO storage was only 62.12 % of that in NA at 18th month. The total sugar content of AMR polysaccharides in ULO storage was 107.28 % of that in NA and the molar ratios of monosaccharides were also relatively constant. All the results indicated that ULO preservation slowed down the chemical transformation of AMR, including small molecules and polysaccharides. Therefore, the quality of AMR stored in ULO is more stable and it is proposed to be an efficient preservation method for AMR.
研究领域:
中药学
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分析化学
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植物化学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2020
·
IF 8.758
Peiqi Luo,Liping Wang,Lixia Jiang,Jie Sun,Yafeng Li,Huihui Liu,Caiqiao Xiong,Zongxiu Nie
Graphdiyne (GD) is a new kind of carbon nanomaterial which has carbon–carbon triple bonds to form a layered structure. Here, we report the application of GD as the matrix for small molecule analysis in laser desorption ionization mass spectrometry (LDI MS). The GD matrix displayed two advantages: little background in the low mass range and good molecular ion signal in negative ion mode for many small molecules, e.g., fatty acids, amino acids, peptides, and drugs can be obtained in negative ion mode. By comparing the signal intensity of tetraphenylborate and juglone with and without GD existing, it was found that GD can enhance both of the desorption efficiency and ionization efficiency in LDI. Through analysis of the serum samples from liver cancer patients and healthy people, the GD-assisted LDI MS results showed that fatty acids could be used as potential biomarkers for the early diagnosis of liver cancer.
研究领域:
分析化学
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医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
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2021
·
IF 3.205
Xiao-Pan Liu,Wen-Qian Sun,Tong-Xin Liu,Bing-Bing Liu,Chang-Po Chen
Due to the strong background interferences in the low-mass region and poor reproducibility of conventional organic matrices, it is of great importance to develop a novel matrix for matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) to qualitatively and quantitatively analyze small molecules. In this work, water-soluble fullerenol C 60 (OH) 24–26 was selected as a MALDI matrix for the analysis of low-molecular-weight compounds in consideration of optical absorption property, water solubility and stability. Compared with the traditional matrices, fullerenol demonstrated lower background interference and stronger peak intensity. In addition, the hydrophilic fullerenol could avoid the heterogeneous crystallization in sample preparation, increase the reproducibility and sensitivity of MALDI-MS, and ameliorate quantitative analysis of small molecules. With saccharin as model analyte, quantitative analysis was carried out using fullerenol as matrix. The results demonstrated satisfying reproducibility and good tolerance to salt. The limit-of-detection of the quantitative analysis was as low as 4 pmol, and the linear range is 1–100 μg mL −1 with R 2 greater than 0.99. The analytical results also showed excellent precision and accuracy, low matrix effect and good recovery rate. Fullerenol as a potential matrix was further validated in the quantification of saccharin sodium in different real food samples, such as nuts and drinks. This work not only confirms the potential of fullerenol for the quantitative analysis in food field, but also provides a new technique for rapid analysis of small molecules.
研究领域:
分析化学
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食品科学
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质谱技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2023
·
IF 3.4
Wen Sun,Jin-Di Xu,Wei Zhang,Meng-Fei Guo,Ming Kong,He Zhu,Shan-Shan Zhou,Cheng-Yin Wu,Song-Lin Li,Qian Mao
Callicarpae Formosanae Folium (CFF), derived from the leaves of Callicarpa formosana Rolfe, is a common Chinese medicinal herb used for the treatment of hematemesis . Phytochemical studies found that phenylpropanoids , flavonoids , terpenoids and polysaccharides were the main ingredients of CFF. However, there is limited scientific information concerning holistic quality method and quality consistency evaluation of CFF. In this study, a strategy integrating HPGPC-ELSD, HPLC-PDA, UV–VIS and UPLC-QTOF-MS/MS was firstly developed to simultaneously qualify and quantify polysaccharides, as well as representative small molecules in CFF. HPGPC-ELSD was applied to characterize the molecular weight distribution of polysaccharides, HPLC-PDA was developed to qualitatively and quantitatively determine monosaccharides . UV-VIS was used to determine the total polysaccharides content, and UPLC-QTOF-MS/MS was established to characterize the small molecules. The quality consistency of commercial CFF (CM-CFF) was also evaluated. It was shown that the relative molecular weights , the compositional monosaccharides and small molecules composition in CM-CFF and self-collected CFF (SC-CFF) samples were similar. A total of 32 small molecules including 6 phenylpropanoids, 7 flavonoids and 19 terpenoids were characterized in CFF. However, the variation was observed in the content of polysaccharides, luteolin , ursolic acid , as well as total contents of terponoids in CM-CFF samples, which implied that the holistic quality of CM-CFF was inconsistent. The results suggested that the proposed evaluation strategy could be applied as a potential approach for the quality control of CFF. And the quality of CM-CFF should be improved by Good Agriculture Practice (GAP) base and standard processing method.
研究领域:
中药学
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分析化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NEW JOURNAL OF CHEMISTRY
·
2024
·Vol. 48
·期 16
·7300-7307
·
IF 2.7
Chunxiong Lu,Dandan Zhu,Peng Zhou,Kangxia Yu,Yaling Liu,Hongyong Wang,Hao Wu,Jun Wu,Guoqing Han,Pei Zou
Enormous success has been achieved in antitumor therapy with PD-1/PD-L1 inhibitors; however, less than 3 out of 10 patients show clinical benefits. An interesting phenomenon of patients who experienced durable clinical responses to PD-L1 blockade usually being the patients with high PD-L1 expression was noticed. Accordingly, the evaluation of PD-L1 is of great benefit to predict the immunotherapy response against PD-1/PD-L1. A small-molecule single photon emission computed tomography (SPECT) tracer [99mTc]Tc-SG2C-CBM containing a biphenyl moiety was designed and synthesized for the measurement of PD-L1 expression. The radiolabeling yield (RLY) and radiochemical purity (RCP) of [99mTc]Tc-SG2C-CBM were detected to be over 93% under the optimized labeling conditions. [99mTc]Tc-SG2C-CBM was discovered to be equipped with not only good stability but also suitable lipophilicity. In the cellular assays, [99mTc]Tc-SG2C-CBM showed moderate affinity to PD-L1 and 6.87-fold higher uptake in A375-hPD-L1 cells than in A375 cells. Then, the in vivo biodistribution results of the A375-hPD-L1 tumor-bearing mice showed that the radioactivity uptake in tumors was about 2.96 ± 0.76 and 2.31 ± 0.26 fold that in muscles and bones at 2 h post-injection, respectively. SPECT imaging was consistent with the biological distribution of [99mTc]Tc SG2C-CBM, with the uptake being mainly in the liver and less pronounced in tumors. The results of these studies indicate that [99mTc]Tc-SG2C-CBM may be a probe for imaging PD-L1 expression, but further research is needed.
研究领域:
医学影像学
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肿瘤学
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药物化学
✓ 已验证
DOI
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2025
·
IF 5.2
Jiawei Han,Zhimin Yue,Wen Sun,Weitao Fang,Yunran Zhang,Xiaoqian Liu,Jue Wang,Jiaxin Chen
With the expansion of gel research, organic small molecule gels are beginning to gain attention. Whether the small-molecule gel approach can be a new formulation strategy of solubilization and permeation promotion for poorly soluble drugs needs to be explored in this study. The model ingredient indomethacin (IND) as a nonsteroidal anti-flammatory drug shows limited therapeutic application mainly due to its low water solubility. Herein, the IND small molecule hydrogel was design to co-formed with a small molecule ligand by integrating theory-model-experiment techniques. Then, the formed IND small molecule hydrogels (i.e., IND-MEG hydrogel and IND-ARG hydrogel) with meglumine (MEG) or arginine (ARG) appeared typical 3-D network with good rheology. In comparison to crystalline IND, the solubilities of IND-MEG hydrogel and IND-ARG hydrogel exhibited 506.71-fold and 479.63-fold improvements, respectively. Meanwhile, both IND hydrogels performed significantly enhanced release rate and degree, and maintained supersaturation for a long time arising from the complexation reaction of IND and ligand, which was revealed by phase solubility and fluorescence quenching studies. Furthermore, the designed IND hydrogels significantly promoted IND membrane permeability compared to the commercial IND hydrogel, and enhanced the development potential of novel IND hydrogels for oral and transdermal applications. Therefore, this study provides a new formulation technique to increase the solubility/release and permeability of poorly water-soluble drugs by designing their small molecule hydrogel systems.
研究领域:
药剂学
·
药物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHINESE JOURNAL OF CHEMICAL ENGINEERING
·
2017
·
IF 1.174
Chunxi Qin,Jie Tang,Fenglei Bi,Zhenhao Xi,Ling Zhao
The solid–liquid extraction process of nylon 6 to eliminate small molecules, i.e. , caprolactam (CL), cyclic dimers (CD) and cyclic trimers (CT), is investigated in detail by both batch extraction experiments and numerical simulations. In the batch extraction experiments, due to the small molecules attaching to the polymeric surface, the basic physical mechanism shifts from surface diffusion to internal diffusion as the extraction proceeded. The experimental data are well reproduced by a diffusion model consisting of two distinct steps, characterized as surface diffusion and internal diffusion. Furthermore, based on the established mass transfer mechanism and diffusion model of the two distinct steps, the equilibrium constants and internal diffusion coefficients of CL, CD and CT are acquired. An industrial countercurrent extraction tower is further simulated. It is found that the extraction efficiency of CL can be significantly improved by increasing the temperature at the bottom portion of the tower. The elimination of CD, which can be greatly promoted by a high-concentration CL-water solution, is controlled by mass transfer resistance, whereas the removal of CL is mainly affected by the equilibrium.
研究领域:
化学工程
·
材料科学
✓ 已验证
产品关联
DOI
高影响因子
Nature Communications
·
2025
·Vol. 16
·期 1
·1-14
·
IF 15.7
Hu Hao,Guo Songcheng,Li Yiyuan,Dong Kejun,Lu Yan,Ye Keyi,Li Longjie,Zhou Xiaoyu,Cheng Liming,Xiao Xianjin
Detecting small molecules is pivotal across fields like clinical diagnostics, environmental monitoring, and food safety. The CRISPR-Cas12a system, known for its simplicity and sensitivity, offers a promising basis for small molecule detection. However, current CRISPR-based detection methods face challenges, including complex design requirements, high background noise, and limited adaptability to different targets. In our study, we introduce the SBS-Cas system, leveraging a split crRNA mode to induce spatial hindrance on the scaffold strand through molecular binding. This approach prevents the assembly with Cas12a, effectively masking its trans-cleavage activity. By introducing small molecules that competitively bind to the macromolecule, we eliminate this spatial hindrance, activating Cas12a. Our results demonstrate high sensitivity, versatility, and adaptability in small molecule detection across multiple reactions, with successful intracellular imaging and responsive fluctuations in complex environments underscoring the system’s robustness. This innovative CRISPR-Cas12a-based approach establishes a low-background, highly sensitive platform for small molecule detection. SBS-Cas promises not only to enhance tools for clinical, environmental, and food safety applications but also to advance CRISPR research, providing insights and expanding possibilities in molecular detection science.
研究领域:
分子生物学
·
临床诊断
·
环境科学
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食品安全
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BRITISH JOURNAL OF PHARMACOLOGY
·
2025
·
IF 7.7
Junli Peng,Nan Yang,Zhen Qiao,Ningning Wei,KeWei Wang,Yanru Zhang
Background and Purpose As a polymodal biosensor, the TRPA1 ion channel undergoes rapid opening and closing, a dynamic process known as gating that defines the fundamental function and modulation of ion channels. TRPA1 gating is primarily regulated by chemical and mechanical stimuli. However, whether and how TRPA1 gating transduces the biological function of pain sensation is poorly understood. Experimental Approach A series of photoswitchable TRPA1 probes (PSTRAPs1–4) were designed and synthesized. Whole-cell patch clamp recordings of hTRPA1 channels expressed in CHO cells were performed to test whether PSTRAPs could optically switch TRPA1 channel function. Site-directed mutagenesis was conducted to identify the binding site of PSTRAPs on the extracellular surface of TRPA1. In a mouse model of cheek pain, intracutaneous injection of PSTRAPs elicited pain sensation in response to photoswitching. Key Results PSTRAP-2 and PSTRAP-4 reversibly modulate TRPA1 channel function with spatiotemporal resolution. These azobenzene photoswitches can activate and deactivate TRPA1 currents expressed in CHO cells upon switching between blue light and darkness. Structural-activity relationship (SAR) analysis of PSTRAPs1–4 combined with site-directed mutagenesis revealed a residue Y926 between the pore helix 1 and 2 critical for the interaction between the PSTRAPs and TRPA1. In a mouse cheek pain model, photochemical gating of TRPA1 by intracutaneous injections of photoswitchable PSTRAP-2 and PSTRAP-4 induced pain perception in response to photoswitching cycles. Conclusion and Implications Our identification of these photoswitches not only provides small molecule tools for probing and understanding TRPA1 channel gating but also holds developmental potential for pain modulation. Graphical
研究领域:
神经科学
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药理学
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生物化学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）