IMMUNITY
·
2024
·
IF 25.5
Jun Xiao,Shuang Wang,Longlong Chen,Xinyu Ding,Yuanhao Dang,Mingshun Han,Yuxiao Zheng,Huan Shen,Sifan Wu,Mingchang Wang,Dan Yang,Na Li,Chen Dong,Miao Hu,Chen Su,Weiyun Li,Lijian Hui,Youqiong Ye,Huiru Tang,Bin Wei,Hongyan Wang
Macrophages are critical to turn noninflamed “cold tumors” into inflamed “hot tumors”. Emerging evidence indicates abnormal cholesterol metabolites in the tumor microenvironment (TME) with unclear function. Here, we uncovered the inducible expression of cholesterol-25-hydroxylase (Ch25h) by interleukin-4 (IL-4) and interleukin-13 (IL-13) via the transcription factor STAT6, causing 25-hydroxycholesterol (25HC) accumulation. scRNA-seq analysis confirmed that CH25H hi subsets were enriched in immunosuppressive macrophage subsets and correlated to lower survival rates in pan-cancers. Targeting CH25H abrogated macrophage immunosuppressive function to enhance infiltrating T cell numbers and activation, which synergized with anti-PD-1 to improve anti-tumor efficacy. Mechanically, lysosome-accumulated 25HC competed with cholesterol for GPR155 binding to inhibit the kinase mTORC1, leading to AMPKα activation and metabolic reprogramming. AMPKα also phosphorylated STAT6 Ser564 to enhance STAT6 activation and ARG1 production. Together, we propose CH25H as an immunometabolic checkpoint, which manipulates macrophage fate to reshape CD8 + T cell surveillance and anti-tumor response.
研究领域:
免疫学
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肿瘤学
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代谢生物学
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分子生物学
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DOI
PubMed
高影响因子
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY
·
2018
·Vol. 47
·期 6
·2420-2431
·
IF 5.5
Zhu Zhendong,Li Rongnan,Ma Gongzhen,Bai Wenjing,Fan Xiaoteng,Lv Yinghua,Luo Jun,Zeng Wenxian
Background/Aims: ATP is essential for mammalian sperm to survive and maintain fertilizing capacity. AMP-activated protein kinase (AMPK) is a sensor of cellular energy status. The aims of the present study were to explore the localization of AMPK in goat sperm and to investigate whether and how AMPK regulates sperm functions in vitro. Methods: Sperm were treated with AMPK modulators (AICAR, metformin and Compound C) during incubation. Sperm motility was assessed with a computer-assisted spermatozoa analysis system (CASA). Membrane integrity, acrosome reaction and mitochondrial membrane potentials were detected by SYBR-14/PI, FITC-PNA and JC-1 staining, respectively. And the lactate content, ATP content, AMPK activity, activity of pyruvate kinase (PK) and lactate dehydrogenase (LDH) were also measured with the commercial assay kits. Immunofluorescence staining was used to analyze the distribution of PK, LDH, AMPK and phospho-Thr172-AMPK in sperm. The role of AMPK was further studied during induction of capacitation and acrosome reaction. Results: We found that AMPKα was localized in the entire acrosomal region, the midpiece and the flagellum, while the phospho-Thr172-AMPK was distributed in the head, the midpiece and flagellum. Activation of AMPK by AICAR and metformin significantly improved sperm motility, membrane integrity and acrosome reaction, largely maintained sperm mitochondrial membrane potentials, lactate content and ATP content, and enhanced the activity of AMPK, PK and LDH, whereas inhibition by Compound C triggered the converse effects. Moreover, PK was localized in the acrosomal area and the midpiece, while LDH was distributed in the tail. Induction of capacitation and acrosome reaction led to AMPK phosphorylation. AMPK phosphorylation regulated the activity of energetic enzymes. Conclusion: This study for the first time provides evidence that AMPK governs goat sperm functions through energy metabolism in vitro. This finding will help to improve assisted reproductive techniques in goats and the other species
研究领域:
生殖生物学
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分子生物学
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DOI
PubMed
高影响因子
ECS Journal of Solid State Science and Technology
·
2024
·Vol. 13
·期 5
·054001
·
IF 1.8
Changxin Dong,Xinhuan Niu,Jianghao Liu,Ni Zhan,Yida Zou,Chao He,Xinjie Li,Fu Luo,Yunhui Shi,Jiabao Cheng
For Ruthenium (Ru)-based copper (Cu) interconnects Cu film chemical mechanical polishing (CMP), it is crucial to select appropriate pH regulators in the slurry to ensure the chemical reactions and maintain the stability of the polishing chemical environment. In this study, the effects of inorganic pH regulator KOH, organic pH regulator diethanolamine (DEA), and 2-amino-2-methyl-1-propanol (AMP) on CMP and slurry properties of Cu film were compared. It was found when using AMP as a pH regulator, the Cu/Ru removal rate selectivity (RRS) can reach 598:1, the surface roughness of Cu film decreased to 0.76 nm, and the slurry can remain stable for at least 7 d. The performance order of the three pH regulators is AMP＞KOH＞DEA. Meanwhile, through experimental results and test analysis, it has been confirmed that AMP can also play a multifunctional role as a complexing agent, dispersant, and surfactant. Therefore, AMP can replace KOH as a new pH regulator in weak alkaline slurries. This result plays an important role in guiding the selection of organic pH regulators in the optimization of Cu film CMP slurry.
研究领域:
材料科学
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化学工程
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DOI
高影响因子
Frontiers in Pharmacology
·
2020
·
IF 4.225
Zhang Jiaqi,Liang Xiaoqiang,Li Jiacheng,Yin Hao,Liu Fangchen,Hu Cheng,Li Ling
Overuse of acetaminophen (APAP) is a major cause of drug-induced liver failure at the clinics. Apigenin (API) is a natural flavonoid derived from Matricaria chamomilla. The aim of the present study was to investigate the amelioration function of API in APAP-induced hepatotoxicity both in vitro and in vivo and investigate its potential mechanisms. Analysis results of the activities of serum alanine and aspartate aminotransferases (ALT and AST), malondialdehyde, myeloperoxidase (MPO), and reactive oxygen species (ROS) demonstrated therapeutic effects of API. MTT assay results revealed that API attenuated APAP and its metabolic product, N-acetyl-p-benzoquinone imine (NAPQI) induced cytotoxicity in a dose-dependent manner in human liver cells, L-02 cells. Subsequently, metabolomic results of cells and serum analyses demonstrated an aberrant level of carnitine palmitoyltransferase I (CPT1A). We established that API stimulated CPT1A activity in mice liver tissues and L-02 cells. Molecular docking analyses revealed potential interaction of API with CPT1A. Further investigation of the role of CPT1A in L0-2 cells revealed that API reversed cytotoxicity via the AMP-activated protein kinase (AMPK)/GSK-3β signaling pathway and compound C, which is a selective AMPK inhibitor, inhibited activation of CPT1A induced by API. API was bound to the catalytic region of AMPK as indicated by molecular docking results. In addition, compound C suppressed nuclear translocation of nuclear factor erythroid 2–related factor 2 (NRF2) that is enhanced by API and inhibited the antioxidative function of API. In summary, the study demonstrates that API attenuates APAP-induced hepatotoxicity by activating the AMPK/GSK-3β signaling pathway, which subsequently promotes CPT1A activity and activates the NRF2 antioxidant pathway.
研究领域:
药理学
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毒理学
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细胞生物学
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分子生物学
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DOI
PubMed
高影响因子
SEPARATION AND PURIFICATION TECHNOLOGY
·
2025
·
IF 9
Derui Zheng,Yu Wang,Jianhua Zu,Siyu Liu
This study developed a novel defective composite material (UiO-66/D-AMP) based on defect engineering and in situ synthesis of ammonium phosphomolybdate (AMP) for the highly selective capture of Cs + and Sr 2+ . The changes in adsorption capacity and surface functional groups of the composite before and after defect engineering were analyzed by adsorption experiment and FT-IR characterization. It was found that the defect-engineered composite had obvious carboxyl groups, and the adsorption efficiency of Sr 2+ was effectively improved. Several analytical methods were employed to verify the effective incorporation of AMP onto the UiO-66 framework. SEM-EDS was utilized to examine surface morphology and elemental composition. FTIR confirmed the presence of functional groups, while XRD analysis validated the crystalline structure. Additionally, TG assessed thermal stability, and BET measurements determined the material's surface area and porosity, collectively confirming AMP loading. The UiO-66/D-AMP composite exhibited significant adsorption affinity for both Cs + and Sr 2+ ions, demonstrating its potential for radioactive wastewater treatment. Under alkaline conditions (pH 10), the composite demonstrated exceptional removal efficiencies of 98.43% for Cs + and 99.54% for Sr 2+ . The maximum adsorption capacities were determined to be 104.3 mg/g for Cs + and 20.18 mg/g for Sr 2+ . Notably, the adsorption kinetics revealed rapid equilibration times of 5 min for Cs + and 60 min for Sr 2+ . The adsorption kinetics of Cs + and Sr 2+ followed the pseudo-second-order model, while the adsorption isotherms fitted well with the Langmuir model. In mixed solutions containing Cs + , Sr 2+ , and four competing ions, UiO-66/D-AMP exhibited excellent selectivity for both Cs + and Sr 2+ . Remarkably, the adsorption capacities for Cs + and Sr 2+ remained stable following exposure to various adsorbed doses. XPS provided direct evidence for the ion exchange mechanism between Cs + and NH 4 + during adsorption. Sr 2+ first exchanged with H + on UiO-66/D-AMP, then coordinated with the oxygen atom in the carboxyl group to be adsorbed.
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高影响因子
JOURNAL OF HAZARDOUS MATERIALS
·
2021
·
IF 10.588
Hao Wang,Shuai Wang,Shixing Wang,Jiali Tang,Yingbi Chen,Libo Zhang
A new zirconium-based adsorption material (UiO-66-AMP) was prepared by modifying UiO-66-NH 2 with 5-adenosine to effectively remove Pb(II) and Cr(VI) from wastewater. The SEM, EDS, XRS and FT-IR characterization confirmed the successful synthesis of UiO-66-AMP. We conducted a sets of experiments to test the adsorption effectiveness of UiO-66-AMP for Pb(II) and Cr(VI). The maximum adsorption capacity of UiO-66-AMP for Cr(VI) (pH=2) and Pb(II) (pH=4) are 196.60 and 189.69 mg/g, respectively. The adsorption process conforms to the pseudo-second-order and Langmuir models, which indicates that the adsorption is a single-layer chemical process. Gibbs free energy ( ∆G) indicates that the adsorption of Pb(II) is an exothermic reaction , while the adsorption of Cr(VI) is an endothermic reaction . At the same time, the adsorbent maintains excellent adsorption capacity at least after 4 cycles. The good adsorption performance of UiO-66-AMP towards the metal ions was attributed to the surface complexation and electrostatic interactions. Therefore, the new adsorbent has obvious application prospect to remove Pb(II) and Cr(VI) from wastewater.
研究领域:
环境科学
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材料科学
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DOI
PubMed
高影响因子
Journal of Environmental Chemical Engineering
·
2024
·
IF 7.4
Yaxuan Zhen,Chunying Zhu,Taotao Fu,Youguang Ma
Blended organic amine solutions are considered an effective strategy for developing highly efficient and low energy-consuming absorbents due to the possibility of combining the advantages of single amine. The 2-amino-2-methyl-1-propanol (AMP) and 2-(ethylamino)ethanol (EAE) amine blends were prepared in three molar ratios: blend-1 ( n AMP : n EAE = 3:1), blend-2 ( n AMP : n EAE = 1:1), and blend-3 ( n AMP : n EAE = 1:3). The impacts of gas-liquid flow rate, amine concentration, molar ratio, temperature, and CO 2 concentration on absorption performance were investigated using the serpentine microchannel. Additionally, the effects of amine concentration and molar ratio on the desorption performance of saturated solutions were also explored. The performance of amine blends in absorption and desorption was evaluated by measuring absorption rate, efficiency, and loading, as well as desorption efficiency, energy consumption, cycle capacity, and average desorption rate. The desorption results were compared to those of the benchmark solvent, 30 wt% MEA, under identical operating conditions. The results indicate that the 25 wt% blend-2 solution performs exceptionally well, exhibiting a 15 % increase in absorption efficiency compared to the AMP aqueous solution at a gas-liquid ratio of 20. Additionally, the cycle capacity and average desorption rate are 1.7 times higher than those of the 30 wt% MEA solution. Notably, the energy consumption of the 25 wt% blend-2 solution for desorption is only 60 % of the 30 wt% MEA solution.
研究领域:
化学工程
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环境科学
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DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2021
·
IF 6.953
Qingming Bao,Tsogzolmaa Ganbold,Qiburi Qiburi,Mingming Bao,Shuqin Han,Huricha Baigude
Receptor-mediated endocytosis has been used for tissue targeted delivery of short interfering RNA (siRNA) drugs. Herein, we investigated adenosine receptor (AR) as a candidate for receptor-mediated siRNA internalization. We synthesized adenosine functionalized cationic curdlan derivatives (denote CuAMP polymers). One of these polymers, CuAMP4, efficiently delivered siRNA to breast cancer cells expressing high level of A 2B receptor. The internalization of siRNA loaded CuAMP4 by cancer cells was inhibited by free AMP as well as endocytosis inhibitors. Moreover, knockdown of A 2B R by siRNA, or pre-treatment of the cells with anti-A 2B R antibody, strongly inhibited the cellular uptake of CuAMP4. Our findings confirmed that A 2B R can be utilized for cell type specific siRNA delivery, and CuAMP4 NP may be a promising delivery system for cancer cell targeted delivery of therapeutic siRNAs.
研究领域:
药理学
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纳米技术
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癌症研究
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分子生物学
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DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2022
·Vol. 32
·期 17
·2111344
·
IF 19.924
Kaicheng Tang,Xiaoyou Wang,Miaomiao Niu,Xinyu Wang,Guanghua Zhou,Jinjin Shi,Yang Yu,Zhangbao Chen,Chong Li
Antimicrobial peptides (AMPs) have aroused extensive attention due to their low incidences of resistance, yet their clinical transformation is thwarted by inferior selectivity and metabolic stability concerns, manifesting as rapid degradation, off-target, and non-selective toxicity. Here, a captivating affinity-filtering strategy is proposed as a feasible solution for such challenges. Specifically, based on the selective affinity of AMPs toward distinct phospholipids, the membrane of host cells (e.g., erythrocytes) is pre-bound to AMPs as the “filter,” which could screen out off-target substances with non-specific affinity while maintaining effective interaction with high-affinity pathogens through competitive binding, realizing precise targeting, and enhanced stability. The practicability of the affinity-filtering strategy has been demonstrated both in vitro and in vivo, through systematic studies on various AMPs and AMPs-modified delivery systems with multiple fungal infection models ( Candida albicans and Cryptococcus neoformans ), which pose severe threats to human health worldwide yet are often neglected. AMP-modified nanoparticles with affinity filtering exhibit reduced off-target toxicity, sufficient binding with target pathogen, as well as a substantially elevated 21-day survival rate from 30% (conventional drug-loaded nanoparticles) to 70%. In summary, this strategy may provide inspiration for overcoming off-target effects in drug targeting and further promote the clinical application of AMPs.
研究领域:
药学
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微生物学
·
药物递送系统
·
传染病学
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DOI
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Anteng Dai,Xu Chen,Hengyu Li,Zhangfeng Dong,Xiaoyun Chen,Qinghai Long,Bihong Lv,Zuoming Zhou,Guohua Jing
Solid-liquid biphasic solvents(SLBS) are considering as promising absorption for CO 2 chemical capture because of their potential energy-saving potential and easily separation of solid products. Nevertheless most of the SLB systems still with some defects, such as premature phase transition and viscous solid products. This work proposed a novel non-aqueous biphasic absorbent with controllable solid–liquid phase transition, composed of piperazine (PZ), 2-amino-2-methyl-1-propanol (AMP), and N-methylformamide (NMF). When NMF is 90 % by volume as solvent and the volume ratio of PZ and AMP is 3:1, the absorbent maintained a homogeneous phase with CO 2 loading below 0.729 mol/mol, which was about 60.6 % of the saturated loading (1.202 mol/mol). As the loading further increased, the solid products generated and the solution separated into solid–liquid two phases. And the solid product into the saturated solution was only 14 % of the total volume while contained about 93.29 % of total loading. The phase-transition mechanism was investigated by using 13 C NMR analysis and molecular simulations. Due to the higher reactivity of PZ with CO 2 compared to AMP, CO 2 initially reacted with PZ to form PZCOO − and PZH + . The enhanced polarity of the final products, PZ(COO − ) 2 and PZ(H + ) 2 , together with a marked increase in ESP difference, promotes the formation of small-volume, CO 2 -rich solids in the later stages of absorption. During this process, intermediate products (PZCOO − and PZH + ) interact with AMPCOO − and AMPH + , allowing early-stage dissolution of products in the solvent and ultimately producing easily separable solids with high CO 2 enrichment. The regeneration heat duty of the novel SLBS was estimated about 0.76 GJ/ton CO 2 , representing just 20.0 % of the industry standard for MEA (3.80 GJ/ton CO 2 ), which indicated extremely energy-saving advantage of the novel solvent.
研究领域:
化学工程
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环境科学
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DOI
高影响因子
PHARMACOLOGICAL RESEARCH
·
2022
·
IF 10.334
Jingjing Liu,Wanghui Jing,Tianyu Wang,Zhe Hu,Haitao Lu
Pancreatic cancer (PC) is one of the most malignant cancers, owing to extremely high aggressiveness and mortality. Yet, this condition currently incurs widely drug resistance and therapeutic deficiency. In this study, we proposed a novel functional metabolomics strategy as Spatial Temporal Operative Real Metabolomics (STORM) to identify the determinant functional metabolites in a dynamic and visualized pattern whose level changes are mechanistically associated with therapeutic efficiency of gemcitabine against PC. Integrating quantitative analysis and spatial-visualization characterization of functional metabolites in vivo, we identified that the AMP-cAMP axis was a novel therapeutic target of PC to intermediate therapeutic efficiency of gemcitabine. Gemcitabine could induce the dual accumulation of cyclic AMP (cAMP) and AMP in tumor tissues. Quantitative analysis of associated biosynthetic enzymes and genes revealed that two independent intracellular ATP derived biosynthetic pathways to promote the dual activation of AMP-cAMP axis in a lower-level energetic environment. Then, gemcitabine induced the dual accumulation of AMP and cAMP can separately activate signaling pathways of AMPK and PKA, leading to the inhibition of tumor growth by the upregulation of the downstream tumor suppressor GADD45A. Collectively, our new STORM strategy was the first time to identify novel target of PC from a metabolic perspective as the dual activation of AMP-cAMP axis induced by gemcitabine can efficiently suppress PC tumor growth. In addition, such discovery has the capability to lower drug resistance of gemcitabine by specifically interacting with novel target, contributing to the improvement of therapeutic efficiency.
研究领域:
肿瘤学
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代谢组学
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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
MOLECULES
·
2025
·Vol. 30
·期 1
·180
·
IF 4.6
Xiaojing Si,Yue Huang,Mei Han,Liqiang Luo
Dihydromyricetin (DMY), as the main active ingredient inAmpelopsis grossedentata, is a naturally occurring flavonoid that has attracted extensive attention for its multiple biological activities. For the quick and accurate measurement of DMY, a novel electrochemical sensor based on a glassy carbon electrode (GCE) modified with a cobalt metal-organic framework (Co-MOF) was proposed in this work. The Co-MOF was synthesized via a single-step hydrothermal process using Co(NO3)2·6H2O. Fourier infrared spectroscopy, X-ray photoelectron spectroscopy and scanning electron microscopy were used to study the morphology and structure of the synthesized Co-MOF. Utilizing differential pulse voltammetry and cyclic voltammetry methods, the effectiveness of DMY electro-oxidation on the Co-MOF/GCE was examined. The results showed that, in comparison to the bare GCE, the electro-oxidation peak current of DMY was considerably increased by the Co-MOF/GCE. The detection limit was 0.07 μM, and the peak current demonstrated two linear relationships in the ranges of 0.2−20 μM and 20−100 μM, with the linear equations of Ip (μA) = 0.4729c (μM) + 1.0822 (R2= 0.9913) and Ip (μA) = 0.0939c (μM) + 8.4178 (R2= 0.9971), respectively. The average DMY content inAmpelopsis grossedentatasamples was measured to be 3.275 μM, with a good recovery of 108.27% and a relative standard deviation value of 3.46%. The proposed method is simple, rapid and sensitive and can be used for the determination of DMY inAmpelopsis grossedentata.
研究领域:
分析化学
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植物化学
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药理学
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产品关联
DOI
PubMed
高影响因子
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