Advanced Science
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2025
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IF 14.1
Xiaxia Fan,Dan Guo,Songtao Li,Jinmiao Tian,Chaotong Zhang,Zhuoyu Li
ABC transporter protein-mediated drug efflux is a significant contributor to induced resistance in breast cancer (BC). Novel therapies are therefore urgently needed to thwart chemoresistance. Herein, it is demonstrated that fusidic acid (FA) reduces the expression of ABC transporter proteins MRP1, P-gp, and BCRP, promotes the in vivo accumulation of agents, and exertes chemosensitizing effects. Further, DDX6 is identified as a direct target of FA by DARTS and biotin pull-down. Mechanistically, the results indicates that FA directly binds to H378 of DDX6, promotes its degradation, and downregulates its downstream p-GSK-3β, which in turn enhances the phosphorylation and ubiquitin-dependent hydrolysis of β-catenin S33/37/45/T41, blocks pro-resistance β-catenin signaling, and further prevents chemoresistance. The inhibitory effect of FA on chemoresistance is blocked following the knockout of DDX6 using CRISPR/Cas9. More importantly, FA also enhances the interaction between DDX6 and HSC70, while it facilitates DDX6 degradation via chaperone-mediated autophagy (CMA), thereby impairing the GSK-3β/β-catenin axis to enhance the efficacy of FA. Consistently, the effect of FA in combating chemoresistance by targeting DDX6 is evident in a xenograft mouse model. These findings reveal a direct protein target and molecular mechanism for FA to reverse chemoresistance, thus supporting the further development of FA as a chemosensitizing agent. Graphical FA directly binds to residue H378 of DDX6 and promotes its interaction with HSC70, leading to CMA degradation of DDX6, thereby impairing GSK-3β/β-catenin signaling, inhibiting ABC transporter proteins, and enhancing chemosensitivity.
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高影响因子
Materials Today Physics
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2025
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IF 9.7
Mingliu Li,Hongbin Wang,Shuo Yang,Lin Yang,Peng Li,Jiangang Ma,Yichun Liu
High sensitivity and fast response dual-band photodetectors (PDs) covering the deep-ultraviolet (DUV) to visible spectrum are highly desired for industrial and scientific applications. Herein, a sandwich-architecture PD covering the range from DUV to visible was prepared by stacking a β -Ga 2 O 3 DUV absorbing layer, interdigitated Au electrodes, and a Cs 2 AgBiBr 6 (CABB) visible absorbing layer. At 5 V bias voltage, the sandwich-architecture PD achieves responsivities of 37.74 mA/W at 240 nm and 0.07 mA/W at 450 nm with microsecond response time, respectively, which is superior to the PDs using monolayer β -Ga 2 O 3 or CABB. Furthermore, it demonstrates self-powered dual-band detection capability with maximum responsivity of 8.13 mA/W. Enhanced performance arises from two synergistic mechanisms: a vertical built-in electric field at the β -Ga 2 O 3 /CABB interface spatially separates photogenerated carriers, while a higher hole mobility in CABB facilitates the charge collection under a lateral bias field between Au electrodes. Importantly, the β -Ga 2 O 3 /Au/CABB PD demonstrates high-resolution images under 240 nm and 450 nm illumination. This work provides a route for developing high-performance DUV-visible dual-band photodetectors, highlighting their potential for advanced multispectral imaging applications.
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Journal of Translational Medicine
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2025
·Vol. 23
·期 1
·1349
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IF 7.5
Zhu Ganggui,Li Qiaxuan,Yao Qifeng,Zhao Jin,Ding Shuo,Mai Shixiong,Yue Bingqin,Chen Jingyu,Huang Man
Background Lung ischemia-reperfusion injury (LIRI) is associated with a variety of postoperative complications and affects patient prognosis. β-Nicotinamide mononucleotide (NMN) has attracted much attention due to its potential role in cellular energy metabolism and antioxidant properties. Exploring the mitigating role of NMN in ischemia-reperfusion injury after lung transplantation is crucial for improving lung transplantation success and patient quality of life. Methods A LIRI model was established using the mouse left lung portal clamp method, and the cold ischemia-reperfusion (CI/R) model with BEAS-2B cells in vitro was used to simulate the lung transplantation environment. The protective effect of NMN against lung ischemia-reperfusion injury was analyzed by histopathology, ELISA, immunofluorescence, Western blot and RT-PCR. Combined multi-omics profiling were used to study the mechanisms by which NMN attenuated lung ischemia-reperfusion injury. Results NMN significantly attenuated ischemia-reperfusion-induced structural abnormalities, pulmonary edema, inflammatory infiltration and oxidative stress injury in mouse lung tissue. Similarly, NMN attenuated CI/R-induced oxidative stress and inflammatory responses in BEAS-2B cells. Based on multi-omics analysis, we found that NMN ameliorated the apoptosis after ischemia/reperfusion through down-regulation of cleaved Caspase 3, BAX and up-regulation of BCL-2. Moreover, NMN also affected mitochondrial metabolic processes, including promoting mitochondrial oxidative phosphorylation, increasing ATP synthesis, enhancing mitochondrial complex activity, decreasing ROS generation, slowing down the decrease of mitochondrial membrane potential, and inhibiting the opening of the mitochondrial membrane permeability transition pore. Mechanistically, we found that NMN attenuates inflammation and oxidative damage through activation of the SIRT1 and NF-κB signaling pathways, and that SIRT1-specific inhibition of EX527 reversed these protective effects of NMN against inflammation and oxidative damage in vivo and in vitro. Conclusion NMN has a protective effect on inflammation and oxidative damage induced by ischemia-reperfusion injury after lung transplantation, and the SIRT1/NF-κB pathway may be involved in one of the mechanisms of the protective effect.
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PHYTOMEDICINE
·
2025
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IF 8.3
Yigong Chen,Jie Liang,Meiqiu Yan,Lan Xu,Fanxiang Jin,Mingting Jiang,Dorota Kołodyńska,Guiyuan Lv,Suhong Chen
Background Changfa Zirong Powder (CFZRS) is a traditional Chinese medicine (TCM) formula from Imperial Medicine Formulas , primarily used to treat hair loss. It consists of a mixture of ginseng powder and roasted ginger peel powder, which is applied topically by rubbing fresh ginger slices. Modified Changfa Zirong Powder (MCFZRS) replaces roasted ginger peel powder with whole ginger powder for better accessibility, while retaining ginseng powder. This study is the first to examine and compare the efficacy and mechanisms of TCM formulations in treating androgenetic alopecia (AGA), providing a modern perspective on an ancient formula. Unlike existing literature, which mainly focuses on individual components or synthetic drugs, this research validates how these formulations regulate the Wnt/β-catenin pathway. Additionally, it emphasizes the thermoregulatory effects of topical ginger and its potential to enhance drug delivery. Purpose This study aims to assess the effects of MCFZRS and CFZRS treatments on AGA in mice, concentrating on the Wnt/β-catenin signaling pathway. Methods Male mice were induced with AGA via dorsal hair removal and testosterone propionate injections. MCFZRS and CFZRS were applied topically for 30 days using fresh ginger slices to rub the powders onto the skin. The treatment efficacy was assessed through hair growth scoring, skin darkening, dermatoscopy, histopathology, and enzyme-linked immunosorbent assays to measure androgen levels. Additionally, the proteins involved in the Wnt/β-catenin signaling pathway were analyzed using immunohistochemistry, immunofluorescence, and Western blot. Results MCFZRS and CFZRS significantly improved AGA symptoms, promoting hair regrowth, skin darkening, hair shaft elongation, dermal thickness, and local hormonal balance, without altering systemic levels. Both treatments activated the Wnt/β-catenin pathway, resulting in the upregulation of β-catenin and protein phosphatase 2A expression. Conclusions MCFZRS and CFZRS improved androgen-related profiles and normalized α-melanocyte-stimulating hormone and vascular endothelial growth factor levels in AGA model skin. MCFZRS revealed comparable or superior effects on hair growth, dermal thickness, follicle preservation, and Wnt/β-catenin modulation. This modified formula offers a safer and more accessible approach to topical TCM, with potential for clinical translation.
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ACS Synthetic Biology
·
2025
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IF 3.9
Jing Wu,Ziqian Xiao,Yuhui Du,Minglan Luo,Jiacheng Zhang,Pei Guo,Zhipeng Chen,Binyuan Yang,Tingjian Chen
Aptamer-based sensors (aptasensors) have been extensively employed in biosensing and diagnostics. However, the broader application of aptasensors fabricated with DNA and RNA aptamers has been limited due to the intolerance of DNA and RNA to nucleases in biological fluids. A majority of sugar-modified nucleic acids, in particular 2’-F and 2’-OMe-modified nucleic acids, demonstrate a remarkable resistance to nuclease degradation and thus hold great potential in the development of more stable aptamers and aptasensors. In this work, employing enzymes including a laboratory-evolved polymerase for 2’-modified nucleic acids, we carried out systematic evolution of ligands by exponential enrichment (SELEX) experiments to obtain 2’-F/OMe-RNA aptamers for Bacillus cereus 5/B/6 metallo-β-lactamase (B. cereus 5/B/6 MBL), a crucial marker of many penicillin-resistant strains. Three aptamers composed of 2’-OMe-A, 2’-F-U, 2’-F-C, and 2’-OMe-G nucleotides (Apt-FUC1, Apt-FUC2, and Apt-FUC3) have been obtained and systematically characterized. All of them exhibited excellent target binding affinities, with equilibrium dissociation constant (Kd ) values of 95.9, 70.0, and 81.3 nM, and outstanding biological stability. Combining FAM-labeled Apt-FUC1, Apt-FUC2, and Apt-FUC3 with graphene oxide (GO), which could quench the fluorescence of FAM, we successfully constructed three sensitive and biologically stable 2’-F/OMe-RNA aptasensors for B. cereus 5/B/6 MBL, with the limit of detection (LOD) values of 0.38, 0.27, and 0.29 nM. Moreover, these three aptasensors all demonstrated good specificity for target detection in biological samples. This work has established a streamlined strategy for generating stable 2’-F/OMe-RNA aptamers and aptasensors, which should broaden the application of sugar-modified nucleic acids in biosensing and diagnostics.
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JOURNAL OF HAZARDOUS MATERIALS
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2025
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IF 11.3
Changchun Zhu,Qiang Xue,Chenglong Yu,Hongqing Zhu,Yuanying Huang,Yao Liu,Zeyu Liu,Haijiao Xie,Shengyan Pu
Detecting carbendazim (CBZ) poses a significant challenge, which underscores the urgency for reliable monitoring methods. To address this, we have developed a high-performance electrochemical sensor to detect CBZ. This sensor achieves this through the integration of β-cyclodextrin (β-CD, for selective adsorption) and zinc-cobalt layered double hydroxides (ZnCo-LDHs, for efficient catalysis and electron transfer). Comprehensive characterization and density functional theory (DFT) calculations revealed a synergistic effect. The adsorption energy of CBZ by β-CD is 3.4 times higher than that by ZnCo-LDHs, thereby enabling targeted enrichment. ZnCo-LDHs reduces the electrode charge transfer resistance by 2.69 times to enhance electron transfer. This sensor achieves a wide linear response (0.005–1 mg/L), a detection limit of 0.35 μg/L, and a quantitative limit of 1.17 μg/L. It also exhibits a high sensitivity of 111.99 μA·μM⁻¹ ·cm⁻², along with excellent selectivity, stability, and reproducibility. The recovery rates in tap water, river water, and groundwater range from 94.50 % to 105.22 % (RSD≤8.20 %). Comparison with liquid chromatography-mass spectrometry analysis confirmed its reliability. This work provides a powerful platform for rapid, on-site pesticide monitoring in aquatic environments, offering a viable strategy to mitigate contamination risks and advance sustainable environmental management.
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APOPTOSIS
·
2025
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IF 8.1
Miao Jintian,Jiang Xinyan,Wang Siyun
Cisplatin resistance significantly hinders the efficacy of ovarian cancer treatment, presenting a major challenge in improving patient outcomes. This study identifies the m6A reader protein YTHDF1 as a key regulator of cisplatin resistance in ovarian cancer through its modulation of the FZD7/Wnt/β-catenin signaling pathway. Using cisplatin-resistant ovarian cancer cell lines (A2780/DDP and SKOV3/DDP), we observed elevated YTHDF1 expression, which positively correlated with tumor cell proliferation and migration. Silencing YTHDF1 reduced FZD7 expression, inhibited Wnt/β-catenin signaling, and restored cisplatin sensitivity both in vitro and in vivo. Mechanistic investigations revealed that YTHDF1 binds to m6A-modified FZD7 mRNA, enhancing its stability and translation. Functional studies in xenograft mouse models demonstrated that targeting YTHDF1 suppressed tumor growth and enhanced apoptosis in cisplatin-resistant ovarian cancer cells. These findings highlight the YTHDF1-FZD7 axis as a novel therapeutic target for overcoming cisplatin resistance, paving the way for improved treatment strategies in ovarian cancer.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2025
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IF 8.5
Li Wen,Jinxia Zheng,Zhijie Ke,Jian Dong
Enzymes catalyze cascade reactions in a crowded cellular environment where as much as half of cell volume is occupied by various macromolecules. Nonspecific interaction between enzymes and crowders and excluded volume of the crowders can superimpose on each other and complicate catalytic activity of the enzymes. This study investigates the interaction between a β-galactosidase (β-Gal) and glycosylated acrylamide polymer (P(Glc-β-EAAm)) and unravels the macromolecular crowding effect of the glycopolymer on enzymatic cascade catalysis consisting of β-Gal, glucose oxidase and hydrogen peroxidase. Binding of the glycopolymer induced conformational alterations in β-Gal and gave rise to static fluorescence quenching and stable complex formation with β-Gal via nonspecific interaction. Fluorescence resonance energy transfer assays further demonstrated a compact association between β-Gal and glycopolymer crowders, with binding affinity correlating with the molecular weight of glycopolymer. The reduction of the apparent kinetic constants of the catalysis with the glycopolymer size showed the role of the multivalent effect in enzyme-substrate interactions. The kinetics also depended on the chain overlapping conditions of the crowders. Therefore, the macromolecular crowding effect on the cascade reaction is jointly associated with the crowder's multivalent effect, chain overlapping conditions of the crowders, in addition to the volume exclusion effect of the crowders.
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METABOLIC ENGINEERING
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2025
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IF 6.8
Yapeng Zhang,Chenwen Liu,Wenqiang Li,Zhidong Ma,Bo Lv,Lei Qin,Chun Li
β-caryophyllene, a plant-derived sesquiterpene, serves as a food flavoring, anti-inflammatory agent, antioxidant, and high-energy fuel source. Extraction of β-caryophyllene from plants is a costly and inefficient process. Therefore, microbial cell factories have been employed for the production of β-caryophyllene. However, the limited yield is insufficient for its industrial application. In this study, we balanced the utilization of cellular resources for growth and production by systematically regulating the sterol synthesis pathway to maximize the synthesis of β-caryophyllene. In the competitive pathways concerning sterol and fatty acid synthesis, genes expression was suppressed by substituting the original promoters with a glucose-sensing promoter P HXT1 and a sterol synthesis promoter P ERG7 , respectively. This approach effectively increased the production of β-caryophyllene by 6.8 times, reaching 854.7 mg/L. Engineering glucose-sensing pathway altered the strength of P HXT1 , resulting in an increase in β-caryophyllene production to 1.25 g/L. The cell growth and β-caryophyllene production were further boosted through diploid fusion, resulting in 21.4 g/L β-caryophyllene in fed-batch fermentation. This represents the highest reported production of β-caryophyllene to date. This study provides a valuable reference for the production of sesquiterpenes in microbial cell factories.
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Food Bioscience
·
2025
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IF 5.9
Wenyuchu Chen,Fang Tian,Yongjing Xu,Yujin Li,Weiliang Guan,Chenyang Lu,Sheng Hu,Luyun Cai
Fish oils (FOs) are rich in omega-3 polyunsaturated fatty acids, which provide several health benefits. However, their oral bioavailability and stability are often limited due to the oxidation of polyunsaturated fatty acids, which degrade the oil's nutritional and sensory properties over time. In this study, FO microcapsules were prepared using pea protein isolate (PPI), β-cyclodextrin (β-CD), and carbon quantum dots (CQDs) as wall materials through a freeze-drying method. The results demonstrated that the use of PPI/β-CD/CQDs composite significantly improved the encapsulation efficiency, stability, and antioxidant properties of the microcapsules, suggesting a promising approach for enhancing the shelf-life and health benefits of fish oil. Additionally, the peroxide value (POV) and thiobarbituric acid (TBA) values of the microcapsules increased with temperature and storage time. Notably, the incorporation of CQDs markedly improved the antioxidant properties of the microcapsules, thereby extending their storage stability. In vitro gastrointestinal digestion simulations demonstrated that microencapsulation facilitated the absorption of beneficial substances in fish oil within the human gut. This study offers valuable insights into the development of more efficient fish oil microcapsules for potential applications in food and pharmaceutical applications.
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FOOD CHEMISTRY
·
2025
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IF 9.8
Lining Pan,Kunling Liu,Bing Wang,Nan Wang,Fuwei Xie,Cong Nie,Yaqiong Qin,Xiaoyu Wang,Wenjie Zhao
A β-cyclodextrin-functionalized fluorinated covalent triazine framework (β-CD/FCTF) was developed as a high-performance solid-phase microextraction (SPME) coating for efficient extraction of aflatoxins (AFs) from cereals. The composite synergistically combines the high surface area of FCTF with the host-guest recognition capability of β-CD and polar interactions afforded fluorine/triazine groups. Coupled with high-performance liquid chromatography with fluorescence detection, the method achieved detection limits of 0.02–0.11 ng/g and quantification limits of 0.06–0.36 ng/g. Recoveries from spiked cereal samples ranged from 84.5 to 130 % (RSD ≤ 10.2 %). Density functional theory (DFT) calculations confirmed enhanced adsorption through synergistic host-guest inclusion, hydrogen bonding, and F–π interactions. The coating showed 2.1–2.3 fold higher enrichment than pure FCTF, excellent anti-interference, and reusability. This work establishes a reliable and robust analytical platform for trace AFs detection in food commodities and proposes a generalizable covalent grafting strategy for the rational design of functional porous materials in food safety monitoring.
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JOURNAL OF LUMINESCENCE
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2025
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IF 3.6
Xu Sun,Yumeng Jia,Jing Wang,Yingnan Dong,Yanhua Sun,Zhongxiang Shi
Na-β"-Al 2 O 3 matrix materials, featuring a stable layered structure and Na + ions double sites, are promising as host materials for luminescent applications. In this work, a series of broadband Na-β"-Al 2 O 3 : x Eu 2+ , 0.08Ce 3+ cyan phosphors were designed and synthesized. Based on the ability of Eu 2+ to occupy two Na + sites in the Na-β"-Al 2 O 3 matrix, the photoluminescence (PL) spectra displayed dual-peak emissions centered at 470 and 500 nm, with a full width at half maximum (FWHM) of 140 nm. The Na-β"-Al 2 O 3 : Eu 2+ , Ce 3+ phosphors have excellent thermal stability (95.1 %@448 K). Finally, the fabricated white-light-emitting diodes (WLEDs) with CIE 1931 chromaticity coordinates of (0.32, 0.35) and a correlated color temperature (CCT) of 6015 K, indicating their potential for application in full-spectrum WLEDs.
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危险品化学品经营许可证（带存储）