Acta Pharmaceutica Sinica B
·
2025
·
IF 14.6
Danni Li,Xingyu Liu,Yanhong Wang,Boyu Cai,Chao Cheng,Changjing Zuo,Fei Tan
Cancer-associated fibroblasts (CAFs) are crucial in tumor progression and treatment resistance. Fibroblast activation protein (FAP) is an important molecular target in nuclear medicine for cancer diagnosis and therapy. Through comprehensive bioinformatic analysis and experimental validation, FAP was identified as a potential regulator of ferroptosis in CAFs. In this study, we developed a targeted radionuclide therapy (TRT) using a novel radiopharmaceutical, 131 I-labeled FAP inhibitor ( 131 I-FAPi), to specifically target CAFs and induce ferroptosis. Mechanistically, 131 I-FAPi TRT triggered three synergistic pathways. First, β -radiation-mediated water radiolysis generated hydrated electrons (e aq - ), which drove the conversion of Fe 3+ to Fe 2+ , disrupting iron homeostasis. Second, β -radiation-mediated water radiolysis produced primary ROS, providing an oxidative stress source promoting lipid peroxidation. Third, 131 I-FAPi TRT suppressed the expression of key antioxidant proteins SLC7A11 and GPX4, weakening the antioxidant defenses of CAFs. Furthermore, the study demonstrated that the combination of 131 I-FAPi TRT with cold atmospheric plasma (CAP) treatment significantly enhanced ferroptosis through efficient Fenton reaction activation. This study revealed the mechanism of β -radionuclide therapy in modulating cellular redox status and iron metabolism and provided a rational basis for developing combination therapies, such as TRT with CAP, to overcome treatment resistance and improve cancer outcomes.
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Antioxidants
·
2025
·Vol. 14
·期 11
·1297
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IF 6.6
Huatao Che,Yiqing Lu,Tong Li,Xiaoli Fang,Xinfa Wang,Hanzhong Wang,Xiaoling Dun,Zhenna Chen
Cadmium (Cd) is a recognized environmental contaminant, present in soil, water, and food, which has been reported to cause male reproductive damage in vivo and vitro. Selenium-enriched rapeseed flowering stalks exhibit protective effects against Cd-induced reproductive damage, yet the bioactive components and underlying mechanisms remain unclear. We optimized the process of obtaining the crude extract (CE) via single-factor experiments. Subsequent bioassay-guided fractionation identified the water extract (WE) as significantly more effective in alleviating Cd-induced cytotoxicity compared to the petroleum ether extract, ethyl acetate extract, and n-butanol extract. High-performance liquid chromatography–inductively coupled plasma mass spectrometry (HPLC-ICP-MS) analysis revealed that WE contained the highest contents of methylselenocysteine (MeSeCys) and selenocystine (SeCys2) among four fractions. Both MeSeCys and SeCys2exhibited protective effects against Cd-induced cytotoxicity. To further elucidate the underlying mechanisms, network pharmacology, RNA-Seq, qPCR, and Western blotting analysis were employed. The results revealed that WE exhibited good free radical scavenging capabilities, and the protective mechanisms of WE, MeSeCys, and SeCys2against Cd-induced cytotoxicity were related to a reduction in oxidative damage, the inhibition of the ERK/p38 MAPK signaling pathway, and the suppression of cell cycle arrest, inflammation, and apoptosis triggered by Cd exposure. Collectively, these findings suggest that selenium-enriched rapeseed flowering stalks may serve as a promising dietary supplement in the prevention of Cd-induced reproductive toxicity.
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NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
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2025
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IF 3.1
Man Tian,Yu Huiyong,Li Lei,Nie Weicheng,Wang Chengxiang
Multidrug-resistant Klebsiella pneumoniae (MDR-KP) infections present a global health crisis, with escalating resistance to last-line antibiotics. Traditional Chinese medicines (TCMs) demonstrate multi-component synergy against resistant pathogens. This study deciphered the antibacterial mechanisms of bioactive TCM components targeting MDR-KP through integrative pharmacology and experimental validation. Four core TCMs ( Scutellaria baicalensis , Forsythia suspensa , Lonicera japonica , Aloe vera ) were screened via Chinese Pharmacopoeia and TCMSP database. Network pharmacology identified core components and enriched pathways. Clinically isolated MDR-KP strains (resistant to meropenem, polymyxin E, and tigecycline) were characterized. Synergistic effects were evaluated using checkerboard assays, biofilm quantification, and membrane permeability assays. Molecular docking and RT-qPCR analyzed target interactions, while ELISA and CCK-8 assessed anti-inflammatory activity and cytotoxicity. Consequently, luteolin, wogonin, and kaempferol were identified as key components targeting PI3K/AKT and MAPK pathways. Their triple combination (2/4/8 μg/mL) exhibited potent synergy (FIC = 0.38), reducing biofilm biomass by 68% (p < 0.001) and extracellular polysaccharide thickness from 15.1 μm to 3.1 μm (p < 0.001). Flow cytometry confirmed a 144.8% increase in membrane permeability. Molecular docking revealed high-affinity binding to PI3K (− 6.78 kcal/mol), AKT1 (− 6.60 kcal/mol), and MAPK1 (− 7.24 kcal/mol), with RT-qPCR showing significant downregulation of these genes (p < 0.001). The combination suppressed LPS-induced TNF-α and IL-6 release by 72% and 65%, respectively, while maintaining 95.5% cell viability at therapeutic concentrations. In Conclusion, this study unveils a triple-action mechanism of luteolin-wogonin-kaempferol against MDR-KP, simultaneously disrupting resistance pathways, biofilms, and hyperinflammation. The regimen offers a safe, multi-target therapeutic strategy for combating drug-resistant infections.
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Nature Communications
·
2025
·Vol. 16
·期 1
·1-24
·
IF 15.7
Zheng Liu-Ting,Yan Zeng-Shuai,Li Xin-Yue,Chang Jia-Jia,Tan Xiao-Qi,Wang Yu-Xing,Ding Hong-Ming,Liu Qin,Ma Yu-Qiang,Huo Da
Membraneless organelles form by phase separation and regulate cell behavior. We show that cholesterol-patterned AuNPs program nanomaterial-induced stress granules (NSGs) by lowering G3BP1 condensation barriers through a solid–liquid–liquid triphasic sequence: nanomaterials recruit hnRNPC, which then engages G3BP1 to nucleate gel-like condensates. We map NSG microenvironments (temperature, polarity, pH, and proteasome activity), uncover dual disassembly—a slow VCP/19S-dependent route and a rapid SUMO/20S-dependent backup—and show that NSGs remodel chemo-plasticity: they mitigate doxorubicin/cisplatin toxicity in normal tissues yet sensitize tumors to nocodazole in vivo. Local induction and selective dissolution of NSGs thus offers a strategy to decouple efficacy from toxicity. Our results establish design rules linking nanomaterial surface chemistry to condensate programming and provide actionable levers to steer therapeutic outcomes.
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Bioresources and Bioprocessing
·
2025
·Vol. 12
·期 1
·1-17
·
IF 5.1
Lv Mengying,Shuai Jinhao,Wang Yang,Lu Qianwen,He Xinlong,Zhen Junjie,Ling Ling,Yao Jun,Xu Fengguo
Pulmonary hypertension (PH) is a deadly disease with limited treatment options and poor long-term survival, necessitating the discovery of novel therapeutics. Our previous study has revealed that dimeric proanthocyanidins (PACs) mainly existed in the ethyl acetate extract from the roots of Ephedra sinica Stapf (ERE), however, its therapeutic effects on SU5416/hypoxia-induced pulmonary hypertension (PH) rats remain elusive. In this study, column chromatography combined with UPLC-LTQ-Orbitrap-HRMS analysis was performed to comprehensively characterize polyphenols in ERE. The therapeutic effects of ERE were investigated using the SU5416/hypoxia rat model, in which the rats were injected with SU5416 (20 mg/kg), followed by a three-week hypoxia exposure (10% O 2 ). Hemodynamic indicators determined by right heart catheterization, pulmonary arterial morphological changes assessed by histopathological analysis, cardiac function and pulmonary hemodynamics using echocardiography, as well as oxidative stress markers measured by corresponding kits were used to test the therapeutic effects of ERE. Moreover, 16S rRNA sequencing combined with untargeted metabolomics was employed to capture changes in gut microbiota and serum metabolites after ERE treatment. Comprehensive chemical analysis of polyphenols in ERE revealed various levels of proanthocyanidin monomers, dimers and trimers, especially A-type dimers. In vivo experiments showed that ERE decreased pulmonary arterial pressure, right ventricular hypertrophy, right ventricular free wall (RVFW) thickness and oxidative stress levels, increased pulmonary acceleration time (PAT) and alleviated pulmonary vascular remodeling in rats exposed to SU5416/hypoxia treatment. Meanwhile, ERE improved gut microbial dysbiosis and the disturbed glycerophospholipid metabolism. Collectively, this study presents the first report on the efficacy of A-type PACs from Ephedra sinica for the treatment of PH through regulating gut microbiota and host metabolism. Graphical abstract
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JOURNAL OF HAZARDOUS MATERIALS
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2025
·
IF 11.3
Yanfei Li,Ting Shu,Jialuo Chen,Jiaqi Li,Xincheng Li,Zhijun Zhang,Xiaojing Guo,Nan Hu
The discharge of colored effluents into the environment causes significant ecological disruption. Selectively separating individual dyes from multi-component systems remains a critical challenge in foam fractionation. Herein, we investigated a novel foam fractionation method for the selective removal of organic dyes, employing whey soybean protein (WSP) for environmentally friendly treatment. WSP, a natural protein extracted from abundantly available soybean meal (SBM) agro-industrial waste, was utilized to remove the anionic dye Congo red (CR) and the cationic dye Malachite green (MG) from aqueous solutions. WSP exhibited remarkable surface activity and formed robust interfacial films, enhancing both foaming capacity and stability. Furthermore, we elucidated the interaction mechanisms between the dyes (CR and MG) and WSP through spectroscopic methods and molecular docking simulations, including electrostatic interactions, hydrogen bonding, hydrophobic interactions, salt bridges, and π-cation interactions. Building upon single-dye removal experiments, we developed a novel two-stage pH adjustment strategy. This strategy enabled the selective removal of 97.1 % of CR from the mixed dye solution at pH 3. Subsequently, subjecting the pre-treated solution to foam fractionation at pH 9 achieved remarkable removals of 97.9 % of MG. This work provides an effective approach for developing foam fractionation agents, addressing the urgent need for mixed-dyes wastewater treatment.
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DESALINATION
·
2025
·
IF 9.8
Jiadi Ying,Zhen Cui,Tiancun Liu,Song Lu,Qi Shen,Min Guo,Yeqing Wang,Zhen Yang,Minfeng Zeng,Zhixin Yu,Yuqing Lin
The development of thin, charge-selective surface layers on cation exchange membranes (CEMs) is crucial for advancing electrodialysis technology, particularly for achieving both high ion permeability and precise selectivity. In this study, we developed an innovative approach to fabricate ultrathin polyaniline (PANI) nanolayers on CEM substrates through pre-adsorption of protonated aniline monomers followed by in-situ polymerization. The resulting membranes feature a uniform Turing-type nanostructure through FESEM characterizations, which significantly enhances surface positive charge density. Our optimized membrane demonstrates exceptional performance, achieving a Li + /Mg 2+ selectivity of 6.75 while maintaining a high lithium permeation rate of 0.18 mmol·cm −2 ·h −1 . These results compare favorably with current state-of-the-art permselective membranes and surpass the commercial membrane CSO (5.26 for the Li + /Mg 2+ selectivity and 0.16 mmol·cm −2 ·h −1 for the lithium permeation rate). Mechanistic studies including electrochemical impedance spectroscopy and molecule dynamics simulation reveal that PANI layers with optimal thickness and pore structure minimize resistance to monovalent cations while effectively blocking divalent cations, enabling efficient ion separation during electrodialysis. This work highlights the remarkable potential of nanostructured PANI layers for selective ion transport and provides a practical strategy for designing advanced electrodialysis membranes. The simple fabrication method and outstanding performance characteristics make this approach particularly promising for lithium extraction and other ion separation applications.
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REACTIVE & FUNCTIONAL POLYMERS
·
2025
·
IF 5.1
Fuhan Mai,Jianguo Deng,Xing Li,Xue Liu,Yingchun Lu,Wanjia Tian,Lanxiang Ji,Xiaofeng Bai
Radiation protection products with excellent radiation shielding properties and wear comfort are essential for individuals working in X-ray environments. Unfortunately, commercially available rubber composites and lead aprons cannot simultaneously meet the requirements for radiation protection safety and wear comfort. Here, a microfiber synthetic leather is proposed to solve this challenge. Hydrothermal synthesis of flower shaped WO 3 and investigation of its growth mechanism. Then, a titanate coupling agent is applied to synergistically modify with sodium carboxymethyl cellulose to construct hydrogen bonds and improve the interfacial compatibility between flower shaped WO 3 and waterborne polyurethane. Next, WO 3 is grown in-situ on microfiber nonwoven fabric by hydrothermal method. Finally, the waterborne polyurethane is coated onto the WO 3 in-situ grown microfiber nonwoven fabric. Monte Carlo simulations demonstrate that multilevel structures increase the probability of X-ray collisions with extranuclear electrons in materials, thereby enhancing X-ray shielding. In-situ growth of WO 3 resulted in an enhancement of the mechanical engagement points between microfiber nonwoven fabric and waterborne polyurethane, thereby improving their interfacial compatibility. The sample exhibits excellent durability. Importantly, the prepared samples exhibit x-ray shielding (55 %–90 %), light weight (0.835 g/cm 3 ), water vapor permeability (372 g/m 2 ·24h), and flexibility. These excellent properties demonstrate its potential for application in radiation protection, and bring broad prospects for the development of new radiation protection products.
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JOURNAL OF CONTROLLED RELEASE
·
2025
·
IF 11.5
Ruiqi Ming,Dingjie Suo,Zhongjie Wang,Shujun Liu,Chuyu Li,Chenguang Wang,Fan Zhang,Guihong Lu,Lin Mei,Li-Li Huang
The activation of stimulator of interferon genes (STING) pathways holds immense potential for cancer immunotherapy. Nevertheless, the challenge lies in achieving precise and efficient STING activation within tumors while avoiding systemic immunotoxicity. Here, we develop a novel nanotherapeutic platform, termed HAL@SyBVs, by simply electroporating FDA-approved prodrug 5-aminolevulinate hydrochloride (HAL) into the synthetic bacterial vesicles (SyBVs), which allows for the spatiotemporal orchestration of STING pathways. Following systemic injection, HAL@SyBVs target tumor tissues, where HAL induces the confined biosynthesis and accumulation of sonosensitizer protoporphyrin IX (PpIX) within mitochondria. Upon ultrasound irradiation, PpIX-induced reactive oxygen species (ROS) trigger the release of double-stranded DNA (dsDNA), thereby achieving precise STING activation. Simultaneously, SyBVs enhance STING signaling by impeding its degradation, thereby amplifying the immune response. This intelligent synergy effectively ameliorates the immunosuppressive tumor microenvironment and elicits a robust antitumor T cell immune response, resulting in comprehensive tumor regression without apparent adverse effects.
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POSTHARVEST BIOLOGY AND TECHNOLOGY
·
2025
·
IF 6.8
Dan Li,Huirong Cheng,Ling Xie,Hong Luo,Dandan Zhang,Jupeng Zhao,Yueming Jiang,Liang Gong
To address the challenges of postharvest oxidation and microbial contamination in litchi fruit, this study utilized sodium periodate oxidation to synthesize oxidized gum arabic (OGA) with varying aldehyde contents as an eco-friendly crosslinking agent. Chitosan (CS) was used as the film-forming matrix, with ε-polylysine (ε-PL) and gallic acid (GAL) incorporated to construct a composite film exhibiting synergistic enhancement. FT-IR, XPS, and XRD analyses revealed that aldehyde groups in OGA covalently crosslinked with amino groups in CS/ε-PL via Schiff base reactions, forming C N bonds (accounting for 26.29 %, higher than the 21.55 % in the control group), while GAL interacted with the film materials via non-covalent hydrogen bonding. Crosslinking significantly enhanced the film’s compactness, UV-blocking ability, and stability. The maximum mechanical strength and elastic modulus of the films reached 19.25 MPa and 492.88 MPa, respectively, which were approximately two times higher than those of the control group. As the degree of crosslinking increased, the film’s water solubility, water vapor permeability, and oxygen permeability significantly decreased, while its thermal stability improved. The incorporation of GAL significantly enhanced the antioxidant capacity, with a maximum free radical scavenging rate of 56.82 % within 1 h, about 1.6 times higher than that of the control group. Antibacterial tests showed that the composite film exhibited 100 % inhibition against Escherichia coli , Staphylococcus aureus , and Pestalotiopsis litchii . Litchi preservation experiment demonstrated that the film significantly outperformed the traditional preservative prochloraz in delaying nutrient loss and inhibiting microbial growth. In conclusion, the edible crosslinked composite film developed in this study shows great potential for application in food preservation packaging.
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JOURNAL OF INVERTEBRATE PATHOLOGY
·
2025
·
IF 2.4
Shangning Yang,Zhichu Huang,Ruike Wei,Dandan Liu,Xiaoling Su,Huoqing Zheng
The Israeli acute paralysis virus (IAPV), widespread in honeybee ( Apis mellifera ) colonies, causes paralysis, tremors, and eventual mortality, while strongly associated with colony collapse disorder (CCD). Currently, there are no widely approved antiviral therapies for IAPV infection; however, several natural compounds have shown promising antiviral efficacy. In this study, we evaluated the effects of eight natural compounds (myrcene, citral, menthol, chlorogenic acid, resveratrol, curcumin, quercetin, and tea polyphenols) on IAPV-infected honeybees. Bees were artificially or naturally infected with IAPV and subsequently fed sucrose solution supplemented with these compounds. Quantitative RT-PCR analysis revealed that curcumin was the most effective compound in reducing viral load. After seven days of treatment with 10 µM curcumin, IAPV levels decreased by 46.2 % in artificially infected bees and 84.0 % in naturally infected bees. Transcriptomic analysis showed that curcumin upregulated genes involved in nutritional metabolism (e.g., Vg ) and the RNA interference (RNAi) pathways (e.g., dicer , hsp90 ), which play a critical role in antiviral defense. Interestingly, it downregulated antimicrobial peptide genes ( hymenoptaecin , abaecin , defensin 1 ). These findings demonstrated that curcumin mediated a strategic immune reconfiguration in honeybees, concentrating more resources on the RNAi pathway, while reducing energetically costly antimicrobial peptide synthesis. This optimized antiviral defense, combined with improved vitellogenin expression, suggests a metabolic efficiency adaptation that preferentially directs resources toward more effective IAPV countermeasures. Our results suggest that curcumin is a dual-action therapeutic candidate that simultaneously strengthens crucial antiviral defenses and maintains host vitality, offering significant promise for sustainable honeybee health management.
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Food Chemistry-X
·
2025
·
IF 8.2
Yunxiao Xie,Yuru Shui,Erhao Zhang,Zhendong Liu,Zhang Luo,Jinqiu Wang,Fang Geng
The quality changes of frozen chicken during thawing directly affect its safety and flavor. However, traditional physicochemical analysis struggles to explain the underlying molecular mechanisms, creating a research gap. This study used metabolomics to investigate thawing Tibetan chicken breasts and identify key differential metabolites and their metabolic pathways. A total of 788 metabolites were identified, with total abundance increasing significantly during thawing. Key differentially abundant metabolites, including 18β-glycyrrhetinic acid and FFA (22:6), were identified. KEGG enrichment analysis showed that “glycerolipid metabolism” and “necroptosis” were significantly enriched during early thawing, while “ABC transporter” and “biosynthesis of phenylalanine, tyrosine, and tryptophan” pathways were significantly enriched in later stages. Metabolite accumulation during thawing had dual effects on flavor. Small peptides and nucleotide metabolites enhanced flavor, while bitter substances and biogenic amines caused off-flavors and potential safety risks. Monitoring metabolites during thawing could optimize strategies for frozen chicken, improving safety and flavor.
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危险品化学品经营许可证（带存储）