MOLECULAR PHARMACEUTICS
·
2026
·Vol. 23
·期 8
·4341-4359
·
IF 4.9
Zhang Jieke,Li Yafang,Tian Chaoying,Zhang Xiaodi,Guo Jialing,Liu Chenxin,Wu Ligang,Du Bin,Cheng Genyang
Acute kidney injury (AKI) is a clinical syndrome with
high incidence
and mortality involving oxidative stress, ferroptosis, and inflammation,
yet there are no clinically effective interventions. Herein, HA@PDA@EGCG
nanoparticles were constructed using polydopamine (PDA) as carriers,
loaded with epigallocatechin gallate (EGCG) via π-π stacking,
and further surface-modified with hyaluronic acid (HA) through electrostatic
interaction. The nanoparticles had uniform morphology with a size
of approximately 50 nm and an EGCG loading capacity of 15.4 ±
0.8%. They exhibited prominent broad-spectrum antioxidant activity
and hydrogen peroxide-responsive EGCG release, with a cumulative release
rate of 58.2 ± 2.2% within 2 h and close to 80% at 12 h. Cellular
uptake and in vivo distribution confirmed the efficient CD44 receptor-mediated
internalization of the nanoparticles by human kidney-2 (HK-2) cells
as well as renal-targeted accumulation. Reactive oxygen species (ROS)
staining, mitochondrial morphology and apoptosis assays showed that
the nanoparticles effectively scavenged ROS, alleviated mitochondrial
damage, and inhibited cell apoptosis. In a cisplatin-induced in vivo
AKI model, HA@PDA@EGCG significantly restored renal function: blood
urea nitrogen and creatinine decreased to 12.3% and 27.2% of model
group levels, respectively, while alleviating renal pathological damage
and inflammation. Mechanistically, HA@PDA@EGCG inhibited ferroptosis
by downregulating acyl-CoA synthetase long-chain family member 4 (ACSL4)
to suppress lipid synthesis, chelating ferrous ions, and stabilizing
glutathione peroxidase 4 (GPX4) protein. Collectively, HA@PDA@EGCG
achieved renal protection by ameliorating oxidative stress, suppressing
inflammation and inhibiting ferroptosis through multiple pathways,
offering a novel strategy for targeted AKI therapy.
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Cell Reports
·
2026
·Vol. 45
·期 7
·
IF 7.7
Xiangyu Zhao,Tao Wu,Sanan Wu,Yujin Chen,Yu Zhang,Jing Chen,Kaixuan Diao,Zaoke He,Jiawei Yan,Tianzhu Lu,Chao Xu,Lu Liu,Gaofeng Fan,Dongliang Xu,Xinxiang Li,Xiaopeng Xiong,Jianjun Cheng,Fang Bai,Xue-Song Liu
Hypoxia, a hallmark of solid tumors, drives malignant progression and represents a major therapeutic challenge. Metabolic reprogramming induced by hypoxia creates unique metabolic vulnerabilities that can be exploited therapeutically. Here, we systematically compared the metabolic network differences between hypoxic and normoxic cells, and developed DepFormer, a transformer-based deep learning model, to nominate hypoxia-dependent metabolic genes in tumor cells. Oxidative phosphorylation was identified as the most significantly hypoxia-dependent metabolic pathway, and FLAD1 was predicted to be one of the key hypoxia-dependent metabolic genes. FLAD1 locus is amplified, and FLAD1 expression is upregulated across various tumor types, especially in hypoxic tumors. FLAD1 depletion disrupts activity of mitochondrial complex II, causing succinate/fumarate imbalance, which in turn prevents cancer cells from adapting to hypoxia. We further identified a drug-like inhibitor of FLAD1, which selectively inhibits growth of hypoxic tumor cells. Our study establishes DepFormer as an effective framework for predicting state-specific metabolic dependencies and reveals FLAD1 as a metabolic vulnerability and an innovative therapeutic target for hypoxic tumors.
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Asian Journal of Pharmaceutical Sciences
·
2026
·
IF 12.6
Xianbin Sun,Xinyi Wang,Fangying Zheng,Ruofei Xu,Xinyi Shen,Ding Tan,Xudong Li,Ya Wang,Kaiming Peng,Haijun Chen,Xiumei Li,Yu Gao
The rising threat of antibiotic resistance severely compromises the treatment of bacterial pneumonia, underscoring the urgent need for innovative and comprehensive therapeutic strategies. Here, we developed an innovative theranostic nanoplatform (Dex/BTGd) through the coordinated assembly of tetracycline, gadolinium ion (Gd 3+ ) and baicalin (Ba), which acts synergistically to combat infection, enable non-invasive magnetic resonance imaging (MRI), and regulate the lung microenvironment. Dex/BTGd demonstrated potent antibacterial activity against clinically relevant pathogens, effectively disrupting biofilms and overcoming tetracycline resistance. The incorporated Gd 3+ allowed targeted visualization of pulmonary infection sites by MRI, facilitating timely disease assessment. Beyond its direct antibacterial effects, the nanoplatform modulated the inflammatory microenvironment by scavenging reactive oxygen species, promoting macrophage polarization from the pro-inflammatory to the anti-inflammatory phenotype, and suppressing profibrotic transforming growth factor-β signaling. In a murine model of tetracycline-resistant Pseudomonas aeruginosa pneumonia, Dex/BTGd significantly reduced bacterial load, alleviated pulmonary edema and fibrosis, and enabled targeted MRI visualization of infected lesions. This integrated strategy of pathogen clearance, microenvironment modulation, and tissue repair offers a multifaceted solution to drug-resistant bacterial pneumonia, providing a promising blueprint for next-generation anti-infective systems.
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PEST MANAGEMENT SCIENCE
·
2026
·
IF 4.2
Hanchen Wei,Rui Xie,Shaoxiong Zhu,Feihu Bi,Linna Pan,Qiao Ye,Dalong Ren,Qingqing Wang,Yulong Wang,Bo Huang,Guang Yang
BACKGROUND Fungal diseases caused by Colletotrichum spp . severely threaten global agricultural productivity. Silver nanoparticles (AgNPs) offer potent antifungal activity, but their practical use is limited by instability, aggregation, and potential toxicity. This study aims to develop a safe, stable, and highly effective antifungal agent of carbohydrate-derived positively-charged glycopolymer-stabilized AgNPs (PGM@AgNPs) nanocomposites. RESULTS PGM@AgNPs exhibited an exceptionally narrow size distribution (7.41 ± 4.27 nm). The nanocomposite with the highest positive charge density ( m/n = 2:1) achieved almost 100% inhibition of Colletotrichum fructicola spore germination at 8 μg mL −1 , significantly outperforming naked AgNPs in inhibiting mycelial growth and cicada wing penetration. On pears, mangoes, and kiwifruits, PGM@AgNPs reduced anthracnose lesion sizes by 46–70%. Transcriptomic analysis revealed that the antifungal mechanism involves inducing oxidative stress, disrupting cellular integrity, and triggering autophagic cell death. Moreover, PGM@AgNPs showed negligible hemolysis and low cytotoxicity toward L929 cells and zebrafish. CONCLUSION The carbohydrate-derived PGM@AgNPs combine superior stability, enhanced antifungal efficacy, and favorable preliminary biocompatibility. By effectively alleviating anthracnose symptoms in postharvest fruits, these nanocomposites represent a promising, environmentally friendly alternative to chemical pesticides for sustainable agricultural disease management. © 2026 Society of Chemical Industry.
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Nature Communications
·
2026
·
IF 18.1
Huang Kai,Liu Hui-Zhi,Liu Yuan,Lyu Jia-Yan,Zhang Qing-Yi,Feng Zi-Yuan,Wang Zi-Lin,Dong Hui,Nie Rong,Zhang Yi-Wen,Zhang Yue-Qi,Zeng Yi,Xie Hui-Qi,Zhou Zhou,Shen Bin
Osteoarthritis (OA) remains difficult to treat because drug transport within cartilage is restricted by its dense extracellular matrix and rapid joint clearance. Here we show that hybrid exosomal nanomotors (CAP-Mn/140@hyExos) convert pathological reactive oxygen species (ROS) into transport-driving cues to overcome diffusion-limited transport within cartilage. In the oxidative OA microenvironment, manganese dioxide (MnO₂) catalyzes H₂O₂ decomposition, driving ROS-responsive transport, while a cartilage-targeting peptide enhances matrix interaction, together promoting cartilage accumulation. This strategy achieves deeper penetration (~140 μm), greater cellular uptake (~2.5-fold), and prolonged intra-articular retention (~30% remaining at two weeks). Enhanced transport enables efficient intracellular delivery of miR-140 and MnO₂ nanoparticles, attenuating oxidative stress and promoting cartilage regeneration. In a rat OA model, this therapeutic strategy improves gait performance, restores subchondral bone microarchitecture, and suppresses OA progression. These findings establish pathological microenvironments as endogenous drivers of intratissue drug transport, providing a transport-regulated strategy for drug delivery in transport-restricted tissues.
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TOXICOLOGY AND APPLIED PHARMACOLOGY
·
2026
·
IF 3.6
Yedan Liu,Dezhi Xu,Yun Shi,Xinran Li,Mengru Li,Jiajie Zhang,Xudong Yu,Weicheng Peng,Huizhen Chen,Xinying Guan,Jingquan Dong
Liquiritigenin (LG), a flavonoid compound extracted from licorice, possesses diverse pharmacological activities, including anti-inflammatory and antioxidant effects. A high-salt diet (HSD) is a common dietary risk factor associated not only with hypertension but also with central nervous system injury. However, the underlying mechanisms and potential therapeutic interventions remain insufficiently explored. In this study, we investigated the neuroprotective effects of LG against HSD-induced brain pathology and cognitive impairment in mice. The mechanism of action was further examined using NaCl-treated HT22 cells with LG intervention. By establishing HSD-related mouse and cellular models, administering different doses of LG, and performing neurobehavioral assessments, we evaluated its effects on brain tissue structure, cognitive performance, neuroinflammation, and mitochondrial function. The results demonstrated that in HSD-fed mice, LG attenuated hippocampal neuronal atrophy and death, thereby improving brain tissue morphology. Behavioral testing further revealed that LG enhanced motor performance and exploratory behavior, alleviating cognitive deficits. At the molecular level, LG reduced the expression of pro-inflammatory mediators while upregulating anti-inflammatory cytokines, effectively suppressing neuroinflammation. In addition, LG decreased cytoplasmic expression of mitochondrial DNA–related genes (d-loop, cox1, non-numt), increased ATP production, and improved mitochondrial function. Mechanistic studies further indicated that LG inhibits HSD-induced nuclear factor kappa-B p65 phosphorylation, reducing neuroinflammation and mitochondrial dysfunction, whereas NF-κB p65 overexpression abrogated these protective effects. In summary, LG protects against neuroinflammation and mitochondrial impairment by suppressing NF-κB signaling, thereby mitigating neurological dysfunction. These findings suggest that LG holds promise as a potential therapeutic agent for the prevention and treatment of HSD-related neurological disorders.
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ADVANCED MATERIALS
·
2026
·
IF 29.1
Yijie Fan,Jingning Zhang,Cong Liu,Wei Liu,Ruizeng Luo,Yingying Ren,Zhou Li,Zhong Lin Wang,Dan Luo
The clinical efficacy of platinum-based chemotherapeutics is frequently diminished by the emergence of resistance during prolonged treatment. Cisplatin (DDP)-resistant tumors adapt to chemotherapeutic stress by establishing a new state of adaptive homeostasis that sustains cellular survival under drug pressure, albeit at the expense of high metabolic burden and acquired vulnerability. Exploiting this intrinsic weakness, we designed a DDP-doped black phosphorus (BP) nanomedicine protected by polydopamine coating (DDP-BP@PDA) that synergistically delivered DDP and piezoelectric BP to precisely disrupt resistance homeostasis and thereby reverse DDP resistance. DDP-BP@PDA altered the intracellular uptake pathway of DDP and disrupted the redox balance of resistant cells via piezocatalysis. Concurrently, piezoelectric polarization enhanced the peroxidase-like activity via electron injection, leading to the generation of substantial reactive oxygen species (ROS). This ROS burst compromised the integrity of the endoplasmic reticulum (ER) membrane and exacerbated the protein-folding burden, thereby amplifying ER stress. Mechanism study reveals that excessive ER stress downregulated the expression of DNA repair proteins, making resistant cells highly sensitive to DDP-induced DNA damage. Through these synergistic effects, DDP-BP@PDA disrupted the adaptive homeostasis of DDP-resistant cells, thereby significantly inhibiting the progression of DDP-resistant tumors. This study establishes a promising therapeutic strategy to combat DDP-resistance via piezoelectric-driven disruption of adaptive homeostasis.
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BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
·
2026
·
IF 5
Guihong Li,Ting Lei,Erpeng Liu,Jing Shen,Dun Liu,Xuqiang Zhu
USP53 upregulation is identified as an independent risk factor for GBM progression. • USP53 upregulation is associated with poor prognosis of GBM patients. • USP53 promotes cell growth and the tumorigenicity of GBM cells. • USP53 removes ubiquitination from ALKBH5 and enhances its stability. • ALKBH5 removes the m6A modification of TERT and increases its RNA stability. Glioblastoma (GBM) is the most common malignant glioma, with a high recurrence rate and a poor prognosis. Deubiquitinating enzyme ubiquitin-specific peptidase 53 (USP53), known to enhance the stability of downstream proteins, exhibits distinct functions in different tumors. The function of USP53 in GBM progression remains unclear. Analysis of GSE104267 and GSE4290 datasets revealed significant USP53 upregulation in GBM tissues, a finding confirmed by TCGA data comparing GBM ( n = 163) with normal brain tissues ( n = 207). In univariate and multivariate cox regression analysis, USP53 was identified as an independent risk factor (univariate, hazard ratio (HR) =1.5357, p = 0.0229; multivariate, HR =1.4851, p = 0.0385) for GBM progression. Patients with high expression of USP53 had worse prognosis compared to those with low expression of USP53. Functionally, USP53 knockdown potently inhibited proliferation and induced apoptosis in LN229 and A172 cells in vitro and attenuated tumorigenicity of LN229 cells in vivo . Conversely, forced expression of USP53 had a carcinogenic effect. Mechanistically, USP53 targeted ALKB homolog 5 (ALKBH5) for deubiquitination, thereby stabilizing the protein and prolonging its half-life. Restoring ALKBH5 expression rescued the proliferative deficit in USP53-silenced LN229 cells. Telomerase catalytic subunit telomerase reverse transcriptase (TERT) was identified as a downstream effector of the USP53/ALKBH5 axis, where ALKBH5 upregulated TERT RNA expression by erasing m6A modifications at position 1989 bp on TERT mRNA. Collectively, those observations demonstrate that USP53/ALKBH5 axis drives GBM progression by targeting TERT, indicating that USP53/ALKBH5 axis may serve as a potential therapeutic target for GBM. Download: Download high-res image (229KB) Download: Download full-size image
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2026
·
IF 8.7
Yan-Ping Lin,Dong-Yan Zhou,Shang-Guang Du,Zi-Fan Yu,Rui-Na Zhou,Hao-Miao Li,Wei-Ming Chai
Protocatechualdehyde (PCA) is a better PPO inhibitor than ellagic acid. • PCA causes structural stretching and conformational change of PPO. • PCA is demonstrated as a potent anti-browning agent. • PCA regulates phenolic metabolism, reduces lipid peroxidation, boosts AsA-GSH cycle. • PCA regulates cell wall metabolism, inhibiting senescence-related browning. Polyphenol oxidase (PPO) is a vital polyphenol-metabolizing enzyme responsible for the enzymatic browning of fruits and vegetables. This study assessed the anti-PPO activity of protocatechualdehyde (PCA), yielding an IC 50 value of 94 μM (95% CI: 91.8 to 96.4 μM). Kinetic analysis revealed that PCA acted as a reversible and competitive inhibitor of PPO. Molecular docking indicated that hydrogen bonding and hydrophobic interactions were the main driving forces for PCA-PPO binding. Fluorescence spectroscopy further demonstrated that PCA binding altered the microenvironments around tyrosine and tryptophan residues, leading to conformational rearrangements and partial unfolding of the enzyme, evidenced by significant fluorescence quenching. Molecular dynamics simulation demonstrated that PCA perturbed the secondary structure of PPO and caused stretching of its overall structure, thereby inhibiting the catalytic activity of the enzyme. Furthermore, PCA demonstrated excellent anti-browning activity by regulating phenolic metabolism, reducing membrane lipid peroxidation, enhancing the ascorbic acid-glutathione cycle, and modulating cell wall metabolism to delay cellular senescence. Collectively, these findings offer some valuable insights into the development of PPO inhibitor and anti-browning agent, and provide a theoretical foundation for the potential application of PCA in the area of food preservation. Download: Download high-res image (249KB) Download: Download full-size image
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DIAMOND AND RELATED MATERIALS
·
2026
·
IF 5.2
Dong Sui,Zhanghan Shi,Zhirong Sun,Linqi Si,Wenwen Liu,Yanliang Yang,Yongsheng Zhang
With the merit of abundant resources, SiO 2 is emerging as a high-capacity and cost-effective anode for lithium-ion battery (LIB). Nevertheless, the inherently low conductivity and severe volume change of silica result in inferior rate capability and poor cycling life, which impede its practical applications. To overcome these shortcomings, designing novel nanostructures and coating with highly conductive carbon are two commonly used strategies to realize high-performance SiO 2 anodes. Herein, glucose-derived carbon coated SiO 2 nanotubes (SNTs@C) were designed and fabricated through a facile hydrothermal reaction and pyrolysis. Benefiting from the one-dimensional tubular structure and uniform carbon coating, SNTs@C can provide excellent transfer paths for electrons and ions, expose more active sites and accommodate the large volume variation. Therefore, the optimized SNTs@C could deliver a high specific capacity of 615 mAh g −1 , excellent rate capability of 220 mAh g −1 at 3 A g −1 , and superior cycling stability with a capacity of 400 mAh g −1 after 600 cycles. Our work offers a facile but feasible method to fabricate SiO 2 -based anode for LIB.
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Frontiers in Pharmacology
·
2026
·
IF 5.4
Yongchang Zeng,Dandan Xu,Xinping Li,Qianqian Jiang,Shaoyu Liang
With the intensification of population aging, age-related cognitive decline has emerged as a significant global health issue. Neuroinflammation, neuronal apoptosis, and pyroptosis have been identified as key factors in neuronal loss, a hallmark of age-related neurodegenerative conditions. Dihydroquercetin (DHQ), a natural flavonoid and a new food resource, demonstrates remarkable antioxidant and anti-inflammatory properties; however, its capacity to mitigate cognitive impairment in context of apoptosis and pyroptosis remains to be fully elucidated. In this study, an ageing rat modelling by intraperitoneal injection of D-galactose was utilised to assess the therapeutic potential of DHQ. A comprehensive analytical technique, incorporating behavioural tests, TCM symptom scoring, histopathological evaluation (Hematoxylin-eosin staining and Nissl staining), ELISA, Western blotting, and molecular docking analysis, was performed to investigate its pharmacodynamic effects and potential mechanisms. DHQ supplementation significantly alleviated D-gal-induced aging phenotypes and improved learning and memory function in the Morris water maze test. Histopathological examinations indicated that DHQ mitigated neuronal damage and loss in the hippocampus whilst concomitantly increasing the number of Nissl bodies. Furthermore, DHQ administration suppressed neuroinflammation in hippocampus, as indicated by decreased levels of TNF-α, IL-1β, and IL-6. At the molecular level, DHQ treatment was associated with altered expression of proteins involved in apoptosis, specifically increasing the expression of the anti-apoptotic protein BCL2 and reducing the expression of the pro-apoptotic proteins BAX and CASP3. Crucially, DHQ supplementation significantly suppressed the activation of the TLR4/NF-κB/NLRP3/CASP1 pyroptosis-related pathway, as evidenced by decreased protein expression of TLR4, NF-κB p65, p-NF-κB p65, NLRP3, CASP1, and mature IL-1β. Molecular docking predictions suggested potential binding interactions between DHQ and key targets within both apoptotic and pyroptotic pathways. DHQ exerts a mitigating effect on age-associated cognitive impairment, possibly through its association with reduced neuroinflammation and dual modulation of neuronal apoptosis and the NLRP3 inflammasome-mediated pyroptosis pathway. This positions DHQ as a promising candidate for further investigation as a therapeutic agent or dietary supplement in ageing-related neurodegenerative conditions.
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Cell Reports Medicine
·
2026
·Vol. 7
·期 2
·
IF 14
Yuhan Wang,Pengfei Diao,Pin Lv,Na Qi,Ziyu Wang,Enshi Yan,Jin Li,Yanling Wang,Dongmiao Wang,Yaping Wu,Jie Cheng
Oral squamous cell carcinoma (OSCC) remains a significant clinical challenge due to frequent recurrence, metastasis, and therapeutic resistance. Here, we establish a living biobank of OSCC patient-derived organoids (PDOs) comprising 46 lines using optimized culture medium. These PDOs are long-term passaged, cryopreserved, and recovered with stable viability and tumorigenicity. Comprehensive morphological, genomic, and transcriptomic analyses confirm that PDOs faithfully recapitulate the histopathological, genetic, and molecular features of parental tumors. These PDOs enable disease modeling, genetic manipulation, and drug screening. Through transcriptomic profiling and functional assays, we find that CDCP1 mediates cisplatin resistance by modulating Wnt/β-catenin signaling-driven stemness. Notably, we develop a pH-sensitive nanoparticle delivering siCDCP1, which effectively restores chemosensitivity and impairs tumor growth in cisplatin-resistant patient-derived xenograft (PDX) models with favorable safety profile. These findings establish PDOs as robust preclinical models for mechanistic explorations and therapeutics development and highlight CDCP1-targeting strategies as promising approaches to overcome cisplatin resistance in OSCC.
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