Advanced Science
·
2024
·Vol. 11
·期 46
·2309053
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IF 14.3
Lan Chen,Qiqi Yin,Handan Zhang,Jie Zhang,Guizhu Yang,Lin Weng,Tao Liu,Chenghui Xu,Pengxin Xue,Jinchao Zhao,Han Zhang,Yanli Yao,Xin Chen,Shuyang Sun
Oral squamous cell carcinoma (OSCC) often recurs aggressively and metastasizes despite surgery and adjuvant therapy, driven by postoperative residual cancer cells near the primary tumor site. An implantable in situ vaccine hydrogel was designed to target residual OSCC cells post-tumor removal. This hydrogel serves as a reservoir for the sustained localized release of δ-aminolevulinic acid (δ-ALA), enhancing protoporphyrin IX-mediated photodynamic therapy (PDT), and a polydopamine-hyaluronic acid composite for photothermal therapy (PTT). Additionally, immune adjuvants, including anti-CD47 antibodies (aCD47) and CaCO 3 nanoparticles, are directly released into the resected tumor bed. This approach induces apoptosis of residual OSCC cells through sequential near-infrared irradiation, promoting calcium interference therapy (CIT). The hydrogel further stimulates immunogenic cell death (ICD), facilitating the polarization of tumor-associated macrophages from the M2 to the M1 phenotype. This facilitates phagocytosis, dendritic cell activation, robust antigen presentation, and cytotoxic T lymphocyte-mediated cytotoxicity. In murine OSCC models, the in situ vaccine effectively prevents local recurrence, inhibits orthotopic OSCC growth and pulmonary metastases, and provides long-term protective immunity against tumor rechalle nge. These findings support postoperative in situ vaccination with a biocompatible hydrogel implant as a promising strategy to minimize residual tumor burden and reduce recurrence risk after OSCC resection.
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EUROPEAN JOURNAL OF PHARMACOLOGY
·
2024
·
IF 4.2
Yongmei Li,Fengxin Zheng,Shiqi Zhong,Kunlu Zhao,Hui Liao,Jiacheng Liang,Qiang Zheng,Huicong Wu,Shifan Zhang,Ying Cao,Ting Wu,Jianxin Pang
Hyperuricemic nephropathy (HN) is characterized by renal fibrosis and tubular necrosis caused by elevated uric acid levels. Ferroptosis, an iron-dependent type of cell death, has been implicated in the pathogenesis of kidney diseases. The objective of this study was to explore the role of ferroptosis in HN and the impact of a ferroptosis inhibitor, ferrostatin-1 (Fer-1). The study combined adenine and potassium oxonate administration to establish a HN model in mice and treated HK-2 cells with uric acid to simulate HN conditions. The effects of Fer-1 on the renal function, fibrosis, and ferroptosis-associated molecules were investigated in HN mice and HK-2 cells treated with uric acid. The HN mice presented with renal dysfunction characterized by elevated tissue iron levels and diminished antioxidant capacity. There was a significant decrease in the mRNA and protein expression levels of SLC7A11, GPX4, FTL-1 and FTH-1 in HN mice. Conversely, treatment with Fer-1 reduced serum uric acid, serum creatinine, and blood urea nitrogen, while increasing uric acid levels in urine. Fer-1 administration also ameliorated renal tubule dilatation and reduced renal collagen deposition. Additionally, Fer-1 also upregulated the expression levels of SLC7A11, GPX4, FTL-1, and FTH-1, decreased malondialdehyde and iron levels, and enhanced glutathione in vivo and in vitro . Furthermore, we first found that Fer-1 exhibited a dose-dependent inhibition of URAT1, with the IC 50 value of 7.37 ± 0.66 μM. Collectively, the current study demonstrated that Fer-1 effectively mitigated HN by suppressing ferroptosis, highlighting the potential of targeting ferroptosis as a therapeutic strategy for HN.
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Food Bioscience
·
2024
·
IF 4.8
Lian Xia,Jia Zheng,Jian Su,Hongli Yang,Zhengmin Xie,Yue Tang,Yuangen Wu
Ethyl carbamate (EC) is a small compound produced and stored during fermentation processes from ethanol, urea, citrulline, and carbamoyl phosphate. EC is commonly found in fermented foods and alcoholic beverages. Prolonged exposure to EC can cause nervous system diseases and liver damage in human beings. EC lacks stable physicochemical properties, and the presence of numerous interfering substances in alcoholic beverages poses challenges for its detection. Herein, it is found that EC1-34 aptamer bound to EC can enhance the laccase-like activity of cubic Ag 2 O nanoparticles (NPs). Subsequently, Ag 2 O NPs are wrapped with EC1-34 aptamer to prepare recognition probes, which are immobilized on a carrier membrane. Thus, a portable paper-based sheet for EC detection in Chinese Baijiu is designed. The visual detection limit of the developed paper-based sheet for EC is 10 μg⋅L −1 , and shows an outstanding linear relationship within the range of 10–200 μg⋅L −1 . Moreover, this colorimetric paper-based sheet has a good practicality in various Chinese Baijiu samples. It is believed that such paper-based sheet can facilitate portable inspection for EC in Baijiu, and may also become a beneficial tool for monitoring EC molecules in other fermented foods.
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ADVANCED MATERIALS
·
2025
·
IF 26.8
Dazhi Chen,Li Yang,Shulan Ni,Chaofan Jin,Chunyi Xu,Xingjie Zan,Yang Wang,Hong Zhu
Developing high-payload systems that dynamically respond to physiological fluctuations is crucial not only for improving the precision, safety, and efficacy of protein therapies but also for addressing biosafety concerns associated with carriers, reducing administration frequency, minimizing infection risks, and enhancing patient compliance. However, achieving precise control over protein release in the high-payload carriers remain a major challenge. In this study, a physiology-responsive, high-payload insulin (Ins) granule is engineered for long-term glucose management, using Ins as a model—an essential hormone that must be released in response to blood glucose changes for effective glycemic control in diabetic patients. The [(Ins&GOx)@Zn]@[TA&Fe] granules achieve an Ins loading capacity (LC%) exceeding 80%, significantly higher than the previously reported maximum of ≈40%. These granules extend the glucose-regulating effect of free Ins, typically limited to 3 h, to 6 days with a single injection, without any observed risk of hypoglycemia. Long-term administration (28 days, 4 injection cycles, 7 days injection −1 ) shows no significant physiological toxicity or immune response. This approach offers a promising strategy for developing intelligent, high-payload delivery systems for protein-based therapeutics, advancing more precise, safe, and patient-compliant treatments.
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Advanced Science
·
2025
·
IF 14.1
Qi-tao Chen,Qiao-ling Huang,Ming-zhi Han,Xue-hui Hong,De-yi Feng,Lu-ming Yao,Wen-bin Hong,Yue Chen,Ya-ying Huang,Hang-zi Chen,Qiao Wu
Integral membrane protein 2B (ITM2B), a transmembrane protein, frequently undergoes cleavage. The physiological functions of ITM2B are primarily studied in the context of neurological disorders, but their roles in cancers are largely overlooked. Here, it is demonstrated that in renal cell carcinoma (RCC) cells, N-terminal truncation of ITM2B facilitates migrasome swelling through the recruitment of TSPAN4 and promotes migrasome formation. Moreover, ITM2B truncation acts as a carrier, sorting active caspase-7 into migrasomes for migracytosis. The active caspase-7-enriched migrasomes are then taken up by macrophages, leading to caspase-7-induced IL-6 secretion from macrophages, which eventually aggravates RCC growth through a feedback mechanism. Physiologically, hyperuricemia enhances ITM2B cleavage to aggravate RCC growth. Clinically, RCC tissues tend to produce ITM2B truncations compared with corresponding para-carcinoma tissues. Moreover, compared with the urine from normal volunteers, that from RCC patients contains higher levels of ITM2B truncation-enriched migrasomes. This study not only highlights novel functions of ITM2B truncation in migrasome formation and active caspase-7 migracytosis but also elucidates the role of hyperuricemia in RCC progression via regulation of the ITM2B truncation–migrasome axis.
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DRUG METABOLISM AND DISPOSITION
·
2025
·
IF 4
Yong Li,Ying Ding,Chenxu Liu,Yunchao Li,Xinyu Guo,Meidan Huo,Linjing Jia,Haiwei Xu,Hailing Qiao,Na Gao
Cytochrome P450 2E1 (CYP2E1) plays an important role in inflammatory disease, but the role of CYP2E1 in gout remains elusive. The pharmacokinetics in rats of Q11, a CYP2E1 inhibitor synthesized by our group, were measured. The anti-inflammatory and uric acid (UA)-lowering levels mechanism of Q11 was investigated in hyperuricemic (HUA) mice and acute gouty arthritis (AGA) rats, and in macrophage cells stimulated by monosodium urate (MSU). The half-life (t 1/2 ) of Q11 in the ankle joint and kidney was approximately 9 h, which was more than 4 times longer than that in plasma. The expression of CYP2E1 was increased in the kidneys of HUA mice and in the ankles of AGA rats. Q11 reduced plasma UA levels in HUA mice by decreasing xanthine oxidase (XOD) activity. In addition, Q11 also decreased renal inflammatory injury in HUA mice. Moreover, Q11 decreased the levels of IL-1β and TNF-α in AGA rats, increased the levels of catalase (CAT) and glutathione (GSH), and blocked the activation of the NLRP3 inflammasome. A similar phenomenon was observed in J774A.1 and THP-1 cells treated with sodium urate.CYP2E1 may be a new therapeutic target for the treatment of gout and Q11 has the dual effect of being anti-inflammatory and lowering UA. Significance Statement The specific cytochrome P450 2E1 (CYP2E1) inhibitor Q11 reduced plasma uric acid (UA) levels by decreasing xanthine oxidase (XOD) activity in a gout animal model, while attenuating joint and renal inflammatory injury through the inhibition of oxidative stress and NLRP3 inflammasome activation.
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FOOD CHEMISTRY
·
2025
·
IF 9.8
Qian Hou,Tong Zhou,Xinjing Li,Cuimin Hua,Heping Cui,Foxin Zhang,Khizar Hayat,Xiaoming Zhang,Chi-Tang Ho
The browning degree in light-colored Maillard reaction products (L-MRPs), derived from the glycine-xylose system with cysteine (Cys) addition increased during storage. This secondary browning reaction might compromise their long-term stability. To elucidate the underlying mechanism, accelerated storage and model systems (glycine-xylose Amadori compound (GX-ARP) and GX-ARP/cystine) were employed. The findings demonstrated that cysteine undergoes oxidative conversion to cystine, triggering adverse changes including promoted degradation of GX-ARP and retro-aldolization of deoxyosones (DXs) into glyoxal (GO) and methylglyoxal (MGO), thereby accelerating secondary browning. Storage tests with different Cys levels indicated low concentrations insufficiently inhibited browning, while high levels exacerbated darkening from cystine accumulation, and 2 mmol/L Cys achieved optimal balance between browning inhibition and minimized side reactions. In conclusion, the conversion of Cys to cystine and its interference in the GX-ARP degradation pathway cause the instability of L-MRPs. This finding provides a novel theoretical basis for improving the color stability of L-MRPs.
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Chinese Medicine
·
2025
·Vol. 20
·期 1
·1-24
·
IF 5.7
Yin Xuanying,Qiu Jinmei,Cheng Guowang,Wu Jiaxin,Wang Chen,Zheng Chunye,Huang Shuiqing,Chen Tongkai
Background Parkinson’s disease (PD) has emerged as a critical public health challenge amidst global population aging. The pathogenesis of PD is extremely complex. Notably, evidence showed that neuroinflammation due to microglial activation is a critical driver of dopaminergic neuron loss in patients with PD. Therefore, several strategies aimed at alleviating neuroinflammation are currently being tested for the treatment of PD. However, current anti-inflammatory agents exhibit limited therapeutic efficacy in vivo due to hindrances caused by the blood–brain barrier (BBB). To overcome BBB-related challenges, we developed a biomimetic nanodelivery system (DCM@Nar-NCs) by encapsulating naringenin nanocrystals (Nar-NCs) within differentiated HL-60 cell membranes. Our analysis demonstrated that DCM@Nar-NCs could act as an innovative nanoplatform for PD therapy, showing BBB penetration capabilities and exhibiting precise accumulation at sites of neuroinflammation. This targeted delivery enables more precise and potent treatment than existing therapeutic modalities. Methods The BBB penetration efficiency and brain-targeted delivery of DCM@Nar-NCs were assessed both in vitro and in vivo. The neuroprotective effects were comprehensively investigated in cellular and animal levels. Finally, the ability of DCM@Nar-NCs to ameliorate motor dysfunction and cognitive impairment was validated in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse models. Results DCM@Nar-NCs exhibited significantly enhanced BBB permeability and could exert dual therapeutic effects. Notably, DCM@Nar-NCs modulated microglial polarization (pro-inflammatory M1 phenotype to neuroprotective M2 phenotype), thereby attenuating neuroinflammatory cascades. Additionally, DCM@Nar-NCs could ameliorate mitochondrial dysfunction and thereby prevent the apoptosis and destruction of dopaminergic neurons. Finally, behavioral assessments in animal models confirmed the remarkable capacity of DCM@Nar-NCs to reverse PD-related motor deficits and cognitive impairment. Conclusion Collectively, the novel PD treatment approach developed in this study offers superior biosafety and treatment efficacy, highlighting its strong potential for clinical translation. Graphical
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Regenerative Biomaterials
·
2025
·
IF 8.1
Kang Shaoyang,Ding Sheng,Lyu Donghao,Gao Rui,Peng Sirui,Liu Jing,Zhang Chuangnian,Feng Zujian,Huang Pingsheng,Kong Deling,Wang Weiwei
Artificial energy supply modules that can produce adenosine triphosphate (ATP) through natural or synthetic structures, are crucial for supporting artificial cells with therapeutic purposes. However, their advanced biomedical application is hindered by poor stability, short lifespan and low output efficiency. In this study, an artificial light-controlled energetic module with long-term activity, termed thylakoid-loaded microgel (TM), is created by encapsulating spinach-derived thylakoid into alginate/gelatin microgels. The TM effectively retains the photosynthetic light reactions of thylakoids, including the electron transfer capacity of photosystem II and ATP production, and releases the produced ATP to external environment. As a proof of concept, the TM successfully drives the luciferin/luciferase reaction both within and outside the microgel compartment. In addition, the encapsulated thylakoids exhibit a significantly prolonged activity, with the high photosystem II activity and ATP production lasting for at least 96 hours. The long-term activity is attributed to the oxidation shielding efficacy, protein and pigment degradation inhibition, and membrane structural stabilization. This study presents a strategy for developing artificial energy supply modules with efficient energy output and long-term activity, holding great promise in artificial cell construction and biosynthesis.
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INORGANICA CHIMICA ACTA
·
2025
·
IF 3.2
Pengxiao Guo,Rongqi Wang,Yadong Zhou,Chaochuang Yin,Yizhu Lei,Yinyan Wang,Kang Chen,Li Sun,Ziao Zong,Hu Wang
Herein, we explore the development of three copper(II) Schiff base complexes (Cu-SBC, C1 - C3 ) aimed at inhibiting urease (UA), achieved through the thoughtful design of ligands. By integrating a fluorinated Schiff base ligand (SBL) with auxiliary ligands—namely, 2-methylimidazole, 2-ethylimidazole, and 6,6′-dimethyl-2,2′-bipyridine—this research systematically examines the impact of steric factors on the inhibition of the UA enzyme. The synthesized complexes underwent comprehensive characterization, including crystallographic analysis. The three synthesized Cu(II) complexes exhibit two distinct coordination geometries dictated by their auxiliary ligands. C1 and C2 display four-coordinate distorted square planar geometries, while C3 adopts a five-coordinate distorted square pyramidal configuration. The biological evaluation revealed that C1 demonstrated a markedly enhanced UA inhibitory activity compared to the standard reference acetohydroxamic acid (IC 50 : 6.12 ± 0.44 vs. 27.73 ± 2.93 μM). Computational methodologies were employed to complement the experimental investigations, elucidating the molecular underpinnings of the observed activity disparities among the complexes. Consequently, the structure-activity relationship analysis indicates that steric hindrance is crucial in modulating the UA inhibitory activity, providing important perspectives for the development of new UA inhibitors and their potential uses in biomedicine.
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SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
·
2025
·
IF 4.6
Quanfang Wang,Heping Wu,Chuqi Bai,Jingjing Lan,Yu Wei,Jiaojiao Chen,Shidi Zhao,Gang Niu,Yalin Dong,Taotao Wang
Voriconazole (VOR) is a first-line drug for the treatment of invasive aspergillosis, while its pharmacokinetic parameters exhibit significant individual variability, necessitating therapeutic drug monitoring (TDM) to ensure optimal outcomes. Given the limitations of current monitoring techniques, it is imperative to develop new point-of-care testing (POCT) methods for detecting antimicrobial drugs. Surface-enhanced Raman spectroscopy (SERS) has shown considerable potential in the field of blood antimicrobial concentration monitoring. In this study, the theoretical Raman spectra of VOR were firstly predicted using dispersion-corrected density functional theory with the B3LYP/6–311++G(d,p) basis set. Subsequently, using gold nanoparticles as the SERS substrate and a 96-well plate padded with Al foil at the bottom as the measuring carrier, the detection conditions were optimized regarding the particle size and state of the gold nanoparticles, the type, concentration, and amount of the aggregating agents, as well as the volume of the VOR solution added. Finally, a novel SERS method for determining VOR concentration was established by combining ethyl acetate extraction and enrichment techniques. The clinical utility of the SERS method was verified using 18 patient blood samples, with an enzyme-multiplied immunoassay technique serving as the control. This preliminary study developed a rapid, label-free, high-throughput, and small sample size method for TDM of VOR, representing a potential novel strategy for POCT of clinical antimicrobial drugs.
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Nature Communications
·
2025
·Vol. 16
·期 1
·10766
·
IF 15.7
Zhang Jia,Guo Lu-Yao,Lin Xiao-Qian,Wen Gui-Hua,Zhang Xue-Feng,Yu Li-Hong,He Mei-Qian,He Yu-Mei,Zou Long,Zhang Meng-Tian,Cao Li-Ming,He Chun-Ting
Developing efficient chemical modification technologies for upgrading classic non-noble metal based electrocatalysts to further meet the demands of practical water electrolysis industry is of vital challenge. Here, we propose an organic-inorganic dual-modulation strategy to construct a cobalt hydroxide-based electrocatalyst, MEC-17, synthesized by an eco-friendly and facile microbial-mediated vulcanization method. This electrocatalyst, modified with both 2-methylimidazole and inorganic sulfur exhibits notable oxygen evolution reaction performance, achieving an overpotential of 285.6 ± 1.7 mV and exceeding 300 h of durability at a high current density of 1000 mA cm −2 . The operando characterizations and theoretical calculations reveal that sulfur dopant primarily shortens the Co−Co distances to support oxide path mechanism, while 2-methylimidazole plays a more critical role by modulating the d -band center of the Co sites, which optimizes intermediate adsorption for ensuring efficient O−O coupling. This work offers insights into the design of organic-inorganic hybrid electrocatalysts and contributes to understanding the origin of their electrocatalytic activities.
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