Materials Today Bio
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2026
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IF 11
Xiaohang Liu,Zhiyang Fan,Liya Xie,Wei Zang,Li Li,Yueyang He,Dongfang Ding,Jianwu Chen,Yun Zhang,Xiaolong Liu,Yao Huang,Yang Li
Photodynamic therapy (PDT) utilizing organic photosensitizers like indocyanine green (ICG) faces several intrinsic limitations. These challenges include a propensity to aggregate, insufficient stability, and low intersystem crossing (ISC) efficiency that yields inadequate reactive oxygen species (ROS). Furthermore, the tumor microenvironment imposes additional restrictions on its efficacy. To address these challenges, we implemented a cetyltrimethylammonium bromide (CTAB)–templated metal coordination approach and rationally designed cerium(IV)-coordinated, self-assembled ICG nanoparticles (CINPs). Cooperative coordination between Ce 4+ and ICG, combined with hydrophobic interactions, significantly enhances ICG stability. It also optimizes the energy gap between the lowest singlet excited state (S 1 ) and the lowest triplet state (T 1 ), thereby promoting ISC and equipping the system with robust ROS-generating capacity. Moreover, Ce 4+ exhibits dual catalytic activity, on the one hand catalyzing the decomposition of endogenous hydrogen peroxide (H 2 O 2 ) to generate oxygen and alleviate tumor hypoxia, and on the other hand oxidizing and depleting intracellular glutathione (GSH) to weaken antioxidant defenses. In a hepatocellular carcinoma model, CINPs harnessed efficient ROS production to induce mitochondrial dysfunction, lipid peroxidation (LPO), and DNA strand breaks, which collectively activated multiple cell death pathways and significantly suppressed tumor growth. Unlike nanoplatforms that require elaborate designs, complex compositions, and fine chemical synthesis, the nanoparticles developed here are assembled from a small set of reliable, clinically established materials and can be rapidly formed through a simple process in less than 30 minutes. Despite the streamlined preparation, CINPs effectively remodel the tumor microenvironment, induce vigorous ROS generation during treatment, and achieve potent antitumor activity via oxidative stress-related mechanisms across multiple pathways, highlighting strong translational potential and broad prospects for clinical application.
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ACS Applied Materials & Interfaces
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2026
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IF 7.8
Yanjiao Ding,Daogong Zhang,Jinye Li,Lei Xu,Haibo Wang
Hearing loss is a widespread global disability, commonly treated using dexamethasone (Dex). However, targeted delivery of Dex to the inner ear remains a significant challenge due to the blood-perilymph barrier (BLB), which limits its therapeutic efficacy. In this study, we aimed to develop a strategy to enhance Dex delivery to the inner ear and improve its treatment outcome by the noninvasive intranasal approach. Also, poly(ethylene glycol) (PEG)─liposomal nanoparticles were used as a drug carrier and loaded with Dex (PLN-Dex). For intranasal delivery, a thermosensitive hydrogel was fabricated by methylcellulose. The PLN-Dex nanocomposite was incorporated into the hydrogel to obtain PLN-Dex@Gel. PLN-Dex@Gel could be administrated intranasally and their transport pathway from olfactory mucosa to the cochlea was explored. In vivo magnetic resonance and fluorescence microscopy showed that drugs delivery into the olfactory mucosa reached the inner ear by dispersive transport via the brain. Interestingly, we found that beyond the cochlear duct, the cochlear axis may serve as a crucial pathway for the transportation of drugs from the brain to the inner ear. In guinea pig models of LPS-induced and noise-induced hearing loss, intranasal PLN-Dex@Gel treatment significantly reduced auditory brainstem response thresholds, ameliorated cochlear blood flow, and protected hair cells and synapses. Our findings underscore the potential of intranasal Dex delivery as a noninvasive and effective strategy for treating hearing loss. The target drug delivery to the inner ear, combined with the enhanced formulation of Dex-loaded liposomal hydrogels, offers promising prospects for future research in the treatment of inner ear disorders, with potential for clinical translation. This study expands the understanding of delivery route from nose to inner ear and suggests a method for utilizing intranasal administration as a strategy for treating hearing loss.
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BIOORGANIC CHEMISTRY
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2026
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IF 5.1
Meng Liu,Peng Jiang,Binghui Ruan,Yunfei Cui,Junjie Zhang,Yuxiu Ye,Dongting Zhangsun,Sulan Luo,Yong Wu
Antimicrobial resistance (AMR) is an increasing global concern, while the development of new antibiotics remains limited. Antimicrobial peptides (AMPs) offer an alternative due to their broad-spectrum and membrane-targeting features, but their translation is restricted by instability and cytotoxicity. Here, we describe a β-turn engineering strategy that incorporates a Pro-Gly motif and aromatic residues to create a short, disulfide-free β-hairpin-like AMP (W2PG). W2PG showed broad-spectrum activity (MIC 4–8 μM) with low hemolysis and cytotoxicity, along with improved protease and serum stability. It caused concentration-dependent membrane permeabilization and depolarization, consistent with molecular dynamics simulations indicating aromatic-assisted anchoring and stable insertion. In murine infection models, W2PG achieved efficacy comparable to polymyxin B without observable organ toxicity. These results suggest that β-turn-guided design can balance stability, selectivity, and activity, providing a useful scaffold for peptide antibiotic development.
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Biomaterials Research
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2026
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IF 9.8
Dan Wang,Lei Sun,Juan Wang,Lirong Wang,Zhongyu Wang,Yutong Zhang,Qi Zhou,Yuhang Chen,Jue Jiang
Anaplastic thyroid carcinoma (ATC), as the most malignant pathological type, is prone to local invasion and even distant metastasis with a poor prognosis and a high recurrence rate. Herein, we developed an iron-based metal organic framework (FL@M) as an effective sonosensitizer and biomimetic nanocarrier through the incorporation of lenvatinib (Len) and further coating with homologous tumor cell membranes, achieving the synergistic sonodynamic therapy/chemotherapy for ATC. With the homologous tumor membrane camouflage, FL@M nanoparticles exhibited good biocompatibility, drug loading, and excellent tumor targeting ability both in vitro and in vivo. After absorption, FL@M was decomposed and released Len and Fe 3+ /Fe 2+ . Under ultrasound irradiation, FL@M exhibited excellent sonodynamic effects, rapidly generating a large amount of reactive oxygen species (ROS), which induced oxidative stress and cell apoptosis. In addition, Fe 3+ /Fe 2+ had good catalase enzyme activity and peroxidase enzyme activity, which could catalyze H 2 O 2 to produce O 2 and cytotoxic •OH, respectively, further enhancing the efficacy of sonodynamic therapy (SDT). Moreover, Len exerted a synergistic effect by promoting ROS production during SDT at a lower concentration, which could decrease the occurrence of side effects. In summary, our findings demonstrated that FL@M is a safe and effective metal-organic framework-based nanoplatform to inhibit tumor proliferation, recurrence, and metastasis, offering a promising SDT/chemotherapy combination strategy on thyroid cancer.
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JOURNAL OF DISPERSION SCIENCE AND TECHNOLOGY
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2026
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IF 2.2
Yaohui Ni,Shicheng Tang,Haiyang Wu,Yufei Zhang,Saijiao Tang,Lexin Chen,Tianjian Lu,Defeng Xu,Hang Hu
Dimethylcurcumin (DMC) is a derivative of curcumin. Studies have shown that DMC can enhance the degradation of androgen receptors (AR), thereby inhibiting AR-related diseases. However, the extremely poor water solubility and fast metabolism in vivo of DMC greatly limit its clinical applications. In the present study, poly(ethylene glycol)-modified liposomes loaded with DMC (DMC@PEG-Liposomes) were prepared by an improved membrane hydration method. The prescription of the liposomes was optimized to obtain DMC@PEG-Liposomes with a particle size between 110 and 150 nm, moderate encapsulation efficiency and good freeze-drying stability. In vitro release studies showed that DMC@PEG-Liposomes displayed Fickian release at pH 7.4 and non-Fickian release at pH 5.0. Compared with free DMC, DMC@PEG-Liposomes were more toxic to 22Rv1 and HepG2 cells in vitro. DMC@PEG-Liposomes also exhibited enhanced AUC0-t as compared to free DMC in in vivo pharmacokinetic studies. These results suggest that DMC@PEG-Liposomes are a promising DMC formulation for anticancer DMC delivery.
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Advanced Healthcare Materials
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2026
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IF 11
Zi Zhu,Dan Yang,Hao Sun,Nizhaoyue Wei,Zhenkun Fu,Jia Zhang,Zhangdi Yan,Piaoping Yang,He Ding,Lei Zhong
Tumor immunotherapy exerts transformative effects in cancer treatment by leveraging intrinsic immunity and acting broadly effective across cancers, while first-line chemotherapy plays a direct role by disrupting tumor DNA and reducing burden. However, the clinical utility of immunotherapy is notably constrained by the immunosuppressive tumor microenvironment (ITME), while chemotherapy suffers from intrinsic systemic toxicity and acquired resistance. Herein, multifunctional nanozymes on cerium oxide sacrificial templates were designed via precursor engineering, with zirconium introduced to leverage the Kirkendall effect, whereby differing migration rates of zirconium and cerium ions form hierarchical porous structures. Accordingly, such structural features facilitate efficient mass transfer, thereby notably enhancing their triple enzymatic activity. Hierarchical architectures, coupled with hyaluronic acid moieties, further enable high-capacity cisplatin loading and high-specificity tumor targeting, effectively addressing poor drug delivery and off-target issues. Moreover, ultrasound-amplified redox homeostasis modulation driven by the nanozymes’ enzymatic activity acts as a key regulator for disrupting tumor cell redox balance. Meanwhile, synergy between oxidative stress and cisplatin-induced DNA damage acts as a dual stimulus to intervene in tumor survival pathways, not only reversing ITME but also mitigating chemotherapy-associated limitations, thereby fostering concurrent tumor cell death and immunogenic cell death and consequently highlighting promising prospects for malignancy therapy.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2026
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IF 8.7
Yumei Hu,Yuhang Xu,Biyu He,Du Niu,Xuechun Yang,Jiaping Huang,Zhenzhen Xie,Panpan Shen,Xian Li,Maosen Bai,Ziwei Liu,Hao Li,Yunyun Yang,Jian-Wen Huang,Chun-Chi Chen,Rey-Ting Guo,Longhai Dai
Ochratoxin A (OTA) is a pervasive and significant mycotoxin that poses serious health risks to humans and animals. The development of efficient biocatalysts for the enzymatic detoxification of OTA is of great importance. In this study, we enhanced the OTA-degrading activity of three amidohydrolases (ADHs) by up to ninefold. This improvement was achieved by reducing steric hindrance in the binding pocket and fine-tuning the hydrophilic interactions between the enzyme and substrate. The most efficient variant, Pw ADH/DM, was immobilized onto magnetic Fe 3 O 4 nanoparticles functionalized by the co -deposition of dopamine and polyethyleneimine. Under optimal conditions, this immobilization process achieved a high immobilization efficiency (85.4%) and activity recovery (76.9%). The immobilized enzyme exhibited enhanced pH stability and thermostability, along with good storage stability, reusability, and recyclability. More importantly, the immobilized enzyme completely degraded 100 ng/mL OTA in contaminated milk without affecting the milk's properties. These findings expand our understanding of the molecular mechanisms governing substrate binding and catalysis in OTA-degrading ADHs. Furthermore, they provide a blueprint for enzyme-based OTA decontamination during food processing.
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Cell Communication and Signaling
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2026
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IF 11.6
Deng Weiqian,Yang Xiaoting,Wu Hao,Tang Haojun,Wang Xiaodan,Tu Shuangxi,Yin Kai,Zhu Xiao
Metabolic-associated fatty liver disease (MAFLD), the most prevalent chronic hepatic disorder globally, is pathologically characterized by excessive intrahepatic lipid deposition, oxidative stress, and chronic low-grade inflammation. Apolipoprotein A-I binding protein (AIBP), a critical modulator of lipid metabolism, cellular signaling pathways, inflammatory responses, and metabolic homeostasis, has not been thoroughly investigated in the context of MAFLD pathogenesis. In this study, we identified a significant downregulation of AIBP expression in both high-fat diet (HFD)-induced MAFLD murine models and palmitic acid (PA)-treated HepG2 cells. Systemic AIBP deficiency exacerbated metabolic dysregulation and induced profound perturbations in hepatic architecture and function, culminating in aggravated liver injury. This was evidenced by enhanced steatosis, elevated pro-inflammatory cytokine production, and increased serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. Transcriptomic profiling and molecular characterization of AIBP-deficient HepG2 cells corroborated these pathological alterations. Mechanistic investigations revealed that AIBP silencing potentiates hepatic damage through integrin β3 (ITGβ3)-mediated hyperactivation of the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling cascade. Notably, hepatocyte-specific AIBP overexpression effectively ameliorated these metabolic and inflammatory aberrations. Collectively, our findings establish AIBP as a pivotal hepatoprotective regulator in MAFLD pathogenesis and propose a novel therapeutic paradigm for MAFLD and associated metabolic disorders through targeted AIBP modulation. This study provides compelling evidence for the development of AIBP-centered therapeutic strategies to mitigate MAFLD progression.
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JOURNAL OF NANOBIOTECHNOLOGY
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2026
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IF 15
Tu Maopu,Deng Xiaoyu,Zhou Zhiyong,Li Xiaodong,Mao Shengxun,Lai Bin,Pang Lisong,Zhong Qilin,Cao Jiaqing,Liu Haipeng,Ouyang Xi
Microsatellite-stable (MSS) colorectal cancer (CRC) resists immunotherapy due to its immunosuppressive tumor microenvironment (TME). The cGAS-STING pathway, a key regulator of innate immunity, offers a promising strategy to overcome the immunotherapy resistance in CRC. However, its limited endogenous activation, coupled with the immunosuppression driven by lactate accumulation, significantly compromises the efficacy of standalone STING activation. In response, we developed a multifunctional copper-based metal-organic framework (Cu-MOF) nanoparticle co-loaded with the STING agonist SR-717 and the glycolysis inhibitor 3-bromopyruvate (3-BP), coated with tumor cell membranes (termed BR@CuM@CM), to achieve integrated metabolic modulation and immune activation. BR@CuM@CM nanoparticle achieves tumor-specific accumulation via homotypic targeting and undergo glutathione-responsive degradation to trigger drug release. The released SR-717 activates the STING pathway, promoting dendritic cell (DC) maturation and thereby enhancing cytotoxic T-cell recruitment. Concurrently, Cu²⁺ triggers Fenton-like reactions to generate reactive oxygen species (ROS), inducing mitochondrial DNA release and further amplifying STING signaling. Meanwhile, 3-BP suppresses lactate production by inhibiting glycolysis, which not only repolarizes M2-type tumor-associated macrophages toward the M1 phenotypes and suppresses regulatory T cell (Treg) infiltration, but also alleviates cGAS lactylation to enhance cGAS activity and amplifying STING-mediated immune responses. When combined with anti-PD-1, the nanoparticle significantly inhibits tumor growth and liver metastasis. Collectively, BR@CuM@CM synergistically modulates metabolism and immune signaling to convert immunologically “cold” tumors into “hot” tumors, demonstrating translational potential to overcome immunotherapy resistance in CRC. Graphical
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Journal of Translational Medicine
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2026
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IF 9.7
Gao Hengyuan,Lin Junqing,Chen Xiaobing,Su Yingshi,Huang Yibin,Zhang Yubo,Zhang Junchang,Xu Nan,Dai Xiaoyong
Background Inter-tumor heterogeneity poses significant challenges for precision therapy in thyroid cancer (TC). The conventional organoid models are limited by inefficiency and poor physiological relevance. Methods We developed droplet-engineered organoids (DEOs) using microfluidic 3D bioprinting to rapidly generate patient-derived TC models. These DEOs were characterized via histology, whole-exome and RNA sequencing, and utilized for drug sensitivity testing and metastasis modeling. Results DEOs were generated within 10 days, exhibiting superior uniformity (CV: 2.54%) and a high success rate (76%). They faithfully recapitulated the histopathological architecture, genomic landscape (92% driver gene concordance), and native immune microenvironment (CD3+/CD56+/CD68+/α-SMA+) of parental tumors. Drug screening revealed patient-specific heterogeneity, accurately mirroring clinical responses, including cisplatin sensitivity and anti-PD-1 resistance. We established a novel TC and lung organoids co-culture model, which could be used to study the TC lung metastasis. Crucially, transcriptomics identified stage-specific maturation driven by NF-κB signaling. Pharmacological inhibition of NF-κB synergistically enhanced the efficacy of dasatinib, anti-PD-1, and paclitaxel, with combination index (CI) values of 0.58, 0.45, and 0.80, respectively. Conclusions Our microfluidic platform enables rapid, high-fidelity modeling of TC, offering a scalable and physiologically relevant tool for mechanistic studies, drug screening, and personalized therapy prediction, with highly promising translational potential.
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Cancer Communications
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2026
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IF 28.4
Chenchen Hu,Feiming Hu,Changjian Shao,Yuanli He,Liping Su,Daimei Shi,Lingying Yu,Yuanjie Sun,Jing Wang,Xiyang Zhang,Hongtao Duan,Junqi Zhang,Yubo Sun,Dongbo Jiang,Xiaolong Yan,Shuya Yang,Kun Yang
Background: Lung cancer remains a major global health burden. RNA-binding proteins (RBPs) play crucial roles in post-transcriptional gene regulation, and their dysregulation is frequently implicated in tumorigenesis. The present study aimed to elucidate the molecular network governed by the highly expressed RBP TIMELESS in lung adenocarcinoma (LUAD) and determine its mechanistic role in LUAD progression. Methods: The Cancer Genome Atlas-LUAD, Gene Expression Omnibus, and single-cell RNA sequencing datasets were analyzed to identify aberrantly expressed RBP genes. The RBP gene TIMELESS exhibited the most significant effect on LUAD cell death and was selected for further study. Photoactivatable ribonucleoside-enhanced crosslinking and immunoprecipitation sequencing and RNA sequencing were employed to identify ferroptosis-related targets directly bound by TIMELESS. Molecular mechanisms underlying the TIMELESS-mediated regulation of ferroptosis in LUAD were investigated via immunoprecipitation–mass spectrometry, glutathione S -transferase pull-down, immunofluorescence–fluorescence in situ hybridization, RNA immunoprecipitation, poly(A)-tail, and RNA stability assays. In an orthotopic lung cancer mouse model treated with erastin (a ferroptosis inducer) and programmed cell death protein 1 (PD-1) blockade, the role of TIMELESS in therapeutic response was assessed via flow cytometry and multiplex immunofluorescence (mIF). Infiltrating immune cells in LUAD were analyzed by tissue microarrays (TMAs) via mIF. Results: TIMELESS significantly affected LUAD cell proliferation and death, and TIMELESS knockdown significantly enriched RNA-binding and ferroptosis pathways. Transferrin (TF) was identified as a direct TIMELESS target governing ferroptosis. TIMELESS was revealed to bind Ccr4-Not transcription complex subunit 3 (CNOT3) to promote TF mRNA degradation. TIMELESS depletion combined with erastin and PD-1 blockade enhances efficacy, prolongs survival, increases T cell and M1 macrophage infiltration, and reduces M2 macrophage infiltration. Further, high TIMELESS expression was inversely correlated with ferroptosis marker 4-hydroxynonenal but positively correlated with programmed cell death ligand 1 (PD-L1), reduced T cell and M1 macrophage infiltration, and increased M2 macrophage infiltration. Conclusions: TIMELESS recruits CNOT3 to accelerate TF mRNA degradation, thereby suppressing ferroptosis and promoting LUAD growth. These findings suggest that the TIMELESS/TF regulatory axis may be a promising therapeutic target for LUAD.
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Advanced Science
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2026
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IF 14.1
Yongyuan Kang,Pai Peng,Liang Song,Qiaoxuan Wang,Zilong Zhong,Dongchao Qiu,Yunfan Liu,Kefei Zhao,Xiaofei Dong,Changyou Gao
Lactate plays a central role in regulating wound metabolism and has been implicated in fibrosis through mechanisms such as histone lactylation and endothelial-to-mesenchymal transition. However, strategies to modulate lactate-driven metabolic imbalance and oxidative stress remain limited. Herein, a metabolism-regulating and inflammation-modulatory artificial enzyme, Metazyme, was developed, which exhibited dual lactate oxidase (LOX)-like and catalase (CAT)-like activities to oxidize lactate and decompose hydrogen peroxide (H 2 O 2 ), enabling efficient oxygen recycling. Embedding Metazyme into a rod-shaped microgel matrix yielded MetaRgel, a localized and sustained catalytic platform for wound microenvironment modulation. The MetaRgel reduced lactate and reactive oxygen species (ROS) levels, relieved hypoxia, and downregulated glycolysis-related enzymes such as pyruvate kinase (PKM2) and pyruvate dehydrogenase kinase isoform 1 (PDK1) in vitro and thereby suppressed the pro-inflammatory cytokine interleukin-6 (IL-6) and the fibrotic mediator transforming growth factor-β1 (TGF-β1). In a rat full-thickness wound model in vivo, the MetaRgel significantly accelerated healing, enhanced granulation and collagen organization, and notably reduced glycolytic enzyme activity as well as the fibrotic marker α-smooth muscle actin (α-SMA) and hypoxia-inducible factor 1α (HIF-1α). The targeting of lactate-centered metabolic dysregulation with cascade artificial enzymes offers a promising approach to interrupt inflammation-metabolism-fibrosis crosstalk and promote scarless skin regeneration.
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