FREE RADICAL BIOLOGY AND MEDICINE
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2025
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IF 8.2
Yunpeng Zhu,Lingjiang Li,Yunshan Guo,Renji Wang,Yiguang Hao,Xin He
The formation of neutrophil extracellular traps (NETs) at the injury site contributes to secondary damage in spinal cord injury (SCI). This study investigated the function of EDIL3 in spinal cord ischemia-reperfusion injury (SCIRI) and its connection to NET formation. We established a mouse SCIRI model, which revealed significant neutrophil infiltration and NET formation within the injured spinal cord at 48 hours post-reperfusion. Therapeutic disruption of NETs with DNase1 or EDIL3 overexpression ameliorated multiple aspects of SCIRI pathology, including tissue damage, blood-spinal cord barrier (BSCB) disruption, neuroinflammation, neuronal death, and motor deficits. Endothelial cell-specific knockout of EDIL3, however, intensified these injuries. Mechanistically, EDIL3 inhibited PMA-induced NET formation in vitro by attenuating NF-κB activation and protected the endothelial barrier from NET-mediated damage in co-culture assays. Moreover, NSUN2 promoted m5C methylation of EDIL3 mRNA, facilitating its YBX1-dependent stabilization. Crucially, the exacerbation of SCIRI following NSUN2 knockdown was abrogated by EDIL3 upregulation. Collectively, the NSUN2-EDIL3 axis represents a key endogenous pathway that limits BSCB disruption and neuronal death in SCIRI by restraining NET formation.
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PEST MANAGEMENT SCIENCE
·
2026
·
IF 4.2
Yang Yang,Yu-Xin Zhou,Le-Yao Jia,Xin-Yang Song,Ya-Jie Lai,Si-Yuan Liu,Su-Yan Wang,Pedro Laborda,Xin-Chi Shi
BACKGROUND The spoVF operon, encoding the dipicolinic acid (DPA) synthase, is critical for sporulation in Bacillus subtilis . A recent study suggested that spoVF expression in vegetative cells promotes biofilm formation, yet the detailed regulatory pathways and the underlying metabolic connections remain to be fully elucidated. RESULTS In this study, deletion of spoVF subunits spoVFA and spoVFB severely reduced DPA synthesis, downregulated mreB gene expression, and impaired biofilm formation, with mutant ΔA showing stronger effects than mutant ΔB. Although wild type B. subtilis 168 cells exhibited rod shape, double mutant ΔAΔB cells were spherical. In the MT strain, engineered for enhanced spoVF expression during vegetative growth, the upregulation of key TCA cycle genes (e.g., citC ) and glutamate synthesis genes (e.g., gltA ) was observed. This metabolic reprogramming was accompanied by the promotion of Spo0A phosphorylation. The activated Spo0A~P then inhibited the SinR and AbrB repressors, which led to the activation of the eps and tasA biofilm operons. The MT strain showed superior stress tolerance to high temperature (42 °C), salt, acidic and alkaline pH, and UV-A and UV-B radiation. Additionally, the MT strain exhibited higher nutrient competition ability, and in vitro and in vivo antifungal activities against the sweet potato ( Ipomoea batatas L. Lam) storage root pathogen Ceratocystis fimbriata compared to mutant ΔA, ΔB, and ΔAΔB strains. CONCLUSIONS This study elucidates how the spoVF operon links the central metabolic pathways with B. subtilis cell morphology and biofilm formation, offering a novel target for engineering advanced Bacillus -based biocontrol agents. © 2026 Society of Chemical Industry.
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ENVIRONMENT INTERNATIONAL
·
2026
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IF 9.7
Kehao Liu,Xuehui Hu,Mingcong Yang,Tao Chen,Qi Huang,Ying Xie,He Zhang,Yuzhou Li,Sheng Yang
Environmental pollutants are increasingly linked to sleep disorders (SD), affecting 27% of people globally, yet their synergistic effects remain understudied. Network toxicology identified 252 shared targets between sleep-related environmental pollutants (SREPs: NO 2 , formaldehyde, benzene) and SD. PPI network and diagnostic model identified four hub genes ( HSP90AA1 , RELA , PTGS2 , MMP9 ) with moderate-to-high predictive value (AUC: 0.708–0.979). Immune infiltration analysis showing elevated T cells and reduced astrocytes and neurons in patients with SD. Molecular simulations confirmed stable SREP-hub protein binding, with benzene exhibiting the highest affinity. Crucially, mixed SREPs exposure induced more severe toxicity than individual pollutants, demonstrating true synergistic disruption. In vivo , SREPs metabolites disrupted sleep architecture, impaired the blood–brain barrier (BBB), and induced neurobehavioral deficits. In vitro studies using brain endothelial cells (BMVECs) revealed that SREPs directly increase permeability, suppress tight junctions, and activate a pro-inflammatory cascade involving NF-κB signaling, enhanced MMP9 activity, and prostaglandin E2 synthesis. Curcumin intervention effectively counteracted these effects, restoring BBB integrity, normalizing sleep patterns, and suppressing hub gene expression and neuroinflammation in vivo and in vitro by targeting the identified hub gene network. Our integrated computational-experimental strategy establishes a novel “pollutant-BBB-neuroimmune-sleep” axis, providing a mechanistic framework for assessing cumulative environmental risks and advancing targeted interventions.
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Applied Biological Chemistry
·
2026
·Vol. 69
·期 1
·5
·
IF 2.7
Lee Serim,Kim Moonsu,Shin Seong-Ah,Moon Sun Young,Choi Seyeon,Kim Minji,Lee Jun Hyuck,Youn Ui Joung,Lee Chang Sup
An allergy is an exaggerated immune response to an otherwise harmless substance. These reactions are triggered largely by mast cell activation and the subsequent release of inflammatory mediators. Although current allergy therapies effectively relieve symptoms, they are generally accompanied by side effects, highlighting the need for safer alternatives. In this study, we investigated the anti-allergic effect of ethyl-2-oxo-2H-chromene-3-carboxylate (EtCC), a coumarin derivative. Rat basophilic leukemia (RBL-2H3) cells and a passive cutaneous anaphylaxis (PCA) model were used for in vitro and in vivo evaluations, respectively. In RBL-2H3 cells sensitized with dinitrophenyl (DNP)-specific-immunoglobulin (Ig) E and stimulated with DNP-human serum albumin (HSA), EtCC inhibited histamine and beta-hexosaminidase release, and downregulated mRNA expression of interleukin (IL)-4, IL-13, and TNF-α. EtCC also suppressed phosphorylation of MAPK, AKT, and NF-kB. In vivo, EtCC attenuated ear edema and Evans blue extravasation in a PCA model. These findings demonstrate that EtCC effectively suppresses mast-cell-mediated allergic responses, suggesting its potential as a novel allergy treatment.
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BIOMACROMOLECULES
·
2026
·
IF 5.4
Jiao Sun,Yiqing Wang,Rongjing Zhou,Xian Zou,Qiqi Ge,Zheng Xing,Cheng Wang,Jianhao Wang
Conventional tumor starvation via embolization or glucose oxidase (GOx) is often hampered by poor specificity and enzyme instability. Herein, we developed a pH-responsive, amphiphilic GOx-conjugated polymer (LPHF-GOx) for synergistic cascade starvation therapy. Triggered by the acidic tumor microenvironment, LPHF-GOx undergoes rapid aggregation, achieving dual metabolic disruption through localized vascular embolization and GOx-mediated glucose depletion. LPHF-GOx demonstrated robust pH-dependent self-assembly while maintaining high catalytic activity. In vitro and in vivo evaluations confirmed that this dual-action system induces profound nutrient deprivation and oxidative stress, leading to significant tumor growth inhibition with negligible systemic toxicity. By integrating vessel occlusion with biochemical enzymatic interference, this study provides a potent and targeted platform for sustainable starvation therapy against malignant tumors.
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SEPARATION AND PURIFICATION TECHNOLOGY
·
2026
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IF 9.1
Yan Pan,Chuanming Tu,Xueyong Li,Luteng Gao,Wei Lan,Wenhai Zhang,Hong Meng
Compared with traditional polyamide membranes, polyimine membranes possess a more rigid structure and exhibit significantly enhanced swelling resistance in organic solvent nanofiltration, enabling highly selective separation. However, their intrinsic broad pore size distribution limits their application in high-precision separation scenarios. To address this issue, this study proposes a post-modification pore shrinkage strategy: first, a polyimine composite membrane is prepared via interfacial polymerization, followed by the in-situ polymerization of residual free p -phenylenediamine within the membrane initiated by ammonium persulfate, to construct an interpenetrating network composite membrane structure composed of porous polyimine and poly( p -phenylenediamine). Experimental results demonstrate that this method effectively improves the rejection performance of polyimine membranes toward small solute molecules. The optimized PPa-5@TpPa-2 composite membrane exhibits a methanol permeance of 4.1 L m −2 h −1 bar −1 , a molecular weight cut-off as low as 320 Da, along with excellent solvent resistance, operational stability.
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MATERIALS & DESIGN
·
2026
·
IF 8.2
Xiaotian Zhang,Qian Zhu,Ziqing Zhu,Peiran Chan,Zhiyuan Chen,Yongxin Huang,Fuqiang Chen,Zhe Yu,Juan Wang,Yantian Su
FSA-pretreated Huc-MSCs generate potent exosomes to promote BSCB repair via TJs. • VAP peptide targets FSA-Exos to SCI endothelium via GRP78 for precise repair. • VAP-Exos promote BSCB repair by regulating endothelial cell autophagy. Spinal cord injury (SCI) disrupts the blood-spinal cord barrier (BSCB), triggering secondary damage and permanent neurological deficits. Forsythiaside A is a natural bioactive compound isolated from Forsythia suspensa. It boasts robust anti-inflammatory and tissue-repairing capacities and can precondition stem cells to enhance the therapeutic potency of their secreted exosomes. To equip FSA-primed exosomes with precise targeting, we utilized SNTRVAP (VAP), a GRP78-specific peptide with the sequence SNTRVAP. Here, we constructed VAP-Exos by conjugating VAP onto FSA-preconditioned human umbilical cord mesenchymal stem cell exosomes, which effectively restore BSCB integrity. Binding GRP78 to target endothelial cells, VAP-Exos upregulates tight junction proteins (ZO-1, Occludin, Claudin5) and lowers BSCB permeability. Single-nucleus sequencing proves they stimulate endothelial proliferation, elevate Itga5, and activate autophagy pathways; elevated autophagic flux is validated by increased LC3-II/I ratio and P62 degradation. Meanwhile, VAP-Exos alleviate oxidative stress, shift microglia toward the anti-inflammatory M2 phenotype, and rebalance the spinal immune microenvironment. In vivo assays on SCI mice show smaller lesions, attenuated glial scarring and recovered motor function. Collectively, VAP-Exos safeguard BSCB integrity through endothelial autophagy modulation, representing a promising engineered exosome candidate for SCI therapy. Download: Download high-res image (184KB) Download: Download full-size image
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Advanced Science
·
2026
·
IF 14.1
Jiawei Wang,Yaozhi He,Yanjiao Wang,Jingjing Zhang,Qishun Liang,Mengxian Jia,Yumin Wu,Zongjie Yuan,Ziwei Fan,Yuxuan Li,Huihui Zhang,Qinjiao Fu,Ying Wang,Zhihui Huang,Honglin Teng
After spinal cord injury (SCI), the blood-spinal cord barrier (BSCB) is disrupted, and endothelial cells, a critical component of BSCB, undergo proliferation and remodeling to maintain barrier integrity. However, the molecular mechanisms underlying BSCB remodeling remain unclear after SCI. Here, we reveal that Yes-associated protein (YAP), a principal downstream effector of the Hippo signaling pathway, promotes endothelial proliferation and BSCB repair in mice after SCI. First, we found that YAP expression was significantly upregulated and activated in endothelial cells after SCI. Endothelial YAP knockout (YAP TEK-cre/ERT2 -CKO mice) impaired endothelial proliferation, endothelial-astrocyte end-feet reorganization, and tight junction (TJ) integrity, thereby aggravating BSCB disruption and impairing BSCB remodeling and motor functional recovery after SCI. Mechanistically, endothelial YAP-dependent BSCB repair was associated with angiopoietin-1 (ANGPT1) expression and PI3K/AKT pathway activation after SCI. Exogenous ANGPT1 treatment mitigated YAP deficiency-induced inhibition of endothelial proliferation and endothelial barrier disruption via PI3K/AKT signaling in vitro. Finally, activation of YAP signaling partially mitigated SCI-induced BSCB disruption, ultimately improving motor function recovery. Together, these results identify endothelial YAP signaling as a critical regulator of BSCB remodeling associated with ANGPT1/PI3K/AKT pathway and provide a potential therapeutic target for SCI.
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Advanced Healthcare Materials
·
2026
·
IF 11
Xi Lin,Jian Lin,Yezi Zhang,Xinyan Zhang,Xinghua Liu,Hongying Cao,Huan Shen,Jianming Liang,Zhenhua Dai,Siyuan Xu,Xingdong Lin
Acute lung injury (ALI) is a lethal respiratory disease. The inflammatory storm triggered by neutrophil extracellular traps (NETs) is the critical pathogenesis of pulmonary injury. But the effective clinical treatments remain limited for ALI. Hence, developing a pulmonary-targeting nano-drug is urgent in the clinic. Lonicera japonica -derived nanovesicles (LDNVs) was isolated and characterized. Distribution of LDNVs were enriched in the pulmonary neutrophils. LDNVs restored the body weight, physical activity and attenuated the pulmonary injury of LPS-induced ALI mice. The inflammatory cytokines and neutrophil-associated chemokines were decreased with LDNVs treatment. LDNVs also decreased pulmonary accumulation of neutrophils and NETs. The LC3B II was suppressed and p62 was enhanced by LDNVs treatment. Finally, LDNVs suppressed the translocation of LC3 in nuclear and lysosomal damage. But these therapeutic effects of LDNVs in ALI and NETs were both blocked by a neutrophils and NETs activator, phorbol myristate acetate (PMA). LDNVs attenuate LPS-induced ALI by inhibiting NETs formation. These effects may be associated with LDNVs suppressing the autophagic flux.
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International Journal of Biological Sciences
·
2026
·Vol. 22
·期 13
·7427
·
IF 11.7
Hong Xu,Hongyu Chen,Fengling He,Xinlan Li,Wanxin Li,Qingqing Yang,Tingting Zhang,Jin Liu,Xiaoke Shi,Shilin Chen,Defang Li,Jun Lu
Aberrant activation of macrophages and their amplification of inflammatory responses constitute the core pathological basis driving the progression of acute lung injury (ALI). Celastrol (CE), despite its potent anti-inflammatory activity, suffers from poor aqueous solubility and substantial systemic toxicity, which severely limit its clinical translation. Capitalizing on the metabolic signature of pro-inflammatory M1 macrophages, specifically their high expression of glucose transporter 1 (GLUT1), we designed a glucose-modified CE prodrug that self-assembled into carrier-free nanoparticles CG NPs. With markedly improved solubility and systemic stability, CG NPs rapidly and persistently accumulated in the inflammatory lungs of LPS-induced ALI mice facilitated by GLUT1-mediated targeting and uptake by M1 macrophages. Compared with free CE, CG NPs exhibited enhanced overall therapeutic efficacy while significantly reducing hepatorenal toxicity. Mechanistic studies revealed that by targeting Drp1, CG NPs disrupt Drp1-MiD51 interaction, thus inhibiting excessive mitochondrial fission and ROS accumulation, which blocks NF-κB-mediated inflammatory signaling and M1-driven cytokine release. Molecular docking suggested that glucose conjugation may confer CG with a superior ability to regulate mitochondrial homeostasis over CE, potentially driven by its unique U-shaped conformation that inserts into Drp1 and forms a denser hydrogen-bond network, which could contribute to enhanced binding affinity. In summary, this study proposes a nanoprodrug strategy that combines precise targeting with mitochondrial protection, offering a promising therapeutic avenue for inflammatory diseases such as ALI.
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Materials Today Bio
·
2025
·
IF 10.2
Yaozhi He,Siyuan Zou,Jiawei Wang,Wenbin Zhang,Sheng Lu,Mengxian Jia,Yumin Wu,Xiaowu Lin,Ziwei Fan,Qishun Liang,Yizhe Sheng,Qichuan Zhuge,Bi Chen,Minyu Zhu,Honglin Teng
Spinal cord injury (SCI) causes devastating neurological deficits, and cellular senescence critically contributes to the pathogenesis of various diseases. Notably, endothelial cells (ECs) senescence exerts a pivotal effect on the pathogenesis following SCI. In this study, we found that the number of senescent ECs increased by 18.87% ± 5.91%, and the disruption of the blood-spinal cord barrier (BSCB) was aggravated with an 18% increase in Evans Blue dye extravasation in diabetic mice with spinal cord injury (DM-SCI). To address this pathological process, a bioinspired nanotherapeutic platform utilizing milk-derived small extracellular vesicles with platelet membrane fusion (PM-sEVs) was developed for the targeted delivery of curcumin (Cur). In vitro , PM-sEVs-Cur effectively mitigated HG/IL-1β-induced HUVECs senescence by 54.19% ± 5.39% and increased expression of the tight junction protein ZO-1 by 4.33-fold. Mechanistically, Cur attenuated HUVECs senescence by activating the NRF2/HO-1 pathway. In vivo , platelet membrane modification enhanced the lesion targeting of sEVs. Treatment with PM-sEVs-Cur attenuated ECs senescence by 34.96% ± 6.59%, preserved BSCB integrity with a 17% reduction in Evans Blue dye extravasation, promoted axonal regeneration with a 6.36-fold increase in neurofilament expression, and improved motor function recovery with an increase of 2.4 ± 0.55 points in Basso Mouse Scale score in DM-SCI. This study highlights PM-sEVs-Cur as a promising therapeutic delivery platform for DM-SCI treatment.
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JOURNAL OF NANOBIOTECHNOLOGY
·
2025
·Vol. 23
·期 1
·1-26
·
IF 12.6
Jia Wenjing,Yue Huilan,Liu Liying,Wang Luya,Zhang Lin,Tao Jihong,Zhou Guoying,Wei Lixin,Dong Hongxin,Dhondrup Rinchen,Zhao Xiaohui
β-HgS as the main component of Tibetan medicine Zuotai (ZT) is widely used in the treatment of central nervous system diseases. Although the synergism of HgS has been clinically verified for more than 2000 years, its synergetic mechanism is still an unsolved mystery and a huge challenge. Notably, we clearly and intuitively demonstrate that Zuotai or β-HgS is auto-synthesized by organisms into spherical HgS nanoparticles with protein corona, with an overall particle size of 30–195 nm and a core of HgS NPs of 5–7 nm. Further research showed that HgS NPs facilitated the transport of Oxiracetam (ORT), Memantine Hydrochloride (MH) and Entinostat (MS-275) across the blood-brain barrier (BBB), especially the brain accumulation of MS-275 increased by more than three times. Meanwhile, HgS NPs enhanced the effect of MS-275 on spatial learning and memory ability of APP/PS1 mice. Further studies confirmed that HgS NPs increased the permeability of the blood-brain barrier (BBB) by regulating endocytosis (Upregulation of caveolin, clathrin, and dynamin, downregulation P-gp) thereby facilitate the transport of drugs across BBB with more than threefold higher brain accumulation and long-lasting efficiency enhancement (4 days). Our findings reveal that these in vivo-generated HgS NPs provide an efficient, convenient, and biocompatible drug delivery platform for crossing the BBB. Importantly, our findings offer new hopes and ideas for in-depth research on highly valuable and mysterious metal preparations in classic Chinese and Tibetan medicine. Graphical
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