bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Combination of Aligned PDA‐Fe@PLCL Conduit with Aligned GelMA Hydrogel Promotes Peripheral Nerve Regeneration
Authors: Wang Penghui , You Jiongming , Liu Guang , Wang Qiming , Zhang Linjie , Lu Xinwu , Qin Jinbao , Dong Zhihui , Yi Bingcheng , Huang Qun 
Published: December 2024

AbstractBiomaterial‐assisted therapeutic strategies enable precise modulation to direct endogenous cellular responses and harness regenerative capabilities for nerve repair. However, achieving effective cellular engagement during nerve remodeling remains challenging. Herein, a novel composite nerve guidance conduit (NGC), the GelMA/PLys@PDA‐Fe@PLCL conduit is developed by combining aligned poly(l‐lactide‐co‐caprolactone) (PLCL) nanofibers modified with polydopamine (PDA), ferrous iron (Fe3⁺), and polylysine (PLys) with aligned methacrylate‐anhydride gelatin (GelMA) hydrogel nanofibers. PDA films exhibit strong adhesion and metal coordination properties, allowing Fe3⁺ irons to chelate with phenolic hydroxyl groups of dopamine derivatives, forming a metal‐phenolic network on PLCL. PLys molecules are then grafted onto PDA‐Fe3⁺ coating via Schiff base and Michael addition reactions. This multifunctional coating enhances surface roughness and zeta potential of PLCL nanofibers, imparts superhydrophilicity with anisotropic wetting behavior, and maintains wet tensile properties of substrates. In vitro studies show that the PLys@PDA‐Fe coating significantly promotes aligned distribution of Schwann cells, improves cell adhesion and differentiation, and demonstrates notable antioxidant and anti‐inflammatory properties. When implanted into nerve defects in rats, the multifunctional coating conduit combined with aligned GelMA hydrogel effectively accelerates axonal regeneration, remyelination, and angiogenesis, leading to enhanced motor function recovery. Overall, the GelMA/PLys@PDA‐Fe@PLCL conduit presents a promising strategy for advancing peripheral nerve repair.
Ru‐Ph Nanozyme‐Based Hydrogels for Tumor Chemodynamic Therapy by Enhancing Enzyme Catalytic Efficiency Through Multiple Pathways
Authors: Xiao Min , Zhang Yiqun , Xing Jianghao , Qiao Kun , Ba Yuling , Wang Xianwen , Gao Song , Yuan Zhennan 
Published: December 2024

AbstractThe discovery of nanozymes has opened new possibilities for tumor therapy. However, their reliance on the tumor microenvironment and limited catalytic efficiency hinder broader applications. In this study, ruthenium‐phenanthroline nanoparticles (Ru‐Phs) are synthesized by combining ruthenium with phenanthroline and subsequently coloaded with the proton pump inhibitor (PPI) pantoprazole into sodium alginate (ALG) to form a Ru‐Phs‐PPI‐ALG hydrogel for in situ tumor therapy. This hydrogel demonstrates excellent chemodynamic properties, forming a gel within tumor tissues and gradually releasing Ru‐Phs, which generates highly toxic reactive oxygen species (ROS) via peroxidase‐like (POD‐like) activity. The inclusion of PPI reduced the intracellular pH of tumor cells, accelerating the Fenton reaction and ROS accumulation. Additionally, the high photothermal conversion efficiency of Ru‐Phs‐PPI‐ALG enables heat generation under near‐infrared (NIR) irradiation, which not only disrupts tumor cell structures but also further enhances the POD‐like catalytic activity of Ru‐Phs. The hydrogel effectively killed 4T1 cells in vitro, and transcriptomic analysis confirms its potent chemodynamic efficacy. In vivo experiments demonstrate significant tumor ablation and excellent biocompatibility. This multipathway strategy to increase enzyme activity and improve chemodynamic effects provides a promising approach for advancing nanozyme applications in tumor therapy.
Nuclear Control of Mitochondrial Homeostasis and Venetoclax Efficacy in AML via COX4I1
Authors: Zhang Leisi , Zhang Honghai , Wang Ting‐Yu , Li Mingli , Chan Anthony K.N. , Kang Hyunjun , Foong Lai C. , Liu Qiao , Pokharel Sheela Pangeni , Mattson Nicole M. , Singh Priyanka , Elsayed Zeinab , Kuang Benjamin , Wang Xueer , Rosen Steven T. , Chen Jianjun , Yang Lu , Chou Tsui‐Fen , Su Rui , Chen Chun‐Wei David 
Published: December 2024

AbstractCell signaling pathways are enriched for biological processes crucial for cellular communication, response to external stimuli, and metabolism. Here, a cell signaling‐focused CRISPR screen identified cytochrome c oxidase subunit 4 isoform 1 (COX4I1) as a novel vulnerability in acute myeloid leukemia (AML). Depletion of COX4I1 hindered leukemia cell proliferation and impacted in vivo AML progression. Mechanistically, loss of COX4I1 induced mitochondrial stress and ferroptosis, disrupting mitochondrial ultrastructure and oxidative phosphorylation. CRISPR gene tiling scans, coupled with mitochondrial proteomics, dissected critical regions within COX4I1 essential for leukemia cell survival, providing detailed insights into the mitochondrial Complex IV assembly network. Furthermore, COX4I1 depletion or pharmacological inhibition of Complex IV (using chlorpromazine) synergized with venetoclax, providing a promising avenue for improved leukemia therapy. This study highlights COX4I1, a nuclear encoded mitochondrial protein, as a critical mitochondrial checkpoint, offering insights into its functional significance and potential clinical implications in AML.
Pathophysiology‐Directed Engineering of a Combination Nanoanalgesic for Neuropathic Pain
Authors: Wang Wenkai , Wang Yan , Huang Xinle , Wu Peng , Li Lanlan , Zhang Yang , Chen Yihui , Chen Zhiyu , Li Changqing , Zhou Yue , Zhang Jianxiang 
Published: December 2024

AbstractNeuropathic pain, one of the most refractory pain diseases, remains a formidable medical challenge. There is still an unmet demand for effective and safe therapies to address this condition. Herein, a rat model of nerve injury‐induced neuropathic pain is first established to explore its pathophysiological characteristics. Recognizing the role of neuroinflammation, an inflammation‐resolving amphiphilic conjugate PPT is designed and synthesized by simultaneously conjugating polyethylene glycol, phenylboronic acid pinacol ester, and Tempol onto a cyclic scaffold. PPT can self‐assemble into nanomicelles (termed PPTN). Following intravenous injection, PPTN preferentially accumulates in the injured nerve, ameliorates the neuroinflammatory milieu, and promotes nerve regeneration, thereby shortening neuropathic pain duration in rats. Moreover, the Ca2+ channel α2δ1 subunit is identified as a therapeutic target by RNA‐sequencing analysis of the injured nerve. Based on this target, a mimicking peptide (AD peptide) is screened as an analgesic. By packaging AD peptide into PPTN, a combination nano‐analgesic APTN is developed. Besides potentiated anti‐hyperalgesic effects due to site‐specific delivery and on‐demand release of AD peptide at target sites, APTN simultaneously inhibits neuroinflammation and promotes nerve regeneration by reprogramming macrophages via regulating MAPK/NF‐kB signaling pathways and NLRP3 inflammasome activation, thus affording synergistic efficacies in treating nerve injury‐induced neuropathic pain.
Biomimetic Vascularized iPSC‐Hepatocyte Spheroids for Liver Regeneration
Authors: Wang Jinglin , Huang Danqing , Ren Haozhen , Zhao Yuanjin 
Published: December 2024

AbstractHuman induced pluripotent stem cell derived hepatocytes (hiPSC‐heps) hold promising value for acute liver failure (ALF) treatment, while their therapeutic efficacy is usually limited by low cell bioactivity and untargeted in vivo accumulation. Here, inspired by vascularity supporting cellular architectures in the tissues and organs, a novel vascularized hiPSC‐heps spheroid based on microfluidic microcapsules is presented for liver repair via orthotopic transplantation. The microcapsules are comprised of aqueous cores that facilitate hiPSC‐hep aggregating into spheroids, and hybrid hydrogel shells of sodium alginate and hyaluronic acid methacryloyl (HAMA). By selectively degrading the alginate, the microcapsules are imparted with porous HAMA shells, which not only allowed human umbilical vein endothelial cells (HUVECs) to attach and form vascularized networks, but also facilitated communication between HUVECs and hiPSC‐heps. The specific spatial distributions of these cells in the vascularized hiPSC‐hep spheroids can provide nutrition support, promote the hepatic functions, and avoid immune cell attacks. Based on these features, it is illustrated that the vascularized hiPSC‐hep spheroids can repair the acute failing liver more effectively, indicating their practical values in clinical liver repair.
Halbach Array Induced Magnetic Field Alignment in Boron Nitride Nanocomposites
Authors: Ghai Viney , Mishra Ases Akas , Huang Enling , Ngaloy Roselle , Dash Saroj P. , Matic Aleksandar , Kádár Roland 
Published: December 2024

AbstractThermal conductivity enhancement in polymers is vital for advanced applications. This study introduces a novel method to align hexagonal boron nitride (hBN) nanosheets within polydimethylsiloxane (PDMS) matrices using a Halbach array to create a highly uniform magnetic field. This technique achieves significant improvements in thermal conductivity by effectively aligning hBN nanosheets. This research shows that hBN nanosheets, when aligned, can drastically enhance thermal conductivity in PDMS composites. Specifically, 10 wt.% vertically aligned hBN nanosheets in a rotating magnetic field achieve a thermal conductivity of 3.58 W mK−1, an impressive 1950% increase over pure PDMS. Additionally, the study explores the effects of orientation on dielectric properties, finding that the orientation of hBN nanosheets also improves electrical insulation and increases the dielectric constant while maintaining extremely low dielectric losses. For a vertically oriented sample, the dielectric constant reaches ≈14, and dielectric losses are as low as 0.0049 at 100 Hz, highlighting their potential for energy storage capacitors. This approach not only enhances thermal management but also maintains or improves electrical insulation, offering promising advances for polymer composites in various technological applications.
Metabolic Reprogramming of Macrophages by Biomimetic Melatonin‐Loaded Liposomes Effectively Attenuates Acute Gouty Arthritis in a Mouse Model
Authors: Ma Chuchu , Jiang Yuyu , Xiang Yan , Li Chang , Xie Xiaoying , Zhang Yunkai , You Yang , Xie Laozhi , Gong Jianing , Sun Yinzhe , Tong Shiqiang , Song Qingxiang , Chen Jun , Xiao Wenze 
Published: December 2024

AbstractGouty arthritis is characterized by an acute inflammatory response triggered by monosodium urate (MSU) crystals deposited in the joints and periarticular tissues. Current treatments bring little effects owing to serious side effects, necessitating the exploration of new and safer therapeutic options. Macrophages play a critical role in the initiation, progression, and resolution of acute gout, with the cellular profiles closely linked to their activation and polarization. This suggests that metabolic regulation can be of significance in managing gouty inflammation. In this study, it is demonstrated that melatonin, a natural hormone, modulates the metabolic remodeling of inflammatory macrophages by shifting their metabolism from glycolysis to oxidative phosphorylation, further altering functions of the pathogenic macrophage. To improve melatonin delivery to the inflamed sites, macrophage membrane‐coated melatonin‐loaded liposomes (MLT‐MLP) are developed. Benefiting from the inflammation‐homing characteristic of macrophage membrane, such engineered liposomes effectively target the inflamed site and demonstrate potent anti‐inflammatory effects, achieving an enhanced amelioration of acute gouty arthritis. In conclusion, this study proposes a novel strategy aimed at metabolic reprogramming of macrophages to attenuate the pathological injuries in acute gout, providing a potential therapeutic strategy of gout‐associated diseases, especially gouty arthritis.
SENP6‐Mediated deSUMOylation of Nrf2 Exacerbates Neuronal Oxidative Stress Following Cerebral Ischemia and Reperfusion Injury
Authors: Xia Qian , Que Mengxin , Zhan Gaofeng , Zhang Longqing , Zhang Xue , Zhao Yilin , Zhou Huijuan , Zheng Lu , Mao Meng , Li Xing 
Published: December 2024

AbstractOxidative stress is believed to play critical pathophysiological roles in ischemic brain injury, and the nuclear factor erythroid 2‐related factor 2 (Nrf2) signaling pathway is recognized as the most crucial endogenous antioxidant stress damage route. Some research have demonstrated that Nrf2 play critical roles in oxidative stress after ischemic stroke, but the underlying mechanism are not fully elucidated. This study reveals that Nrf2 is modified by SUMOylation and identifies Sentrin/SUMO‐specific protease 6 (SENP6) as a negative regulator of Nrf2 SUMOylation. Notably, SENP6 binds to and mediates the deSUMOylation of Nrf2, which in turn inhibits antioxidant response by enhancing ubiquitination‐dependent degradation of Nrf2, thereby reducing its transcriptional activity, inducing oxidative stress and aggravating neuronal apoptosis after ischemic stroke. Additionally, blocking the interaction between SENP6 and Nrf2 with a cell membrane‐permeable peptide (Tat‐Nrf2) preserves the SUMOylation of Nrf2, effectively attenuates oxidative stress, and rescues neurological functions in mice subjected to ischemic stroke. Furthermore, no toxicity is observed when high doses Tat‐Nrf2 are injected into nonischemic mice. Collectively, this study uncovers a previously unidentified mechanism whereby SUMOylation of Nrf2 regulates oxidative stress and strongly indicates that interventions targeting SENP6 or its interaction with Nrf2 may provide therapeutic benefits for ischemic stroke.
In Vivo Neurodynamics Mapping via High‐Speed Two‐Photon Fluorescence Lifetime Volumetric Projection Microscopy
Authors: Li Yanping , Xu Xiangcong , Zhang Chao , Sun Xuefeng , Zhou Sisi , Li Xuan , Guo Jiaqing , Hu Rui , Qu Junle , Liu Liwei 
Published: December 2024

AbstractMonitoring the morphological and biochemical information of neurons and glial cells at high temporal resolution in three‐dimensional (3D) volumes of in vivo is pivotal for understanding their structure and function, and quantifying the brain microenvironment. Conventional two‐photon fluorescence lifetime volumetric imaging speed faces the acquisition speed challenges of slow serial focal tomographic scanning, complex post‐processing procedures for lifetime images, and inherent trade‐offs among contrast, signal‐to‐noise ratio, and speed. This study presents a two‐photon fluorescence lifetime volumetric projection microscopy using an axially elongated Bessel focus and instant frequency‐domain fluorescence lifetime technique, and integrating with a convolutional network to enhance the imaging speed for in vivo neurodynamics mapping. The proposed method is validated by monitoring intracellular Ca2+ concentration throughout whole volume, tracking microglia movement and microenvironmental changes following thermal injury in the zebrafish brain, analyzing structural and functional variations of gap junctions in astrocyte networks, and measuring the Ca2+ concentration in neurons in mouse brains. This innovative methodology enables quantitative in vivo visualization of neurodynamics and the cellular processes and interactions in the brain.
Microphysiological System‐Generated Physiological Shear Forces Reduce TNF‐α‐Mediated Cartilage Damage in a 3D Model of Arthritis
Authors: Damerau Alexandra , Nguyen Duc Ha Do , Lubahn Christina , Renggli Kasper , Pfeiffenberger Moritz , Krönke Gerhard , Herrmann Matthias , Leeuw Thomas , Buttgereit Frank , Gaber Timo 
Published: December 2024

AbstractOsteoarthritis (OA) is a leading cause of disability, often resulting from overuse or injury, but inactivity can also contribute to cartilage degeneration. Conventional in vivo models struggle to isolate and study the specific effects of mechanical stress on cartilage health. To address this limitation, a microphysiological system (MPS) is established to examine how varying levels of shear stress impact cartilage homeostasis. The system allows for the cultivation of 3D chondrogenic microconstructs (CMCs) derived from human mesenchymal stromal cells, simulating both physiological and pathophysiological shear stress. Inflammation is induced via TNF‐α or activated peripheral blood mononuclear cells to model cartilage damage, enabling the evaluation of therapeutic interventions. The study demonstrates the development of an arthritis‐like phenotype and successful restoration of cartilage conditions through a JAK inhibitor under physiological shear stress. Physiological shear stress is identified as a critical factor in maintaining cartilage integrity. This MPS offers a standardized method to study shear stress, replicate cytokine‐induced cartilage damage, and simulate key features of arthritis, providing a valuable alternative to animal models.
Real‐Time Monitoring of Volatile Organic Compound‐Mediated Plant Intercommunication Using Surface‐Enhanced Raman Scattering Nanosensor
Authors: Choi Yun Sik , Son Won Ki , Kwak Hyuna , Park Jiyeun , Choi Sumin , Sim Daeseob , Kim Min Gyeong , Kimm Hyungsuk , Son Hokyoung , Jeong Dae Hong , Kwak Seon‐Yeong 
Published: December 2024

AbstractPlants communicate through volatile organic compounds (VOCs), but real‐time monitoring of VOCs for plant intercommunication is not practically possible yet. A nanobionic VOC sensor plant is created to study VOC‐mediated plant intercommunication by incorporating surface‐enhanced Raman scattering (SERS) nanosensors into a living plant. This sensor allows real‐time monitoring of VOC with a sensitivity down to the parts per trillion level. A quantitative VOC diffusion model in plants is proposed to describe this extreme sensitivity. The sensor plant is paired with a customized portable Raman device, demonstrating its ability to detect multiple VOCs on‐field. The sensor demonstrated that plants collect VOCs emitted from neighboring plants and hazardous volatile chemicals in the air at a certain distance. As a feasibility study, this nanobionic VOC sensor plant successfully monitored the early stages of fungal infection in strawberry fruits. This result suggests that interfacing nanosensors with plants offers an innovative approach to studying interplant communication and can be used as a compelling tool for monitoring VOC occurrence.
Interface‐Driven Catalytic Enhancements in Nitrogen‐Doped Carbon Immobilized CoNi2S4@ReS2/CC Heterostructures for Optimized Hydrogen and Oxygen Evolution in Alkaline Seawater‐Splitting
Authors: Lu Yanhui , Zhao Zhengqiang , Liu Xiaotong , Yu Xu , Li Wenqiang , Pei Chengang , Park Ho Seok , Kim Jung Kyu , Pang Huan 
Published: December 2024

AbstractThe rational design of multicomponent heterostructure is an effective strategy to enhance the catalytic activity of electrocatalysts for water and seawater electrolysis in alkaline conditions. Herein, MOF‐derived nitrogen‐doped carbon/nickel‐cobalt sulfides coupled vertically aligned Rhenium disulfide (ReS2) on carbon cloth (NC‐CoNi2S4@ReS2/CC) are constructed via hydrothermal and activation approaches. Experimental and theoretical analysis demonstrates that the strong interactions between multiple interfaces promote electron redistribution and facilitate water dissociation, thereby optimizing *H adsorption energy for the hydrogen evolution reaction (HER). Meanwhile, the adsorption energies of oxygenated intermediates are balanced to reduce the thermodynamic barrier for the oxygen evolution reaction (OER). Consequently, NC‐CoNi2S4@ReS2/CC shows smaller overpotentials of 87 and 253 mV for HER and OER at 10 mA cm−2, with a lower Tafel slope and Rct than control samples. Superior catalytic stability is confirmed by cyclic voltammetry (CV) for 1000 cycles and CA test for 56 h. Furthermore, NC‐CoNi2S4@ReS2/CC presents exceptional electrocatalytic activity in both alkaline water/seawater electrolytes. Stability assessments reveal that NC‐CoNi2S4@ReS2/CC maintains a highly catalytic activity in both water and seawater, owing to the corrosion‐resistant properties of the sulfur species at the interface. These findings highlight the importance of designing heterostructure electrocatalysts for clean hydrogen production.
FGF19‐Activated Hepatic Stellate Cells Release ANGPTL4 that Promotes Colorectal Cancer Liver Metastasis
Authors: Fan Xueying , Li Baoting , Zhang Fan , Liu Meng , Kwan Hiu‐Yee , Liu Zhongqiu , Su Tao 
Published: December 2024

AbstractLiver and lung are the most common metastatic sites in colorectal cancer (CRC), where the tumor microenvironment (TME) plays a crucial role in the progression and metastasis of CRC. Understanding the interactions between various types of cells in the TME can suggest innovative therapeutic strategies. Using single‐cell RNA sequencing (scRNA‐Seq) and clinical samples, fibroblast growth factor‐19 (FGF19, rodent FGF15) is found to mediate a significant interaction between CRC cells and cancer‐associated fibroblasts (CAFs), activating the hepatic stellate cells (HSCs)‐to‐CAFs differentiation. In various CRC metastatic mouse models, it is shown that FGF15 has a more pronounced effect on liver metastasis compared to pulmonary metastasis. More importantly, the differentially expressed genes (DEGs) are also identified from the RNA‐Seq dataset upon the activation of HSCs by FGF19 and compared the DEGs in matched primary and metastatic mRNA samples from patients with CRC liver metastasis (CRCLM), it is found that the ANGPTL4 gene is significantly associated with HSCs activation. Different mouse models also demonstrated the impact of the FGF19/ANGPTL4 axis on the severity of CRCLM. Importantly, disruption of this axis significantly inhibits CRCLM in vivo. This study is among the first to demonstrate the impact of the FGF19/ANGPTL4 axis on CRCLM, offering a novel therapeutic strategy.
Triple‐Combination Therapy with a Multifunctional Yolk–Shell Nanozyme Au@CeO2 Loaded with Dimethyl Fumarate for Periodontitis
Authors: Li Tiancheng , Shu Mengmeng , Zhu Cheng , Liu Qicheng , Li Yixin , Wang Ruike , Chen Lihan , Shi Wenxiao , Sun Zhaoxuan , Hou Zhiyao , Fang Bing , Xia Lunguo 
Published: December 2024

AbstractPeriodontitis, a chronic inflammatory disease, is the leading cause of tooth loss in adults and is one of the most prevalent and complex oral conditions. Oxidative stress induced by the excessive generation of reactive oxygen species (ROS) leads to periodontitis, which is closely associated with pathological processes, including mitochondrial dysfunction of periodontal cells and local immune dysregulation. However, current treatment modalities that target single pathological processes have limited long‐term therapeutic effects. Herein, a multifunctional Yolk–Shell nanozyme, Au@CeO2‐dimethyl fumarate (DMF), which comprehensively addresses the oxidative stress‐induced pathophysiological processes of periodontitis through antioxidant activity, mitochondrial maintenance, and immune modulation mechanisms, is described. For material design logic, functionally complementary Au and CeO2 formed an excellent photothermally regulated high‐efficiency nanozyme, which also provided an ideal drug carrier for DMF. As for the therapeutic logic, Au@CeO2‐DMF restores mitochondrial dysfunction and immune dysregulation, which also contributes to endogenous ROS elimination, thereby achieving long‐term stable therapeutic effects. In a rat model, local Au@CeO2‐DMF photothermal therapy effectively alleviated ROS‐induced tissue damage and restored periodontal homeostasis. Altogether, this study presents a novel antioxidant nanozyme for managing alveolar bone loss under prolonged oxidative stress and demonstrates the importance of comprehensive intervention in key pathological processes in periodontitis treatment design.