bluuebunny/crossref_metadata_2025_split huggingface dataset:
Angstrom‐Scale Defect‐Free Crystalline Membrane for Sieving Small Organic Molecules
Authors: Liu Guozhen , Chen Cailing , Mo Binyu , Zhou Guangyuan , Li Jiahui , Zhang Yaxin , Liu Gongping , Han Yu , Jin Wanqin 
Published: December 2024

AbstractCrystalline membranes, represented by the metal‐organic framework (MOF) with well‐defined angstrom‐sized apertures, have shown great potential for molecular separation. Nevertheless, it remains a challenge to separate small molecules with very similar molecular size differences due to angstrom‐scale defects during membrane formation. Herein, a stepwise assembling strategy is reported for constructing MOF membranes with intrinsic angstrom‐sized lattice aperture lattice to separate organic azeotropic mixtures separation. The membrane is synthesized by redesigning the metal source, which reduces the coordination reaction rate to avoid cluster‐missing defects. Then, extra ligands are introduced to overcome the coordination steric hindrance to heal the linker‐missing defects. Ultralow‐dose transmission electron microscopy is used to realize a direct observation of the angstrom‐scale defects. For separating the challenging methanol‐containing ester or ether azeotropic mixtures with molecular size difference as small as <1 Å, the angstrom‐scale defect‐free MOF membrane exhibits an outstanding flux of ≈3700 g·m−2 h−1 and separation factor of ≈247–524, far beyond the upper‐bound of state‐of‐the‐arts membranes. This study offers a feasible strategy for precisely constructing angstrom‐confined spaces for diverse applications (e.g., separation, catalysis, and storage).
A Milk Extracellular Vesicle‐Based Nanoplatform Enhances Combination Therapy Against Multidrug‐Resistant Bacterial Infections
Authors: Qu Shaoqi , Yang Shuo , Xu Qingjun , Zhang Mengying , Gao Feng , Wu Yongning , Li Lin 
Published: December 2024

AbstractThe increasing occurrence of infections caused by multidrug‐resistant (MDR) bacteria drives the need for new antibacterial drugs. Due to the current lack of antibiotic discovery and development, new strategies to fight MDR bacteria are urgently needed. Efforts to develop new antibiotic adjuvants to increase the effectiveness of existing antibiotics and design delivery systems are essential to address this issue. Here, a bioinspired delivery system equipped with combination therapy and paracellular transport is shown to enhance the efficacy against bacterial infections by improving oral delivery. A screening platform is established using an in vitro‐induced high polymyxin‐resistant strain to acquire plumbagin, which enhances the efficacy of polymyxin. Functionalized milk extracellular vesicles (FMEVs) coloaded with polymyxin and plumbagin cleared 99% of the bacteria within 4 h. Mechanistic studies revealed that the drug combination damaged the membrane, disrupted energy metabolism, and accelerated bacterial death. Finally, FMEVs are efficiently transported transcellularly through the citric acid‐mediated reversible opening of the tight junctions and showed high efficacy against an MDR Escherichia coli‐associated peritonitis–sepsis model in mice. These findings provide a potential therapeutic strategy to improve the efficacy of combination therapy by enhancing oral delivery using a biomimetic delivery platform.
OTUD5 Protects Dopaminergic Neurons by Promoting the Degradation of α‐Synuclein in Parkinson's Disease Model
Authors: Song Xiaomeng , Liu Tengfei , Yu Lu , Ji Qiuran , Guo Xin , Zong Runzhe , Li Yiquan , Huang Gan , Xue Qidi , Fu Qingyi , Liu Bingyu , Zheng Yi , Chen Lin , Gao Chengjiang , Liu Huiqing 
Published: December 2024

AbstractDefective clearance and accumulation of α‐synuclein (α‐Syn) is the key pathogenic factor in Parkinson's disease (PD). Recent studies emphasize the importance of E3 ligases in regulating the degradation of α‐Syn. However, the molecular mechanisms by which deubiquitinases regulate α‐Syn degradation are scarcely studied. In this study, it is found that the protein levels of α‐Syn are negatively regulated by ovarian tumor protease deubiquitinase 5 (OTUD5) which protects dopaminergic (DA) neurons in the PD model. Mechanistically, OTUD5 promotes K63‐linked polyubiquitination of α‐Syn independent of its deubiquitinating enzyme activity and mediates its endolysosomal degradation by recruiting the E3 ligase neural precursor cell expressed developmentally downregulated 4 (NEDD4). Furthermore, OTUD5 conditional knockout in DA neurons results in more severe α‐Syn related pathology and dyskinesia after injection of α‐Syn preformed fibrils (PFF). Overall, the data unveil a novel mechanism to regulate the degradation of α‐Syn and provide a new therapeutic strategy to alleviate DA neurodegeneration.
Lactylation of Histone H3k18 and Egr1 Promotes Endothelial Glycocalyx Degradation in Sepsis‐Induced Acute Lung Injury
Authors: Lu Zongqing , Fang Pu , Li Shuai , Xia Dunling , Zhang Jingjing , Wu Xianghui , Pan Jingjing , Cai Haijian , Fu Lin , Sun Gengyun , You Qinghai 
Published: December 2024

AbstractCirculating lactate is a critical biomarker for sepsis‐induced acute lung injury (S‐ALI) and is strongly associated with poor prognosis. However, whether elevated lactate directly promotes S‐ALI and the specific mechanism involved remain unclear. Here, this work shows that lactate causes pulmonary endothelial glycocalyx degradation and worsens ALI during sepsis. Mechanistically, lactate increases the lactylation of K18 of histone H3, which is enriched at the promoter of EGR1 and promotes its transcription, leading to upregulation of heparanase in pulmonary microvascular endothelial cells. In addition, multiple lactylation sites are identified in EGR1, and lactylation is confirmed to occur mainly at K364. K364 lactylation of EGR1 facilitates its interaction with importin‐α, in turn promoting its nuclear localization. Importantly, this work identifies KAT2B as a novel lactyltransferase whose GNAT domain directly mediates the lactylation of EGR1 during S‐ALI. In vivo, suppression of lactate production or genetic knockout of EGR1 mitigated glycocalyx degradation and ALI and improved survival outcomes in mice with polymicrobial sepsis. Therefore, this study reveals that the crosstalk between metabolic reprogramming in endothelial cells and epigenetic modifications plays a critical role in the pathological processes of S‐ALI.
Neurotransmitter‐Mimicking Nanovesicles Facilitate Postoperative Glioblastoma Stem Cell‐Specific Treatment for Preventing Tumor Recurrence
Authors: Liang Fuming , You Qing , Yu Bin , Wang Chen , Yang Yanlian , Zhu Ling , He Zhaohui 
Published: December 2024

AbstractSurvival quality of glioblastoma (GBM) patients remains undesirable despite the aggressive multimodal treatment methods implemented, which are strongly associated with tumor recurrence after surgical resection. Self‐renewal and strong tumourigenic capacity of glioblastoma stem cells (GSCs) at the narrow margin of the incision are essential factors driving tumor secondary strikes. Currently, the challenges in treating postoperative residual GSCs are mainly due to the lack of materials for incision and GSCs targeting. In this study, a neurotransmitter‐mimicking nanovesicle (PMVS‐P) based on platelet membrane‐derived vesicle (PMV) with anti‐GSC drug salinomycin (SAL)‐loading and polydopamine (PDA)‐surface is synthesized. PMVS‐P exhibits surgical incision targeting ability and specifically identified GSCs with highly expressed D2 dopamine receptor (D2DR), a central nervous system neurotransmitter receptor, thus suppressing GBM recurrence. This neurotransmitter‐mimicking nanovesicle primed GSC‐specific tumoricidal treatment with broadened applications for preventing tumor recurrence.
Functional Monomers Equipped Microgel System for Managing Parkinson's Disease by Intervening Chemokine Axis‐mediated Nerve Cell Communications
Authors: Jiang Lin , Zhang Xu , Wang Shun , Zhang Jiangkuan , Chen Junyang , Lu Jiachuan , Yao Liting , Jin Weiwei , Li Nan , Li Qing 
Published: December 2024

AbstractThe complex pathology of Parkinson's disease (PD) requires comprehensive understanding and multi‐pronged interventions for communication between nerve cells. Despite new developments in nanotechnology in the treatment of PD, in‐depth exploration of their biological effects, in particular, the specific mechanisms of inflammation inhibition are lacking. Herein, using the stable cascade catalysis channel formed by polydopamine (PDA), imidazole groups, and Cu ions, a microgel system comprising functional monomers [superoxide dismutase (SOD) with double bonds, PDA, 2‐methacryloyloxy ethyl phosphorylcholine (MPC), and Cu ions] is proposed for managing PD. The microgel can be efficiently delivered to the brain aided by MPC, after which a multi‐level regulatory strategy targeting neurons and microglia can be initiated. The catalytic activity cascade elicited by SOD and Cu ions can regulate the anti‐inflammatory phenotypic transformation of microglia by relieving oxidative stress. Meanwhile, the dopamine (DA) released from PDA can facilitate DA storage and neurogenesis, inhibiting CX3CL1 release and the CX3CR1 receptor on microglia and further regulating the CX3CL1/CX3CR1‐NF‐κB‐NLRP3 signaling pathway in microglia to inhibit neuroinflammation. Therefore, the proposed microgel delivery system with functional monomers represents a promising therapeutic strategy for managing neuroinflammation and promoting neurogenesis in PD by intervening chemokine axis‐mediated communication between neurons and microglia.
Propagation of Orientation Across Lengthscales in Sheared Self‐Assembling Hierarchical Suspensions via Rheo‐PLI‐SAXS
Authors: Ghanbari Reza , Terry Ann , Wojno Sylwia , Bek Marko , Sekar Kesavan , Sonker Amit Kumar , Nygård Kim , Ghai Viney , Bianco Simona , Liebi Marianne , Matic Aleksandar , Westman Gunnar , Nypelö Tiina , Kádár Roland 
Published: December 2024

AbstractSimultaneous rheological, polarized light imaging, and small‐angle X‐ray scattering experiments (Rheo‐PLI‐SAXS) are developed, thereby providing unprecedented level of insight into the multiscale orientation of hierarchical systems in simple shear. Notably, it is observed that mesoscale alignment in the flow direction does not develop simultaneously across nano‐micro lengthscales in sheared suspensions of rod‐like chiral‐nematic (meso) phase forming cellulose nanocrystals. Rather, with increasing shear rate, orientation is observed first at mesoscale and then extends to the nanoscale, with influencing factors being the aggregation state of the hierarchy and concentration. In biphasic systems, where an isotropic phase co‐exists with self‐assembled liquid crystalline mesophase domains, the onset of mesodomain alignment towards the flow direction can occur at shear rates nearing one decade before a progressive increase in preferential orientation at nanoscale is detected. If physical confinement prevents the full formation of a cholesteric phase, mesoscale orientation occurs in shear rate ranges that correspond to de‐structuring at nanoscale. Interestingly, nano‐ and mesoscale orientations appear to converge only for biphasic suspensions with primary nanoparticles predominantly made up of individual crystallites and in a high‐aspect ratio nematic‐forming thin‐wall nanotube system. The nano‐micro orientation propagation is attributed to differences in the elongation and breakage of mesophase domains.
SPP1‐ITGα5/β1 Accelerates Calcification of Nucleus Pulposus Cells by Inhibiting Mitophagy via Ubiquitin‐Dependent PINK1/PARKIN Pathway Blockade
Authors: Gu Hanwen , Li Qi , Liu Zhenchuan , Li Yanlin , Liu Kaiwen , Kong Xiangzhen , Zhang Yuanqiang , Meng Qunbo , Song Kangle , Xie Qing , Gao Yuan , Cheng Lei 
Published: December 2024

AbstractLow back pain (LBP) caused by nucleus pulposus degeneration and calcification leads to great economic and social burden worldwide. Unexpectedly, no previous studies have demonstrated the association and the underlying mechanism between nucleus pulposus tissue degeneration and calcification formation. Secreted Phosphoprotein 1 (SPP1) exerts crucial functions in bone matrix mineralization and calcium deposition. Here, a novel function of SPP1 is reported, namely that it can aggravate nucleus pulposus cells (NPs) degeneration by negatively regulating extracellular matrix homeostasis. The degenerated NPs have a higher mineralization potential, which is achieved by SPP1. Mechanistically, SPP1 can accelerate the degeneration of nucleus pulposus cells by activating integrin α5β1 (ITGα5/β1), aggravating mitochondrial damage and inhibiting mitophagy. SPP1‐ITGα5/β1 axis inhibits mitophagy by PINK1/PARKIN pathway blockade. In conclusion, SPP1 activates ITGα5/β1 to inhibit mitophagy, accelerates NPs degeneration, and induces calcification, thereby leading to intervertebral disc degeneration (IVDD) and calcification, identifying the potentially unknown mechanism and relationship between IVDD and calcification. Important insights are provided into the role of SPP1 in nucleus pulposus calcification in IVDD by inducing nucleus pulposus cell senescence through inhibition of mitophagy and may help develop potential new strategies for IVDD treatment.
Hybrid Cell Membrane‐Engineered Nanocarrier for Triple‐Action Strategy to Address Pseudomonas aeruginosa Infection
Authors: Zhang Shunhao , Chen Tianyu , Lu Weitong , Lin Yunfeng , Zhou Mi , Cai Xiaoxiao 
Published: December 2024

AbstractBacterial infections resistant to antimicrobial treatments, particularly those caused by Pseudomonas aeruginosa (P. aeruginosa), frequently lead to elevated mortality rates. Tackling this resistance using therapeutic combinations with varied mechanisms has shown considerable promise. In this study, a bioinspired nanocarrier is successfully designed and engineered for targeted antibiotic delivery and toxin/bacteria clearance. This is achieved by encapsulating antibiotic‐loaded framework nucleic acids with hybrid cell membranes acquired from neutrophils and platelets. By coating the hybrid membrane outside the shell, nanocarriers are endowed with the function of neutrophil‐like chemotaxis and platelet‐like bacteria adhesion to achieve the first stage of inflammation targeting. Based on the specific binding of bacteria toxin to the hybrid membrane, the release of antibiotic‐loaded framework nucleic acids is triggered by toxin‐mediated membrane lysis to fulfill the second stage of toxin neutralization and bacteria killing. Meanwhile, the immunomodulation potential of framework nucleic acids enables nanocarriers to accomplish the third stage of reversing the immunosuppressive microenvironment. In mouse models of acute and chronic P. aeruginosa pneumonia, the nanocarriers can reduce bacterial burden at a low dosage and decrease mortality with negligible toxicity. In sum, these findings have illustrated the remarkable capability of nanocarriers in treating recalcitrant bacterial infections.
Expanding Cas12a Activity Control with an RNA G‐Quadruplex at the 5′ end of CRISPR RNA
Authors: Huang Wenjuan , Wang Jiaqi , Wang Cheng , Liu Yuanfang , Li Wentao , Chen Qiaozhen , Zhai Junqiu , Xiang Zhenyang , Liu Chaoxing 
Published: December 2024

AbstractPrecise control of Cas12a activity is essential for the improvement of the detection limit of clinical diagnostics and the minimization of errors. This study addresses the challenge of controlling Cas12a activity, especially in the context of nucleic acid detection where the inherent incompatibility between isothermal amplification and CRISPR reactions complicates accurate diagnostics. An RNA G‐quadruplex (RG4) structure at the 5′ end of crRNA is introduced to modulate Cas12a activity accurately without the need for chemical modifications. The results indicate that the presence of RG4 does not significantly impact Cas12a's cleavage activity but can be controlled by RG4 stabilizers, enabling the suppression and subsequent restoration of Cas12a activity with potential for precise activity control. Moreover, the use of RG4 is expanded by incorporating it into split crRNA, introducing RG4 directly at the 5′ end of the direct repeat (DR) region, enabling tailored activity regulation for different targets by matching with various Spacer regions. Additionally, a light‐controlled one‐pot method for activating Cas12a is developed, thereby enhancing the accuracy and sensitivity of clinical samples. This study showcases the pioneering use of RG4 in manipulating Cas12a activity, streamlining diagnostics, and paving the way for advances in clinical nucleic acid testing.
3D Printing of Porous Ceramics for Enhanced Thermal Insulation Properties
Authors: Lin He , Shen Qintao , Ma Ming , Ji Renquan , Guo Huijun , Qi Huan , Xing Wang , Tang Huiping 
Published: December 2024

AbstractPorous thermal insulating ceramics play a pivotal role in both industrial processes and daily life by offering effective insulation solutions that reduce energy consumption, enhance building comfort, and contribute to the sustainability of industrial production. This review offers a comprehensive examination of porous thermal insulating ceramics produced by 3D printing, providing an in‐depth analysis of various 3D printing techniques and materials used to produce porous ceramics, detailing the fabrication processes, advantages, and limitations of these methods. Recent advances in 3D printed porous thermal insulating ceramics are thoroughly examined, with a particular focus on pore structure design and optimization strategies for high‐performance thermal insulation. This review also addresses the challenges and barriers to widespread adoption while highlighting future research directions and emerging trends poised to drive innovation. By showcasing the transformative potential of 3D printing in revolutionizing traditional porous ceramics manufacturing methods and enhancing thermal insulation performance, this review underscores the critical role of 3D printed porous ceramics in advancing thermal insulation technology.
Nanoenzymes‐Integrated and Microenvironment Self‐Adaptive Hydrogel for the Healing of Burn Injury and Post‐Burn Depression
Authors: Zhao Weitao , Chen Xi , Han Ziwei , Xun Zengyu , Qi Yilin , Wang Heping , Chen Chang , Gong Zhongying , Xue Xue 
Published: December 2024

AbstractBurn injuries often cause prolonged oxidative stress and inflammatory pain due to an initial increase in inflammatory responses, consequently exacerbating depressive disorders and severely impairing patients’ quality of life. The primary function of traditional burn dressings is to prevent infection and facilitate tissue repair. However, these dressings are not intended for the inflammatory pain and depression that often occur during recovery. This study describes a self‐healing hydrogel H@EFCP, which is designed to alleviate inflammatory pain and post‐burn depression in burn injuries. This hydrogel is synthesized through the cross‐linking of carboxymethyl chitosan with borate ester chelates formed from epigallocatechin gallate and 4‐formylphenylboronic acid. The incorporated Prussian blue nanoparticles increase the ability of H@EFCP to regulate the inflammatory process. H@EFCP is effective in the treatment of skin burns by reducing oxidative stress and improving the microenvironment of peripheral inflammation in mice. This modulation consists of a reduction of central nervous system inflammation and the risk of post‐burn depression. Behavioral assays indicate that the hydrogel significantly reduces feelings of despair and anxiety after burns. Consequently, H@EFCP provides a dual‐effect solution for the care and recovery of burn patients, including both burn repair and the associated psychological effects.
Berberine Derivative B68 Promotes Tumor Immune Clearance by Dual‐Targeting BMI1 for Senescence Induction and CSN5 for PD‐L1 Degradation
Authors: Hu Hongmei , Wang Qun , Yu Dianping , Tao Xiaoyu , Guo Mengmeng , Tian Saisai , Zhang Qing , Xu Mengting , Geng Xiangxin , Zhang Hongwei , Xu Hanchi , Li Linyang , Xie Shize , Chen Kaixian , Zhu Weiliang , Li Xu‐Wen , Xu Hanchen , Li Bo , Zhang Weidong , Liu Sanhong 
Published: December 2024

AbstractPromoting tumor cell senescence arrests the cell cycle of tumor cells and activates the immune system to eliminate these senescent cells, thereby suppressing tumor growth. Nevertheless, PD‐L1 positive senescent tumor cells resist immune clearance and possess the ability to secret various cytokines and inflammatory factors that stimulate the growth of tumor cells. Consequently, drugs capable of both triggering senescence in tumor cells and concurrently diminishing the expression of PD‐L1 to counteract immune evasion are urgently needed. Here, a berberine derivative B68 is developed, which specifically induces tumor cell senescence by targeting BMI1. B68 also involves the degradation of PD‐L1 by targeting CSN5, thereby disrupting the immunosuppressive PD‐1/PD‐L1 interaction and enabling rapid clearance of senescent tumor cells. This approach simultaneously inhibits tumor progression and activates T cell immunity, as evidenced by the robust antitumor response following B68‐induced immunization of senescent cancer cells. Moreover, the synergistic effect of B68 with anti‐CTLA4 therapy further enhances antitumor immunity, and its ability to induce senescence in cancer cells triggers a strong protective response by dendritic and CD8+ T cells. These findings provide a scientific basis for developing a new tumor treatment strategy based on senescence induction and lay the foundation for further preclinical research.
Hyper‐Thick Electrodes for Lithium‐Ion Batteries Enabled by Micro‐Electric‐Field Process
Authors: Plateau Tazdik Patwary , Boyer Gracie , Park Jonghyun 
Published: December 2024

AbstractIncreasing electrode thickness is a key strategy to boost energy density in lithium‐ion batteries (LIBs), which is essential for electric vehicles and energy storage applications. However, thick electrodes face significant challenges, including poor ion transport, long diffusion paths, and mechanical instability, all of which degrade battery performance. To overcome these barriers, a novel micro‐electric‐field (μ‐EF) process is introduced that enhances particle alignment during fabrication with reduced distance between anode and cathode. This process produces hyper‐thick (≈700 µm) electrodes with low tortuosity and improved ion diffusion. The μ‐EF electrodes achieve high areal capacities (≈8 mAh cm−2), while maintaining power density and long cycle life. The electrodes show stable performance under high C‐rate cycling and retain structural integrity after 1000 cycles at 2 C. By offering a scalable solution to the challenges of thick electrode fabrication, the μ‐EF process represents a significant advancement for high‐capacity LIBs in electric vehicles and energy storage systems.