bluuebunny/crossref_metadata_2025_split huggingface dataset:
Osteomimix: A Multidimensional Biomimetic Cascade Strategy for Bone Defect Repair
Authors: Wu Xiaoyi , Yang Hongye , Liu Gufeng , Sun Wei , Li Jiyun , Zhao Yaning , Gao Xin , Liu Xuzheng , Song Fangfang , Wang Shilei , Lu Ziyang , Chen Chaoji , Huang Cui 
Published: February 2025

AbstractDespite advancements in biomimetic mineralization techniques, the repair of large‐scale bone defects remains a significant challenge. Inspired by the bone formation process, a multidimensional biomimetic cascade strategy is developed by replicating the biomineralization cascade, emulating the hierarchical structure of bone, and biomimicking its biological functions for efficient bone regeneration. This strategy involves the photocrosslinking of sodium methacrylate carboxymethyl cellulose‐stabilized amorphous magnesium‐calcium phosphate with methacrylate‐modified type I collagen to create a self‐mineralizing hydrogel. The hydrogel is then integrated with either naturally derived or synthetic oriented bulk scaffolds. The resulting composite, named Osteomimix, provides excellent mechanical support and can be customized for irregular bone defects using CAD/CAM technology. Through in vitro and in vivo studies, this work finds that Osteomimix exhibits spontaneous in situ biomimetic mineralization in a cell‐free environment, while modulating immune responses and promoting vascularized bone formation in a cell‐dependent manner. Built on bone‐specific insights, this strategy achieves biomimicry across temporal, spatial, and functional dimensions, facilitating the seamless integration of artificial constructs with the natural tissue repair dynamics.
Chiral Inorganic Nanomaterial‐Based Diagnosis and Treatments for Neurodegenerative Diseases
Authors: Dong Jingqi , Xu Liguang , Qu Aihua , Hao Changlong , Sun Maozhong , Xu Chuanlai , Hu Shudong , Kuang Hua 
Published: February 2025

AbstractChiral nanomaterials are widely investigated over recent decades due to their biocompatibility and unique chiral effects. These key properties have significantly promoted the rapid development of chiral nanomaterials in bioengineering and medicine. In this review, the basic principles of constructing chiral nanomaterials along with the latest progress in research are comprehensively summarized. Then, the application of chiral nanomaterials for the diagnosis of neurodegenerative diseases (NDDs) is systematically described. In addition, the significant potential and broad prospects of chiral nanomaterials in the treatment of NDDs are highlighted from several aspects, including the disaggregation of neurofibrils, the scavenging of reactive oxygen species, regulation of the microbial–gut–brain axis, the elimination of senescent cells, and the promotion of directed differentiation in neural stem cells. Finally, a perspective of the challenges and future development of chiral nanomaterials for the treatment of NDDs is provided.
“Pumping” Trace Cu Impurity out of Zn Foil for Sustainable Aqueous Battery Interface
Authors: Zhong Rui , Wang Shengbo , He Kun , Wang Wei , Mo Guixing , Ma Weidong , He Xiaobin , Liang Wenhao , Li Jun , Jin Huile , Ju Zhijin , Wang Yao , Wang Shun , Yuan Yifei 
Published: February 2025

AbstractDendritic zinc (Zn) electrodeposition presents a significant obstacle to the large‐scale development of rechargeable zinc‐ion batteries. To mitigate this challenge, various interfacial strategies have been employed. However, these approaches often involve the incorporation of foreign materials onto Zn anode surface, resulting in increased material costs and processing complexities, not to mention the compromised interface endurability due to structural and compositional heterogeneity. Realizing that Cu atoms typically exist as trace impurities in commercial Zn, a novel approach is demonstrated that leverages these Cu impurities to create a Cu‐rich surface for effective modulation of Zn electrodeposition. By simply heating commercially available Zn foil with a naturally oxidized surface, not only the internal Cu atoms are thermally activated to become diffusible, their diffusion is also navigated toward the surface via oxygen attraction. The resulting Cu‐rich surface effectively regulates Zn electrodeposition, comparable to conventional interfacial strategies, yet exhibits superior cycling durability. 3D in situ microscopy confirms that this Cu‐rich surface enables dendrite‐free, compact, and (101)‐oriented Zn electrodeposition, contrasting with the traditional (002)‐oriented dendrite‐suppression mechanism. By transforming trace Cu impurity within Zn foil into a Cu‐rich surface, this work demonstrates a straightforward, cost‐effective and efficient method for controlling Zn electrodeposition.
Effective and Practical Stereoselective Synthesis of Nutlins Precursors by Immobilization of Privileged Chiral Mono‐Amidine Catalyst
Authors: Toldo Sofia , Poletti Lorenzo , Di Carmine Graziano , Bortolini Olga , De Risi Carmela , Felletti Simona , Compagnin Greta , Massi Alessandro , Ragno Daniele 
Published: February 2025

AbstractA strategy for the immobilization of Johnston's Mono(AMidine) catalyst (MAM) onto polystyrene, silica and hybrid silica‐polystyrene nanoparticles is presented. The catalyst activity was evaluated in the stereoselective aza‐Henry reaction leading to the pivotal β‐amino nitroalkane precursors of the anti‐cancer agents Nutlins (with Nutlin‐3a as the most active drug). The effect of the support and the linker on the catalytic performance was investigated, observing an interesting match/mismatch effect when using a chiral linker. The polystyrene‐supported 3‐pyrrolidinol‐linked PS‐(S)‐Pyr‐MAM organocatalyst showed the best activity among the tested catalysts, behaving very similarly to the homogeneous counterpart in the synthesis of a library of Nutlins precursors: yield up to 95%, ee up to 99%, and dr up to >99:1. The catalyst recyclability was also assessed through simple filtration, yielding a satisfactory 93% ee after 5 cycles, showing only a moderate decrease in conversion efficiency (ca. 5% after each cycle), which resulted in an accumulated turnover number (TON) of 69.7.
Effectiveness and Safety of Oral Azvudine for Elderly Hospitalized Patients With COVID‐19: A Multicenter, Retrospective, Real‐World Study
Authors: Sun Ranran , Wang Haiyu , Sun Junyi , Yang Mengzhao , Zhang Shixi , Hu Xinjun , Yu Bo , Song Zhan , Han Na , Luo Hong , Cheng Ming , Li Guangming , Li Guotao , Yuan Yiqiang , Liang Lili , Zhang Yanyang , Zhang Donghua , Li Silin , Kan Quancheng , Liang Hongxia , Ren Zhigang 
Published: February 2025

AbstractAzvudine is recommended as a priority treatment for patients with Coronavirus Disease 2019 (COVID‐19) during Omicron wave in China, but its efficacy and safety in elderly patients is unknown. In this multicenter, retrospective study, we identified 19763 elderly patients (aged over 60 years) with COVID‐19 from nine hospitals in Henan Province, China. The primary outcome is all‐cause death and the secondary outcome is composite disease progression. After propensity score matching, 4109 Azvudine recipients and 4109 matched controls is included, with average age of 75.15 years. Kaplan–Meier analysis reveales a notably survival and progression‐free benefit in Azvudine treatment. The Cox analysis shows that compared with controls, Azvudine recipients have a 33% lower risk of all‐cause death (95% confidence Interval (CI): 0.580–0.772, p < 0.001), but have no significant difference in composite disease progression (hazard ratio: 0.93, 95% CI: 0.833‐1.046, p = 0.234). Subgroup analysis suggested Azvudine have a stronger protective effect in patients concomitant with antibiotics. Three sensitive analyses confirm the robustness of the findings. The safety of Azvudine in elderly patients is acceptable. These findings indicate that Azvudine therapy can reduce the rate of all‐cause death in hospitalized elderly patients with COVID‐19, and without obvious adverse events.
The FBXW7‐RPAP2 Axis Controls the Growth of Hepatocellular Carcinoma Cells and Determines the Fate of Liver Cell Differentiation
Authors: Cui Danrui , Shao Shengpeng , Qu Ruirui , Chen Xiaoyu , Jiang Shanghong , Wang Linchen , Gong Longyuan , Li Tianqi , Zhai Danyi , Song Wenfeng , Song Penghong , Sun Yi , Liang Tingbo , Xiong Xiufang , Zhao Yongchao 
Published: February 2025

AbstractRNA polymerase II‐associated protein 2 (RPAP2) plays a critical role in transcriptional regulation. However, little is known about whether and how RPAP2 regulates hepatocellular carcinoma (HCC) cell growth, and how the RPAP2 stability is precisely maintained. Here it is reported that high RPAP2 levels in HCC tissues correlate with poor patient survival. RPAP2 depletion suppresses the growth and survival of HCC cells. F‐box and WD repeat domain‐containing 7 (FBXW7) targets RPAP2 for polyubiquitylation and degradation after RPAP2 being pre‐phosphorylated at Ser562 and Thr565 by p38 and GSK3, respectively. HSP90 inhibition significantly promotes RPAP2 degradation by CRL5FBXW7 ligase, whereas USP7 deubiquitylates and stabilizes RPAP2. FBXW7 knockdown promotes HCC cell growth via RPAP2 accumulation in vitro and in vivo. In mice, the hepatic‐specific deletion of Fbxw7 leads to hepatic cystogenesis with consequential accumulation of RPAP2. Simultaneous deletion of Rpap2 completely reverses the hepatic cystogenesis, indicating a causal role of RPAP2. Taken together, this study demonstrates that the RPAP2 stability is negatively regulated by FBXW7, but positively regulated by HSP90 and USP7. The FBXW7‐RPAP2 axis regulates HCC cell growth and modulates the fate of liver cell differentiation. These findings provide proof‐of‐concept evidence that oncogenic RPAP2 could be a promising therapeutic target for HCC.
High‐Speed Embedded Ink Writing of Anatomic‐Size Organ Constructs
Authors: Hua Weijian , Zhang Cheng , Cui Haoran , Mitchell Kellen , Hensley Dale K. , Chen Jihua , Do Changwoo , Raymond Lily , Coulter Ryan , Bandala Erick , Rubbi Fazlay , Chai Guangrui , Zhang Zhengyi , Liao Yiliang , Zhao Danyang , Wang Yan , Gaharwar Akhilesh K. , Jin Yifei 
Published: February 2025

AbstractEmbedded ink writing (EIW) is an emerging 3D printing technique that fabricates complex 3D structures from various biomaterial inks but is limited to a printing speed of ∼10 mm s−1 due to suboptimal rheological properties of particulate‐dominated yield‐stress fluids when used as liquid baths. In this work, a particle‐hydrogel interactive system to design advanced baths with enhanced yield stress and extended thixotropic response time for realizing high‐speed EIW is developed. In this system, the interactions between particle additive and three representative polymeric hydrogels enable the resulting nanocomposites to demonstrate different rheological behaviors. Accordingly, the interaction models for the nanocomposites are established, which are subsequently validated by macroscale rheological measurements and advanced microstructure characterization techniques. Filament formation mechanisms in the particle‐hydrogel interactive baths are comprehensively investigated at high printing speeds. To demonstrate the effectiveness of the proposed high‐speed EIW method, an anatomic‐size human kidney construct is successfully printed at 110 mm s−1, which only takes ∼4 h. This work breaks the printing speed barrier in current EIW and propels the maximum printing speed by at least 10 times, providing an efficient and promising solution for organ reconstruction in the future.
Artificial Intelligence‐Based Approaches for AAV Vector Engineering
Authors: Tan Fangzhi , Dong Yue , Qi Jieyu , Yu Wenwu , Chai Renjie 
Published: February 2025

AbstractAdeno‐associated virus (AAV) has emerged as a leading vector for gene therapy due to its broad host range, low pathogenicity, and ability to facilitate long‐term gene expression. However, AAV vectors face limitations, including immunogenicity and insufficient targeting specificity. To enhance the efficacy of gene therapy, researchers have been modifying the AAV vector using various methods. Traditional experimental approaches for optimizing AAV vector are often time‐consuming, resource‐intensive, and difficult to replicate. The advancement of artificial intelligence (AI), particularly machine learning, offers significant potential to accelerate capsid optimization while reducing development time and manufacturing costs. This review compares traditional and AI‐based methods of AAV vector engineering and highlights recent research in AAV engineering using AI algorithms.
Optogenetically Activatable MLKL as a Standalone Functional Module for Necroptosis and Therapeutic Applications in Antitumoral Immunity
Authors: Jeong Da‐Hye , Kim Seokhwi , Park Han‐Hee , Woo Kyoung‐Jin , Choi Jae‐Il , Choi Minji , Shin Jisoo , Park So Hyun , Seon Myung‐Wook , Lee Dakeun , Cha Jong‐Ho , Kim You‐Sun 
Published: February 2025

AbstractNecroptosis plays a crucial role in the progression of various diseases and has gained substantial attention for its potential to activate antitumor immunity. However, the complex signaling networks that regulate necroptosis have made it challenging to fully understand its mechanisms and translate this knowledge into therapeutic applications. To address these challenges, an optogenetically activatable necroptosis system is developed that allows for precise spatiotemporal control of key necroptosis regulators, bypassing complex upstream signaling processes. The system, specifically featuring optoMLKL, demonstrates that it can rapidly assemble into functional higher‐order “hotspots” within cellular membrane compartments, independent of RIPK3‐mediated phosphorylation. Moreover, the functional module of optoMLKL significantly enhances innate immune responses by promoting the release of iDAMPs and cDAMPs, which are critical for initiating antitumor immunity. Furthermore, optoMLKL exhibits antitumor effects when activated in patient‐derived pancreatic cancer organoids, highlighting its potential for clinical application. These findings will pave the way for innovative cancer therapies by leveraging optogenetic approaches to precisely control and enhance necroptosis.
Customization of Ethylene Glycol (EG)‐Induced BmoR‐Based Biosensor for the Directed Evolution of PET Degrading Enzymes
Authors: Li Min , Chen Zhenya , Zhang Wuyuan , Wu Tong , Qi Qingsheng , Huo Yi‐Xin 
Published: February 2025

AbstractThe immense volume of plastic waste poses continuous threats to the ecosystem and human health. Despite substantial efforts to enhance the catalytic activity, robustness, expression, and tolerance of plastic‐degrading enzymes, the lack of high‐throughput screening (HTS) tools hinders efficient enzyme engineering for industrial applications. Herein, we develop a novel fluorescence‐based HTS tool for evolving polyethylene terephthalate (PET) degrading enzymes by constructing an engineered BmoR‐based biosensor targeting the PET breakdown product, ethylene glycol (EG). The EG‐responsive biosensors, with notably enhanced dynamic range and operation range, are customized by fluorescence‐activated cell sorting (FACS)‐assisted transcription factor engineering. The ingeniously designed SUMO‐MHETase‐FastPETase (SMF) chimera successfully addresses the functional soluble expression of MHETase in Escherichia coli and mitigates the inhibitory effect of mono‐(2‐hydroxyethyl) terephthalic acid (MHET) intermediate commonly observed with PETase alone. The obtained SMM3F mutant demonstrates 1.59‐fold higher terephthalic acid (TPA) production, with a 1.18‐fold decrease in Km, a 1.29‐fold increase in Vmax, and a 1.52‐fold increase in kcat/Km, indicating stronger affinity and catalytic activity toward MHET. Furthermore, the SMM3F crude extract depolymerizes 5 g L−1 bis‐(2‐hydroxyethyl) terephthalic acid (BHET) into TPA completely at 37 °C within 10 h, which is then directedly converted into value‐added protocatechuic acid (PCA) (997.16 mg L−1) and gallic acid (GA) (411.69 mg L−1) at 30 °C, establishing an eco‐friendly ‘PET‐BHET‐MHET‐TPA‐PCA‐GA’ upcycling route. This study provides a valuable HTS tool for screening large‐scale PET and MHET hydrolases candidates or metagenomic libraries, and propels the complete biodegradation and upcycling of PET waste.
High‐Impulse, Modular, 3D‐Printed CubeSat Electrospray Thrusters Throttleable via Pressure and Voltage Control
Authors: Kim Hyeonseok , Velásquez‐García Luis Fernando 
Published: February 2025

AbstractThis study reports the proof‐of‐concept demonstration of novel, additively manufactured, droplet‐emitting electrospray emitter arrays for CubeSat thruster applications. The modular thruster design incorporates multiscale features by employing two different vat photopolymerization technologies, i.e., digital light processing for defining mesoscale features, and two‐photon polymerization for creating microscale features. The thruster design includes optimized, 50 µm‐diameter microfluidic channels to attain uniform emitter array operation. Devices with up to 8 modules of 4 emitters were tested in a vacuum to assess their performance. Stable and uniform electrospray emission was achieved across all emitters, with a near 100% transmission across the extractor. Both pressure (flow rate) and voltage modulation are investigated as methods for controlling the emitted current and, by extension, the thrust generated by the devices. The per‐emitter current followed a well‐known square root relationship with flow rate; in addition, a linear relationship between per‐emitter current and extractor voltage is observed. Compared to pressure control, modulating thrust via voltage control simplifies system design, eliminating the need for complex valves and enabling a wider throttle range. Estimated thrust and specific impulse are comparable to, or better than reported droplet‐emitting electrospray thrusters. These findings demonstrate the potential of additive manufacturing to implement electrospray propulsion hardware.
One‐Pot Construction of NHS‐Activated Magnetic Particles for Chemoselective Capture of Carboxyl Metabolites
Authors: Liu Shuai , Yu Meng , Luo Xin‐Yao , Liu Jie , Zou Zhong‐Mei 
Published: February 2025

AbstractChemoselective probes immobilize on magnetic materials show great promise in simplifying sample handling and enhancing detection sensitivity. However, their complicated preparation and associated expense limit broader application. In this study, novel magnetic particles with abundant N‐hydroxysuccinimide (NHS) esters on the surface are conveniently synthesized using a one‐pot method without carbodiimide activation carboxylate molecules. Subsequently, multifunctional probes are synthesized by immobilizing high‐density chemical probes on the surface of the magnetic materials through a postsynthetic modification strategy. This versatile probe facilitates the rapid capture of carboxylated compounds from complex matrices, with the labeled metabolites release from the magnetic materials subsequently analyzed using ultra‐high performance liquid chromatography‐mass spectrometry (UHPLC‐MS). The advantages of this innovative chemical biological tool include the simplicity and low cost of the synthesis, as well as the capability to analyze polar and volatile carboxylated metabolites via LC‐MS. This new strategy is successfully applied to analyze short‐chain fatty acids (SCFAs) in rat cecal contents, demonstrating the reliability of the analytical method. This study presents a cost‐effective and easy‐to‐implement approach for preparing NHS‐activated magnetic particles and offers a versatile probe with chemoselective extraction and labeling capabilities, providing a practical tool for analyzing SCFAs in the gut.
Thermoplastic Elastomer‐Reinforced Hydrogels with Excellent Mechanical Properties, Swelling Resistance, and Biocompatibility
Authors: Liu Zhanqi , Zhang Hechuan , Zhou Ruigang , Gao Haiyang , Wu Yongchuan , Wang Yuqing , Wu Haidi , Guan Cheng , Wang Ling , Tang Longcheng , Song Pingan , Xue Huaiguo , Gao Jiefeng 
Published: February 2025

AbstractStrong and tough hydrogels are promising candidates for artificial soft tissues, yet significant challenges remain in developing biocompatible, anti‐swelling hydrogels that simultaneously exhibit high strength, fracture strain, toughness, and fatigue resistance. Herein, thermoplastic elastomer‐reinforced polyvinyl alcohol (PVA) hydrogels are prepared through a synergistic combination of phase separation, wet‐annealing, and quenching. This approach markedly enhances the crystallinity of the hydrogels and the interfacial interaction between PVA and thermoplastic polyurethane (TPU). This strategy results in the simultaneous improvement of the mechanical properties of the hydrogels, achieving a tensile strength of 11.19 ± 0.80 MPa, toughness of 62.67 ± 10.66 MJ m−3, fracture strain of 1030 ± 106%, and fatigue threshold of 1377.83 ± 62.78 J m−2. Furthermore, the composite hydrogels demonstrate excellent swelling resistance, biocompatibility, and cytocompatibility. This study presents a novel approach for fabricating strong, tough, stretchable, biocompatible, and fatigue‐ and swelling‐resistant hydrogels with promising applications in soft tissues, flexible electronics, and load‐bearing biomaterials.
Structure‐Guided Engineering of a Versatile Urethanase Improves Its Polyurethane Depolymerization Activity
Authors: Li Zhishuai , Han Xu , Cong Lin , Singh Parinita , Paiva Pedro , Branson Yannick , Li Wenshuo , Chen Yangyang , Jaradat Da'san M. M. , Lennartz Frank , Bayer Thomas , Schmidt Louis , Garscha Ulrike , You Song , Fernandes Pedro Alexandrino , Ramos Maria João , Bornscheuer Uwe T. , Weber Gert , Wei Ren , Liu Weidong 
Published: February 2025

AbstractPolyurethane (PUR), the fifth most prevalent synthetic polymer, substantially contributes to the global plastic waste problem. Biotechnology‐based recycling methods have recently emerged as innovative solutions to plastic waste disposal and sparked interest among scientific communities and industrial stakeholders in discovering and designing highly active plastic‐degrading enzymes. Here, the ligand‐free crystal structure of UMG‐SP2, a metagenome‐derived urethanase with depolymerization activities, at 2.59 Å resolution, as well as its (co‐)structures bound to a suicide hydrolase inhibitor and a short‐chain carbamate substrate at 2.16 and 2.40 Å resolutions, respectively, is reported. Structural analysis and molecular dynamics simulations reveal that the flexible loop L3 consisting of residues 219–226 is crucial for regulating the hydrolytic activity of UMG‐SP2. The semi‐rational redesign of UMG‐SP2 reveals superior variants, A141G and Q399A, exhibiting over 30.7‐ and 7.4‐fold increased activities on polyester‐PUR and a methylene diamine derivative of PUR, respectively, compared to the wild‐type enzyme. These findings advance the understanding of the structure–function relationship of PUR‐hydrolyzing enzymes, which hold great promise for developing effective industrial PUR recycling processes and mitigating the environmental footprint of plastic waste.