bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optimized and Uniform Strain Control in Intrinsic Stretchable Mechanochromic Materials with Color‐ and Polarization‐Separating Encryption Using Kirigami Cuts and Rigid Strain‐Stoppers
Authors: Shin Jun Hyuk , Yang Hak Jun , Park Ji Yoon , Han Sang Hyun , Kim Dongjun , Nam Seungmin , Choi Su Seok 
Published: December 2024

AbstractIntrinsically stretchable devices often suffer from non‐uniform strain distributions under direct‐stretching conditions due to their large‐scale, patterned designs, leading to inconsistent performance. To address these issues, mechanochromic materials—substances that change color in response to strain—for precise and intuitive strain monitoring are employed. Leveraging this data, strategic design modifications, including extrinsic techniques such as rigid‐island with soft‐substrate and kirigami cuts are implemented, to mitigate strain non‐uniformity. Thus, highly desired uniform and homogenous strain control in a multi‐pixel stretchable system is achieved. By integrating these strain‐stopping with uniform strain control methods into arrays of rigid and soft chiral liquid crystal elastomers (CLCEs), effective color separation is demonstrated for encrypted information with enhanced strain uniformity and strain control. Additionally, the dynamic optical selectivity of circularly polarized light (CPL) of the CLCEs under specific conditions is explored, using uniaxial stretching to achieve both optical color changes and refined CPL separation. Consequently, leveraging the inherent optical properties of CLCEs, a uniform and highly functional multi‐pixel operating stretchable system is devised. The application of these extrinsic strain control strategies not only resolves issues of strain uniformity but also advances the field of stretchable smart materials, offering new possibilities for dynamic color‐ and polarization‐separating based on encrypted applications.
Enhanced Vascular Smooth Muscle Cell and Extracellular Matrix Repair Using a Metal‐Organic Framework‐Based Co‐Delivery System for Abdominal Aortic Aneurysm Therapy
Authors: Lei Jiahao , Dong Xunzhong , Huang Yong , Wu Zhaoyu , Peng Zhiyou , Li Bo , Wang Ruihua , Pan Ying , Zheng Xiangtao , Zhao Zhen , Lu Xinwu 
Published: December 2024

AbstractThe abdominal aortic aneurysm (AAA) is a severe and complex condition characterized by the pathological dilation of the abdominal aorta. Current therapeutic strategies are limited, with surgical repair being the most effective intervention due to the lack of medications that can slow aneurysmal expansion or prevent adverse events. In this study, an innovative nanoplatform, Mn‐UiO‐66‐NH2@HA, designed to repair vascular smooth muscle cells (VSMCs), and the extracellular matrix (ECM) is developed, thereby enhancing arterial wall integrity. This nanoplatform utilizes the classic metal‐organic framework (MOF) UiO‐66‐NH2, doped with manganese ions (Mn2+) and coated with hyaluronate tetrasaccharide (4‐mer HA). The Mn‐UiO‐66‐NH2@HA nanoparticles demonstrates excellent drug‐loading efficiency, sustained release properties, and biocompatibility. In vitro, these nanoparticles significantly increases VSMC contractility and up‐regulated elastin and lysyl oxidase expressions, crucial for ECM repair, while inhibiting matrix metalloproteinases. In vivo studies on an Ang II‐induced AAA mouse model reveals that Mn‐UiO‐66‐NH2@HA effectively reduces aneurysmal expansion and improves aortic structural integrity. This study presents a promising co‐delivery system leveraging MOF carriers coated with 4‐mer HA and Mn2+, offering a novel therapeutic strategy for the treatment and management of AAA.
Light‐Activatable Ubiquitin for Studying Linkage‐Specific Ubiquitin Chain Formation Kinetics
Authors: Banerjee Sudakshina , Cakil Zeyneb Vildan , Gallant Kai , Boom Johannes van den , Palei Shubhendu , Meyer Hemmo , Gersch Malte , Summerer Daniel 
Published: December 2024

AbstractUbiquitination is a dynamic post‐translational modification governing protein abundance, function, and localization in eukaryotes. The Ubiquitin protein is conjugated to lysine residues of target proteins, but can also repeatedly be ubiquitinated itself, giving rise to a complex code of ubiquitin chains with different linkage types. To enable studying the cellular dynamics of linkage‐specific ubiquitination, light‐activatable polyubiquitin chain formation is reported here. By incorporating a photocaged lysine at specific sites within ubiquitin through amber codon suppression, light‐dependent activation of ubiquitin chain extension is enabled for the monitoring of linkage‐specific polyubiquitination. The studies reveal rapid, minute‐scale ubiquitination kinetics for K11, K48, and K63 linkages. The role of individual components of the ubiquitin‐proteasome system in K48‐initiated chain synthesis is further studied by small molecule inhibition. The approach expands current perturbation strategies with the ability to control linkage‐specific ubiquitination with high temporal resolution and should find broad application for studying ubiquitinome dynamics.
Diversified Fluoroalkylation of Alkenes Using Quaternary Fluoroalkyl Alcohols as the Fluoroalkylating Reagents
Authors: Lu Heng , Fan Zhoulong , Zou Yike , Zhang Ao 
Published: December 2024

AbstractGiven the widespread presence of fluoroalkyl functionalities in bioactive molecules, the development of fluoroalkylation reactions with bench‐stable and easy‐to‐use fluoroalkylating reagents is highly desirable. In addition, realization of mono‐, di‐, tri‐, or polyfluoroalkyation usually requires distinct types of fluoroalkylating reagents under different or even harsh reaction conditions, and a universal method to accomplish different hydrofluoroalkylation of alkenes is lacking. Herein, the use of quaternary fluoroalkyl alcohols is reported as the universal fluoroalkylating reagents to readily facilitate mono‐, di‐, tri‐, or polyfluoroalkylation of a wide range of alkene substrates in high yields. Moreover, a cascade reaction of hydrofluoroalkylation followed by intramolecular fluoroalkylation facilitates the construction of a variety of high‐value complex heterocycles bearing diverse fluoroalkyl functionalities from alkenes. Mechanistic studies suggest that a proton‐coupled electron transfer (PCET) process may be involved through a radical‐generating pathway. The utility of this method is showcased by the late‐stage fluoroalkylation of various high‐value complex molecules derived from either natural products or drug‐like compounds. Of note is that a continuous‐flow system is amenable to this homogeneous photoredox conditions, thereby opening up a possibility of using this protocol to realize large‐scale manufacturing of fluoroalkyl products with industrial interests.
TTK Inhibition Alleviates Postinjury Neointimal Formation and Atherosclerosis
Authors: Wu Jie‐Hong , Liu Yu‐Xiao , Zong Jia‐Bin , Qiu Min , Zhou Yi‐Fan , Li Ya‐Nan , Aili Tuersun , Zhao Xin‐Ran , Hu Bo 
Published: December 2024

AbstractAtherosclerosis and its associated cardio‐cerebrovascular complications remain the leading causes of mortality worldwide. Current lipid‐lowering therapies reduce only approximately one‐third of the cardiovascular risk. Furthermore, vascular restenosis and thrombotic events following surgical interventions for severe vascular stenosis significantly contribute to treatment failure. This highlights the urgent need for novel therapeutic targets to manage atherosclerosis and prevent restenosis and thrombosis after vascular injury. This study identifies TTK protein kinase (TTK) as a key regulator of vascular smooth muscle cell (VSMC) phenotypic switching in the context of postinjury neointimal formation and atherosclerosis. Mechanistically, TTK upregulation in VSMCs phosphorylates p120‐catenin, leading to β‐catenin nuclear accumulation and dissociation of the myocardin (MYOCD)/serum response factor (SRF) complex. Deletion of TTK specifically in VSMCs reduces postinjury neointimal formation in vascular injury models and attenuates atherosclerotic lesions in ApoE−/− mice. Notably, oral administration of the TTK inhibitor CFI‐402257 mitigated neointimal formation without impairing reendothelialization and reduced atherosclerotic lesions in ApoE−/− mice without altering lipid levels. These findings suggest that targeting TTK, through inhibitors or alternative strategies, represents a promising approach to simultaneously prevent postinjury restenosis and treat atherosclerosis.
CXCL16/CXCR6/TGF‐β Feedback Loop Between M‐MDSCs and Treg Inhibits Anti‐Bacterial Immunity During Biofilm Infection
Authors: Wu Xiaoyu , Pan Baiqi , Chu Chenghan , Zhang Yangchun , Ma Jinjin , Xing Yang , Ma Yuanchen , Zhu Wengang , Zhong Huan , Alimu Aerman , Zhou Guanming , Liu Shuying , Chen Weishen , Li Xiang , Puyi Sheng 
Published: December 2024

AbstractStaphylococcus aureus (S. aureus) is a leading cause of Periprosthetic joint infection (PJI), a severe complication after joint arthroplasty. Immunosuppression is a major factor contributing to the infection chronicity of S. aureus PJI, posing significant treatment challenges. This study investigates the relationship between the immunosuppressive biofilm milieu and S. aureus PJI outcomes in both discovery and validation cohorts. This scRNA‐seq analysis of synovium from PJI patients reveals an expansion and heightened activity of monocyte‐related myeloid‐derived suppressor cells (M‐MDSCs) and regulatory T cells (Treg). Importantly, CXCL16 is significantly upregulated in M‐MDSCs, with its corresponding CXCR6 receptor also elevated on Treg. M‐MDSCs recruit Treg and enhance its activity via CXCL16‐CXCR6 interactions, while Treg secretes TGF‐β, inducing M‐MDSCs proliferation and immunosuppressive activity. Interfering with this cross‐talk in vivo using Treg‐specific CXCR6 knockout PJI mouse model reduces M‐MDSCs/Treg‐mediated immunosuppression and alleviates bacterial burden. Immunohistochemistry and recurrence analysis show that PJI patients with CXCR6high synovium have poor prognosis. This findings highlight the critical role of CXCR6 in Treg in orchestrating an immunosuppressive microenvironment and biofilm persistence during PJI, offering potential targets for therapeutic intervention.
A Novel Nuclear Protein Complex Controlling the Expression of Developmentally Regulated Genes in Toxoplasma Gondii
Authors: Xue Lilan , Zhang Jingwen , Zhang Lihong , Fan Fuqiang , Yin Xiaoyan , Tian Hengrui , Shen Bang 
Published: December 2024

AbstractToxoplasma gondii is a ubiquitous protozoan parasite with a complex life cycle containing multiple developmental stages. The parasites have distinct gene expression patterns at different stages to enable stage specific life activities, but the underlying regulatory mechanisms are largely unknown. In this study, a nuclear complex is identified that controls the expression of developmentally regulated genes. This complex consists of the AP2 family transcription factor AP2XII‐5, the epigenetic factors MORC and HDAC3, as well as a novel AP2XII‐5 interacting protein 1 (AIP1) that stabilizes this complex. At the tachyzoite stage when the parasites proliferate rapidly by asexual endodyogeny, AP2XII‐5 binds to the promoter regions of developmentally activated genes and recruits MORC and HDAC3 to suppress their expression. When sexual commitment and merozoite development are triggered, the abundance of AP2XII‐5 decreases and its suppression on target genes is relieved. In contrast to MORC and HDAC3, which regulate Toxoplasma development but are also essential for tachyzoite growth, AP2XII‐5 and AIP1 are dispensable for tachyzoite proliferation in vitro. These data suggest that while MORC and HDAC3 have broad regulatory activities, forming a complex with AP2XII‐5 and AIP1 enables them to specifically regulate gene expression during development.
A Comprehensive Transcriptome Atlas Reveals the Crucial Role of LncRNAs in Maintaining Nodulation Homeostasis in Soybean
Authors: Lin Yanru , Chen Chong , Chen Weizhen , Liu Hangcheng , Xiao Renhao , Ji Hongtao , Li Xia 
Published: December 2024

AbstractSymbiotic nitrogen fixation (SNF) provides nitrogen for soybean. A primary challenge in enhancing yield through efficient SNF lies in striking a balance between its high energy consumption and plant growth. However, the systemic transcriptional reprogramming during nodulation remains limited. Here, this work conducts a comprehensive RNA‐seq of the roots, cotyledons and leaves of inoculated‐soybean. This work finds 88,814 mRNAs and 6,156 noncoding RNAs (ncRNAs) across various organs. Notably, this work identifies 6,679 nodulation‐regulated mRNAs (NR‐mRNAs), 1,681 long noncoding RNAs (lncRNAs) (NR‐lncRNAs), and 59 miRNAs (NR‐miRNAs). The majority of these NR‐RNAs are associated with plant‐microbial interaction and exhibit high organ specificity. Roots display the highest abundance of NR‐ncRNAs and the most dynamic crosstalk between NR‐lncRNAs and NR‐miRNAs in a GmNARK‐dependent manner. This indicates that while each tissue responds uniquely, GmNARK serves as a primary regulator of the transcriptional control of nodulated‐plants. Furthermore, this work proves that lnc‐NNR6788 and lnc‐NNR7059 promote nodulation by regulating their target genes. This work also shows that the nodulation‐ and GmNARK‐regulated (NNR) lnc‐NNR4481 negatively regulates nodulation through miR172c within a competing endogenous RNA (ceRNA) network. The spatial organ‐type transcriptomic atlas establishes a benchmark and provides a valuable resource for integrative analyses of the mechanism underlying of nodulation and plant growth balance.
A Versatile Drift‐Free Super‐Resolution Imaging Method via Oblique Bright‐Field Correlation
Authors: Ma Hongqiang , Nguyen Phuong , Liu Yang 
Published: December 2024

AbstractHigh‐resolution optical microscopy, particularly super‐resolution localization microscopy, requires precise real‐time drift correction to maintain constant focus at nanoscale precision during the prolonged data acquisition. Existing methods, such as fiducial marker tracking, reflection monitoring, and bright‐field image correlation, each provide certain advantages but are limited in their broad applicability. In this work, a versatile and robust drift correction technique is presented for single‐molecule localization‐based super‐resolution microscopy. It is based on the displacement analysis of bright‐field image features of the specimen with oblique illumination. By leveraging the monotonic relationship between the displacement of image features and axial positions, this method can precisely measure the drift of the imaging system in real‐time with sub‐nanometer precision in all three dimensions, over a broad axial range, and for various samples, including those with closely matched refractive indices. The performance of this method is validated against conventional marker‐assisted techniques and demonstrates its high precision in super‐resolution imaging across various biological samples. This method paves the way for fully automated drift‐free super‐resolution imaging systems.
How Highly Heterogeneous Sensors with Single‐Molecule Resolution can Result in Robust Continuous Monitoring Over Long Time Spans
Authors: Vu Chris , Yan Junhong , de Jong Arthur M. , Prins Menno W. J. 
Published: December 2024

AbstractBiomolecular sensors with single‐molecule resolution are composed of multitudes of transducers that measure state changes related to single‐molecular binding and unbinding events. Conventionally, signals are aggregated from many individual transducers in order to achieve sufficient statistics. However, by aggregating signals, transducer‐to‐transducer differences are lost and heterogeneities cannot be studied. Here, transducers with single‐molecule resolution over long time spans are studied, enabling the collection of sufficient statistics from independent transducers. This allows comparisons between transducers that reveal fundamental heterogeneities in their molecular assemblies related to stochastic variations. The study is performed with biosensing by particle motion, a sensing methodology with thousands of particles that dynamically interact with a sensing surface. The signals of individual particles are studied for series of modulations of analyte concentration over 25 h. The results show large differences in individual concentration‐dependent responses. Monte Carlo simulations clarify that heterogeneities can be attributed to stochastic fluctuations in the numbers of binder molecules, and that gradual changes of the response characteristics can be related to losses of molecules in the single‐particle transducers. The results give insights into molecular and temporal heterogeneities of continuous transducers with single‐molecule resolution and explain how sensors can be engineered to achieve robust, precise, and stable biomolecular monitoring.
Spin Excitations of High Spin Iron(II) in Metal–Organic Chains on Metal and Superconductor
Authors: Liu Jung‐Ching , Li Chao , Chahib Outhmane , Wang Xing , Rothenbühler Simon , Häner Robert , Decurtins Silvio , Aschauer Ulrich , Liu Shi‐Xia , Meyer Ernst , Pawlak Rémy 
Published: December 2024

AbstractMany‐body interactions in metal–organic frameworks (MOFs) are fundamental for emergent quantum physics. Unlike their solution counterpart, magnetization at surfaces in low‐dimensional analogues is strongly influenced by magnetic anisotropy (MA) induced by the substrate and still not well understood. Here, on‐surface coordination chemistry is used to synthesize on Ag(111) and superconducting Pb(111) an iron‐based spin chain by using pyrene‐4,5,9,10‐tetraone (PTO) precursors as ligands. Using low‐temperature scanning probe microscopy, their structures and low‐energy spin excitations of coordinated Fe atoms are compared with high S = 2 spin‐state. Although the chain and coordination centers are identical on both substrates, the long‐range spin–spin coupling due to a superexchange through the ligand on Ag is not experimentally observed on Pb(111). This reduction of spin‐spin interactions on Pb in tunneling spectra is ascribed to the depletion of electronic states around the Fermi level of the Pb(111) superconductor as compared to silver.
Single‐Cell and Spatial Transcriptomics Delineate the Microstructure and Immune Landscape of Intrahepatic Cholangiocarcinoma in the Leading‐Edge Area
Authors: Zuyin Li , Zhao Li , Qian Cheng , Changkun Zhang , Delin Ma , Jialing Hao , Zhuomiaoyu Chen , Yuzi Li , Jiaxi Zheng , Jie Gao , Jiye Zhu 
Published: December 2024

AbstractIntrahepatic cholangiocarcinoma (ICC) tumor cells and their interactions with the immune microenvironment, particularly at the leading‐edge area, have been underexplored. This study employs single‐cell RNA sequencing (scRNA‐seq) and spatial transcriptome (ST) analysis on samples from the tumor core, adjacent non‐tumorous tissue, and the leading‐edge area of nine ICC patients. These findings indicate that tumor cells at the leading‐edge area demonstrate enhanced proliferation and are tightly associated with the stroma, including endothelial cells and POSTN+ FAP+ fibroblasts. Notably, CD8+ T cells in this region exhibit a naive phenotype with low cytotoxicity and signs of exhaustion, likely due to compromised antigen presentation by antigen‐presenting cells (APCs). The predominant CD8+ T cell subset, mucosal‐associated invariant T (MAIT) cells, recruits SPP1+ macrophages within the stroma. This interaction, along with the presence of POSTN+ cancer‐associated fibroblasts (CAFs) and endothelial cells, forms a unique “triad structure” that fosters tumor growth and ICC progression. The research highlights the intricate characteristics and interactions of ICC tumor cells in the leading‐edge area, offering insights into potential therapeutic targets for intervention.
Targeting CDK2 Confers Vulnerability to Lenvatinib Via Driving Senescence in Anaplastic Thyroid Cancer
Authors: Ma Ben , Sang Youzhou , Du Xiaoxue , Zhang Yanzhi , Yin Min , Xu Weibo , Liu Wanlin , Lu Jiayi , Guan Qing , Wang Yunjun , Liao Tian , Wang Yuting , Xiang Jun , Shi Rongliang , Qu Ning , Ji Qinghai , Zhang Jiwei , Ji Dongmei , Wang Yu 
Published: December 2024

AbstractAnaplastic thyroid cancer (ATC) is the most lethal tumor arising from thyroid follicular epithelium. Lenvatinib is an off‐label use option for ATC patients in many countries but an approved prescription in Japan. However, lenvatinib resistance is a substantial clinical challenge. Clinical ATC samples including lenvatinib‐resistant tumors are used to build patient‐derived cells and patient‐derived xenografts. High‐throughput drug screening and synergy analyses are performed to identify an effective combination partner for lenvatinib. Cellular functions are detected by cell senescence, apoptosis, cell cycle, cell viability and colony formation assays. CDK2 inhibition showed the significant synthetic lethality with lenvatinib via inhibiting G1/S transition and inducing cell senescence in ATC. High expression of CDK2 is associated with lenvatinib resistance and poor clinical outcomes of ATC patients. Lenvatinib increased protein expression of CDK2 in lenvatinib‐resistant ATC cells. Mechanistically, lenvatinib inhibited protein degradation of CDK2 via reducing CDK2's interaction with the RACK1‐FBW7 complex, which is involved in ubiquitination and subsequent proteasomal degradation of CDK2. Combination of CDK2 inhibitors in clinical trials (Dinaciclib or PF‐07104091) and lenvatinib markedly suppressed growth of xenograft tumors from the lenvatinib‐resistant patient. The findings support the combination therapy strategy of lenvatinib and CDK2 inhibitor for lenvatinib‐resistant ATC patients with high CDK2 expression.
A Synergistic Dual‐Atom Sites Nanozyme Augments Immunogenic Cell Death for Efficient Immunotherapy
Authors: Ning Shipeng , Zhang Zeyuan , Ren Yujing , Hou Yaxin , Li Dan , Chen Jingqi , Zhai Yujie , Fan Kelong , Zhang Weiqing 
Published: December 2024

AbstractInducing immunogenic cell death (ICD) is a promising approach to elicit enduring antitumor immune responses. Hence, extensive efforts are being made to develop ICD inducers. Herein, a cascaded dual‐atom nanozyme with Fe and Cu sites (FeCu‐DA) as an efficient ICD inducer is presented. The Fe and Cu dual‐atom sites synergistically enhance peroxidase (POD) and catalase activities, effectively converting intratumoral hydrogen peroxide (H2O2) to hydroxyl radicals (·OH) and oxygen (O2). Moreover, FeCu‐DA exhibits superior glutathione‐oxidase (GSH‐OXD) activity, catalyzing GSH oxidation to generate H2O2, enabling cascaded catalysis for sustainable ∙OH generation and reducing reactive oxygen species (ROS) resistance by consuming GSH. Steady–state kinetic analysis and density functional theory calculations indicate that FeCu‐DA exhibits a higher catalytic rate and efficiency than Fe single‐atom nanozymes (Fe‐SA) because of its stronger interactions with H2O2. Its POD activity is 948.05 U mg−1, which is 2.8‐fold greater than that of Fe‐SA. Furthermore, FeCu‐DA exhibits impressive photothermal effects and photothermal‐enhanced cascaded catalysis kinetics for ROS generation, thereby inducing potent ICD. Combined with anti‐PD‐L1 antibody (αPD‐L1) blockade, FeCu‐DA shows synergistic enhancement in treatment under near‐infrared irradiation. This study provides insights for designing efficient dual‐atom nanozymes and demonstrates their potential in ICD‐induced cancer immunotherapy.