bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dissecting the Spatial and Single‐Cell Transcriptomic Architecture of Cancer Stem Cell Niche Driving Tumor Progression in Gastric Cancer
Authors: Zhang Guangyu , Zhang Xin , Pan Wenting , Chen Xizhao , Wan Lingfei , Liu Chunjie , Yong Yuting , Zhao Yue , Sang Shuli , Zhang Lihua , Yao Sheng , Guo Yushu , Wang Mingmei , Wang Xinhui , Peng Guangdun , Yan Xinlong , Wang Yanchun , Zhang Min 
Published: February 2025

AbstractDespite significant advancements in identifying novel therapeutic targets and compounds, cancer stem cells (CSCs) remain pivotal in driving therapeutic resistance and tumor progression in gastric cancer (GC). High‐resolution knowledge of the transcriptional programs underlying the role of CSC niche in driving tumor stemness and progression is still lacking. Herein, spatial and single‐cell RNA sequencing of 32 human gastric mucosa tissues at various stages of malignancy, illuminating the phenotypic plasticity of tumor epithelium and transcriptional trajectory from mature gastric chief cells to the CSC state, which is associated with activation of EGFR and WNT signaling pathways, is conducted. Moreover, the CSCs interact with not only the immunosuppressive CXCL13+ T cells and CCL18+ M2 macrophages to evade immune surveillance, but also the inflammatory cancer‐associated fibroblasts (iCAFs) to promote tumorigenesis and maintain stemness, which construct the CSC niche leading to inferior prognosis. Notably, it is uncovered that amphiregulin (AREG) derived from iCAFs promotes tumor stemness by upregulating the expression of SOX9 in tumor cells, and contributes to drug resistance via the AREG‐ERBB2 axis. This study provides valuable insight into the characteristics of CSC niche in driving tumor stemness and progression, offering novel perspective for designing effective strategies to overcome GC therapy resistance.
Cobalt Single‐Atom Intercalation in Molybdenum Disulfide Enhances Piezocatalytic and Enzyodynamic Activities for Advanced Cancer Therapeutics
Authors: Bai Haomiao , Ding Sujun , Dai Yanfei , Liu Jiefu , Chen Huangjing , Feng Wei , Yu Dehong , Chen Yu , Ni Xuejun 
Published: February 2025

AbstractPiezoelectric semiconductor nanomaterials have attracted considerable interest in piezocatalytic tumor treatment. However, piezocatalytic therapy encounters obstacles such as suboptimal piezoelectric responses, rapid electron‐hole recombination, inefficient energy harvesting, and the complexities of the tumor microenvironment. In this study, sulfur vacancy‐engineered cobalt (Co) single‐atom doped molybdenum disulfide (SA‐Co@MoS2) nanoflowers are strategically designed, which exhibit enhanced piezoelectric effects. Specifically, the introduction of Co single atom not only induces lattice distortion and out‐of‐plane polarization but also leads to the formation of numerous sulfur vacancies. These changes collectively narrow the intrinsic bandgap of the material, facilitating effective separation and migration of charge carriers, and enabling efficient production of reactive oxygen species under ultrasound stimulation. Additionally, the SA‐Co@MoS2 nanoflowers demonstrate improved enzymatic activity and exhibit glutathione depletion capabilities attributed to the mixed valence states of Co, intensifying oxidative stress in tumor cells, and leading to cell cycle arrest and apoptosis, while the inactivation of glutathione peroxidase 4 induces ferroptosis. Both in vitro and in vivo results indicate that SA‐Co@MoS2 nanoflowers can significantly eliminate tumor cells. This study offers valuable insights into the exploration of single‐atom doping‐enhanced piezoelectric sonosensitizers for cancer treatment, potentially paving the way for advancements in the field of piezocatalytic synergistic enzyodynamic therapy.
ACAT1‐Mediated ME2 Acetylation Drives Chemoresistance in Ovarian Cancer by Linking Glutaminolysis to Lactate Production
Authors: Zheng Cuimiao , Tan Hao , Niu Gang , Huang Xi , Lu Jingyi , Chen Siqi , Li Haoyuan , Zhu Jiayu , Zhou Zhou , Xu Manman , Pan Chaoyun , Liu Junxiu , Li Jie 
Published: February 2025

AbstractLactate derived from aerobic glycolysis is crucial for DNA damage repair and chemoresistance. Nevertheless, it is frequently noted that cancer cells depend on glutaminolysis to replenish essential metabolites. Whether and how glutaminolysis might enhance lactate production and facilitate DNA repair in cancer cells remains unknown. Here, it is shown that malate enzyme 2 (ME2), which metabolizes glutamine‐derived malate to pyruvate, contributes to lactate production and chemotherapy resistance in ovarian cancer. Mechanistically, chemotherapy reduces the expression of glucose transporters and impairs glucose uptake in cancer cells. The resultant decrease in intracellular glucose levels triggers the acetylation of ME2 at lysine 156 by ACAT1, which in turn potentiates ME2 enzyme activity and facilitates lactate production from glutamine. ME2‐derived lactate contributes to the development of acquired chemoresistance in cancer cells subjected to prolonged chemotherapy, primarily by facilitating the lactylation of proteins involved in homologous recombination repair. Targeting ACAT1 to inhibit ME2 acetylation effectively reduced chemoresistance in both in vitro and in vivo models. These findings underscore the significance of acetylated ME2‐mediated lactate production from glutamine in chemoresistance, particularly under conditions of reduced intracellular glucose within cancer cell, thereby complementing the Warburg effect and offering new perspectives on the metabolic links to chemotherapy resistance.
Advanced Microarrays as Heterogeneous Force‐Remodeling Coordinator to Orchestrate Nuclear Configuration and Force‐Sensing Mechanotransduction in Stem Cells
Authors: Wang Nana , Hou Yan , Lin Lili , Xu Shihui , Lee Kyubae , Yang Yingjun , Chen Yazhou , Li Yachun , Wang Xiuhui , Wang Yongtao , Chen Tao 
Published: February 2025

AbstractIntegrin and focal adhesion can regulate cytoskeleton distribution to govern actin‐related force remodeling and play an important role in nuclear configuration and force‐sensing mechanotransduction of stem cells. However, further exploration of the interaction between actinin complex and myosin, kinetics, and molecular mechanism of cytoskeleton structures to nucleate within the engineered stem cells is vague. An extensive comprehension of cell morphogenesis, force remodeling, and nuclear force‐sensing mechanotransduction is essential to reveal the basic physical principles of cytoskeleton polymerization and force‐related signaling delivery. Advanced microarrays are designed to determine heterogeneous cell morphology and cell adhesion behaviors in stem cells. The heterogeneity from the engineered microarrays is transferred into nuclei to regulate nuclear configuration and force‐sensing mechanotransduction by the evaluation of Lamins, YAP, and BrdU expression. Tuning the activation of adhesion proteins and cytoskeleton nucleators to adjust heterogeneous cell mechanics may be the underlying mechanism to change nuclear force‐sensing configuration in response to its physiological mechanotransduction in microarrayed stem cells.
Single‐Molecule Insight Into α‐Synuclein Fibril Structure and Mechanics Modulated by Chemical Compounds
Authors: Li Xiang , Bi Lulu , Zhang Shenqing , Xu Qianhui , Xia Wencheng , Tao Youqi , Wu Shaojuan , Li Yanan , Le Weidong , Kang Wenyan , Li Dan , Sun Bo , Liu Cong 
Published: February 2025

Abstractα‐Syn fibrils, a key pathological hallmark of Parkinson's disease, is closely associated with disease initiation and progression. Several small molecules are found to bind or dissolve α‐syn fibrils, offering potential therapeutic applications. Here, an innovative optical tweezers‐based, fluorescence‐combined approach is developed to probe the mechanical characteristics of α‐syn fibrils at the single‐molecule level. When subjected to axial stretching, local deformation within α‐syn fibrils appeared at forces above 50 pN. These structural alternations occurred stepwise and are irreversible, suggesting unfolding of individual α‐syn molecules or subdomains. Additionally, α‐syn fibrils exhibits high heterogeneity in lateral disruption, with rupture force ranging from 50 to 500 pN. The impact of different compounds on the structure and mechanical features of α‐syn fibrils is further examined. Notably, epigallocatechin gallate (EGCG) generally attenuates the rupture force of fibrils by wedging into the N‐terminal polar groove and induces fibril dissociation. Conversely, copper chlorophyllin A (CCA) attaches to four different sites wrapping around the fibril core, reinforcing the stability of the fibril against rupture forces. The work offers an effective method for characterizing single‐fibril properties and bridges compound‐induced structural alternations with mechanical response. These insights are valuable for understanding amyloid fibril mechanics and their regulation by small molecules.
Unveiling the Mechanism of Mn Dissolution Through a Dynamic Cathode‐Electrolyte Interphase on LiMn2O4
Authors: Ou Wenhan , Marks Samuel D. , de Menezes Rafael Ferreira , He Rong , Zhang Zihan , Sindt Collin , Thurston Jonathan , Jaye Cherno , Cowie Bruce , Thomsen Lars , Zhuo Zengqing , Guo Jinghua , Yang Wanli , Dong Ziyue , Tenent Robert , Sprenger Kayla G. , Toney Michael F. 
Published: February 2025

AbstractUnderstanding the formation and evolution of the cathode‐electrolyte interphase (CEI), which forms at the interface between the cathode and electrolyte, is crucial for revealing degradation mechanisms in cathode materials, especially for developing strategies to stabilize the interphase in the strongly oxidizing conditions that evolve at high operating voltages in next‐generation Li‐ion batteries. However, The present understanding of the CEI is challenged by its complex and dynamic nature. In this work, near‐edge X‐ray absorption fine structure spectroscopy, electrochemical characterization, and reactive molecular dynamics simulations are combined to reveal a mechanism for CEI formation and evolution above model LiMn2O4 (LMO) thin‐film electrodes in contact with conventional carbonate‐based electrolytes. It is found that Mn dissolution from LMO can be understood in terms of repetitive Mn3O4 formation and dissolution behavior during cycling, which is closely connected to electrolyte decomposition and a key aspect of the CEI formation and growth. The behavior of the CEI in this model system offers detailed insight into the dynamic chemistry of the interphase, underscoring the important role of electrolyte composition and cathode surface structure in interphase degradation.
A Concise and High‐Yielding Synthesis of Dechlorotrichotoxin A
Authors: Bae Dawon , Chaudhary Prakash , Kim Jung‐Ae , Lee Hyunji , Jeong Byeong‐Seon 
Published: February 2025

AbstractAn efficient 11‐step synthesis of (±)‐dechlorotrichotoxin A, a dechlorinated analog of the cytotoxic marine natural product trichotoxin A, has been developed. The synthesis, featuring key steps such as cross‐metathesis, Grignard reaction, and Tebbe olefination, encountered significant challenges. These arose from the volatility and instability of intermediates, as well as the difficulty of selective introduction of functional groups. These issues were overcome through strategic protecting group manipulations and careful reaction optimizations. The successful development of this synthetic route, with an overall yield of 16 %, corresponding to an average step yield of approximately 85 %, provides a robust platform for generating a diverse library of trichotoxin A analogs. This will facilitate comprehensive structure‐activity relationship studies to identify key structural features responsible for biological activity.
circNR3C2 promotes chondrogenic differentiation and cartilage repair of human adipose‐derived stem cells via the hsa‐miR‐647/SOX9 pathway
Authors: Hou Dabiao , Wang Huajun , Guo Hao , Luo Dongbin , Zheng Xiaofei , Luo Simin 
Published: February 2025

AbstractBackgroundHuman adipose‐derived stem cells (hADSCs) are seed cells with application prospects in cartilage repair. However, the mechanism of hADSC chondrogenic differentiation is still unclear. This study identifies a novel circRNA, circNR3C2, which is significantly upregulated during the chondrogenic differentiation of hADSCs.MethodsTo analyze their role in hADSC chondrogenic differentiation, hADSCs were separated and identified by flow cytometry. Thereafter, we conducted Alcian Blue staining to assess chondrogenic differentiation levels. Additionally, RT‐qPCR was carried out to detect levels of the cartilage‐related genes COL2, Aggrecan and SOX9. Moreover, overlapping target SOX9 and circNR3C2 miRNAs were detected by bioinformatics and luciferase analyses. Finally, the role of circNR3C2 was confirmed in vivo using animal models.ResultsWe confirmed that the cell surface receptors CD44, CD90 and CD105 were positively expressed on hADSCs, and their cartilage differentiation levels dramatically increased after 2 weeks. Expression of the cartilage‐related genes COL2 and Aggrecan and circNR3C2 also markedly increased. CircNR3C2 overexpression enhanced cartilage differentiation of hADSCs, while up‐regulating COL2, SOX9 and Aggrecan. Bioinformatics analysis identified hsa‐miR‐647 as the target miRNA of circNR3C2 and SOX9. Hsa‐miR‐647 overexpression in hADSCs can antagonize the effect of circNR3C2 on chondrogenic differentiation, and reverse its effect on regulating the expression of COL2, Aggrecan, and SOX9. We also showed that hADSCs overexpressing circNR3C2 promote cartilage repair in vivo.ConclusionsWe show that circNR3C2 modulates SOX9 expression to promote hsa‐miR‐647‐mediated hADSC chondrogenic differentiation; targeting circNR3C2 may help to develop new treatments to manage cartilage‐related disorders.
Edelgas bietet eine Lösung für die Herausforderung der Synthese ausgedehnter kovalenter Nanostrukturen auf inerten Oberflächen
Authors: Grossmann Lukas , Korn Sascha , Breuer Rochus , Schmittel Michael , Weber Heiko B. , Heckl Wolfgang M. , Lackinger Markus 
Published: February 2025

AbstractEin wichtiger Meilenstein auf dem Gebiet der Oberflächensynthese (On‐Surface‐Synthesis – OSS) ist die Entwicklung generischer Protokolle für die kovalente Kupplung auf inerten Oberflächen. Normalerweise werden für die OSS Metalloberflächen verwendet. Jedoch beeinflussen ihre starken Wechselwirkungen die intrinsischen Eigenschaften der synthetisierten Nanostrukturen und beeinträchtigen daher ihre Anwendbarkeit. Inerte Oberflächen hingegen bewahren die einzigartigen Eigenschaften der Nanostrukturen, stellen aber eine Herausforderung bei der Synthese dar: Die Aktivierungsenergien sind in der Regel höher als auf Metalloberflächen, wodurch die thermisch aktivierte Kupplung auf inerten Oberflächen durch konkurrierende vorzeitige Desorption der Reaktanden erheblich eingeschränkt wird. Anhand der Kupplung von 1,3,5‐Tris(4‐Mercaptophenyl)Benzol (TMB) über Kohlenstoff‐Schwefel‐Kohlenstoff Thioether‐Bindungen demonstrieren wir, dass beim Heizen in einer Edelgasatmosphäre statt im Vakuum die Desorption kinetisch gehemmt ist. Dies ermöglicht die kovalente Vernetzung sowohl auf inerten Graphitoberflächen als auch auf noch schwächer wechselwirkenden Graphenoberflächen. Wir antizipieren generisches Potenzial für diese Methode. In zukünftigen Experimenten wird untersucht, ob das Heizen bei Umgebungsdruck auf andere Kopplungsprotokolle ausgeweitet werden kann.
Structural and Mechanistic Insight into the Enantioselectivity of (R)‐Selective Styrene Monooxygenases: A Tug‐of‐War between Proximal and Distal Residues
Authors: Li Zhi‐Pu , Wang Lanteng , Liu Yan , Pei Xiao‐Qiong , Fatmi M. Qaiser , Shen Zhuanglin , Zhao Jian , Lin Hui , Zhou Jiahai , Wu Zhong‐Liu 
Published: February 2025

AbstractGroup E flavoprotein monooxygenases (GEMs) are well‐known for catalyzing enantioselective epoxidation reactions. However, engineering their enantioselectivity remains a significant challenge, largely due to a limited understanding of the underlying mechanisms. Among these enzymes, (R)‐selective styrene monooxygenases ((R)‐SMOs) stand out due to their unusual enantio‐switch behavior when catalyzing the reactions of p‐substituted styrenes. This unique property provides an exceptional opportunity to investigate the enantiocontrol mechanisms within GEMs. In this study, we resolved the first crystal structure of an (R)‐SMO, SeStyA, derived from Streptomyces. By integrating this structural information with molecular docking and molecular dynamics (MD) simulations, we identified four key residues critical to enantiodivergency: two distal residues (S178 and A219) and two proximal residues (A59 and A312). Strikingly, a “tug‐of‐war” mechanism was revealed through saturation mutagenesis, wherein the side‐chain sizes of proximal and distal residues exerted opposing influences on enantioselectivity at the C=C bond. Leveraging this mechanistic insight, we successfully engineered SMOs with excellent (R)‐ or (S)‐enantioselectivity.
Identifying the Key Photosensitizing Factors over Metal–Organic Frameworks for Selective Control of 1O2 and O2⋅− Generation
Authors: Ma Xiao‐Liang , Ma Li‐Hua , Guo Song , Zhang Zhi‐Ming , Lu Tong‐Bu 
Published: February 2025

AbstractThe reaction pathway, product selectivity and catalytic efficiency of photo‐oxidation are highly dependent on the specific reactive oxygen species (ROS), such as singlet oxygen (1O2) and superoxide (O2⋅−), generated via the sensitization of O2 by photosensitizers. Studies on uncovering the role of photosensitizing factors on the selective control of 1O2 and O2⋅− generation are significant but remain underexplored. Here, we constructed a photosensitizing metal–organic framework molecular platform (UiO‐1–UiO‐4) by elaborately engineering Ir(III) complex ligands with pyrenyl group for modulating photosensitizing factors and elucidating their impact on ROS generation. Impressively, the ratios of 1O2 and O2⋅− generation varied from 0 : 100 for UiO‐1 to 94 : 6 for UiO‐4 by modulating photosensitizing factors. UiO‐2 and UiO‐4 were respectively immobilized in a continuous‐flow reactor, achieving gram‐scale photosynthesis of phenol and juglone with high purity (>94 %) via O2⋅− and 1O2 pathway, respectively. Investigations reveal that UiO‐4 with ligand localized excited state and long excited state lifetime contributed to triggering energy transfer to afford 1O2, whereas UiO‐1 with charge‐transfer state and negative reduction potential facilitates charge transfer to produce O2⋅−. This work offers a novel insight into regulating ROS generation by modulating the photosensitizing factors at the molecular level.
Höherer Kontrast in 1H‐Observierten NMR Ligandenscreenings mit dem PEARLScreen‐Experiment
Authors: Lorz Nils , Czarniecki Barbara , Loss Sandra , Meier Benno , Gossert Alvar D. 
Published: February 2025

AbstractFür die anfängliche Identifizierung von Liganden im fragmentbasierten Wirkstoffdesign ist NMR mit den etablierten Ligandenscreeningexperimenten T1ρ, waterLOGSY und STD eine der bevorzugten Methoden. Hier stellen wir ein neues Experiment mit überlegener Bindungssensitivität vor, welches auf dem Perfect‐Echo‐Prinzip basiert: Das PEARLScreen. Die Empfindlichkeitssteigerung wird durch längere Relaxationszeiten sowie eine aktive Austauschverbreiterung erzielt, die durch das Perfect‐Echo‐Schema ermöglicht werden. Dadurch konnte die Proteinkonzentration im Vergleich zu herkömmlichen Experimenten um bis zu eine Größenordnung reduziert werden, ohne dass die Bindungsempfindlichkeit beeinträchtigt wurde. Das Experiment wurde im gesamten Feldbereich kommerziell erhältlicher Spektrometer von 80 bis 1200 MHz getestet, wobei beim höchsten Feld dank größerer Fragmentmischungen und verstärkter Austauscheffekte sogar eine Reduzierung der erforderlichen Proteinmenge um den Faktor 40 erreichbar ist. Aufgrund seiner überlegenen Sensitivität, die bereits auf Standardspektrometern erzielt wird, gehen wir davon aus, dass das PEARLScreen zum Standardexperiment für das 1H‐detektierte Ligandenscreening wird.
Design and Synthesis of Flexible Meta‐Aramid With Higher Dyeability
Authors: Fan Shihao , Liu Yi , Jia Wanglong , Zheng Liuchun 
Published: February 2025

ABSTRACTMeta‐aramid (PMIA) is a high‐performance polymer known for its exceptional properties, however, its molecular chain arrangement and strong hydrogen bonding contribute to its rigidity and brittleness. Additionally, the lack of reactive groups in its molecular structure severely affects the dyeing properties of PMIA, and restrains its applications in various fields. To address these issues, this study introduced 4,4′‐thiodianiline (4,4′‐TDA) into the main chain of PMIA molecules through copolymerization modification. This approach enhanced the relative molecular weight of the copolymers, resulting in co‐PMIAs with improved flexibility. The synthesized copolymers demonstrated excellent mechanical properties and thermal stability, maintaining high strength while improving toughness. Furthermore, the incorporation of this thioether‐containing monomer also enhanced the dyeing properties and flame retardancy of PMIA. The modification strategy employed in this research offers valuable insights into the structural modification of aromatic polyamides, and the synthesized novel copolymers show promising applications in the field of protective clothing.
Insights into the Halogen Effects on Regioselectivities of Nucleophilic Haloalkylation of α,β‐Enones
Authors: Zheng Meng‐Meng , Rao Zizhen , Sang Yueqian , Shao Qianzhen , Xu Haoran , Xue Xiao‐Song 
Published: February 2025

AbstractThe halogen effects, specifically the replacement of chlorine with fluorine, on the shift in regioselectivity from 1,4‐ to 1,2‐addition in the nucleophilic haloalkylation of α,β‐enones have been investigated using density functional theory (DFT) calculations. Computational analysis revealed that the difluorocarbanion PhSO2CF2−, being a hard nucleophile with lower energy of the highest occupied molecular orbital (HOMO), selectively undergoes 1,2‐addition of chalcone, primarily dominated by Coulombic interactions. In contrast, the nucleophilic 1,4‐addition of chalcone by a soft dichlorocarbanion PhSO2CCl2− is controlled by frontier molecular orbital interactions. This work provides a deep understanding of the regioselective control in nucleophilic haloalkylation reactions.