bluuebunny/crossref_metadata_2025_split huggingface dataset:
YTH domain family protein 3 accelerates non-small cell lung cancer immune evasion through targeting CD8+ T lymphocytes
Authors: Luo Yisheng , Zeng Chao , Ouyang Zezhong , Zhu Wenbin , Wang Jiazhi , Chen Zhiyin , Xiao Chunyang , Wu Guodong , Li Liang , Qian Youhui , Chen Xin , Liu Yuchen , Wu Hao 
Published: July 2024

AbstractImmune evasion is one of the critical hallmarks of malignant tumors, especially non-small cell lung cancer (NSCLC). Emerging findings have illustrated the roles of N6-methyladenosine (m6A) on NSCLC immune evasion. Here, this study investigated the function and underlying mechanism of m6A reader YTH domain family protein 3 (YTHDF3) on NSCLC immune evasion. YTHDF3 was found to be highly expressed in NSCLC tissue and act as an independent prognostic factor for overall survival. Functionally, up-regulation of YTHDF3 impaired the CD8+ T antitumor activity to deteriorate NSCLC immune evasion, while YTHDF3 silencing recovered the CD8+ T antitumor activity to inhibit immune evasion. Besides, YTHDF3 up-regulation reduced the apoptosis of NSCLC cells. Mechanistically, PD-L1 acted as the downstream target for YTHDF3, and YTHDF3 could upregulate the transcription stability of PD-L1 mRNA. Overall, YTHDF3 targeted PD-L1 to promote NSCLC immune evasion partially through escaping effector cell cytotoxicity CD8+ T mediated killing and antitumor immunity. In summary, this study provides an essential insight for m6A modification on CD8+ T cell-mediated antitumor immunity in NSCLC, which might inspire an innovation for lung cancer tumor immunotherapy.
GolpHCat (TMEM87A), a unique voltage-dependent cation channel in Golgi apparatus, contributes to Golgi-pH maintenance and hippocampus-dependent memory
Authors: Kang Hyunji , Han Ah-reum , Zhang Aihua , Jeong Heejin , Koh Wuhyun , Lee Jung Moo , Lee Hayeon , Jo Hee Young , Maria-Solano Miguel A. , Bhalla Mridula , Kwon Jea , Roh Woo Suk , Yang Jimin , An Hyun Joo , Choi Sun , Kim Ho Min , Lee C. Justin 
Published: July 2024

AbstractImpaired ion channels regulating Golgi pH lead to structural alterations in the Golgi apparatus, such as fragmentation, which is found, along with cognitive impairment, in Alzheimer’s disease. However, the causal relationship between altered Golgi structure and cognitive impairment remains elusive due to the lack of understanding of ion channels in the Golgi apparatus of brain cells. Here, we identify that a transmembrane protein TMEM87A, renamed Golgi-pH-regulating cation channel (GolpHCat), expressed in astrocytes and neurons that contributes to hippocampus-dependent memory. We find that GolpHCat displays unique voltage-dependent currents, which is potently inhibited by gluconate. Additionally, we gain structural insights into the ion conduction through GolpHCat at the molecular level by determining three high-resolution cryogenic-electron microscopy structures of human GolpHCat. GolpHCat-knockout mice show fragmented Golgi morphology and altered protein glycosylation and functions in the hippocampus, leading to impaired spatial memory. These findings suggest a molecular target for Golgi-related diseases and cognitive impairment.
A scalable and cGMP-compatible autologous organotypic cell therapy for Dystrophic Epidermolysis Bullosa
Authors: Neumayer Gernot , Torkelson Jessica L. , Li Shengdi , McCarthy Kelly , Zhen Hanson H. , Vangipuram Madhuri , Mader Marius M. , Gebeyehu Gulilat , Jaouni Taysir M. , Jacków-Malinowska Joanna , Rami Avina , Hansen Corey , Guo Zongyou , Gaddam Sadhana , Tate Keri M. , Pappalardo Alberto , Li Lingjie , Chow Grace M. , Roy Kevin R. , Nguyen Thuylinh Michelle , Tanabe Koji , McGrath Patrick S. , Cramer Amber , Bruckner Anna , Bilousova Ganna , Roop Dennis , Tang Jean Y. , Christiano Angela , Steinmetz Lars M. , Wernig Marius , Oro Anthony E. 
Published: July 2024

AbstractWe present Dystrophic Epidermolysis Bullosa Cell Therapy (DEBCT), a scalable platform producing autologous organotypic iPS cell-derived induced skin composite (iSC) grafts for definitive treatment. Clinical-grade manufacturing integrates CRISPR-mediated genetic correction with reprogramming into one step, accelerating derivation of COL7A1-edited iPS cells from patients. Differentiation into epidermal, dermal and melanocyte progenitors is followed by CD49f-enrichment, minimizing maturation heterogeneity. Mouse xenografting of iSCs from four patients with different mutations demonstrates disease modifying activity at 1 month. Next-generation sequencing, biodistribution and tumorigenicity assays establish a favorable safety profile at 1-9 months. Single cell transcriptomics reveals that iSCs are composed of the major skin cell lineages and include prominent holoclone stem cell-like signatures of keratinocytes, and the recently described Gibbin-dependent signature of fibroblasts. The latter correlates with enhanced graftability of iSCs. In conclusion, DEBCT overcomes manufacturing and safety roadblocks and establishes a reproducible, safe, and cGMP-compatible therapeutic approach to heal lesions of DEB patients.
Aperiodic approximants bridging quasicrystals and modulated structures
Authors: Matsubara Toranosuke , Koga Akihisa , Takano Atsushi , Matsushita Yushu , Dotera Tomonari 
Published: July 2024

AbstractAperiodic crystals constitute a class of materials that includes incommensurate (IC) modulated structures and quasicrystals (QCs). Although these two categories share a common foundation in the concept of superspace, the relationship between them has remained enigmatic and largely unexplored. Here, we show “any metallic-mean” QCs, surpassing the confines of Penrose-like structures, and explore their connection with IC modulated structures. In contrast to periodic approximants of QCs, our work introduces the pivotal role of “aperiodic approximants”, articulated through a series of k-th metallic-mean tilings serving as aperiodic approximants for the honeycomb crystal, while simultaneously redefining this tiling as a metallic-mean IC modulated structure, highlighting the intricate interplay between these crystallographic phenomena. We extend our findings to real-world applications, discovering these tiles in a terpolymer/homopolymer blend and applying our QC theory to a colloidal simulation displaying planar IC structures. In these structures, domain walls are viewed as essential components of a quasicrystal, introducing additional dimensions in superspace. Our research provides a fresh perspective on the intricate world of aperiodic crystals, shedding light on their broader implications for domain wall structures across various fields.
Hyperconfined bio-inspired Polymers in Integrative Flow-Through Systems for Highly Selective Removal of Heavy Metal Ions
Authors: Nakahata Masaki , Sumiya Ai , Ikemoto Yuka , Nakamura Takashi , Dudin Anastasia , Schwieger Julius , Yamamoto Akihisa , Sakai Shinji , Kaufmann Stefan , Tanaka Motomu 
Published: July 2024

AbstractAccess to clean water, hygiene, and sanitation is becoming an increasingly pressing global demand, particularly owing to rapid population growth and urbanization. Phytoremediation utilizes a highly conserved phytochelatin in plants, which captures hazardous heavy metal ions from aquatic environments and sequesters them in vacuoles. Herein, we report the design of phytochelatin-inspired copolymers containing carboxylate and thiolate moieties. Titration calorimetry results indicate that the coexistence of both moieties is essential for the excellent Cd2+ ion-capturing capacity of the copolymers. The obtained dissociation constant, KD ~ 1 nM for Cd2+ ion, is four-to-five orders of magnitude higher than that for peptides mimicking the sequence of endogenous phytochelatin. Furthermore, infrared and nuclear magnetic resonance spectroscopy results unravel the mechanism underlying complex formation at the molecular level. The grafting of 0.1 g bio-inspired copolymers onto silica microparticles and cellulose membranes helps concentrate the copolymer-coated microparticles in ≈3 mL volume to remove Cd2+ ions from 0.3 L of water within 1 h to the drinking water level (<0.03 µM). The obtained results suggest that hyperconfinement of bio-inspired polymers in flow-through systems can be applied for the highly selective removal of harmful contaminants from the environmental water.
Tumor cell-directed STING agonist antibody-drug conjugates induce type III interferons and anti-tumor innate immune responses
Authors: Malli Cetinbas Naniye , Monnell Travis , Soomer-James Jahna , Shaw Pamela , Lancaster Kelly , Catcott Kalli C. , Dolan Melissa , Mosher Rebecca , Routhier Caitlin , Chin Chen-Ni , Toader Dorin , Duvall Jeremy , Bukhalid Raghida , Lowinger Timothy B. , Damelin Marc 
Published: July 2024

AbstractActivating interferon responses with STING agonists (STINGa) is a current cancer immunotherapy strategy, and therapeutic modalities that enable tumor-targeted delivery via systemic administration could be beneficial. Here we demonstrate that tumor cell-directed STING agonist antibody-drug-conjugates (STINGa ADCs) activate STING in tumor cells and myeloid cells and induce anti-tumor innate immune responses in in vitro, in vivo (in female mice), and ex vivo tumor models. We show that the tumor cell-directed STINGa ADCs are internalized into myeloid cells by Fcγ-receptor-I in a tumor antigen-dependent manner. Systemic administration of STINGa ADCs in mice leads to STING activation in tumors, with increased anti-tumor activity and reduced serum cytokine elevations compared to a free STING agonist. Furthermore, STINGa ADCs induce type III interferons, which contribute to the anti-tumor activity by upregulating type I interferon and other key chemokines/cytokines. These findings reveal an important role for type III interferons in the anti-tumor activity elicited by STING agonism and provide rationale for the clinical development of tumor cell-directed STINGa ADCs.
Molecular profiling of 888 pediatric tumors informs future precision trials and data-sharing initiatives in pediatric cancer
Authors: Forrest Suzanne J. , Gupta Hersh , Ward Abigail , Li Yvonne Y. , Doan Duong , Al-Ibraheemi Alyaa , Alexandrescu Sanda , Bandopadhayay Pratiti , Shusterman Suzanne , Mullen Elizabeth A. , Collins Natalie B. , Chi Susan N. , Wright Karen D. , Kumari Priti , Mazor Tali , Ligon Keith L. , Shivdasani Priyanka , Manam Monica , MacConaill Laura E. , Ceca Evelina , Benich Sidney N. , London Wendy B. , Schilsky Richard L. , Bruinooge Suanna S. , Guidry Auvil Jaime M. , Cerami Ethan , Rollins Barrett J. , Meyerson Matthew L. , Lindeman Neal I. , Johnson Bruce E. , Cherniack Andrew D. , Church Alanna J. , Janeway Katherine A. 
Published: July 2024

AbstractTo inform clinical trial design and real-world precision pediatric oncology practice, we classified diagnoses, assessed the landscape of mutations, and identified genomic variants matching trials in a large unselected institutional cohort of solid tumors patients sequenced at Dana-Farber / Boston Children’s Cancer and Blood Disorders Center. Tumors were sequenced with OncoPanel, a targeted next-generation DNA sequencing panel. Diagnoses were classified according to the International Classification of Diseases for Oncology (ICD-O-3.2). Over 6.5 years, 888 pediatric cancer patients with 95 distinct diagnoses had successful tumor sequencing. Overall, 33% (n = 289/888) of patients had at least 1 variant matching a precision oncology trial protocol, and 14% (41/289) were treated with molecularly targeted therapy. This study highlights opportunities to use genomic data from hospital-based sequencing performed either for research or clinical care to inform ongoing and future precision oncology clinical trials. Furthermore, the study results emphasize the importance of data sharing to define the genomic landscape and targeted treatment opportunities for the large group of rare pediatric cancers we encounter in clinical practice.
Organocatalytic asymmetric synthesis of Si-stereogenic silacycles
Authors: Han Jung Tae , Tsuji Nobuya , Zhou Hui , Leutzsch Markus , List Benjamin 
Published: July 2024

AbstractA strong and confined Brønsted acid catalyzed enantioselective cyclization of bis(methallyl)silanes provides enantioenriched Si-stereogenic silacycles. High enantioselectivities of up to 96.5:3.5 er were obtained for a range of bis(methallyl)silanes. NMR and ESI-MS studies reveal that the formation of a covalent adduct irreversibly inhibits turnover. Remarkably, we found that acetic acid as an additive promotes the collapse of this adduct, enabling full turnover. Experimental investigation and density functional theory (DFT) calculations were conducted to elucidate the origin of this phenomenon and the observed enantioselectivity.
Harnessing virus flexibility to selectively capture and profile rare circulating target cells for precise cancer subtyping
Authors: Li Hui-Da , Chen Yuan-Qiang , Li Yan , Wei Xing , Wang Si-Yi , Cao Ying , Wang Rui , Wang Cong , Li Jing-Yue , Li Jian-Yi , Ding Hong-Ming , Yang Ting , Wang Jian-Hua , Mao Chuanbin 
Published: July 2024

AbstractThe effective isolation of rare target cells, such as circulating tumor cells, from whole blood is still challenging due to the lack of a capturing surface with strong target-binding affinity and non-target-cell resistance. Here we present a solution leveraging the flexibility of bacterial virus (phage) nanofibers with their sidewalls displaying target circulating tumor cell-specific aptamers and their ends tethered to magnetic beads. Such flexible phages, with low stiffness and Young’s modulus, can twist and adapt to recognize the cell receptors, energetically enhancing target cell capturing and entropically discouraging non-target cells (white blood cells) adsorption. The magnetic beads with flexible phages can isolate and count target cells with significant increase in cell affinity and reduction in non-target cell absorption compared to magnetic beads having rigid phages. This differentiates breast cancer patients and healthy donors, with impressive area under the curve (0.991) at the optimal detection threshold (>4 target cells mL−1). Immunostaining of captured circulating tumor cells precisely determines breast cancer subtypes with a diagnostic accuracy of 91.07%. Our study reveals the power of viral mechanical attributes in designing surfaces with superior target binding and non-target anti-fouling.
Atomic sawtooth-like metal films for vdW-layered single-crystal growth
Authors: Ko Hayoung , Choi Soo Ho , Park Yunjae , Lee Seungjin , Oh Chang Seok , Kim Sung Youb , Lee Young Hee , Kim Soo Min , Ding Feng , Kim Ki Kang 
Published: July 2024

AbstractAtomic sawtooth surfaces have emerged as a versatile platform for growth of single-crystal van der Waals layered materials. However, the mechanism governing the formation of single-crystal atomic sawtooth metal (copper or gold) films on hard substrates (tungsten or molybdenum) remains a puzzle. In this study, we aim to elucidate the formation mechanism of atomic sawtooth metal films during melting–solidification process. Utilizing molecular dynamics, we unveil that the solidification of the liquid copper initiates at a high-index tungsten facet with higher interfacial energy. Subsequent tungsten facets follow energetically favourable pathways of forming single-crystal atomic sawtooth copper film during the solidification process near melting temperature. Formation of atomic sawtooth copper film is guaranteed with a film thickness exceeding the grain size of polycrystalline tungsten substrate. We further demonstrate the successful growth of centimeter-scale single-crystal monolayer hexagonal boron nitride films on atomic sawtooth copper films and explore their potential as efficient oxygen barrier.
White-light activatable organic NIR-II luminescence nanomaterials for imaging-guided surgery
Authors: Li Chunbin , Du Jian , Jiang Guoyu , Gong Jianye , Zhang Yue , Yao Mengfan , Wang Jianguo , Wu Limin , Tang Ben Zhong 
Published: July 2024

AbstractWhile second near-infrared (NIR-II) fluorescence imaging is a promising tool for real-time surveillance of surgical operations, the previously reported organic NIR-II luminescent materials for in vivo imaging are predominantly activated by expensive lasers or X-ray with high power and poor illumination homogeneity, which significantly limits their clinical applications. Here we report a white-light activatable NIR-II organic imaging agent by taking advantages of the strong intramolecular/intermolecular D-A interactions of conjugated Y6CT molecules in nanoparticles (Y6CT-NPs), with the brightness of as high as 13315.1, which is over two times that of the brightest laser-activated NIR-II organic contrast agents reported thus far. Upon white-light activation, Y6CT-NPs can achieve not only in vivo imaging of hepatic ischemia reperfusion, but also real-time monitoring of kidney transplantation surgery. During the surgery, identification of the renal vasculature, post-reconstruction assessment of renal allograft vascular integrity, and blood supply analysis of the ureter can be vividly depicted by using Y6CT-NPs with high signal-to-noise ratios upon clinical laparoscopic LED white-light activation. Our work provides efficient molecular design guidelines towards white-light activatable imaging agent and highlights an opportunity for precision imaging theranostics.
Spontaneous symmetry breaking in polar fluids
Authors: Gibb Calum J. , Hobbs Jordan , Nikolova Diana I. , Raistrick Thomas , Berrow Stuart R. , Mertelj Alenka , Osterman Natan , Sebastián Nerea , Gleeson Helen F. , Mandle Richard. J. 
Published: July 2024

AbstractSpontaneous symmetry breaking and emergent polar order are each of fundamental importance to a range of scientific disciplines, as well as generating rich phase behaviour in liquid crystals (LCs). Here, we show the union of these phenomena to lead to two previously undiscovered polar liquid states of matter. Both phases have a lamellar structure with an inherent polar ordering of their constituent molecules. The first of these phases is characterised by polar order and a local tilted structure; the tilt direction processes about a helix orthogonal to the layer normal, the period of which is such that we observe selective reflection of light. The second new phase type is anti-ferroelectric, with the constituent molecules aligning orthogonally to the layer normal. This has led us to term the phases the $${{{{{\rm{Sm}}}}}}{{{{{{\rm{C}}}}}}}_{{{{{{\rm{P}}}}}}}^{{{{{{\rm{H}}}}}}}$$
Sm

C

P

H

and SmAAF phases, respectively. Further to this, we obtain room temperature ferroelectric nematic (NF) and $${{{{{\rm{Sm}}}}}}{{{{{{\rm{C}}}}}}}_{{{{{{\rm{P}}}}}}}^{{{{{{\rm{H}}}}}}}$$
Sm

C

P

H

phases via binary mixture formulation of the novel materials described here with a standard NF compound (DIO), with the resultant materials having melting points (and/or glass transitions) which are significantly below ambient temperature. The new soft matter phase types discovered herein can be considered as electrical analogues of topological structures of magnetic spins in hard matter.
Endonucleosis mediates internalization of cytoplasm into the nucleus
Authors: Galanopoulou Ourania , Tachmatzidi Evangelia C. , Deligianni Elena , Botskaris Dimitris , Nikolaou Kostas C. , Gargani Sofia , Dalezios Yannis , Chalepakis Georges , Talianidis Iannis 
Published: July 2024

AbstractSetd8 regulates transcription elongation, mitotic DNA condensation, DNA damage response and replication licensing. Here we show that, in mitogen-stimulated liver-specific Setd8-KO mice, most of the hepatocytes are eliminated by necrosis but a significant number of them survive via entering a stage exhibiting several senescence-related features. Setd8-deficient hepatocytes had enlarged nuclei, chromosomal hyperploidy and nuclear engulfments progressing to the formation of intranuclear vesicles surrounded by nuclear lamina. These vesicles contain glycogen, cytoplasmic proteins and even entire organelles. We term this process “endonucleosis”. Intranuclear vesicles are absent in hepatocytes of Setd8/Atg5 knockout mice, suggesting that the process requires the function of the canonical autophagy machinery. Endonucleosis and hyperploidization are temporary, early events in the surviving Setd8-deficient cells. Larger vesicles break down into microvesicles over time and are eventually eliminated. The results reveal sequential events in cells with extensive DNA damage, which function as part of survival mechanisms to prevent necrotic death.
Perturbed N-glycosylation of Halobacterium salinarum archaellum filaments leads to filament bundling and compromised cell motility
Authors: Sofer Shahar , Vershinin Zlata , Mashni Leen , Zalk Ran , Shahar Anat , Eichler Jerry , Grossman-Haham Iris 
Published: July 2024

AbstractThe swimming device of archaea—the archaellum—presents asparagine (N)-linked glycans. While N-glycosylation serves numerous roles in archaea, including enabling their survival in extreme environments, how this post-translational modification contributes to cell motility remains under-explored. Here, we report the cryo-EM structure of archaellum filaments from the haloarchaeon Halobacterium salinarum, where archaellins, the building blocks of the archaellum, are N-glycosylated, and the N-glycosylation pathway is well-resolved. We further determined structures of archaellum filaments from two N-glycosylation mutant strains that generate truncated glycans and analyzed their motility. While cells from the parent strain exhibited unidirectional motility, the N-glycosylation mutant strain cells swam in ever-changing directions within a limited area. Although these mutant strain cells presented archaellum filaments that were highly similar in architecture to those of the parent strain, N-linked glycan truncation greatly affected interactions between archaellum filaments, leading to dramatic clustering of both isolated and cell-attached filaments. We propose that the N-linked tetrasaccharides decorating archaellins act as physical spacers that minimize the archaellum filament aggregation that limits cell motility.
Polyepitaxial grain matching to study the oxidation of uranium dioxide
Authors: Wasik Jacek , Sutcliffe Joseph , Podor Renaud , Lewis Jarrod , Darnbrough James Edward , Rennie Sophie , Akbar Hussain Syed , Bell Christopher , Chaney Daniel Alexander , Griffiths Gareth , Harding Lottie Mae , Legg Florence , Lawrence Bright Eleanor , Nicholls Rebecca , Sasikumar Yadukrishnan , Siberry Angus , Smith Philip , Springell Ross 
Published: July 2024

AbstractAlthough the principal physical behaviour of a material is inherently connected to its fundamental crystal structure, the behaviours observed in the real-world are often driven by the microstructure, which for many polycrystalline materials, equates to the size and shape of the constituent crystal grains. Here we highlight a cutting edge synthesis route to the controlled engineering of grain structures in thin films and the simplification of associated 3-dimensional problems to less complex 2D ones. This has been applied to the actinide ceramic, uranium dioxide, to replicate structures typical in nuclear fission fuel pellets, in order to investigate the oxidation and subsequent transformation of cubic UO2 to orthorhombic U3O8. This article shows how this synthesis approach could be utilised to investigate a range of phenomena, affected by grain morphology, and highlights some unusual results in the oxidation behaviour of UO2, regarding the phase transition to U3O8.