bluuebunny/crossref_metadata_2025_split huggingface dataset:
The tumor-enriched small molecule gambogic amide suppresses glioma by targeting WDR1-dependent cytoskeleton remodeling
Authors: Qu Jiaorong , Qiu Bojun , Zhang Yuxin , Hu Yan , Wang Zhixing , Guan Zhiang , Qin Yiming , Sui Tongtong , Wu Fan , Li Boyang , Han Wei , Peng Xiaozhong 
Published: November 2023

AbstractGlioma is the most prevalent brain tumor, presenting with limited treatment options, while patients with malignant glioma and glioblastoma (GBM) have poor prognoses. The physical obstacle to drug delivery imposed by the blood‒brain barrier (BBB) and glioma stem cells (GSCs), which are widely recognized as crucial elements contributing to the unsatisfactory clinical outcomes. In this study, we found a small molecule, gambogic amide (GA-amide), exhibited the ability to effectively penetrate the blood-brain barrier (BBB) and displayed a notable enrichment within the tumor region. Moreover, GA-amide exhibited significant efficacy in inhibiting tumor growth across various in vivo glioma models, encompassing transgenic and primary patient-derived xenograft (PDX) models. We further performed a genome-wide clustered regularly interspaced short palindromic repeats (CRISPR) knockout screen to determine the druggable target of GA-amide. By the combination of the cellular thermal shift assay (CETSA), the drug affinity responsive target stability (DARTS) approach, molecular docking simulation and surface plasmon resonance (SPR) analysis, WD repeat domain 1 (WDR1) was identified as the direct binding target of GA-amide. Through direct interaction with WDR1, GA-amide promoted the formation of a complex involving WDR1, MYH9 and Cofilin, which accelerate the depolymerization of F-actin to inhibit the invasion of patient-derived glioma cells (PDCs) and induce PDC apoptosisviathe mitochondrial apoptotic pathway. In conclusion, our study not only identified GA-amide as an effective and safe agent for treating glioma but also shed light on the underlying mechanisms of GA-amide from the perspective of cytoskeletal homeostasis.
Inflammation in the tumor-adjacent lung as a predictor of clinical outcome in lung adenocarcinoma
Authors: Dolgalev Igor , Zhou Hua , Murrell Nina , Le Hortense , Sakellaropoulos Theodore , Coudray Nicolas , Zhu Kelsey , Vasudevaraja Varshini , Yeaton Anna , Goparaju Chandra , Li Yonghua , Sulaiman Imran , Tsay Jun-Chieh J. , Meyn Peter , Mohamed Hussein , Sydney Iris , Shiomi Tomoe , Ramaswami Sitharam , Narula Navneet , Kulicke Ruth , Davis Fred P. , Stransky Nicolas , Smolen Gromoslaw A. , Cheng Wei-Yi , Cai James , Punekar Salman , Velcheti Vamsidhar , Sterman Daniel H. , Poirier J. T. , Neel Ben , Wong Kwok-Kin , Chiriboga Luis , Heguy Adriana , Papagiannakopoulos Thales , Nadorp Bettina , Snuderl Matija , Segal Leopoldo N. , Moreira Andre L. , Pass Harvey I. , Tsirigos Aristotelis 
Published: November 2023

AbstractApproximately 30% of early-stage lung adenocarcinoma patients present with disease progression after successful surgical resection. Despite efforts of mapping the genetic landscape, there has been limited success in discovering predictive biomarkers of disease outcomes. Here we performed a systematic multi-omic assessment of 143 tumors and matched tumor-adjacent, histologically-normal lung tissue with long-term patient follow-up. Through histologic, mutational, and transcriptomic profiling of tumor and adjacent-normal tissue, we identified an inflammatory gene signature in tumor-adjacent tissue as the strongest clinical predictor of disease progression. Single-cell transcriptomic analysis demonstrated the progression-associated inflammatory signature was expressed in both immune and non-immune cells, and cell type-specific profiling in monocytes further improved outcome predictions. Additional analyses of tumor-adjacent transcriptomic data from The Cancer Genome Atlas validated the association of the inflammatory signature with worse outcomes across cancers. Collectively, our study suggests that molecular profiling of tumor-adjacent tissue can identify patients at high risk for disease progression.
Generalised analytical method unravels framework-dependent kinetics of adsorption-induced structural transition in flexible metal–organic frameworks
Authors: Sakanaka Yuta , Hiraide Shotaro , Sugawara Iori , Uematsu Hajime , Kawaguchi Shogo , Miyahara Minoru T. , Watanabe Satoshi 
Published: November 2023

AbstractFlexible metal–organic frameworks (MOFs) exhibiting adsorption-induced structural transition can revolutionise adsorption separation processes, including CO2 separation, which has become increasingly important in recent years. However, the kinetics of this structural transition remains poorly understood despite being crucial to process design. Here, the CO2-induced gate opening of ELM-11 ([Cu(BF4)2(4,4’-bipyridine)2]n) is investigated by time-resolved in situ X-ray powder diffraction, and a theoretical kinetic model of this process is developed to gain atomistic insight into the transition dynamics. The thus-developed model consists of the differential pressure from the gate opening (indicating the ease of structural transition) and reaction model terms (indicating the transition propagation within the crystal). The reaction model of ELM-11 is an autocatalytic reaction with two pathways for CO2 penetration of the framework. Moreover, gas adsorption analyses of two other flexible MOFs with different flexibilities indicate that the kinetics of the adsorption-induced structural transition is highly dependent on framework structure.
Unlocking the potential of allogeneic Vδ2 T cells for ovarian cancer therapy through CD16 biomarker selection and CAR/IL-15 engineering
Authors: Lee Derek , Dunn Zachary Spencer , Guo Wenbin , Rosenthal Carl J. , Penn Natalie E. , Yu Yanqi , Zhou Kuangyi , Li Zhe , Ma Feiyang , Li Miao , Song Tsun-Ching , Cen Xinjian , Li Yan-Ruide , Zhou Jin J. , Pellegrini Matteo , Wang Pin , Yang Lili 
Published: November 2023

AbstractAllogeneic Vγ9Vδ2 (Vδ2) T cells have emerged as attractive candidates for developing cancer therapy due to their established safety in allogeneic contexts and inherent tumor-fighting capabilities. Nonetheless, the limited clinical success of Vδ2 T cell-based treatments may be attributed to donor variability, short-lived persistence, and tumor immune evasion. To address these constraints, we engineer Vδ2 T cells with enhanced attributes. By employing CD16 as a donor selection biomarker, we harness Vδ2 T cells characterized by heightened cytotoxicity and potent antibody-dependent cell-mediated cytotoxicity (ADCC) functionality. RNA sequencing analysis supports the augmented effector potential of Vδ2 T cells derived from CD16 high (CD16Hi) donors. Substantial enhancements are further achieved through CAR and IL-15 engineering methodologies. Preclinical investigations in two ovarian cancer models substantiate the effectiveness and safety of engineered CD16Hi Vδ2 T cells. These cells target tumors through multiple mechanisms, exhibit sustained in vivo persistence, and do not elicit graft-versus-host disease. These findings underscore the promise of engineered CD16Hi Vδ2 T cells as a viable therapeutic option for cancer treatment.
Temporal chromatin accessibility changes define transcriptional states essential for osteosarcoma metastasis
Authors: Pontius W. Dean , Hong Ellen S. , Faber Zachary J. , Gray Jeremy , Peacock Craig D. , Bayles Ian , Lovrenert Katreya , Chin Diana H. , Gryder Berkley E. , Bartels Cynthia F. , Scacheri Peter C. 
Published: November 2023

AbstractThe metastasis-invasion cascade describes the series of steps required for a cancer cell to successfully spread from its primary tumor and ultimately grow within a secondary organ. Despite metastasis being a dynamic, multistep process, most omics studies to date have focused on comparing primary tumors to the metastatic deposits that define end-stage disease. This static approach means we lack information about the genomic and epigenomic changes that occur during the majority of tumor progression. One particularly understudied phase of tumor progression is metastatic colonization, during which cells must adapt to the new microenvironment of the secondary organ. Through temporal profiling of chromatin accessibility and gene expression in vivo, we identify dynamic changes in the epigenome that occur as osteosarcoma tumors form and grow within the lung microenvironment. Furthermore, we show through paired in vivo and in vitro CRISPR drop-out screens and pharmacological validation that the upstream transcription factors represent a class of metastasis-specific dependency genes. While current models depict lung colonization as a discrete step within the metastatic cascade, our study shows it is a defined trajectory through multiple epigenetic states, revealing new therapeutic opportunities undetectable with standard approaches.
Immuno-metabolic dendritic cell vaccine signatures associate with overall survival in vaccinated melanoma patients
Authors: Adamik Juraj , Munson Paul V. , Maurer Deena M. , Hartmann Felix J. , Bendall Sean C. , Argüello Rafael J. , Butterfield Lisa H. 
Published: November 2023

AbstractEfficacy of cancer vaccines remains low and mechanistic understanding of antigen presenting cell function in cancer may improve vaccine design and outcomes. Here, we analyze the transcriptomic and immune-metabolic profiles of Dendritic Cells (DCs) from 35 subjects enrolled in a trial of DC vaccines in late-stage melanoma (NCT01622933). Multiple platforms identify metabolism as an important biomarker of DC function and patient overall survival (OS). We demonstrate multiple immune and metabolic gene expression pathway alterations, a functional decrease in OCR/OXPHOS and increase in ECAR/glycolysis in patient vaccines. To dissect molecular mechanisms, we utilize single cell SCENITH functional profiling and show patient clinical outcomes (OS) correlate with DC metabolic profile, and that metabolism is linked to immune phenotype. With single cell metabolic regulome profiling, we show that MCT1 (monocarboxylate transporter-1), a lactate transporter, is increased in patient DCs, as is glucose uptake and lactate secretion. Importantly, pre-vaccination circulating myeloid cells in patients used as precursors for DC vaccine generation are significantly skewed metabolically as are several DC subsets. Together, we demonstrate that the metabolic profile of DC is tightly associated with the immunostimulatory potential of DC vaccines from cancer patients. We link phenotypic and functional metabolic changes to immune signatures that correspond to suppressed DC differentiation.
Real-time signal processing via chemical reactions for a microfluidic molecular communication system
Authors: Walter Vivien , Bi Dadi , Salehi-Reyhani Ali , Deng Yansha 
Published: November 2023

AbstractSignal processing over the molecular domain is critical for analysing, modifying, and synthesising chemical signals in molecular communication systems. However, the lack of chemical signal processing blocks and the wide use of electronic devices to process electrical signals in existing molecular communication platforms can hardly meet the biocompatible, non-invasive, and size-miniaturised requirements of applications in various fields, e.g., medicine, biology, and environment sciences. To tackle this, here we design and construct a liquid-based microfluidic molecular communication platform for performing chemical concentration signal processing and digital signal transmission over distances. By specifically designing chemical reactions and microfluidic geometry, the transmitter of our platform is capable of shaping the emitted signals, and the receiver is able to threshold, amplify, and detect the chemical signals after propagation. By encoding bit information into the concentration of sodium hydroxide, we demonstrate that our platform can achieve molecular signal modulation and demodulation functionalities, and reliably transmit text messages over long distances. This platform is further optimised to maximise data rate while minimising communication error. The presented methodology for real-time chemical signal processing can enable the implementation of signal processing units in biological settings and then unleash its potential for interdisciplinary applications.
Accessible hotspots for single-protein SERS in DNA-origami assembled gold nanorod dimers with tip-to-tip alignment
Authors: Schuknecht Francis , Kołątaj Karol , Steinberger Michael , Liedl Tim , Lohmueller Theobald 
Published: November 2023

AbstractThe label-free identification of individual proteins from liquid samples by surface-enhanced Raman scattering (SERS) spectroscopy is a highly desirable goal in biomedical diagnostics. However, the small Raman scattering cross-section of most (bio-)molecules requires a means to strongly amplify their Raman signal for successful measurement, especially for single molecules. This amplification can be achieved in a plasmonic hotspot that forms between two adjacent gold nanospheres. However, the small (≈1−2 nm) gaps typically required for single-molecule measurements are not accessible for most proteins. A useful strategy would thus involve dimer structures with gaps large enough to accommodate single proteins, whilst providing sufficient field enhancement for single-molecule SERS. Here, we report on using a DNA origami scaffold for tip-to-tip alignment of gold nanorods with an average gap size of 8 nm. The gaps are accessible to streptavidin and thrombin, which are captured at the plasmonic hotspot by specific anchoring sites on the origami template. The field enhancement achieved for the nanorod dimers is sufficient for single-protein SERS spectroscopy with sub-second integration times. This design for SERS probes composed of DNA origami with accessible hotspots promotes future use for single-molecule biodiagnostics in the near-infrared range.
Emergence of Weyl fermions by ferrimagnetism in a noncentrosymmetric magnetic Weyl semimetal
Authors: Li Cong , Zhang Jianfeng , Wang Yang , Liu Hongxiong , Guo Qinda , Rienks Emile , Chen Wanyu , Bertran Francois , Yang Huancheng , Phuyal Dibya , Fedderwitz Hanna , Thiagarajan Balasubramanian , Dendzik Maciej , Berntsen Magnus H. , Shi Youguo , Xiang Tao , Tjernberg Oscar 
Published: November 2023

AbstractCondensed matter physics has often provided a platform for investigating the interplay between particles and fields in cases that have not been observed in high-energy physics. Here, using angle-resolved photoemission spectroscopy, we provide an example of this by visualizing the electronic structure of a noncentrosymmetric magnetic Weyl semimetal candidate NdAlSi in both the paramagnetic and ferrimagnetic states. We observe surface Fermi arcs and bulk Weyl fermion dispersion as well as the emergence of new Weyl fermions in the ferrimagnetic state. Our results establish NdAlSi as a magnetic Weyl semimetal and provide an experimental observation of ferrimagnetic regulation of Weyl fermions in condensed matter.
Rational design of microRNA-responsive switch for programmable translational control in mammalian cells
Authors: Ning Hui , Liu Gan , Li Lei , Liu Qiang , Huang Huiya , Xie Zhen 
Published: November 2023

AbstractArtificial RNA translation modulation usually relies on multiple components, such as RNA binding proteins (RBPs) or microRNAs (miRNAs) for off-switches and double-inverter cascades for on-switches. Recently, translational circular RNAs (circRNAs) were developed as promising alternatives for linear messenger RNAs (mRNAs). However, circRNAs still lack straightforward and programmable translation control strategies. Here, we rationally design a programmable miRNA-responsive internal ribosome entry site (IRES) translation activation and repression (PROMITAR) platform capable of implementing miRNA-based translation upregulation and downregulation in a single RNA construct. Based on the PROMITAR platform, we construct logic gates and cell-type classifier circRNAs and successfully identify desired mammalian cell types. We also demonstrate the potential therapeutic application of our platform for targeted cancer cell killing by encoding a cytotoxic protein in our engineered circRNAs. We expect our platform to expand the toolbox for RNA synthetic biology and provide an approach for potential biomedical applications in the future.
IL6 suppresses vaccine responses in neonates by enhancing IL2 activity on T follicular helper cells
Authors: Parvathaneni Swetha , Yang Jiyeon , Lotspeich-Cole Leda , Sakai Jiro , Lee Robert C. , Akkoyunlu Mustafa 
Published: November 2023

AbstractThe inability of neonates to develop CD4+FoxP3-CXCR5hiPD-1hi T follicular helper (TFH) cells contributes to their weak vaccine responses. In previous studies, we measured diminished IgG responses when IL-6 was co-injected with a pneumococcal conjugate vaccine (PCV) in neonatal mice. This is in sharp contrast to adults, where IL-6 improves vaccine responses by downregulating the expression of IL-2Rβ on TFH cells and protecting them from the inhibitory effect of IL-2. In this study, we found that splenic IL-6 levels rapidly increased in both adult and neonatal mice following immunization, but the increase in neonatal mice was significantly more than that of adult mice. Moreover, immunized neonatal TFH cells expressed significantly more IL-2 as well as its receptors, IL-2Rα and IL-2Rβ, than the adult cells. Remarkably, IL-6 co-injection with PCV vaccine further increased the production of IL-2 and the expression of its receptors by neonatal TFH cells, whereas excess IL-6 had totally opposite effect in immunized adult mice. Underscoring the role of IL-6 in activating the IL-2 mediated suppression of vaccine responses, immunization of IL-6 knock-out neonates led to improved antibody responses accompanied by expanded TFH cells as well as lower levels of IL-2 and IL-2 receptors on TFH cells. Moreover, CpG containing PCV improved TFH response in neonates by suppressing the expression of IL-2 receptors on TFH cells and inhibiting IL-2 activity. These findings unveil age-specific differences in IL-6 mediated vaccine responses and highlight the need to consider age-related immunobiological attributes in designing vaccines.
An annotated grain kernel image database for visual quality inspection
Authors: Fan Lei , Ding Yiwen , Fan Dongdong , Wu Yong , Chu Hongxia , Pagnucco Maurice , Song Yang 
Published: November 2023

AbstractWe present a machine vision-based database named GrainSet for the purpose of visual quality inspection of grain kernels. The database contains more than 350K single-kernel images with experts’ annotations. The grain kernels used in the study consist of four types of cereal grains including wheat, maize, sorghum and rice, and were collected from over 20 regions in 5 countries. The surface information of each kernel is captured by our custom-built device equipped with high-resolution optic sensor units, and corresponding sampling information and annotations include collection location and time, morphology, physical size, weight, and Damage & Unsound grain categories provided by senior inspectors. In addition, we employed a commonly used deep learning model to provide classification results as a benchmark. We believe that our GrainSet will facilitate future research in fields such as assisting inspectors in grain quality inspections, providing guidance for grain storage and trade, and contributing to applications of smart agriculture.
Emphatic information on bone mineral loss using quantitative ultrasound sonometer for expeditious prediction of osteoporosis
Authors: Ramaraj Kottaimalai , Murugan Pallikonda Rajasekaran , Amiya Gautam , Govindaraj Vishnuvarthanan , Vasudevan Muneeswaran , Thirumurugan M. , Zhang Yudong , Abdullah S. Sheik , Thiyagarajan Arunprasath 
Published: November 2023

AbstractOsteoporosis (OP) and osteoarthritis (OA) are skeletal disorders characterized by a reduction in bone density and quality, resulting in increased fragility and susceptibility to fractures. These illnesses are exhibiting a higher prevalence among both males and females. Fracture risk is determined by using the BMD score (Bone Mineral Density). Looking at the bone loss that comes with osteoarthritis (OA) and osteoporosis (OP), this study also looks at the technological methods used to test for these conditions in order to improve therapies and treatment plans for older people. As a matter of consideration, the prevalence of osteoporosis is higher among postmenopausal women (20%) compared to premenopausal women (14.28%) and males (6.77%). The utilization of a preliminary calcaneal Quantitative Ultrasound (QUS) examination is warranted in order to effectively handle the matter of osteoporosis. The prompt assessment of a patient can provide valuable insights into potential fractures and aid in the prevention of bone injury. In a nutshell, it is imperative to comprehend the impact of OA (osteoarthritis) and OP (osteoporosis) on bone health in order to effectively manage the escalating apprehensions surrounding these conditions. Sophisticated diagnostic techniques, such as the calcaneal quantitative ultrasound (QUS) test, have the potential to enhance the well-being of older individuals by enabling early detection and treatment of many ailments.
Field emission in vacuum resonant tunneling heterostructures with high current densities
Authors: Davidovich Michael V. , Nefedov Igor S. , Glukhova Olga E. , Slepchenkov Michael M. , Rubi J. Miguel 
Published: November 2023

AbstractWe analyse the steady-state thermal regime of a one-dimensional triode resonant tunnelling structure. The high currents generated by resonant tunnelling produce a large amount of heat that could damage the structure. Establishing the conditions under which it can operate at optimum efficiency is therefore a problem of great relevance for applications. The tunnel current is found via eigenvalues of the Schrödinger equation in quantum wells. By calculating the current generated in the device and using the energy conservation law in the electrodes, the temperature reached is obtained for different types of electrodes and the importance of heat conduction and thermal radiation is analysed. In the cases discussed, conduction is dominant. When the electrode material is copper, the temperature reached is similar to that of the thermostat for a wide range of electrode lengths, whereas when the cathode material is diamond-graphite and the anode material is copper, the temperature increases significantly as a function of length. The results obtained allow the temperature to be controlled for optimum performance of the field-emitting triode structures.