bluuebunny/crossref_metadata_2025_split huggingface dataset:
Light-controlled soft bio-microrobot
Authors: Xiong Jianyun , Li Xing , He Ziyi , Shi Yang , Pan Ting , Zhu Guoshuai , Lu Dengyun , Xin Hongbao 
Published: February 2024

AbstractMicro/nanorobots hold exciting prospects for biomedical and even clinical applications due to their small size and high controllability. However, it is still a big challenge to maneuver micro/nanorobots into narrow spaces with high deformability and adaptability to perform complicated biomedical tasks. Here, we report a light-controlled soft bio-microrobots (called “Ebot”) based on Euglena gracilis that are capable of performing multiple tasks in narrow microenvironments including intestinal mucosa with high controllability, deformability and adaptability. The motion of the Ebot can be precisely navigated via light-controlled polygonal flagellum beating. Moreover, the Ebot shows highly controlled deformability with different light illumination duration, which allows it to pass through narrow and curved microchannels with high adaptability. With these features, Ebots are able to execute multiple tasks, such as targeted drug delivery, selective removal of diseased cells in intestinal mucosa, as well as photodynamic therapy. This light-controlled Ebot provides a new bio-microrobotic tool, with many new possibilities for biomedical task execution in narrow and complicated spaces where conventional tools are difficult to access due to the lack of deformability and bio-adaptability.
Precise genome-editing in human diseases: mechanisms, strategies and applications
Authors: Zheng Yanjiang , Li Yifei , Zhou Kaiyu , Li Tiange , VanDusen Nathan J. , Hua Yimin 
Published: February 2024

AbstractPrecise genome-editing platforms are versatile tools for generating specific, site-directed DNA insertions, deletions, and substitutions. The continuous enhancement of these tools has led to a revolution in the life sciences, which promises to deliver novel therapies for genetic disease. Precise genome-editing can be traced back to the 1950s with the discovery of DNA’s double-helix and, after 70 years of development, has evolved from crude in vitro applications to a wide range of sophisticated capabilities, including in vivo applications. Nonetheless, precise genome-editing faces constraints such as modest efficiency, delivery challenges, and off-target effects. In this review, we explore precise genome-editing, with a focus on introduction of the landmark events in its history, various platforms, delivery systems, and applications. First, we discuss the landmark events in the history of precise genome-editing. Second, we describe the current state of precise genome-editing strategies and explain how these techniques offer unprecedented precision and versatility for modifying the human genome. Third, we introduce the current delivery systems used to deploy precise genome-editing components through DNA, RNA, and RNPs. Finally, we summarize the current applications of precise genome-editing in labeling endogenous genes, screening genetic variants, molecular recording, generating disease models, and gene therapy, including ex vivo therapy and in vivo therapy, and discuss potential future advances.
Association of emotional and behavioral problems with the development of the substantia nigra, subthalamic nucleus, and red nucleus volumes and asymmetries from childhood to adolescence: A longitudinal cohort study
Authors: Wang Yanpei , Ma Leilei , Wang Jiali , Liu Ningyu , Men Weiwei , Tan Shuping , Gao Jia-Hong , Qin Shaozheng , He Yong , Dong Qi , Tao Sha 
Published: February 2024

AbstractThe substantia nigra (SN), subthalamic nucleus (STN), and red nucleus (RN) have been widely studied as important biomarkers of degenerative diseases. However, how they develop in childhood and adolescence and are affected by emotional behavior has not been studied thus far. This population-based longitudinal cohort study used data from a representative sample followed two to five times. Emotional and behavioral problems were assessed with the Strengths and Difficulties Questionnaire (SDQ). Linear mixed models were used to map developmental trajectories and behavioral regulation. Using an innovative automated image segmentation technique, we quantified the volumes and asymmetries of the SN, STN and RN with 1226 MRI scans of a large longitudinal sample of 667 subjects aged 6–15 years and mapped their developmental trajectories. The results showed that the absolute and relative volumes of the bilateral SN and right STN showed linear increases, while the absolute volume of the right RN and relative volume of the bilateral RN decreased linearly, these effects were not affected by gender. Hyperactivity/inattention weakened the increase in SN volume and reduced the absolute volume of the STN, conduct problems impeded the RN volume from decreasing, and emotional symptoms changed the direction of SN lateralization. This longitudinal cohort study mapped the developmental trajectories of SN, STN, and RN volumes and asymmetries from childhood to adolescence, and found the association of emotional symptoms, conduct problems, and hyperactivity/inattention with these trajectories, providing guidance for preventing and intervening in cognitive and emotional behavioral problems.
A guardian turned rogue: TP53 promoter translocations rewire stress responses to oncogenic effectors in osteosarcoma
Authors: Herold Nikolas 
Published: February 2024

AbstractOsteosarcoma is the most prevalent malignant bone tumour in children, adolescents and young adults. Despite a multitude of aberrations present in osteosarcoma genomes, no recurrent driver mutations have been identified to date. In addition, unlike for other sarcoma entities, no functional fusion proteins resulting from chromosomal rearrangements have been reported. Part of the genetic complexity of osteosarcoma might, however, be explained by the association of osteosarcoma with germline and somatic mutations of the major tumour suppressor TP53 that safeguards genomic integrity. By demonstrating that TP53 promoter translocations resulting in transcriptionally active fusion genes are a recurrent event in osteosarcoma, long-learnt paradigms are challenged by a recent publication by Saba, Difilippo et al. Osteosarcoma no longer appears to be a fusion-negative tumour, and by hardwiring cellular stress responses that transactivate the TP53 promoter to an oncogenic fusion partner, TP53 can be subverted and turned into an oncogene.
Multimodal detection of molecular residual disease in high-risk locally advanced squamous cell carcinoma of the head and neck
Authors: Sanz-Garcia Enrique , Zou Jinfeng , Avery Lisa , Spreafico Anna , Waldron John , Goldstein David , Hansen Aaron , Cho B. C. John , de Almeida John , Hope Andrew , Hosni Ali , Hahn Ezra , Perez-Ordonez Bayardo , Zhao Zhen , Smith Christopher , Zheng Yangqiao , Singaravelan Nitthusha , Bratman Scott V. , Siu Lillian L. 
Published: February 2024

AbstractUp to 30% of patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC) relapse. Molecular residual disease (MRD) detection using multiple assays after definitive therapy has not been reported. In this study, we included patients with LA-HNSCC (stage III Human Papilloma virus (HPV)-positive, III-IVB HPV-negative) treated with curative intent. Plasma was collected pre-treatment, at 4–6 weeks (FU1) and 8-12 weeks (FU2) post-treatment. Circulating tumor DNA (ctDNA) was analyzed using a tumor-informed (RaDaR®) and a tumor-naïve (CAPP-seq) assay. HPV DNA was measured using HPV-sequencing (HPV-seq) and digital PCR (dPCR). A total of 86 plasma samples from 32 patients were analyzed; all patients with at least 1 follow-up sample. Most patients were stage III HPV-positive (50%) and received chemoradiation (78%). No patients had radiological residual disease at FU2. With a median follow-up of 25 months, there were 7 clinical relapses. ctDNA at baseline was detected in 15/17 (88%) by RaDaR and was not associated with recurrence free survival (RFS). Two patients relapsed within a year after definitive therapy and showed MRD at FU2 using RaDaR; detection of ctDNA during follow-up was associated with shorter RFS (p < 0.001). ctDNA detection by CAPP-seq pre-treatment and during follow-up was not associated with RFS (p = 0.09). HPV DNA using HPV-seq or dPCR during follow-up was associated with shorter RFS (p < 0.001). Sensitivity and specificity for MRD at FU2 using RaDaR was 40% and 100% versus 20 and 90.5% using CAPP-seq. Sensitivity and specificity for MRD during follow-up using HPV-seq was 100% and 91.7% versus 50% and 100% using dPCR. In conclusion, HPV DNA and ctDNA can be detected in LA-HNSCC before definitive therapy. The RaDaR assay but not CAPP-seq may detect MRD in patients who relapse within 1 year. HPV-seq may be more sensitive than dPCR for MRD detection.
Single-cell multi-omics analysis of lineage development and spatial organization in the human fetal cerebellum
Authors: Yang Fuqiang , Zhao Ziqi , Zhang Dan , Xiong Yu , Dong Xinran , Wang Yuchen , Yang Min , Pan Taotao , Liu Chuanyu , Liu Kaiyi , Lin Yifeng , Liu Yongjie , Tu Qiang , Dang Yashan , Xia Mingyang , Mi Da , Zhou Wenhao , Xu Zhiheng 
Published: February 2024

AbstractHuman cerebellum encompasses numerous neurons, exhibiting a distinct developmental paradigm from cerebrum. Here we conducted scRNA-seq, scATAC-seq and spatial transcriptomic analyses of fetal samples from gestational week (GW) 13 to 18 to explore the emergence of cellular diversity and developmental programs in the developing human cerebellum. We identified transitory granule cell progenitors that are conserved across species. Special patterns in both granule cells and Purkinje cells were dissected multidimensionally. Species-specific gene expression patterns of cerebellar lobes were characterized and we found that PARM1 exhibited inconsistent distribution in human and mouse granule cells. A novel cluster of potential neuroepithelium at the rhombic lip was identified. We also resolved various subtypes of Purkinje cells and unipolar brush cells and revealed gene regulatory networks controlling their diversification. Therefore, our study offers a valuable multi-omics landscape of human fetal cerebellum and advances our understanding of development and spatial organization of human cerebellum.
Targeting HDAC6 to treat heart failure with preserved ejection fraction in mice
Authors: Ranjbarvaziri Sara , Zeng Aliya , Wu Iris , Greer-Short Amara , Farshidfar Farshad , Budan Ana , Xu Emma , Shenwai Reva , Kozubov Matthew , Li Cindy , Van Pell Melissa , Grafton Francis , MacKay Charles E , Song Xiaomei , Priest James R , Argast Gretchen , Mandegar Mohammad A. , Hoey Timothy , Yang Jin 
Published: February 2024

AbstractHeart failure with preserved ejection fraction (HFpEF) poses therapeutic challenges due to the limited treatment options. Building upon our previous research that demonstrates the efficacy of histone deacetylase 6 (HDAC6) inhibition in a genetic cardiomyopathy model, we investigate HDAC6’s role in HFpEF due to their shared mechanisms of inflammation and metabolism. Here, we show that inhibiting HDAC6 with TYA-018 effectively reverses established heart failure and its associated symptoms in male HFpEF mouse models. Additionally, in male mice lacking Hdac6 gene, HFpEF progression is delayed and they are resistant to TYA-018’s effects. The efficacy of TYA-018 is comparable to a sodium-glucose cotransporter 2 (SGLT2) inhibitor, and the combination shows enhanced effects. Mechanistically, TYA-018 restores gene expression related to hypertrophy, fibrosis, and mitochondrial energy production in HFpEF heart tissues. Furthermore, TYA-018 also inhibits activation of human cardiac fibroblasts and enhances mitochondrial respiratory capacity in cardiomyocytes. In this work, our findings show that HDAC6 impacts on heart pathophysiology and is a promising target for HFpEF treatment.
NINJ1 mediates inflammatory cell death, PANoptosis, and lethality during infection conditions and heat stress
Authors: Han Joo-Hui , Karki Rajendra , Malireddi R. K. Subbarao , Mall Raghvendra , Sarkar Roman , Sharma Bhesh Raj , Klein Jonathon , Berns Harmut , Pisharath Harshan , Pruett-Miller Shondra M. , Bae Sung-Jin , Kanneganti Thirumala-Devi 
Published: February 2024

AbstractInnate immunity provides the first line of defense through multiple mechanisms, including pyrogen production and cell death. While elevated body temperature during infection is beneficial to clear pathogens, heat stress (HS) can lead to inflammation and pathology. Links between pathogen exposure, HS, cytokine release, and inflammation have been observed, but fundamental innate immune mechanisms driving pathology during pathogen exposure and HS remain unclear. Here, we use multiple genetic approaches to elucidate innate immune pathways in infection or LPS and HS models. Our results show that bacteria and LPS robustly increase inflammatory cell death during HS that is dependent on caspase-1, caspase-11, caspase-8, and RIPK3 through the PANoptosis pathway. Caspase-7 also contributes to PANoptosis in this context. Furthermore, NINJ1 is an important executioner of this cell death to release inflammatory molecules, independent of other pore-forming executioner proteins, gasdermin D, gasdermin E, and MLKL. In an in vivo HS model, mortality is reduced by deleting NINJ1 and fully rescued by deleting key PANoptosis molecules. Our findings suggest that therapeutic strategies blocking NINJ1 or its upstream regulators to prevent PANoptosis may reduce the release of inflammatory mediators and benefit patients.
Transfer learning with graph neural networks for improved molecular property prediction in the multi-fidelity setting
Authors: Buterez David , Janet Jon Paul , Kiddle Steven J. , Oglic Dino , Lió Pietro 
Published: February 2024

AbstractWe investigate the potential of graph neural networks for transfer learning and improving molecular property prediction on sparse and expensive to acquire high-fidelity data by leveraging low-fidelity measurements as an inexpensive proxy for a targeted property of interest. This problem arises in discovery processes that rely on screening funnels for trading off the overall costs against throughput and accuracy. Typically, individual stages in these processes are loosely connected and each one generates data at different scale and fidelity. We consider this setup holistically and demonstrate empirically that existing transfer learning techniques for graph neural networks are generally unable to harness the information from multi-fidelity cascades. Here, we propose several effective transfer learning strategies and study them in transductive and inductive settings. Our analysis involves a collection of more than 28 million unique experimental protein-ligand interactions across 37 targets from drug discovery by high-throughput screening and 12 quantum properties from the dataset QMugs. The results indicate that transfer learning can improve the performance on sparse tasks by up to eight times while using an order of magnitude less high-fidelity training data. Moreover, the proposed methods consistently outperform existing transfer learning strategies for graph-structured data on drug discovery and quantum mechanics datasets.
MarShie: a clearing protocol for 3D analysis of single cells throughout the bone marrow at subcellular resolution
Authors: Mertens Till Fabian , Liebheit Alina Tabea , Ehl Johanna , Köhler Ralf , Rakhymzhan Asylkhan , Woehler Andrew , Katthän Lukas , Ebel Gernot , Liublin Wjatscheslaw , Kasapi Ana , Triantafyllopoulou Antigoni , Schulz Tim Julius , Niesner Raluca Aura , Hauser Anja Erika 
Published: February 2024

AbstractAnalyzing immune cell interactions in the bone marrow is vital for understanding hematopoiesis and bone homeostasis. Three-dimensional analysis of the complete, intact bone marrow within the cortex of whole long bones remains a challenge, especially at subcellular resolution. We present a method that stabilizes the marrow and provides subcellular resolution of fluorescent signals throughout the murine femur, enabling identification and spatial characterization of hematopoietic and stromal cell subsets. By combining a pre-processing algorithm for stripe artifact removal with a machine-learning approach, we demonstrate reliable cell segmentation down to the deepest bone marrow regions. This reveals age-related changes in the marrow. It highlights the interaction between CX3CR1+ cells and the vascular system in homeostasis, in contrast to other myeloid cell types, and reveals their spatial characteristics after injury. The broad applicability of this method will contribute to a better understanding of bone marrow biology.
CCl4 emissions in eastern China during 2021–2022 and exploration of potential new sources
Authors: Li Bowei , Huang Jiahuan , Hu Xiaoyi , Zhang Lulu , Ma Mengyue , Hu Liting , Chen Di , Du Qianna , Sun Yahui , Cai Zhouxiang , Chen Ao , Li Xinhe , Feng Rui , Prinn Ronald G. , Fang Xuekun 
Published: February 2024

AbstractAccording to the Montreal Protocol, the production and consumption of ozone-layer-depleting CCl4 for dispersive applications was globally phased out by 2010, including China. However, continued CCl4 emissions were disclosed, with the latest CCl4 emissions unknown in eastern China. In the current study, based on the atmospheric measurements of ~12,000 air samples taken at two sites in eastern China, the 2021–2022 CCl4 emissions are quantified as 7.6 ± 1.7 gigagrams per year. This finding indicates that CCl4 emissions continued after being phased out for dispersive uses in 2010. Subsequently, our study identifies potential industrial sources (manufacture of general purpose machinery and manufacture of raw chemical materials, and chemical products) of CCl4 emissions.
Phase-selective in-plane heteroepitaxial growth of H-phase CrSe2
Authors: Liu Meizhuang , Gou Jian , Liu Zizhao , Chen Zuxin , Ye Yuliang , Xu Jing , Xu Xiaozhi , Zhong Dingyong , Eda Goki , Wee Andrew T. S. 
Published: February 2024

AbstractPhase engineering of two-dimensional transition metal dichalcogenides (2D-TMDs) offers opportunities for exploring unique phase-specific properties and achieving new desired functionalities. Here, we report a phase-selective in-plane heteroepitaxial method to grow semiconducting H-phase CrSe2. The lattice-matched MoSe2 nanoribbons are utilized as the in-plane heteroepitaxial template to seed the growth of H-phase CrSe2 with the formation of MoSe2-CrSe2 heterostructures. Scanning tunneling microscopy and non-contact atomic force microscopy studies reveal the atomically sharp heterostructure interfaces and the characteristic defects of mirror twin boundaries emerging in the H-phase CrSe2 monolayers. The type-I straddling band alignments with band bending at the heterostructure interfaces are directly visualized with atomic precision. The mirror twin boundaries in the H-phase CrSe2 exhibit the Tomonaga-Luttinger liquid behavior in the confined one-dimensional electronic system. Our work provides a promising strategy for phase engineering of 2D TMDs, thereby promoting the property research and device applications of specific phases.
Transient disome complex formation in native polysomes during ongoing protein synthesis captured by cryo-EM
Authors: Flügel Timo , Schacherl Magdalena , Unbehaun Anett , Schroeer Birgit , Dabrowski Marylena , Bürger Jörg , Mielke Thorsten , Sprink Thiemo , Diebolder Christoph A. , Guillén Schlippe Yollete V. , Spahn Christian M. T. 
Published: February 2024

AbstractStructural studies of translating ribosomes traditionally rely on in vitro assembly and stalling of ribosomes in defined states. To comprehensively visualize bacterial translation, we reactivated ex vivo-derived E. coli polysomes in the PURE in vitro translation system and analyzed the actively elongating polysomes by cryo-EM. We find that 31% of 70S ribosomes assemble into disome complexes that represent eight distinct functional states including decoding and termination intermediates, and a pre-nucleophilic attack state. The functional diversity of disome complexes together with RNase digest experiments suggests that paused disome complexes transiently form during ongoing elongation. Structural analysis revealed five disome interfaces between leading and queueing ribosomes that undergo rearrangements as the leading ribosome traverses through the elongation cycle. Our findings reveal at the molecular level how bL9’s CTD obstructs the factor binding site of queueing ribosomes to thwart harmful collisions and illustrate how translation dynamics reshape inter-ribosomal contacts.
Distance effect of single atoms on stability of cobalt oxide catalysts for acidic oxygen evolution
Authors: Zhang Zhirong , Jia Chuanyi , Ma Peiyu , Feng Chen , Yang Jin , Huang Junming , Zheng Jiana , Zuo Ming , Liu Mingkai , Zhou Shiming , Zeng Jie 
Published: February 2024

AbstractDeveloping efficient and economical electrocatalysts for acidic oxygen evolution reaction (OER) is essential for proton exchange membrane water electrolyzers (PEMWE). Cobalt oxides are considered promising non-precious OER catalysts due to their high activities. However, the severe dissolution of Co atoms in acid media leads to the collapse of crystal structure, which impedes their application in PEMWE. Here, we report that introducing acid-resistant Ir single atoms into the lattice of spinel cobalt oxides can significantly suppress the Co dissolution and keep them highly stable during the acidic OER process. Combining theoretical and experimental studies, we reveal that the stabilizing effect induced by Ir heteroatoms exhibits a strong dependence on the distance of adjacent Ir single atoms, where the OER stability of cobalt oxides continuously improves with decreasing the distance. When the distance reduces to about 0.6 nm, the spinel cobalt oxides present no obvious degradation over a 60-h stability test for acidic OER, suggesting potential for practical applications.
Shaping high-performance wearable robots for human motor and sensory reconstruction and enhancement
Authors: Xia Haisheng , Zhang Yuchong , Rajabi Nona , Taleb Farzaneh , Yang Qunting , Kragic Danica , Li Zhijun 
Published: February 2024

AbstractMost wearable robots such as exoskeletons and prostheses can operate with dexterity, while wearers do not perceive them as part of their bodies. In this perspective, we contend that integrating environmental, physiological, and physical information through multi-modal fusion, incorporating human-in-the-loop control, utilizing neuromuscular interface, employing flexible electronics, and acquiring and processing human-robot information with biomechatronic chips, should all be leveraged towards building the next generation of wearable robots. These technologies could improve the embodiment of wearable robots. With optimizations in mechanical structure and clinical training, the next generation of wearable robots should better facilitate human motor and sensory reconstruction and enhancement.