bluuebunny/crossref_metadata_2025_split huggingface dataset:
UBE2O reduces the effectiveness of interferon-α via degradation of IFIT3 in hepatocellular carcinoma
Authors: Li Heng , Liu Yao , Cheng Can , Wu Yang , Liang Shu-Hang , Wu Liang , Wang Hong , Tu Cong-yin , Yao Han-Hui , Meng Fan-Zheng , Zhang Bo , Wang Wei , Wang Jia-Bei , Liu Lian-Xin 
Published: December 2023

AbstractInterferon (IFN) exerts its effects through interferon-stimulated genes (ISGs), but its efficacy is limited by interferon resistance, which can be caused by the ubiquitination of key proteins. UBE2O was initially identified as a promising therapeutic target based on data from the TCGA and iUUCD 2.0 databases. Through the inhibition of UBE2O, interferon α/β signaling and overall interferon signaling were activated. Integrating data from proteomic, mass spectrometry, and survival analyses led to the identification of IFIT3, a mediator of interferon signaling, as a ubiquitination substrate of UBE2O. The results of in vitro and in vivo experiments demonstrated that the knockdown of UBE2O can enhance the efficacy of interferon-α by upregulating IFIT3 expression. K236 was identified as a ubiquitination site in IFIT3, and the results of rescue experiments confirmed that the effect of UBE2O on interferon-α sensitivity is dependent on IFIT3 activity. ATO treatment inhibited UBE2O and increased IFIT3 expression, thereby increasing the effectiveness of interferon-α. In conclusion, these findings suggest that UBE2O worsens the therapeutic effect of interferon-α by targeting IFIT3 for ubiquitination and degradation.
Structural insights into the regulation, ligand recognition, and oligomerization of bacterial STING
Authors: Hou Mei-Hui , Wang Yu-Chuan , Yang Chia-Shin , Liao Kuei-Fen , Chang Je-Wei , Shih Orion , Yeh Yi-Qi , Sriramoju Manoj Kumar , Weng Tzu-Wen , Jeng U-Ser , Hsu Shang-Te Danny , Chen Yeh 
Published: December 2023

AbstractThe cyclic GMP-AMP synthase (cGAS)/stimulator of interferon gene (STING) signaling pathway plays a critical protective role against viral infections. Metazoan STING undergoes multilayers of regulation to ensure specific signal transduction. However, the mechanisms underlying the regulation of bacterial STING remain unclear. In this study, we determined the crystal structure of anti-parallel dimeric form of bacterial STING, which keeps itself in an inactive state by preventing cyclic dinucleotides access. Conformational transition between inactive and active states of bacterial STINGs provides an on-off switch for downstream signaling. Some bacterial STINGs living in extreme environment contain an insertion sequence, which we show codes for an additional long lid that covers the ligand-binding pocket. This lid helps regulate anti-phage activities. Furthermore, bacterial STING can bind cyclic di-AMP in a triangle-shaped conformation via a more compact ligand-binding pocket, forming spiral-shaped protofibrils and higher-order fibril filaments. Based on the differences between cyclic-dinucleotide recognition, oligomerization, and downstream activation of different bacterial STINGs, we proposed a model to explain structure-function evolution of bacterial STINGs.
Janus particles with tunable patch symmetry and their assembly into chiral colloidal clusters
Authors: Zhang Tianran , Lyu Dengping , Xu Wei , Feng Xuan , Ni Ran , Wang Yufeng 
Published: December 2023

AbstractJanus particles, which have an attractive patch on the otherwise repulsive surface, have been commonly employed for anisotropic colloidal assembly. While current methods of particle synthesis allow for control over the patch size, they are generally limited to producing dome-shaped patches with a high symmetry (C∞). Here, we report on the synthesis of Janus particles with patches of various tunable shapes, having reduced symmetries ranging from C2v to C3v and C4v. The Janus particles are synthesized by partial encapsulation of an octahedral metal-organic framework particle (UiO-66) in a polymer matrix. The extent of encapsulation is precisely regulated by a stepwise, asymmetric dewetting process that exposes selected facets of the UiO-66 particle. With depletion interaction, the Janus particles spontaneously assemble into colloidal clusters reflecting the particles’ shapes and patch symmetries. We observe the formation of chiral structures, whereby chirality emerges from achiral building blocks. With the ability to encode symmetry and directional bonding information, our strategy could give access to more complex colloidal superstructures through assembly.
Magnetic order in 2D antiferromagnets revealed by spontaneous anisotropic magnetostriction
Authors: Houmes Maurits J. A. , Baglioni Gabriele , Šiškins Makars , Lee Martin , Esteras Dorye L. , Ruiz Alberto M. , Mañas-Valero Samuel , Boix-Constant Carla , Baldoví Jose J. , Coronado Eugenio , Blanter Yaroslav M. , Steeneken Peter G. , van der Zant Herre S. J. 
Published: December 2023

AbstractThe temperature dependent order parameter provides important information on the nature of magnetism. Using traditional methods to study this parameter in two-dimensional (2D) magnets remains difficult, however, particularly for insulating antiferromagnetic (AF) compounds. Here, we show that its temperature dependence in AF MPS3 (M(II) = Fe, Co, Ni) can be probed via the anisotropy in the resonance frequency of rectangular membranes, mediated by a combination of anisotropic magnetostriction and spontaneous staggered magnetization. Density functional calculations followed by a derived orbital-resolved magnetic exchange analysis confirm and unravel the microscopic origin of this magnetization-induced anisotropic strain. We further show that the temperature and thickness dependent order parameter allows to deduce the material’s critical exponents characterising magnetic order. Nanomechanical sensing of magnetic order thus provides a future platform to investigate 2D magnetism down to the single-layer limit.
Fast free energy estimates from λ-dynamics with bias-updated Gibbs sampling
Authors: Robo Michael T. , Hayes Ryan L. , Ding Xinqiang , Pulawski Brian , Vilseck Jonah Z. 
Published: December 2023

AbstractRelative binding free energy calculations have become an integral computational tool for lead optimization in structure-based drug design. Classical alchemical methods, including free energy perturbation or thermodynamic integration, compute relative free energy differences by transforming one molecule into another. However, these methods have high operational costs due to the need to perform many pairwise perturbations independently. To reduce costs and accelerate molecular design workflows, we present a method called λ-dynamics with bias-updated Gibbs sampling. This method uses dynamic biases to continuously sample between multiple ligand analogues collectively within a single simulation. We show that many relative binding free energies can be determined quickly with this approach without compromising accuracy. For five benchmark systems, agreement to experiment is high, with root mean square errors near or below 1.0 kcal mol−1. Free energy results are consistent with other computational approaches and within statistical noise of both methods (0.4 kcal mol−1or less). Notably, large efficiency gains over thermodynamic integration of 18–66-fold for small perturbations and 100–200-fold for whole aromatic ring substitutions are observed. The rapid determination of relative binding free energies will enable larger chemical spaces to be more readily explored and structure-based drug design to be accelerated.
Asymmetric coding of reward prediction errors in human insula and dorsomedial prefrontal cortex
Authors: Hoy Colin W. , Quiroga-Martinez David R. , Sandoval Eduardo , King-Stephens David , Laxer Kenneth D. , Weber Peter , Lin Jack J. , Knight Robert T. 
Published: December 2023

AbstractThe signed value and unsigned salience of reward prediction errors (RPEs) are critical to understanding reinforcement learning (RL) and cognitive control. Dorsomedial prefrontal cortex (dMPFC) and insula (INS) are key regions for integrating reward and surprise information, but conflicting evidence for both signed and unsigned activity has led to multiple proposals for the nature of RPE representations in these brain areas. Recently developed RL models allow neurons to respond differently to positive and negative RPEs. Here, we use intracranially recorded high frequency activity (HFA) to test whether this flexible asymmetric coding strategy captures RPE coding diversity in human INS and dMPFC. At the region level, we found a bias towards positive RPEs in both areas which paralleled behavioral adaptation. At the local level, we found spatially interleaved neural populations responding to unsigned RPE salience and valence-specific positive and negative RPEs. Furthermore, directional connectivity estimates revealed a leading role of INS in communicating positive and unsigned RPEs to dMPFC. These findings support asymmetric coding across distinct but intermingled neural populations as a core principle of RPE processing and inform theories of the role of dMPFC and INS in RL and cognitive control.
Unraveling the causal genes and transcriptomic determinants of human telomere length
Authors: Chang Ying , Zhou Yao , Zhou Junrui , Li Wen , Cao Jiasong , Jing Yaqing , Zhang Shan , Shen Yongmei , Lin Qimei , Fan Xutong , Yang Hongxi , Dong Xiaobao , Zhang Shijie , Yi Xianfu , Shuai Ling , Shi Lei , Liu Zhe , Yang Jie , Ma Xin , Hao Jihui , Chen Kexin , Li Mulin Jun , Wang Feng , Huang Dandan 
Published: December 2023

AbstractTelomere length (TL) shortening is a pivotal indicator of biological aging and is associated with many human diseases. The genetic determinates of human TL have been widely investigated, however, most existing studies were conducted based on adult tissues which are heavily influenced by lifetime exposure. Based on the analyses of terminal restriction fragment (TRF) length of telomere, individual genotypes, and gene expressions on 166 healthy placental tissues, we systematically interrogate TL-modulated genes and their potential functions. We discover that the TL in the placenta is comparatively longer than in other adult tissues, but exhibiting an intra-tissue homogeneity. Trans-ancestral TL genome-wide association studies (GWASs) on 644,553 individuals identify 20 newly discovered genetic associations and provide increased polygenic determination of human TL. Next, we integrate the powerful TL GWAS with placental expression quantitative trait locus (eQTL) mapping to prioritize 23 likely causal genes, among which 4 are functionally validated, including MMUT, RRM1, KIAA1429, and YWHAZ. Finally, modeling transcriptomic signatures and TRF-based TL improve the prediction performance of human TL. This study deepens our understanding of causal genes and transcriptomic determinants of human TL, promoting the mechanistic research on fine-grained TL regulation.
Authigenic mineralization in Surtsey basaltic tuff deposits at 50 years after eruption
Authors: Montesano Giovanna , Rispoli Concetta , Petrosino Paola , Jackson Marie D. , Weisenberger Tobias B. , Gudmundsson Magnús T. , Cappelletti Piergiulio 
Published: December 2023

AbstractAlteration of basaltic glass and in situ mineral growth are fundamental processes that influence the chemical and material properties of Earth’s oceanic crust. These processes have evolved at the basaltic island of Surtsey (SW Iceland) since eruptions terminated in 1967. Here, subaerial and submarine lapilli tuff samples from a 192 m-deep borehole drilled in 2017 (SE-02b) are characterized through petrographic studies, X-ray powder diffraction analyses, and SEM–EDS imaging and chemical analyses. The integrated results reveal (i) multi-stage palagonitization processes in basaltic glass and precipitation of secondary minerals from matrix pore fluids, (ii) multi-stage crystallization of secondary phillipsite, analcime and Al-tobermorite in the vesicles of basaltic pyroclasts and (iii) variations in palagonitization processes as a function of thermal and hydrological domains. Although temperature appears to be an important factor in controlling rates of secondary mineralization, the chemistry of original basaltic components and interstitial fluids also influences reaction pathways in the young pyroclastic deposits. The integration of systematic mineralogical analyses of the 50-year-old tuff from one of the most carefully monitored volcanic sites on Earth, together with temperature monitoring in boreholes since 1980, provide a reference framework for evaluating mineralogical evolution in other Surtseyan-type volcanoes worldwide.
Mir-142-3P regulates MAPK protein family by inhibiting 14-3-3η to enhance bone marrow mesenchymal stem cells osteogenesis
Authors: Liu Ya-qian , Xu Yue-chen , Shuai Zong-wen 
Published: December 2023

AbstractClinical studies have found 14-3-3η to be associated with osteoporosis through undefined mechanisms. We aimed to investigate the role of 14-3-3η in osteoporosis and its potential associations with miRNAs. The Gene Expression Omnibus(GEO) and Human Protein Atlas 1 databases were analyzed to examine both the mRNA and protein expression of 14-3-3η in OP. Gene enrichment analyses were performed to explore the underlying mechanism of 14-3-3η based on DAVID. miRWalk was used to predict the associated miRNAs. The statistics were analysed by R software and SPSS software. 14-3-3η was overexpressed and knock down expressed in BMSCs by lentiviral vector transfecting. And BMSCs were induced by hypoxia. qRT-PCR and Western-Blot verified the expression of mRNA and protein. Scratch assay detected the migration of osteocytes. Co-immunoprecipitation and luciferase assay studied the 14-3-3η targeted protein and miRNA. overexpression and knock down of miRNA to verify the relationship of 14-3-3η and target genes. The 14-3-3η mRNA expression level was low in patients with osteoporosis, as corroborated by immunohistochemical staining images. Functional analyses revealed enrichment of the MAPK-associated cascade. 14-3-3η was correlated with MAPK family proteins and five key miRNAs, including mir-142-3p. In addition, 14-3-3η knockdown in BMSCs increased the mRNA and protein expression levels of Hif-α, VEGF, BMP-2, OPN, OST, and Runx2, and enhanced the cells migration ability. Under hypoxic conditions, Hif-α and BMP-2 protein expression levels were upregulated, whereas those of 14-3-3η and MAPK3 were downregulated. Co-immunoprecipitation experiments showed decreased binding of 14-3-3η to MAPK3. 14-3-3η knockdown produced the same results as hypoxia induction. Adding caspase3 inhibitor and knocking down 14-3-3η again prevented MAPK3 cleavage by caspase3 and inhibited BMP-2 expression. Moreover, under hypoxic conditions, miR-142-3P expression was upregulated and luciferase assays revealed 14-3-3η as its target gene. miR-142-3P overexpression decreased mRNA and protein levels of 14-3-3η and MAPK3, while increasing BMP-2 expression. miR-142-3P knockdown reversed these results. BMSC osteogenesis was suppressed by 14-3-3η, whereas miRNA-142-3p promoted it through the inhibition of 14-3-3η.
Inhibition of the Nogo-pathway in experimental spinal cord injury: a meta-analysis of 76 experimental treatments
Authors: Hirt Julian , Khanteymoori Alireza , Hohenhaus Marc , Kopp Marcel A. , Howells David W. , Schwab Jan M. , Watzlawick Ralf 
Published: December 2023

AbstractRecovery after spinal cord injury (SCI) may be propagated by plasticity-enhancing treatments. The myelin-associated nerve outgrowth inhibitor Nogo-A (Reticulon 4, RTN4) pathway has been shown to restrict neuroaxonal plasticity in experimental SCI models. Early randomized controlled trials are underway to investigate the effect of Nogo-A/Nogo-Receptor (NgR1) pathway blockers. This systematic review and meta-analysis of therapeutic approaches blocking the Nogo-A pathway interrogated the efficacy of functional locomotor recovery after experimental SCI according to a pre-registered study protocol. A total of 51 manuscripts reporting 76 experiments in 1572 animals were identified for meta-analysis. Overall, a neurobehavioral improvement by 18.9% (95% CI 14.5–23.2) was observed. Subgroup analysis (40 experiments, N = 890) revealed SCI-modelling factors associated with outcome variability. Lack of reported randomization and smaller group sizes were associated with larger effect sizes. Delayed treatment start was associated with lower effect sizes. Trim and Fill assessment as well as Egger regression suggested the presence of publication bias. Factoring in theoretically missing studies resulted in a reduced effect size [8.8% (95% CI 2.6–14.9)]. The available data indicates that inhibition of the Nogo-A/NgR1pathway alters functional recovery after SCI in animal studies although substantial differences appear for the applied injury mechanisms and other study details. Mirroring other SCI interventions assessed earlier we identify similar factors associated with outcome heterogeneity.
Comparison of markerless and marker-based motion capture systems using 95% functional limits of agreement in a linear mixed-effects modelling framework
Authors: Das Kishor , de Paula Oliveira Thiago , Newell John 
Published: December 2023

AbstractBiomechanics analysis of human movement has been proven useful for maintenance of health, injury prevention, and rehabilitation in both sports and clinical populations. A marker-based motion capture system is considered the gold standard method of measurement for three dimensional kinematics measurements. However, the application of markers to anatomical bony points is a time consuming process and constrained by inter-, intra-tester and session reliability issues. The emergence of novel markerless motion capture systems without the use of reflective markers is a rapidly growing field in motion analysis. However an assessment of the level of agreement of a markerless system with an established gold standard marker-based system is needed to ensure the applicability of a markerless system. An extra layer of complexity is involved as the kinematics measurements are functional responses. In this paper a new approach is proposed to generate 95% functional limits of agreement (fLoA) using the linear mixed-effects modelling framework for hierarchical study designs. This approach is attractive as it will allow practitioners to extend their use of linear mixed models to assess agreement in method comparison studies in all domains where functional responses are recorded.
Identification of the length and location of the A1 pulley combining palpation technique with palm landmarks: a cadaveric study
Authors: Zhong Wei-xing , Li Jun-hua , Chen Zu-jiang , Peng Wei-jie , Gu Rui-bin , Chen Chao , Li Yi-kai 
Published: December 2023

AbstractThrough anatomical morphology, to accumulate the relevant parameters of the A1 pulley of each adult finger. A total of 100 fingers were selected, dissected layer by layer, and the A1 pulley and neurovascular of each finger were observed. Measure the length of the A1 pulley, the distance between the needle knife insertion point and the proximal edge of A1 pulley, and the nerves and blood vessels on both sides. (1) The length of A1 pulleys of each finger is 6.18 ± 0.33 mm, 6.58 ± 0.73 mm, 5.98 ± 0.67 mm, 5.36 ± 1.08 mm, 5.63 ± 1.09 mm. (2) The distances between the needle knife entry point of each finger and the volar proper nerve of the ulnar finger are 7.00 ± 1.55 mm, 8.29 ± 1.46 mm, 5.10 ± 0.25 mm, 5.30 ± 0.24 mm, 0 mm; the distances from the volar proper nerve of the radial finger are 9.08 ± 0.87 mm, 4.70 ± 1.10 mm, 7.03 ± 0.72 mm, 6.81 ± 0.22 mm, 7.81 ± 0.57 mm. (3) The distances between the needle knife entry point of each finger and the proper volar artery of the ulnar finger are 10.40 ± 0.75 mm, 8.89 ± 0.53 mm, 6.35 ± 0.44 mm, 7.26 ± 0.16 mm, 0 mm, respectively; The distances from the volar proper artery of the radial finger are 8.75 ± 1.07 mm, 6.10 ± 0.35 mm, 11.44 ± 0.41 mm, 8.19 ± 0.60 mm, 9.78 ± 0.68 mm, respectively. The landmarks of the needle entry points are located at the position corresponding to the highest point of the metacarpal heads, except the tail finger. From the needle knife entry point to distal, cut the proximal edge of the A1 pulley longitudinally along the midline until the patient can flex autonomously, and pay attention to the distance between the two sides of 3.60–11.85 mm neurovascular bundle.
A hybrid algorithm of grey wolf optimizer and harris hawks optimization for solving global optimization problems with improved convergence performance
Authors: Tu Binbin , Wang Fei , Huo Yan , Wang Xiaotian 
Published: December 2023

AbstractThe grey wolf optimizer is an effective and well-known meta-heuristic algorithm, but it also has the weaknesses of insufficient population diversity, falling into local optimal solutions easily, and unsatisfactory convergence speed. Therefore, we propose a hybrid grey wolf optimizer (HGWO), based mainly on the exploitation phase of the harris hawk optimization. It also includes population initialization with Latin hypercube sampling, a nonlinear convergence factor with local perturbations, some extended exploration strategies. In HGWO, the grey wolves can have harris hawks-like flight capabilities during position updates, which greatly expands the search range and improves global searchability. By incorporating a greedy algorithm, grey wolves will relocate only if the new location is superior to the current one. This paper assesses the performance of the hybrid grey wolf optimizer (HGWO) by comparing it with other heuristic algorithms and enhanced schemes of the grey wolf optimizer. The evaluation is conducted using 23 classical benchmark test functions and CEC2020. The experimental results reveal that the HGWO algorithm performs well in terms of its global exploration ability, local exploitation ability, convergence speed, and convergence accuracy. Additionally, the enhanced algorithm demonstrates considerable advantages in solving engineering problems, thus substantiating its effectiveness and applicability.
Atmospheric pathway of marine heatwaves over the Northwestern Pacific
Authors: Noh El , Kim Joowan , Jun Sang-Yoon , Pak Gyundo , Kim Joo-Hong , Kim Hyeong-Gyu 
Published: December 2023

AbstractThis study analyzes the influence of the Pacific–Japan (PJ) atmospheric teleconnection pattern and its interaction with oceanic processes on sea surface warming over the Northwestern Pacific. The PJ pattern is a thermally driven Rossby wave that originates over the tropical western Pacific through deep convection and propagates toward high latitudes. It plays a significant role in sea surface warming by inducing anticyclonic circulation and the corresponding northwestward extension of the subtropical high over the Northwestern Pacific. This study revealed that the key processes responsible for sea surface warming were an increase in insolation and a decrease in the ocean-to-atmosphere latent heat flux under the anticyclonic conditions driven by the PJ. This finding provides valuable insights into the role of atmospheric processes, we refer to it as the “atmospheric pathway”, in the development of East Asian marine heatwaves (MHWs). A detailed understanding of this process will contribute to the prediction and mitigation of MHWs in East Asian countries.