1,479 research outputs found
Effects of Geometrical Symmetry on the Vortex Nucleation and Penetration in Mesoscopic Superconductors
We investigate how the geometrical symmetry affects the penetration and
arrangement of vortices in mesoscopic superconductors using self-consistent
Bogoliubov-de Gennes equations. We find that the entrance of the vortex happens
when the current density at the hot spots reaches the depairing current
density. Through determining the spatial distribution of hot spots, the
geometrical symmetry of the superconducting sample influences the nucleation
and entrance of vortices. Our results propose one possible experimental
approach to control and manipulate the quantum states of mesoscopic
superconductors with their topological geometries, and they can be easily
generalized to the confined superfluids and Bose-Einstein condensates
BASES: Large-scale Web Search User Simulation with Large Language Model based Agents
Due to the excellent capacities of large language models (LLMs), it becomes
feasible to develop LLM-based agents for reliable user simulation. Considering
the scarcity and limit (e.g., privacy issues) of real user data, in this paper,
we conduct large-scale user simulation for web search, to improve the analysis
and modeling of user search behavior. Specially, we propose BASES, a novel user
simulation framework with LLM-based agents, designed to facilitate
comprehensive simulations of web search user behaviors. Our simulation
framework can generate unique user profiles at scale, which subsequently leads
to diverse search behaviors. To demonstrate the effectiveness of BASES, we
conduct evaluation experiments based on two human benchmarks in both Chinese
and English, demonstrating that BASES can effectively simulate large-scale
human-like search behaviors. To further accommodate the research on web search,
we develop WARRIORS, a new large-scale dataset encompassing web search user
behaviors, including both Chinese and English versions, which can greatly
bolster research in the field of information retrieval. Our code and data will
be publicly released soon
Expression of MDR1, HIF-1α and MRP1 in sacral chordoma and chordoma cell line CM-319
<p>Abstract</p> <p>Background</p> <p>Chordoma was a typically slow-growing tumor. The therapeutic approach to chordoma had traditionally relied mainly on surgical therapy. And the main reason for therapeutic failure was resistance to chemotherapy and radiotherapy. However the refractory mechanism was not clear. The aim of this study was to investigate the expression of three genes (<it>MDR1</it>, <it>HIF-1α</it> and <it>MRP1</it>) associated with resistance to chemotherapy and radiotherapy in chordoma and chordoma cell line CM-319.</p> <p>Materials and methods</p> <p>Using immunohistochemical techniques, the expression of MDR1, HIF-1α and MRP1 was investigated in 50 chordoma specimen. Using RT-PCR and Western blot, the expression of MDR1, HIF-1α and MRP1 was investigated in chordoma and chordoma cell line CM-319.</p> <p>Results</p> <p>Expression of MDR1, HIF-1α and MRP1 was observed in 10%, 80% and 74% of all cases, respectively. Expression of MRP1 was correlated with HIF-1α. On the other hand, expression of MDR1 was not correlated with the expression of HIF-1α or MRP1. The expression of HIF-1α and MRP1 was observed, but MDR1 was not observed in chordoma and CM-319.</p> <p>Conclusion</p> <p>Expression of HIF-1α and MRP1 was observed in most chordoma specimen and CM-319 cell line; expression of HIF-1α correlated with MRP1. HIF-1α and MRP1 may play a role in the multidrug resistance of chordoma to chemotherapy.</p
Virus tracking technologies and their applications in viral life cycle: research advances and future perspectives
Viruses are simple yet highly pathogenic microorganisms that parasitize within cells and pose serious threats to the health, economic development, and social stability of both humans and animals. Therefore, it is crucial to understand the dynamic mechanism of virus infection in hosts. One effective way to achieve this is through virus tracking technology, which utilizes fluorescence imaging to track the life processes of virus particles in living cells in real-time, providing a comprehensively and detailed spatiotemporal dynamic process and mechanism of virus infection. This paper provides a broad overview of virus tracking technology, including the selection of fluorescent labels and virus labeling components, the development of imaging microscopes, and its applications in various virus studies. Additionally, we discuss the possibilities and challenges of its future development, offering theoretical guidance and technical support for effective prevention and control of the viral disease outbreaks and epidemics
Loop-Mediated Isothermal Amplification Assay Targeting the MOMP Gene for Rapid Detection of Chlamydia psittaci Abortus Strain
For rapid detection of the Chlamydia psittaci abortus strain, a loop-mediated isothermal amplification (LAMP) assay was developed and evaluated in this study. The primers for the LAMP assay were designed on the basis of the main outer membrane protein (MOMP) gene sequence of C. psittaci. Analysis showed that the assay could detect the abortus strain of C. psittaci with adequate specificity. The sensitivity of the test was the same as that of the nested-conventional PCR and higher than that of chick embryo isolation. Testing of 153 samples indicated that the LAMP assay could detect the genome of the C. psittaci abortus strain effectively in clinical samples. This assay is a useful tool for rapid diagnosis of C. psittaci infection in sheep, swine and cattle
Autophagy as a dual-faced host response to viral infections
Autophagy selectively degrades viral particles or cellular components, either facilitating or inhibiting viral replication. Conversely, most viruses have evolved strategies to escape or exploit autophagy. Moreover, autophagy collaborates with the pattern recognition receptor signaling, influencing the expression of adaptor molecules involved in the innate immune response and regulating the expression of interferons (IFNs). The intricate relationship between autophagy and IFNs plays a critical role in the host cell defense against microbial invasion. Therefore, it is important to summarize the interactions between viral infections, autophagy, and the host defense mechanisms against viruses. This review specifically focuses on the interactions between autophagy and IFN pathways during viral infections, providing a comprehensive summary of the molecular mechanisms utilized or evaded by different viruses
Establishment of an Efficient and Flexible Genetic Manipulation Platform Based on a Fosmid Library for Rapid Generation of Recombinant Pseudorabies Virus
Conventional genetic engineering of pseudorabies virus (PRV) is essentially based on homologous recombination or bacterial artificial chromosome. However, these techniques require multiple plaque purification, which is labor-intensive and time-consuming. The aim of the present study was to develop an efficient, direct, and flexible genetic manipulation platform for PRV. To this end, the PRV genomic DNA was extracted from purified PRV virions and sheared into approximately 30–45-kb DNA fragments. After end-blunting and phosphorylation, the DNA fragments were separated by pulsed-field gel electrophoresis, the recovered DNA fragments were inserted into the cloning-ready fosmids. The fosmids were then transformed into Escherichia coli and selected clones were end-sequenced for full-length genome assembly. Overlapping fosmid combinations that cover the complete genome of PRV were directly transfected into Vero cells and PRV was rescued. The morphology and one-step growth curve of the rescued virus were indistinguishable from those of the parent virus. Based on this system, a recombinant PRV expressing enhanced green fluorescent protein fused with the VP26 gene was generated within 2 weeks, and this recombinant virus can be used to observe the capsid transport in axons. The new genetic manipulation platform developed in the present study is an efficient, flexible, and stable method for the study of the PRV life cycle and development of novel vaccines
Human Hemoglobin Subunit Beta Functions as a Pleiotropic Regulator of RIG-I/MDA5-Mediated Antiviral Innate Immune Responses
Hemoglobin is an important oxygen-carrying protein and plays crucial roles in establishing host resistance against pathogens and in regulating innate immune responses. The hemoglobin subunit beta (HB) is an essential component of hemoglobin, and we have previously demonstrated that the antiviral role of the porcine HB (pHB) is mediated by promoting type I interferon pathways. Thus, considering the high homology between human HB (hHB) and pHB, we hypothesized that hHB also plays an important role in the antiviral innate immunity. In this study, we characterized hHB as a regulatory factor for the replication of RNA viruses by differentially regulating the RIG-I- and MDA5-mediated antiviral signaling pathways. Furthermore, we showed that hHB directly inhibited MDA5-mediated signaling by reducing the MDA5-double-stranded RNA (dsRNA) interaction. Additionally, hHB required hHB-induced reactive oxygen species (ROS) to promote RIG-I-mediated signaling through enhancement of K63-linked RIG-I ubiquitination. Taken together, our findings suggest that hHB is a pleiotropic regulator of RIG-I/MDA5-mediated antiviral responses and further highlight the importance of the intercellular microenvironment, including the redox state, in regulating antiviral innate immune responses. IMPORTANCE Hemoglobin, the most important oxygen-carrying protein, is involved in the regulation of innate immune responses. We have previously reported that the porcine hemoglobin subunit beta (HB) exerts antiviral activity through regulation of type I interferon production. However, the antiviral activities and the underlying mechanisms of HBs originating from other animals have been poorly understood. Here, we identified human HB (hHB) as a pleiotropic regulator of the replication of RNA viruses through regulation of RIG-I/MDA5-mediated signaling pathways. hHB enhances RIG-I-mediated antiviral responses by promoting RIG-I ubiquitination depending on the hHB-induced reactive oxygen species (ROS), while it blocks MDA5-mediated antiviral signaling by suppressing the MDA5-dsRNA interaction. Our results contribute to an understanding of the crucial roles of hHB in the regulation of the RIG-I/MDA5-mediated signaling pathways. We also provide novel insight into the correlation of the intercellular redox state with the regulation of antiviral innate immunity
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