CRIT:Identifying RNA-binding protein regulator in circRNA life cycle via non-negative matrix factorization

Circular RNAs (circRNAs) are endogenous non-coding RNAs that regulate gene expression and participate in carcinogenesis. However, the RNA-binding proteins (RBPs) involved in circRNAs biogenesis and modulation remain largely unclear. We developed the circRNA regulator identification tool (CRIT), a non-negative matrix-factorization-based pipeline to identify regulating RBPs in cancers. CRIT uncovered 73 novel regulators across thousands of samples by effectively leveraging genomics data and functional annotations. We demonstrated that known RBPs involved in circRNA control are significantly enriched in these predictions. Analysis of circRNA-RBP interactions using two large cross-linking immunoprecipitation (CLIP) databases, we validated the consistency between CRIT prediction and the CLIP experiments. Furthermore, newly discovered RBPs are functionally connected with authentic circRNA regulators by various biological associations, such as physical interaction, similar binding motifs, common transcription factor modulation, and co-expression. When analyzing RNA sequencing (RNA-seq) datasets after short hairpin RNA (shRNA)/small interfering RNA (siRNA) knockdown, we found several novel RBPs that can affect global circRNA expression, which strengthens their role in the circRNA life cycle. The above evidence provided independent confirmation that CRIT is a useful tool to capture RBPs in circRNA processing. Finally, we show that authentic regulators are more likely the core splicing proteins and peripheral factors and usually harbor more alterations in the vast majority of cancers

The Clumpy Structure Of Five Star-bursting Dwarf Galaxies In The MaNGA Survey

The star-forming clumps in star-bursting dwarf galaxies provide valuable insights into the understanding of the evolution of dwarf galaxies. In this paper, we focus on five star-bursting dwarf galaxies featuring off-centered clumps in the Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey. Using the stellar population synthesis software FADO, we obtain the spatially-resolved distribution of the star formation history, which allows us to construct the $g$-band images of the five galaxies at different ages. These images can help us to probe the evolution of the morphological structures of these galaxies. While images of stellar population older than 1 Gyr are typically smooth, images of stellar population younger than 1 Gyr reveal significant clumps, including multiple clumps which appear at different locations and even different ages. To study the evolutionary connections of these five galaxies to other dwarf galaxies before their star-forming clumps appear, we construct the images of the stellar populations older than three age nodes, and define them to be the images of the "host" galaxies. We find that the properties such as the central surface brightness and the effective radii of the hosts of the five galaxies are in between those of dwarf ellipticals (dEs) and dwarf irregulars (dIrrs), with two clearly more similar to dEs and one more similar to dIrrs. Among the five galaxies, 8257-3704 is particularly interesting, as it shows a previous starburst event that is not quite visible from its $gri$ image, but only visible from images of the stellar population at a few hundred million years. The star-forming clump associated with this event may have appeared at around 600 Myr and disappeared at around 40 Myr.Comment: 21 pages, 16 figures, accepted for publication in RA

Research trends and hot spots in global nanotechnology applications in liver cancer: a bibliometric and visual analysis (2000-2022)

BackgroundLiver cancer (LC) is one of the most common malignancies. Currently, nanotechnology has made great progress in LC research, and many studies on LC nanotechnology have been published. This study aims to discuss the current status, hot spots, and research trends in this field through bibliometric analysis.MethodsThe Web of Science Core Collection (WoSCC) database was searched for papers related to hepatocellular carcinoma (HCC) included from January 2000 to November 2022, and its research hotspots and trends were visualized and analyzed with the help of VOSviewer. In addition, a search was conducted to find LC papers related to nanotechnology. Then we used the visual analysis software VOSviewer and CiteSpace to evaluate the contributions of countries/regions, authors, and journals related to the topic and analyze keywords to understand the research priorities and hot spots in the field as well as the development direction.ResultsThere are 1908 papers in the highly cited literature on LC, and its research hotspots are pathogenesis, risk factors, and survival rate. The literature on the application of nanotechnology in LC had 921 papers. Among them, China (n=560, 60.8%) and the United States (n=170, 18.5%) were the countries with the highest number of published papers. Wang Yan (n=11) and Llovet JM (n=131) were the first authors and co-cited authors, respectively. The International Journal of Nanomedicine was the most prolific academic journal (n=41). In addition to “hepatocellular carcinoma” and “nanoparticles”, the most frequent keyword was “drug delivery”. In recent years, “metastasis” and “diagnosis” appeared in the keyword bursts. This indicates that the application of nanoparticles in the early diagnosis and drug delivery of LC (including liver metastasis) has a good prospect.ConclusionNanotechnology has received more and more attention in the medical field in recent years. As nanoparticles are easily localized in organelles and cells, they can increase drug permeability in tumor tissues, improve drug delivery efficiency and reduce drug toxicity. Our research results were the first scientific evaluation of the application of nanotechnology in LC, providing scholars with research hotspots and development trends

Role of GABAAR in the Transition From Acute to Chronic Pain and the Analgesic Effect of Electroacupuncture on Hyperalgesic Priming Model Rats

Chronic pain is a costly health problem that impairs health-related quality of life when not effectively treated. Regulating the transition from acute to chronic pain is a new therapeutic strategy for chronic pain that presents a major clinical challenge. The underlying mechanisms of pain transition are not entirely understood, and strategies for preventing this transition are lacking. Here, a hyperalgesic priming model was used to study the potential mechanism by which γ-aminobutyric acid receptor type A (GABAAR) in the dorsal root ganglion (DRG) contributes to pain transition. Furthermore, electroacupuncture (EA), a modern method of acupuncture, was administered to regulate pain transition, and the mechanism underlying EA's regulatory effect was investigated. Hyperalgesic priming was induced by intraplanar injection of carrageenan (Car)/prostaglandin E2 (PGE2). The decrease in mechanical withdrawal threshold (MWT) induced by PGE2 returned to baseline 4 h after injection in NS + PGE2 group, and still persisted 24 h after injection in Car + PGE2 group. Lower expression of GABAAR in the lumbar DRG was observed in the model rats. Furthermore, activating or blocking GABAAR could reversed the long-lasting hyperalgesia induced by Car/PGE2 injection or produced a persistent hyperalgesia. In addition, GABAAR may be involved in Protein Kinase C epsilon (PKCε) activation in the DRG, a mark molecular of pain transition. EA considerably increased the mechanical pain thresholds of hyperalgesic priming model mammals in both the acute and chronic phases. Furthermore, EA upregulated the expression of GABAAR and inhibited the activation of PKCε in the DRG. In addition, peripheral administration of picrotoxin blocked the analgesic effect of EA on the model rats and abolished the regulatory effect of EA on PKCε activation. These findings suggested that GABAAR plays a key role in both the transition from acute to chronic pain and the analgesic effect of EA on hyperalgesic priming

Mesenchymal stromal cells pretreated with pro‐inflammatory cytokines promote skin wound healing through VEGFC ‐mediated angiogenesis

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MaNGA 8313-1901 : gas accretion observed in a blue compact dwarf galaxy

Gas accretion is an important process in the evolution of galaxies, but it has limited direct observational evidences. In this paper, we report the detection of a possible ongoing gas accretion event in a blue compact dwarf (BCD) galaxy, MaNGA 8313-1901, observed by the Mapping Nearby Galaxies and Apache Point Observatory (MaNGA) program. This galaxy has a distinct off-centered blue clump to the northeast (the NE clump) that shows low metallicity and enhanced star formation. The kinematics of the gas in the NE clump also seems to be detached from the host BCD galaxy. Together with the metallicity drop of the NE clump, it suggests that the NE clump likely has an external origin, such as gas accretion or galaxy interaction, rather than an internal origin, such as an H II complex in the disk. After removing the underlying host component, we find that the spectrum of the “pure” clump can match very well with a modeled spectrum containing a stellar population of the young stars (7 Myr) only. This may imply that the galaxy is experiencing an accretion of cold gas, instead of a merger event involving galaxies with significant preexisting old stars. We also find signs of another clump (the SW clump) at the southwest corner of the host galaxy, and the two clumps may share the same origin of gas accretion

A Search for Light Fermionic Dark Matter Absorption on Electrons in PandaX-4T

We report a search on a sub-MeV fermionic dark matter absorbed by electrons with an outgoing active neutrino using the 0.63 tonne-year exposure collected by PandaX-4T liquid xenon experiment. No significant signals are observed over the expected background. The data are interpreted into limits to the effective couplings between such dark matter and electrons. For axial-vector or vector interactions, our sensitivity is competitive in comparison to existing astrophysical bounds on the decay of such dark matter into photon final states. In particular, we present the first direct detection limits for an axial-vector (vector) interaction which are the strongest in the mass range from 25 to 45 (35 to 50) keV/c$^2$

Computational Drug Repurposing Based on a Recommendation System and Drug–Drug Functional Pathway Similarity

Drug repurposing identifies new clinical indications for existing drugs. It can be used to overcome common problems associated with cancers, such as heterogeneity and resistance to established therapies, by rapidly adapting known drugs for new treatment. In this study, we utilized a recommendation system learning model to prioritize candidate cancer drugs. We designed a drug–drug pathway functional similarity by integrating multiple genetic and epigenetic alterations such as gene expression, copy number variation (CNV), and DNA methylation. When compared with other similarities, such as SMILES chemical structures and drug targets based on the protein–protein interaction network, our approach provided better interpretable models capturing drug response mechanisms. Furthermore, our approach can achieve comparable accuracy when evaluated with other learning models based on large public datasets (CCLE and GDSC). A case study about the Erlotinib and OSI-906 (Linsitinib) indicated that they have a synergistic effect to reduce the growth rate of tumors, which is an alternative targeted therapy option for patients. Taken together, our computational method characterized drug response from the viewpoint of a multi-omics pathway and systematically predicted candidate cancer drugs with similar therapeutic effects

Temperature regulates synaptic subcellular specificity mediated by inhibitory glutamate signaling.

Environmental factors such as temperature affect neuronal activity and development. However, it remains unknown whether and how they affect synaptic subcellular specificity. Here, using the nematode Caenorhabditis elegans AIY interneurons as a model, we found that high cultivation temperature robustly induces defects in synaptic subcellular specificity through glutamatergic neurotransmission. Furthermore, we determined that the functional glutamate is mainly released by the ASH sensory neurons and sensed by two conserved inhibitory glutamate-gated chloride channels GLC-3 and GLC-4 in AIY. Our work not only presents a novel neurotransmission-dependent mechanism underlying the synaptic subcellular specificity, but also provides a potential mechanistic insight into high-temperature-induced neurological defects