MiRPara: a SVM-based software tool for prediction of most probable microRNA coding regions in genome scale sequences

<p>Abstract</p> <p>Background</p> <p>MicroRNAs are a family of ~22 nt small RNAs that can regulate gene expression at the post-transcriptional level. Identification of these molecules and their targets can aid understanding of regulatory processes. Recently, HTS has become a common identification method but there are two major limitations associated with the technique. Firstly, the method has low efficiency, with typically less than 1 in 10,000 sequences representing miRNA reads and secondly the method preferentially targets highly expressed miRNAs. If sequences are available, computational methods can provide a screening step to investigate the value of an HTS study and aid interpretation of results. However, current methods can only predict miRNAs for short fragments and have usually been trained against small datasets which don't always reflect the diversity of these molecules.</p> <p>Results</p> <p>We have developed a software tool, miRPara, that predicts most probable mature miRNA coding regions from genome scale sequences in a species specific manner. We classified sequences from miRBase into animal, plant and overall categories and used a support vector machine to train three models based on an initial set of 77 parameters related to the physical properties of the pre-miRNA and its miRNAs. By applying parameter filtering we found a subset of ~25 parameters produced higher prediction ability compared to the full set. Our software achieves an accuracy of up to 80% against experimentally verified mature miRNAs, making it one of the most accurate methods available.</p> <p>Conclusions</p> <p>miRPara is an effective tool for locating miRNAs coding regions in genome sequences and can be used as a screening step prior to HTS experiments. It is available at <url>http://www.whiov.ac.cn/bioinformatics/mirpara</url></p

Type H vessels: functions in bone development and diseases

Type H vessels are specialized blood vessels found in the bone marrow that are closely associated with osteogenic activity. They are characterized by high expression of endomucin and CD31. Type H vessels form in the cancellous bone area during long bone development to provide adequate nutritional support for cells near the growth plate. They also influence the proliferation and differentiation of osteoprogenitors and osteoclasts in a paracrine manner, thereby creating a suitable microenvironment to facilitate new bone formation. Because of the close relationship between type H vessels and osteogenic activity, it has been found that type H vessels play a role in the physiological and pathological processes of bone diseases such as fracture healing, osteoporosis, osteoarthritis, osteonecrosis, and tumor bone metastasis. Moreover, experimental treatments targeting type H vessels can improve the outcomes of these diseases. Here, we reviewed the molecular mechanisms related to type H vessels and their associated osteogenic activities, which are helpful in further understanding the role of type H vessels in bone metabolism and will provide a theoretical basis and ideas for comprehending bone diseases from the vascular perspective

Towards Cognitive AI Systems: a Survey and Prospective on Neuro-Symbolic AI

The remarkable advancements in artificial intelligence (AI), primarily driven by deep neural networks, have significantly impacted various aspects of our lives. However, the current challenges surrounding unsustainable computational trajectories, limited robustness, and a lack of explainability call for the development of next-generation AI systems. Neuro-symbolic AI (NSAI) emerges as a promising paradigm, fusing neural, symbolic, and probabilistic approaches to enhance interpretability, robustness, and trustworthiness while facilitating learning from much less data. Recent NSAI systems have demonstrated great potential in collaborative human-AI scenarios with reasoning and cognitive capabilities. In this paper, we provide a systematic review of recent progress in NSAI and analyze the performance characteristics and computational operators of NSAI models. Furthermore, we discuss the challenges and potential future directions of NSAI from both system and architectural perspectives.Comment: Workshop on Systems for Next-Gen AI Paradigms, 6th Conference on Machine Learning and Systems (MLSys), June 4-8, 2023, Miami, FL, US

Hydro‐Sensitive, In Situ Ultrafast Physical Self‐Gelatinizing, and Red Blood Cells Strengthened Hemostatic Adhesive Powder with Antibiosis and Immunoregulation for Wound Repair

Abstract Immediate and effective hemostatic treatments for complex bleeding wounds are an urgent clinical demand. Hemostatic materials with characteristics of adhesion, sealing, anti‐infection, and concrescence promotion have drawn growing concerns. However, pure natural multifunctional hemostatic materials with in situ ultrafast self‐gelation are rarely reported. In this study, a hydro‐sensitive collagen/tannic acid (ColTA) natural hemostatic powder is developed that can in situ self‐gel to form adhesive by the non‐covalent crosslinking between tannic acid (TA) and collagen (Col) in liquids. The physical interactions endow ColTA adhesive with the characteristics of instantaneous formation and high adhesion at various substrate surfaces. Crucially, ColTA powder adhesive shows an enhanced adhesion performance in the presence of blood due to the electrostatic interactions between ColTA adhesive and red blood cells, conducive to effective in situ sealing and rapid hemostasis. The biocompatible and hemocompatible ColTA adhesive can effectively control bleeding and seal the wounds of the caudal vein, liver, heart, and femoral arteries in rats. Furthermore, the low‐cost and ready‐to‐use ColTA adhesive powder also possesses good antibacterial and inhibiting biofilm formation ability, and can efficiently regulate immune response by the NF‐κB pathway to promote wound repair, making it a highly promising hemostatic material with great potential for biomedical applications

Structure of a novel PTH-related peptide hPTH' and its interaction with the PTH receptor

We have previously shown that a recombinant human PTH fragment, Pro-Pro-[Arg11] hPTH (134)-Pro-Pro-Asp (hPTH'), could be a potentially better and more cost-effective therapeutic agent than PTH (134) on osteoporosis. In this report, we characterized the solution conformations of hPTH' by NMR spectroscopy and modeled the interactions between the hPTH' and the PTH receptor. By comparing it with PTH (134) structures and their respective interactions with the PTH receptor, we identified two segments of helix extending from Ile5 to Met8 and from Glu22 to Gln29 with a divided kink between the two helixes around Arg20. Mutated arginine makes hPTH' fill the receptor cavity better as well as forms hydrogen bonds with Val193. Understanding the ligand receptor interactions will help us design small molecules to better mimic the activities of PTH. Copyright (c) 2012 European Peptide Society and John Wiley & Sons, Ltd.Natural Science Foundation of China [30730026]; Program of Shanghai Subject Chief Scientist [09XD1405100

Adenovirus-Mediated RNA Interference against Foot-and-Mouth Disease Virus Infection both In Vitro and In Vivo

Foot-and-mouth disease virus (FMDV) infection is responsible for the heavy economic losses in stockbreeding each year. Because of the limited effectiveness of existing vaccines and antiviral drugs, the development of new strategies is needed. RNA interference (RNAi) is an effective means of suppressing virus replication in vitro. Here we demonstrate that treatment with recombinant, replication-defective human adenovirus type 5 (Ad5) expressing short-hairpin RNAs (shRNAs) directed against either structural protein 1D (Ad5-NT21) or polymerase 3D (Ad5-POL) of FMDV totally protects swine IBRS-2 cells from homologous FMDV infection, whereas only Ad5-POL inhibits heterologous FMDV replication. Moreover, delivery of these shRNAs significantly reduces the susceptibility of guinea pigs and swine to FMDV infection. Three of five guinea pigs inoculated with 10(6) PFU of Ad5-POL and challenged 24 h later with 50 50% infectious doses (ID(50)) of homologous virus were protected from the major clinical manifestation of disease: the appearance of vesicles on the feet. Two of three swine inoculated with an Ad5-NT21-Ad5-POL mixture containing 2 × 10(9) PFU each and challenged 24 h later with 100 ID(50) of homologous virus were protected from the major clinical disease, but treatment with a higher dose of adenovirus mixture cannot promote protection of animals. The inhibition was rapid and specific because treatment with a control adenovirus construct (Ad5-LacZ) expressing Escherichia coli galactosidase-specific shRNA showed no marked antiviral activity. Our data highlight the in vivo potential of RNAi technology in the case of FMD

A carbazole compound, 9-ethyl-9H-carbazole-3-carbaldehyde, plays an antitumor function through reactivation of the p53 pathway in human melanoma cells

Abstract p53, the major tumor suppressor, is frequently mutated in many cancers, and up to 84% of human melanomas harbor wild-type p53, which is considered to be an ideal target for melanoma therapy. Here, we evaluated the antitumor activity of a carbazole derivative, 9-ethyl-9H-carbazole-3-carbaldehyde (ECCA), on melanoma cells. ECCA had a selectively strong inhibitory activity against the growth of BRAF-mutated and BRAF-wild-type melanoma cells but had little effect on normal human primary melanocytes. ECCA inhibited melanoma cell growth by increasing cell apoptosis, which was associated with the upregulation of caspase activities and was significantly abrogated by the addition of a caspase inhibitor. In vivo assays confirmed that ECCA suppressed melanoma growth by enhancing cell apoptosis and reducing cell proliferation, and importantly ECCA did not have any evident toxic effects on normal tissues. RNA-Seq analysis identified several pathways related to cell apoptosis that were affected by ECCA, notably, activation of the p53 signaling pathway. Biochemical assays demonstrated that ECCA enhanced the phosphorylation of p53 at Ser15 in melanoma cells harboring wild-type p53, and importantly, the knockdown or deletion of p53 in those cells counteracted the ECCA-induced apoptosis, as well as senescence. Further investigations revealed that ECCA enhanced the phosphorylation of p38-MAPK and c-Jun N-terminal kinase (JNK), and treatment with either a p38-MAPK or a JNK inhibitor rescued the cell growth inhibition elicited by ECCA, which depended on the expression of the p53 gene. Finally, the combination of ECCA with a BRAF inhibitor significantly enhanced the growth inhibition of melanoma cells. In summary, our study demonstrates that the carbazole derivative, ECCA, induces melanoma cell apoptosis and senescence through the activation of p53 to significantly and selectively suppress the growth of melanoma cells without affecting normal human melanocytes, suggesting its potential to develop a new drug for melanoma therapy