SDWPF: A Dataset for Spatial Dynamic Wind Power Forecasting over a Large Turbine Array.

Wind power is a clean and renewable energy, yet it poses integration challenges to the grid due to its variable nature. Thus, Wind Power Forecasting (WPF) is crucial for its successful integration. However, existing WPF datasets often cover only a limited number of turbines and lack detailed information. To bridge this gap and advance WPF research, we introduce the Spatial Dynamic Wind Power Forecasting dataset (SDWPF). The SDWPF dataset not only provides information on power generation and wind speed but also details the spatial distribution of the wind turbines and dynamic contextual factors specific to each turbine. These factors include weather information and the internal status of each wind turbine, thereby enriching the dataset and improving its applicability for predictive analysis. Further leveraging the potential of SDWPF, we initiated the ACM KDD Cup 2022, a competition distinguished as the foremost annual event in data mining, renowned for presenting cutting-edge challenges and attracting top talent from academia and industry. Our event successfully draws registrations from over 2400 teams around the globe.

TFPI from erythroblasts drives heme production in central macrophages promoting erythropoiesis in polycythemia.

Bleeding and thrombosis are known as common complications of polycythemia for a long time. However, the role of coagulation system in erythropoiesis is unclear. Here, we discover that an anticoagulant protein tissue factor pathway inhibitor (TFPI) plays an essential role in erythropoiesis via the control of heme biosynthesis in central macrophages. TFPI levels are elevated in erythroblasts of human erythroblastic islands with JAK2V617F mutation and hypoxia condition. Erythroid lineage-specific knockout TFPI results in impaired erythropoiesis through decreasing ferrochelatase expression and heme biosynthesis in central macrophages. Mechanistically, the TFPI interacts with thrombomodulin to promote the downstream ERK1/2-GATA1 signaling pathway to induce heme biosynthesis in central macrophages. Furthermore, TFPI blockade impairs human erythropoiesis in vitro, and normalizes the erythroid compartment in mice with polycythemia. These results show that erythroblast-derived TFPI plays an important role in the regulation of erythropoiesis and reveal an interplay between erythroblasts and central macrophages.

Identification and characterization of two novel antimicrobial peptides from Japanese sea bass (Lateolabrax japonicus) with antimicrobial activity and MO/MФ activation capability.

Piscidins participate in the innate immune response of fish, which aims to eliminate recognized foreign microbes and restore the homeostasis of immune system. We characterized two piscidin-like antimicrobial peptides (LjPL-3 and LjPL-2) isolated from Japanese sea bass (Lateolabrax japonicus). LjPL-3 and LjPL-2 showed different expression patterns in tissues. After Vibrio harveyi infection, the mRNA expression of LjPL-3 and LjPL-2 was upregulated in the liver, spleen, head kidney, and trunk kidney. The synthetic mature peptides LjPL-3 and LjPL-2 exhibited different antimicrobial spectra. Furthermore, LjPL-3 and LjPL-2 treatments decreased inflammatory cytokine production while promoting chemotaxis and phagocytosis in monocytes/macrophages (MO/MФ). LjPL-2, but not LjPL-3, displayed bacterial killing capability in MO/MФ. LjPL-3 and LjPL-2 administration increased Japanese sea bass survival after V. harveyi challenge, which was accompanied by a decline in bacterial burden. These data suggested that LjPL-3 and LjPL-2 participate in immune response through direct bacterial killing and MO/MФ activation.

Oral Vaccination of Recombinant Saccharomyces cerevisiae Expressing ORF132 Induces Protective Immunity against Cyprinid Herpesvirus-2.

Cyprinid herpesvirus 2 (CyHV-2) is the etiological agent of herpesviral hematopoietic necrosis (HVHN) disease, which causes serious economic losses in the crucian carp culture industry. In this study, by displaying ORF132 on the surface of Saccharomyces cerevisiae cells (named EBY100/pYD1-ORF132), we evaluated the protective efficacy of oral administration against CyHV-2 infection. Intense innate and adaptive immune responses were evoked in both mucosal and systemic tissues after oral vaccination with EBY100/pYD1-ORF132. Importantly, oral vaccination provided significant protection for crucian carp post CyHV-2 infection, resulting in a relative percent survival (RPS) of 64%. In addition, oral administration suppressed the virus load and relieved histological damage in selected tissues. Our results indicated that surface-displayed ORF132 on S. cerevisiae could be used as potential oral vaccine against CyHV-2 infection.

Predicting Drug-Target Interaction Via Self-Supervised Learning.

Recent advances in graph representation learning provide new opportunities for computational drug-target interaction (DTI) prediction. However, it still suffers from deficiencies of dependence on manual labels and vulnerability to attacks. Inspired by the success of self-supervised learning (SSL) algorithms, which can leverage input data itself as supervision,we propose SupDTI, a SSL-enhanced drug-target interaction prediction framework based on a heterogeneous network (i.e., drug-protein, drug-drug, and protein-protein interaction network; drug-disease, drug-side-effect, and protein-disease association network; drug-structure and protein-sequence similarity network). Specifically, SupDTI is an end-to-end learning framework consisting of five components. First, localized and globalized graph convolutions are designed to capture the nodes' information from both local and global perspectives, respectively. Then, we develop a variational autoencoder to constrain the nodes' representation to have desired statistical characteristics. Finally, a unified self-supervised learning strategy is leveraged to enhance the nodes' representation, namely, a contrastive learning module is employed to enable the nodes' representation to fit the graph-level representation, followed by a generative learning module which further maximizes the node-level agreement across the global and local views by learning the probabilistic connectivity distribution of the original heterogeneous network. Experimental results show that our model can achieve better prediction performance than state-of-the-art methods.

Meteorin links the bone marrow hypoxic state to hematopoietic stem/progenitor cell mobilization.

Hematopoietic stem/progenitor cells (HSPCs) are supported and regulated by niche cells in the bone marrow with an important characterization of physiological hypoxia. However, how hypoxia regulates HSPCs is still unclear. Here, we find that meteorin (Metrn) from hypoxic macrophages restrains HSPC mobilization. Hypoxia-induced factor 1α and Yin Yang 1 induce the high expression of Metrn in macrophages, and macrophage-specific Metrn knockout increases HSPC mobilization through modulating HSPC proliferation and migration. Mechanistically, Metrn interacts with its receptor 5-hydroxytryptamine receptor 2b (Htr2b) to regulate the reactive oxygen species levels in HSPCs through targeting phospholipase C signaling. The reactive oxygen species levels are reduced in HSPCs of macrophage-specific Metrn knockout mice with activated phospholipase C signaling. Targeting the Metrn/Htr2b axis could therefore be a potential strategy to improve HSPC mobilization for stem cell-based therapy.

Molecular characterization, expression and functional analysis of large yellow croaker (Larimichthys crocea) peroxisome proliferator-activated receptor gamma.

The peroxisome proliferator-activated receptor gamma (PPARγ) are nuclear receptors with distinct roles in energy metabolism and immunity. Although extensively studied in mammals, immunomodulatory roles of this molecule in teleost fish remain to be investigated. In this study, large yellow croaker (Larimichthys crocea) PPARγ (LcPPARγ) sequence was cloned, which encodes a polypeptide of 541 amino acids that include signature domains belonging to the nuclear receptor superfamily. Phylogenetically, LcPPARγ was most closely related to PPARγ derived from European sea bass (Dicentrarchus labrax). Quantitative analysis shown a ubiquitous expression of this molecule, with highest expression level detected in the intestine. The expression of LcPPARγ was decreased in the intestine, muscle, body kidney, spleen and head kidney-derived monocytes/macrophages (MO/MФs) over the course of Vibrio alginolyticus (V. alginolyticus) infection. In contrast, an up-regulation of LcPPARγ was observed in head kidney-derived MO/MФs following docosahexaenoic acid (DHA) treatment. This increase in LcPPARγ leads to an up-regulation of LcCD11b and LcCD18 and an enhancement of complement-mediated phagocytosis. Furthermore, cytokine secretions of V. alginolyticus-stimulated MO/MФs were modulated following LcPPARγ activations that up-regulated the expression of LcIL-10, while decreased the expression of LcIL-1ß, LcTNF-α and LcTGF-ß1. Overall, our results indicated that LcPPARγ plays a role in regulating functions of MO/MФs and likely contribute to MO/MФs polarization.

Two paralogs of CXCR4 in the Japanese sea bass (Lateolabrax japonica) are involved in the immune response of B lymphocytes.

CXC chemokine receptor 4 (CXCR4), a member of the G-protein-coupled receptor family, plays an important role in host immune responses. Within the teleost lineage, there are two paralogs of CXCR4; however, the role of CXCR4 in teleost B cells is poorly understood. In this study, we determined the cDNA sequences of the two CXCR4 paralogs from the Japanese sea bass (Lateolabrax japonica; LjCXCR4a and LjCXCR4b). Sequence and phylogenetic tree analyses revealed that LjCXCR4a and LjCXCR4b are most closely related to CXCR4a and CXCR4b, respectively, in the large yellow croaker (Larimichthys crocea). CXCR4 transcripts were mainly expressed in the gills, and their expression in different tissues was altered upon infection with Vibrio harveyi. LjCXCR4a and LjCXCR4b protein levels were upregulated in infected B cells. Knockdown of LjCXCR4a and LjCXCR4b in B cells by RNA interference, the phagocytic activity of B cells was not affected. Furthermore, knockdown of LjCXCR4a, not of LjCXCR4b, was observed to inhibit LjIgM expression in lipopolysaccharide-stimulated B cells. In addition, knockdown of LjCXCR4a, not of LjCXCR4b, was found to reduce reactive oxygen species levels in B cells. Our results indicate that LjCXCR4a and LjCXCR4b modulate the immune response of Japanese sea bass B cells against bacterial infection, albeit via different pathways.

Matrix metalloproteinase-25 from Japanese sea bass (Lateolabrax japonicus) is involved in pro-inflammatory responses.

Matrix metalloproteinases (MMPs) are highly expressed in leukocytes and macrophages, which play a role in the innate immune response. Here, the cDNA sequence of MMP25 from Japanese sea bass (Lateolabrax japonicus) (LjMMP25) was identified. Phylogenetic analysis revealed that LjMMP25 was most closely related to large yellow croaker MMP25. Multiple sequence alignment of LjMMP25 with MMP25 sequences from other teleosts revealed that regions of known functional importance were highly conserved. Expression analysis revealed that LjMMP25 was highly expressed in the head kidney and widely expressed in other tissues including gill, spleen, and liver. LjMMP25 was found to regulate inflammatory cytokine production and promote phagocytosis and bacterial killing in monocytes/macrophages (MO/MФ). Furthermore, LjMMP25 regulated the inflammatory response by modulating NF-κB signaling. These findings reveal new information about the role of LjMMP25 in regulating pro-inflammatory responses in this species.

Robust Least-Squares Support Vector Machine Using Probabilistic Inference.

The least-square support vector machine (LS-SVM) has been deeply studied in the machine-learning field and widely applied on a great deal of occasions. A disadvantage is that it is less efficient in dealing with the non-Gaussian noise. In this article, a novel probabilistic LS-SVM is proposed to enhance the modeling reliability even data contaminated by the non-Gaussian noise. The stochastic effect of noise on the kernel function and the regularization parameter is first analyzed and estimated. On the basis of this, a new objective function is constructed under a probabilistic sense. A probabilistic inference method is then developed to construct the distribution of the model parameter, including distribution estimation of both the kernel function and the regularization parameter from data. Using this distribution information, a solving strategy is then developed for this new objective function. Different from the original LS-SVM that uses a deterministic scenario approach to gain the model, the proposed method builds the distribution relation between the model and noise and makes use of this distribution information in the process of modeling; thus, it is more robust for modeling of noise data. The effectiveness of the proposed probabilistic LS-SVM is demonstrated by using both artificial and real cases.

Two ACTH analogs exert differential effects on monocytes/macrophages function regulation in ayu (Plecoglossus altivelis).

Adrenocorticotropic hormone (ACTH), a bioactive peptide of the family of melanocortins, is generated from pro-opiomelanocortin (POMC). So far, the research on the specific functions of ACTH in the immune system of teleosts is limited. We determined two complementary DNA (cDNA) sequences of POMC in ayu (Plecoglossus altivelis), termed PaPOMC-A and PaPOMC-B. PaPOMCs transcripts occurred in all examined tissues, and their expression in immune tissues changed following experimental infection with Vibrio anguillarum. PaACTH-B, but not PaACTH-A, suppressed the phagocytosis of monocytes/macrophages (MO/MФ). Two isoforms of PaACTH increased the bactericidal capacity of MO/MФ. PaACTH-A increased anti-inflammatory cytokine expression, while PaACTH-B decreased pro-inflammatory cytokine expression in MO/MФ. Compared with PaACTH-B treatment, the PaACTH-A treatment improved survival rate and reduced the bacterial load in V. anguillarum-infected ayu through interleukin (IL)-10. Our results indicate that the two PaACTH isoforms exert different effects in the host defense against bacterial infection.

Characterization of large yellow croaker (Larimichthys crocea) osteoprotegerin and its role in the innate immune response against to Vibrio alginolyticus.

Osteoprotegerin (OPG) is a member of the tumor necrosis factor receptor superfamily, contributing to inflammation, apoptosis, and differentiation. However, the function of OPG in the host immune system of teleosts remains unclear. Here, we cloned the cDNA of the LcOPG gene from large yellow croaker. LcOPG mRNA was expressed in all analyzed tissues and was upregulated by Vibrio alginolyticus infection in immune tissues and monocytes/macrophages (MO/MФ). Subsequently, the LcOPG protein was expressed and purified using a prokaryotic expression system. Recombinant LcOPG protein (rLcOPG) treatment suppressed V. alginolyticus-induced pro-inflammatory cytokine and enhanced V. alginolyticus-induced anti-inflammatory cytokine mRNA expression. Furthermore, rLcOPG decreased V. alginolyticus-induced MO/MФ apoptosis. Therefore, the results indicate that LcOPG might play a role in the immune response of V. alginolyticus-infected large yellow croaker.

Pharmacological inhibition of KDM5A for cancer treatment.

Lysine-specific demethylase 5A (KDM5A, also named RBP2 or JARID1A) is a demethylase that can remove methyl groups from histones H3K4me1/2/3. It is aberrantly expressed in many cancers, where it impedes differentiation and contributes to cancer cell proliferation, cell metastasis and invasiveness, drug resistance, and is associated with poor prognosis. Pharmacological inhibition of KDM5A has been reported to significantly attenuate tumor progression in vitro and in vivo in a range of solid tumors and acute myeloid leukemia. This review will present the structural aspects of KDM5A, its role in carcinogenesis, a comparison of currently available approaches for screening KDM5A inhibitors, a classification of KDM5A inhibitors, and its potential as a drug target in cancer therapy.

Hypoxia-inducible factor-1α involved in macrophage regulation in ayu (Plecoglossus altivelis) under hypoxia.

Hypoxia-inducible factor-1α (HIF-1α) plays a critical role in immune and inflammatory responses and is important in controlling a variety of processes in monocytes and macrophages. However, the role of HIF-1α in the teleost immune system remains less known. In this study, we cloned the cDNA sequence of HIF-1α from the ayu (Plecoglossus altivelis, PaHIF-1α). Sequence and phylogenetic tree analysis showed that PaHIF-1α clustered within the fish HIF-1α tree and was closely related to that of Northern pike (Esox lucius). PaHIF-1α was expressed in all tested tissues and expression increased in liver, head kidney, and body kidney upon Vibrio anguillarum infection. PaHIF-1α was found to regulate the expression of cytokines in ayu monocytes/macrophages (MO/MФ). PaHIF-1α mediated hypoxia-induced enhancement of MO/MФ phagocytic and bactericidal activities to enhance host defenses. Compared with the control, intermittent hypoxia further increased the expression of PaHIF-1α mRNA, improved the survival rate, and reduced the bacterial load of V. anguillarum-infected ayu. Therefore, PaHIF-1α may play a predominant role in the modulation of ayu MO/MФ function.

Two transcription factors PU.1a and PU.1b have different functions in the immune system of teleost ayu.

Transcription factor PU.1 is a regulator of macrophage function, however, the specific function of PU.1 in teleost monocytes/macrophages (MO/MФ) remains unknown. We determined the cDNA sequence of two PU.1 genes from ayu (Plecoglossus altivelis; PaPU.1a and PaPU.1b). Sequence comparisons showed that PaPU.1 were most closely related to the PU.1 of rainbow smelt (Osmerus mordax). The PU.1 transcripts were mainly expressed in the spleen, and their expression was altered in various tissues upon infection with Vibrio anguillarum. PaPU.1a and PaPU.1b proteins were upregulated in MO/MФ, after infection. RNA interference was employed to knockdown PaPU.1a and PaPU.1b to investigate their function in MO/MФ. The expression of inflammatory cytokines was regulated by PaPU.1a, but not PaPU.1b, in ayu MO/MФ upon V. anguillarum infection. Both PaPU.1a and PaPU.1b knockdown lowered the phagocytic activity of MO/MФ. Furthermore, PaPU.1b knockdown attenuated MO/MФ bacterial killing capability. Our results indicate that two PaPU.1 genes differentially modulate the immune response in ayu MO/MФ against bacterial infection.

The emerging role of KDM5A in human cancer.

Histone methylation is a key posttranslational modification of chromatin, and its dysregulation affects a wide array of nuclear activities including the maintenance of genome integrity, transcriptional regulation, and epigenetic inheritance. Variations in the pattern of histone methylation influence both physiological and pathological events. Lysine-specific demethylase 5A (KDM5A, also known as JARID1A or RBP2) is a KDM5 Jumonji histone demethylase subfamily member that erases di- and tri-methyl groups from lysine 4 of histone H3. Emerging studies indicate that KDM5A is responsible for driving multiple human diseases, particularly cancers. In this review, we summarize the roles of KDM5A in human cancers, survey the field of KDM5A inhibitors including their anticancer activity and modes of action, and the current challenges and potential opportunities of this field.

Characterization of ayu (Plecoglossus altivelis) urocortin: The function of an endocrine factor in monocyte/macrophage regulation.

Urocortin (UCN) is a hormone in the hypothalamic-pituitary-adrenal axis that is expressed in various immune cells. However, the function of teleost UCN in the immune system remains unclear. In this study, we cloned the cDNA sequence of UCN from ayu Plecoglossus altivelis (PaUCN). Sequence and phylogenetic tree analyses showed that PaUCN clustered within the fish UCN 1 group and was most related to the rainbow trout (Oncorhynchus mykiss) UCN. PaUCN was expressed in all tested tissues and its expression increased in the liver, spleen, head kidney, and gill upon Vibrio anguillarum infection. Mature PaUCN protein (mPaUCN) treatment affected the phagocytosis and bacterial killing of monocytes/macrophages (MO/MФ). mPaUCN reduced pro-inflammatory cytokine expression in MO/MФ, which was partially mediated via interaction with ayu interleukin-6. mPaUCN reduced bacterial load and increased the survival of V. anguillarum-infected ayu. Overall, UCN as an endocrine factor regulates the immune response of ayu after infection by activating MO/MФ, thus contributing to enhance fish survival.

Identification and characterization of a tumor necrosis factor receptor like protein encoded by Cyprinid Herpesvirus 2.

Virus-encoded tumor necrosis factor receptors (vTNFRs) facilitate viral escape from the host immune response during viral propagation. Cyprinid Herpesvirus-2 (CyHV-2) is a double-stranded DNA virus of alloherpesviridae family that causes great economic losses in the aquaculture industry. The present study identified and characterized a novel TNFR homolog termed ORF4 in CyHV-2. ORF4 was identified as a secreted protein and a homolog of herpesvirus entry mediator (HVEM). ORF4 localized to the cytoplasm in infected GiCF cells. ORF4 overexpression enhanced viral propagation, while downregulation of ORF4 via siRNA decreased viral propagation. ORF4 overexpression promoted GiCF proliferation, and its downregulation suppressed CyHV-2-induced apoptosis. GST-pulldown and LC-MS/MS assays identified 44 conditional binding proteins that interact with ORF4 protein, while the GST pulldown test did not support the idea that ORF4 interact with histone H3.3. Taken together, our results contribute to our understanding of the vTNFR function in alloherpesviridae pathogenesis and host immune regulation.