Miracle-dz/UniFAR-FTUs huggingface dataset:
Case report: MicroRNA-10b as a therapeutic target in feline metastatic mammary carcinoma and its implications for human clinical trials

Ninety percent of deaths from cancer are caused by metastasis. miRNAs are critical players in biological processes such as proliferation, metastasis, apoptosis, and self-renewal. We and others have previously demonstrated that miRNA-10b promotes metastatic cell migration and invasion. Importantly, we also showed that miR-10b is a critical driver of metastatic cell viability and proliferation. To treat established metastases by inhibiting miR-10b, we utilized a therapeutic, termed MN-anti-miR10b, composed of anti-miR-10b antagomirs, conjugated to iron oxide nanoparticles, that serve as delivery vehicles to tumor cells in vivo and a magnetic resonance imaging (MRI) reporter. In our previous studies using murine models of metastatic breast cancer, we demonstrated the effectiveness of MN-anti-miR10b in preventing and eliminating existing metastases. With an outlook toward clinical translation of our therapeutic, here we report studies in large animals (companion cats) with spontaneous feline mammary carcinoma (FMC). We first investigated the expression and tissue localization of miR-10b in feline tumors and metastases and showed remarkable similarity to these features in humans. Next, in the first case study involving this therapeutic we intravenously dosed an FMC patient with MN-anti-miR10b and demonstrated its delivery to the metastatic lesions using MRI. We also showed the initial safety profile of the therapeutic and demonstrated significant change in miR-10b expression and its target HOXD10 after dosing. Our results provide support for using companion animals for further MN-anti-miR10b development as a therapy and serve as a guide for future clinical trials in human patients.
Discovering hydrothermalism from Afar: In Situ methane instrumentation and change-point detection for decision-making

Seafloor hydrothermalism plays a critical role in fundamental interactions between geochemical and biological processes in the deep ocean. A significant number of hydrothermal vents are hypothesized to exist, but many of these remain undiscovered due in part to the difficulty of detecting hydrothermalism using standard sensors on rosettes towed in the water column or robotic platforms performing surveys. Here, we use in situ methane sensors to complement standard sensing technology for hydrothermalism discovery and compare sensors on a towed rosette and an autonomous underwater vehicle (AUV) during a 17 km long transect in the Northern Guaymas Basin in the Gulf of California. This transect spatially intersected with a known hydrothermally active venting site. These data show that methane signalled possible hydrothermal-activity 1.5–3 km laterally (100–150 m vertically) from a known vent. Methane as a signal for hydrothermalism performed similarly to standard turbidity sensors (plume detection 2.2–3.3 km from reference source), and more sensitively and clearly than temperature, salinity, and oxygen instruments which readily respond to physical mixing in background seawater. We additionally introduce change-point detection algorithms—streaming cross-correlation and regime identification—as a means of real-time hydrothermalism discovery and discuss related data supervision technologies that could be used in planning, executing, and monitoring explorative surveys for hydrothermalism.
H2B gene family: A prognostic biomarker and correlates with immune infiltration in glioma

The current prognosis of glioma is unfavorable and effective treatments remain limited. However, bioinformatics has created new opportunities for improving glioma treatment. Research indicates that H2B is involved in the pathological process of cancer. Thus, this study conducted bioinformatic analyses of the H2B gene family to evaluate whether these genes can play a role in predicting prognosis and are associated with immune infiltration. High expression of H2B genes was observed in cholangiocarcinoma, esophageal carcinoma, glioblastoma multiforme (GBM), head and neck squamous cell carcinoma, and other cancers. In addition, a rise in H2B gene expression was correlated with an increase in glioma grade. In the Cancer Genome Atlas (TCGA), the Chinese Glioma Genome Atlas (CGGA) database and multiple datasets from the Gene Expression Omnibus (GEO), high expression of H2B gene family members predicted poor prognosis of a variety of tumors including glioma. In particular, high H2BC5, H2BC9, H2BC11, and H2BC21 expression was associated with poor glioma prognosis. H2BC9, H2BC11, and H2BC12 expression were also positively correlated with both immune and stromal scores. Enrichment analysis indicated that H2B family genes may be involved in the pathological process of glioma using various pathways including the cell cycle and immune response. H2B-specific siRNAs were used to verify the role of H2BC5, H2BC9, H2BC11, and H2BC21 expression on cell cycle distribution. In summary, H2BC5, H2BC9, H2BC11, and H2BC21 were independent prognostic indicators of glioma, and H2BC9 and H2BC11 may correlate with tumor immunity.
Transcriptome and morphological analysis on the heart in gestational protein-restricted aging male rat offspring

Background: Adverse factors that influence embryo/fetal development are correlated with increased risk of cardiovascular disease (CVD), type-2 diabetes, arterial hypertension, obesity, insulin resistance, impaired kidney development, psychiatric disorders, and enhanced susceptibility to oxidative stress and inflammatory processes in adulthood. Human and experimental studies have demonstrated a reciprocal relationship between birthweight and cardiovascular diseases, implying intrauterine adverse events in the onset of these abnormalities. In this way, it is plausible that confirmed functional and morphological heart changes caused by gestational protein restriction could be related to epigenetic effects anticipating cardiovascular disorders and reducing the survival time of these animals. Methods: Wistar rats were divided into two groups according to the protein diet content offered during the pregnancy: a normal protein diet (NP, 17%) or a Low-protein diet (LP, 6%). The arterial pressure was measured, and the cardiac mass, cardiomyocytes area, gene expression, collagen content, and immunostaining of proteins were performed in the cardiac tissue of male 62-weeks old NP compared to LP offspring. Results: In the current study, we showed a low birthweight followed by catch-up growth phenomena associated with high blood pressure development, increased heart collagen content, and cardiomyocyte area in 62-week-old LP offspring. mRNA sequencing analysis identified changes in the expression level of 137 genes, considering genes with a p-value < 0.05. No gene was. Significantly changed according to the adj-p-value. After gene-to-gene biological evaluation and relevance, the study demonstrated significant differences in genes linked to inflammatory activity, oxidative stress, apoptosis process, autophagy, hypertrophy, and fibrosis pathways resulting in heart function disorders. Conclusion: The present study suggests that gestational protein restriction leads to early cardiac diseases in the LP progeny. It is hypothesized that heart dysfunction is associated with fibrosis, myocyte hypertrophy, and multiple abnormal gene expression. Considering the above findings, it may suppose a close link between maternal protein restriction, specific gene expression, and progressive heart failure.
PM2b, a CC-NBS-LRR protein, interacts with TaWRKY76-D to regulate powdery mildew resistance in common wheat

Powdery mildew caused by Blumeria graminis f. sp. tritici (Bgt) is a destructive disease of wheat throughout the world. Host resistance is considered the most sustainable way to control this disease. Powdery mildew resistance gene Pm2b was mapped to the same genetic interval with Pm2a and PmCH1357 cloned previously, but showed different resistance spectra from them, indicating that they might be caused by different resistance genes or alleles. In this study, Pm2b was delimited to a 1.64 Mb physical interval using a large segregating population containing 4,354 F2:3 families of resistant parent KM2939 and susceptible cultivar Shimai 15. In this interval, TraesCS5D03G0111700 encoding the coiled-coil nucleotide-binding site leucine-rich repeat protein (CC-NBS-LRR) was determined as the candidate gene of Pm2b. Silencing by barley stripe mosaic virus-induced gene silencing (BSMV-VIGS) technology and two independent mutants analysis in KM2939 confirmed the candidate gene TraesCS5D03G0111700 was Pm2b. The sequence of Pm2b was consistent with Pm2a/PmCH1357. Subcellular localization showed Pm2b was located on the cell nucleus and plasma membrane. Pm2b had the highest expression level in leaves and was rapidly up-regulated after inoculating with Bgt isolate E09. The yeast two-hybrid (Y2H) and luciferase complementation imaging assays (LCI) showed that PM2b could self-associate through the NB domain. Notably, we identified PM2b interacting with the transcription factor TaWRKY76-D, which depended on the NB domain of PM2b and WRKY domain of TaWRKY76-D. TaWRKY76-D negatively regulated the resistance to powdery mildew in wheat. The specific KASP marker K529 could take the advantage of high-throughput and high-efficiency for detecting Pm2b and be useful in molecular marker assisted-selection breeding. In conclusion, cloning and disease resistance mechanism analysis of Pm2b provided an example to emphasize a need of the molecular isolation of resistance genes, which has implications in marker assisted wheat breeding.
Advances in the differential molecular diagnosis of vesicular disease pathogens in swine

Foot-and-mouth disease virus (FMDV), Senecavirus A (SVA) and swine vesicular disease virus (SVDV) are members of the family Picornaviridae, which can cause similar symptoms - vesicular lesions in the tissues of the mouth, nose, feet, skin and mucous membrane of animals. Rapid and accurate diagnosis of these viruses allows for control measures to prevent the spread of these diseases. Reverse transcription-polymerase chain reaction (RT-PCR) and real-time RT-PCR are traditional and reliable methods for pathogen detection, while their amplification reaction requires a thermocycler. Isothermal amplification methods including loop-mediated isothermal amplification and recombinase polymerase amplification developed in recent years are simple, rapid and do not require specialized equipment, allowing for point of care diagnostics. Luminex technology allows for simultaneous detection of multiple pathogens. CRISPR-Cas diagnostic systems also emerging nucleic acid detection technologies which are very sensitivity and specificity. In this paper, various nucleic acid detection methods aimed at vesicular disease pathogens in swine (including FMDV, SVA and SVDV) are summarized.
Norway spruce somatic embryogenesis benefits from proliferation of embryogenic tissues on filter discs and cold storage of cotyledonary embryos

Vegetative propagation opens opportunities for the multiplication of elite tree progeny for forest regeneration material. For conifers such as Norway spruce (Picea abies) the most efficient vegetative propagation method is seed multiplication through somatic embryogenesis. Efficient culture methods are needed for somatic embryogenesis to be commercially viable. Compared to culturing as clumps, filter disc cultures can improve the proliferation of embryogenic tissue (ET) due to more even spread and better developmental synchronization. In this study, ET proliferation on filter discs was compared to proliferation as clumps. The study comprised 28 genotypes in four trials. The benefits of adding a pre-maturation step and the selection of fresh ET for the subculture were evaluated. Pre-maturation on hormone-free media before maturation did not significantly improve embryo yield but improved greenhouse survival from 69% to 80%, although there was high variation between lines. Filter disc cultivation of ET did result in better growth than in clumps but was more dependent on ET selection and the amount of ET than the clump cultivation method. Filter proliferation also favors certain lines. Post-maturation storage can be used to change the storage compound composition of the produced mature embryos. The embryo storage compound profile was analyzed after post-maturation cold storage treatments of 0, 4, 8, 31, and 61 weeks and compared to that of the zygotic embryos. Cold storage made the storage compound profile of somatic embryos closer to that of zygotic embryos, especially regarding the raffinose family oligosaccharides and storage proteins. Sucrose, hexose, and starch content remained higher in somatic embryos even through cold storage. Prolonged storage appeared less beneficial for embryos, some of which then seemed to spontaneously enter the germination process.
Heterogeneity and regulation of oligodendrocyte morphology

Oligodendrocytes form multiple myelin sheaths in the central nervous system (CNS), which increase nerve conduction velocity and are necessary for basic and higher brain functions such as sensory function, motor control, and learning. Structures of the myelin sheath such as myelin internodal length and myelin thickness regulate nerve conduction. Various parts of the central nervous system exhibit different myelin structures and oligodendrocyte morphologies. Recent studies supported that oligodendrocytes are a heterogenous population of cells and myelin sheaths formed by some oligodendrocytes can be biased to particular groups of axons, and myelin structures are dynamically modulated in certain classes of neurons by specific experiences. Structures of oligodendrocyte/myelin are also affected in pathological conditions such as demyelinating and neuropsychiatric disorders. This review summarizes our understanding of heterogeneity and regulation of oligodendrocyte morphology concerning central nervous system regions, neuronal classes, experiences, diseases, and how oligodendrocytes are optimized to execute central nervous system functions.
Identification of in vivo induced antigens of the malacosporean parasite Tetracapsuloides bryosalmonae (Cnidaria) using in vivo induced antigen technology

Tetracapsuloides bryosalmonae is a malacosporean endoparasite that causes proliferative kidney disease (PKD) in wild and farmed salmonids in Europe and North America. The life cycle of T. bryosalmonae completes between invertebrate bryozoan and vertebrate fish hosts. Inside the fish, virulence factors of T. bryosalmonae are induced during infection or interactions with host cells. T. bryosalmonae genes expressed in vivo are likely to be important in fish pathogenesis. Herein, we identify in vivo induced antigens of T. bryosalmonae during infection in brown trout (Salmo trutta) using in vivo induced antigen technology (IVIAT). Brown trout were exposed to the spores of T. bryosalmonae and were sampled at different time points. The pooled sera were first pre-adsorbed with antigens to remove false positive results. Subsequently, adsorbed sera were used to screen a T. bryosalmonae cDNA phage expression library. Immunoscreening analysis revealed 136 immunogenic T. bryosalmonae proteins induced in brown trout during parasite development. They are involved in signal transduction, transport, metabolism, ion-protein binding, protein folding, and also include hypothetical proteins, of so far unknown functions. The identified in vivo induced antigens will be useful in the understanding of T. bryosalmonae pathogenesis during infection in susceptible hosts. Some of the antigens found may have significant implications for the discovery of candidate molecules for the development of potential therapies and preventive measures against T. bryosalmonae in salmonids.
Rabbit manure compost as a peat substitute for compound growing media: Proportioning optimization according to physiochemical characteristics and seedling effects

A large amount of rabbit manure is produced with the development of the rabbit industry, which will cause environmental pollution without proper treatment. Rabbit manure compost may be suitable for seedling cultivation, considering its low moisture, low heavy metal, high lignocellulose, and good fertilizer effect. In this study, a pre-proportioning test of growing media was conducted to optimize the ratio of perlite and vermiculite with peat/rabbit manure compost according to their physicochemical properties. Then, based on the results of the first proportioning optimization, the mixing ratio of rabbit manure compost and peat was further optimized using a bioassay. In this bioassay, salt-tolerant calendula (Calendula officinalis L.) and salt-intolerant cucumber (Cucumis sativus L.) were selected as test plants. The seedling effects (e.g., seedling emergence percentage, plant growth parameters, plant biomass, and nutrient effects) were evaluated. It was shown in the results that the rabbit manure compound growing media could be used for the seedlings, and suitable seedling performance was obtained with the increase of the total porosity (5.0%–61.2%), organic matter content (8.3%–39.9%), and nutrient elements from the rabbit manure compost. From the perspective of seedling emergence, there was no significant difference between rabbit manure compound media and peat treatment, in which the highest emergence percentages were >90%. At the same time, the nutrient performance of plant aboveground was significantly increased in rabbit manure compound growing media compared to peat treatment. In particular, the contents of P and Mg were increased by 31%–141.4% and 80.4%–107.8% for calendula and by 82.6%–117.4% and 35.1%–67.6% for cucumber, respectively. It was indicated in the two-step optimization that the rabbit manure compost proportion of 30%–50% (that is, 60%–100% instead of peat) was more suitable. Additionally, the greenhouse gas emission could be reduced by using rabbit manure compost replacing peat, and the greenhouse gas emission reduction potential would be 3.65 × 105–4.06 × 108 kg CO2-equivalent/year in China, which has important ecological significance.
The bone-protective mechanisms of active components from TCM drugs in rheumatoid arthritis treatment

Rheumatoid arthritis (RA) is an autoimmune disease whose hallmarks are synovial inflammation and irreversible bone destruction. Bone resorption resulting from osteoclasts involves the whole immune and bone systems. Breakdown of bone remodeling is attributed to overactive immune cells that produce large quantities of cytokines, upregulated differentiation of osteoclasts with enhanced resorptive activities, suppressed differentiation of osteoblasts, invading fibroblasts and microbiota dysbiosis. Despite the mitigation of inflammation, the existing treatment in Western medicine fails to prevent bone loss during disease progression. Traditional Chinese medicine (TCM) has been used for thousands of years in RA treatment, showing great efficacy in bone preservation. The complex components from the decoctions and prescriptions exhibit various pharmacological activities. This review summarizes the research progress that has been made in terms of the bone-protective effect of some representative compounds from TCM drugs and proposes the substantial mechanisms involved in bone metabolism to provide some clues for future studies. These active components systemically suppress bone destruction via inhibiting joint inflammation, osteoclast differentiation, and fibroblast proliferation. Neutrophil, gut microenvironment and microRNA has been proposed as future focus.
Unweaving the mitotic spindle: A focus on Aurora kinase inhibitors in lung cancer

Lung cancer is one of the most aggressive malignancies, classified into two major histological subtypes: non-small cell lung cancer (NSCLC), that accounts for about 85% of new diagnosis, and small cell lung cancer (SCLC), the other 15%. In the case of NSCLC, comprehensive genome sequencing has allowed the identification of an increasing number of actionable targets, which have become the cornerstone of treatment in the advanced setting. On the other hand, the concept of oncogene-addiction is lacking in SCLC, and the only innovation of the last 30 years has been the introduction of immune checkpoint inhibitors in extensive stage disease. Dysregulation of cell cycle is a fundamental step in carcinogenesis, and Aurora kinases (AURKs) are a family of serine/threonine kinases that play a crucial role in the correct advance through the steps of the cycle. Hyperexpression of Aurora kinases is a common protumorigenic pathway in many cancer types, including NSCLC and SCLC; in addition, different mechanisms of resistance to anticancer drugs rely on AURK expression. Hence, small molecule inhibitors of AURKs have been developed in recent years and tested in several malignancies, with different results. The aim of this review is to analyze the current evidences of AURK inhibition in lung cancer, starting from preclinical rationale to finish with clinical trials available up to now.
Affine stacks (Champs affines)

This is an expended and revised version of the preprint "Schematization of homotopy types". The purpose of this work is to introduce a notion of \emph{affine stacks}, which is a homotopy version of the notion of affine schemes, and to give several applications in the context of algebraic topology and algebraic geometry. As a first application we show how affine stacks can be used in order to give a new point of view (and new proofs) on rational and $p$-adic homotopy theory. This gives a first solution to A. Grothendieck's \emph{schematization problem} described in \cite{gr}. We also use affine stacks in order to introduce a notion of \emph{schematic homotopy types}. We show that schematic homotopy types give a second solution to the schematization problem, which also allows us to go beyound rational and $p$-adic homotopy theory for spaces with arbitrary fundamental groups. The notion of schematic homotopy types is also used in order to construct various homotopy types of algebraic varieties corresponding to various cohomology theories (Betti, de Rham, $l$-adic, .), extending the well known constructions of the various fundamental groups. Finally, as algebraic stacks are obtained by gluing affine schemes we define \emph{$\infty$-geometric stacks} as a certain gluing of affine stacks. Example of $\infty$-geometric stacks in the context of algebraic topology (moduli spaces of dga structures up to quasi-isomorphisms) and Hodge theory (non-abelian periods) are given.
Glial cells and neurologic autoimmune disorders

Neurologic autoimmune disorders affect people’s physical and mental health seriously. Glial cells, as an important part of the nervous system, play a vital role in the occurrence of neurologic autoimmune disorders. Glial cells can be hyperactivated in the presence of autoantibodies or pathological changes, to influence neurologic autoimmune disorders. This review is mainly focused on the roles of glial cells in neurologic autoimmune disorders and the influence of autoantibodies produced by autoimmune disorders on glial cells. We speculate that the possibility of glial cells might be a novel way for the investigation and therapy of neurologic autoimmune disorders.