Miracle-dz/UniFAR-FTUs huggingface dataset:
Interacting Effects of Sea Louse (Lepeophtheirus salmonis) Infection and Formalin-Killed Aeromonas salmonicida on Atlantic Salmon Skin Transcriptome

Lepeophtheirus salmonis (sea lice) and bacterial co-infection threatens wild and farmed Atlantic salmon performance and welfare. In the present study, pre-adult L. salmonis-infected and non-infected salmon were intraperitoneally injected with either formalin-killed Aeromonas salmonicida bacterin (ASAL) or phosphate-buffered saline (PBS). Dorsal skin samples from each injection/infection group (PBS/no lice, PBS/lice, ASAL/no lice, and ASAL/lice) were collected at 24 h post-injection and used for transcriptome profiling using a 44K salmonid microarray platform. Microarray results showed no clear inflammation gene expression signatures and revealed extensive gene repression effects by pre-adult lice (2,189 down and 345 up-regulated probes) in the PBS-injected salmon (PBS/lice vs. PBS/no lice), which involved basic cellular (e.g., RNA and protein metabolism) processes. Lice repressive effects were not observed within the group of ASAL-injected salmon (ASAL/lice vs. ASAL/no lice); on the contrary, the observed skin transcriptome changes –albeit of lesser magnitude (82 up and 1 down-regulated probes)– suggested the activation in key immune and wound healing processes (e.g., neutrophil degranulation, keratinocyte differentiation). The molecular skin response to ASAL was more intense in the lice-infected (ASAL/lice vs. PBS/lice; 272 up and 11 down-regulated probes) than in the non-infected fish (ASAL/no lice vs. PBS/no lice; 27 up-regulated probes). Regardless of lice infection, the skin’s response to ASAL was characterized by the putative activation of both antibacterial and wound healing pathways. The transcriptomic changes prompted by ASAL+lice co-stimulation (ASAL/lice vs. PBS/no lice; 1878 up and 3120 down-regulated probes) confirmed partial mitigation of lice repressive effects on fundamental cellular processes and the activation of pathways involved in innate (e.g., neutrophil degranulation) and adaptive immunity (e.g., antibody formation), as well as endothelial cell migration. The qPCR analyses evidenced immune-relevant genes co-stimulated by ASAL and lice in an additive (e.g., mbl2b, bcl6) and synergistic (e.g., hampa, il4r) manner. These results provided insight on the physiological response of the skin of L. salmonis-infected salmon 24 h after ASAL stimulation, which revealed immunostimulatory properties by the bacterin with potential applications in anti-lice treatments for aquaculture. As a simulated co-infection model, the present study also serves as a source of candidate gene biomarkers for sea lice and bacterial co-infection.
Pterostilbene Interferes With Lipopolysaccharide-Induced Myocardial Injury Through Oxidative Stress and Inflammasome Pathways

Myocardial contractile dysfunction caused by sepsis is a serious threat to human health, and its pathogenesis is not completely clear. It is generally believed that excessive inflammation and oxidative stress are the main causes of myocardial damage caused by sepsis. Pterostilbene (PTS) has a variety of biological activities, including anti-oxidant, anti-inflammatory, and anti-aging. Whether PTS protect myocardial function in rats with sepsis through anti-inflammatory and anti-oxidant effects has not been reported. In this study, we investigated the role of PTS in septic mice induced by lipopolysaccharide (LPS). Mice were injected intraperitoneally with LPS (20 mg/kg) to simulate sepsis. Use Echocardiography, Masson, DHE, H&E, IHC, IF and other experimental methods to explore the effects of PTS on LPS. The results showed that PTS was indicated to significantly increase the cardiac function of mice with sepsis. PTS treatment also reduced the mRNA expression of IL-1α, IL-6, MCP-1, and IL-1β and the protein expression of NLRP3 in vivo and in vitro, and inhibited the migration of inflammatory cells. PTS treatment also reduced the mRNA expression of collagen I, collagen III and α-SMA, and inhibited fibrosis. PTS treatment reduced the mRNA expression of NOX1, NOX2, and NOX4 and inhibited DHE levels in vivo and in vitro. In summary, our data indicated that PTS played a crucial role in LPS-induced myocardial injured and might be a key target for the prevention and treatment of sepsis-induced myocardial dysfunction.
Swine Interferon-Inducible Transmembrane Proteins Potently Inhibit African Swine Fever Virus Replication

African swine fever virus (ASFV) causes an acute, hemorrhagic, and highly contagious disease in domestic swine, leading to significant economic losses to the global porcine industry. Restriction factors of innate immunity play a critical in host antiviral action. However, function of swine restriction factors of innate immunity on ASFV has been seldomly investigated. In this study, we determined five homologues of swine interferon-induced transmembrane proteins (SwIFITM [named SwIFITM1a, -1b, -2, -3, and -5]), and we found that they all exhibit potent antiviral activity against ASFV. Expression profile analysis indicated that these SwIFITMs are constitutively expressed in most porcine tissues. Whether infected with ASFV or treated with swine interferon, the expression levels of SwIFITMs were induced in vitro. The subcellular localization of SwIFITMs was similar to that of their human homologues. SwIFITM1a and -1b localized to the plasma membrane, SwIFITM2 and -3 focused on the cytoplasm and the perinuclear region, while SwIFITM5 accumulated in the cell surface and cytoplasm. The overexpression of SwIFITM1a, -1b, -2, -3, or -5 could significantly inhibit ASFV replication in Vero cells, whereas knockdown of these genes could enhance ASFV replication in PAMs. We blocked the constitutive expression of endogenous IFITMs in Vero cells using a CRISPR-Cas9 system and then infected them with ASFV. The results indicated that the knockout of endogenous IFITMs could enhance ASFV replication. Finally, we expressed five SwIFITMs in knockout Vero cell lines and then challenged them with ASFV. The results showed that all of the SwIFITMs had a strong antiviral effect on ASFV. This research will further expand the understanding of the anti-ASFV activity of porcine IFITMs.
Genetic Study of Cerebral Small Vessel Disease in Chinese Han Population

Cerebral small vessel disease (CSVD) is a syndrome of clinical, neuroimaging, and neuropathological manifestations caused by disorders that affect small cerebral vessels. Although the pathogenesis of the disease remains unclear, some studies have demonstrated that genetic variants contribute to the development of CSVD. Our study aimed to explore the genetic characteristics of CSVD in the Chinese Han population. We enrolled 182 sporadic CSVD Chinese Han patients whose magnetic resonance imaging results showed grade 2-3 white matter lesions. Target region sequencing of seven monogenic CSVD-related genes, including NOTCH3, HTRA1, COL4A1, COL4A2, GLA, TREX1, and CTSA, was performed, and we identified pathogenic variants by screening the sequencing results and functional predictive analysis. All variants were predicted to be pathogenic by the SIFT Score, Polymorphism Phenotyping-2 score, Mutation Taster, Splice site score calculation, and MaxEntScan. All variants were validated in 300 healthy controls. In total, eight variants were identified in patients with CSVD, including five novel variants, c.1774C>T (NOTCH3), c.3784C>T (NOTCH3), c. 1207C>T (HTRA1), and c. 1274+1G> A (HTRA1), c.1937G>C (COL4A1) and three reported mutations. None of these variants were present in 300 healthy controls. No pathogenic variants in COL4A2, GLA, TREX1, and CTSA were detected. This study identified five novel variants in CSVD-related genes in Chinese Han patients with sporadic CSVD. Our results expand the genetic profile of CSVD.
Cross-Attention and Deep Supervision UNet for Lesion Segmentation of Chronic Stroke

Stroke is an acute cerebrovascular disease with high incidence, high mortality, and high disability rate. Determining the location and volume of the disease in MR images promotes accurate stroke diagnosis and surgical planning. Therefore, the automatic recognition and segmentation of stroke lesions has important clinical significance for large-scale stroke imaging analysis. There are some problems in the segmentation of stroke lesions, such as imbalance of the front and back scenes, uncertainty of position, and unclear boundary. To meet this challenge, this paper proposes a cross-attention and deep supervision UNet (CADS-UNet) to segment chronic stroke lesions from T1-weighted MR images. Specifically, we propose a cross-spatial attention module, which is different from the usual self-attention module. The location information interactively selects encode features and decode features to enrich the lost spatial focus. At the same time, the channel attention mechanism is used to screen the channel characteristics. Finally, combined with deep supervision and mixed loss, the model is supervised more accurately. We compared and verified the model on the authoritative open dataset “Anatomical Tracings of Lesions After Stroke” (Atlas), which fully proved the effectiveness of our model.
Glutamate Scavenging as a Neuroreparative Strategy in Ischemic Stroke

Stroke is the second highest reason of death in the world and the leading cause of disability. The ischemic stroke makes up the majority of stroke cases that occur due to the blockage of blood vessels. Therapeutic applications for ischemic stroke include thrombolytic treatments that are in limited usage and only applicable to less than 10% of the total stroke patients, but there are promising new approaches. The main cause of ischemic neuronal death is glutamate excitotoxicity. There have been multiple studies focusing on neuroprotection via reduction of glutamate both in ischemic stroke and other neurodegenerative diseases that ultimately failed due to the obstacles in delivery. At that point, systemic glutamate grabbing, or scavenging is an ingenious way of decreasing glutamate levels upon ischemic stroke. The main advantage of this new therapeutic method is the scavengers working in the circulating blood so that there is no interference with the natural brain neurophysiology. In this review, we explain the molecular mechanisms of ischemic stroke, provide brief information about existing drugs and approaches, and present novel systemic glutamate scavenging methods. This review hopefully will elucidate the potential usage of the introduced therapeutic approaches in stroke patients.
Copy Number Variation Analysis of Euploid Pregnancy Loss

Objectives: Copy number variant (CNV) is believed to be the potential genetic cause of pregnancy loss. However, CNVs less than 3 Mb in euploid products of conceptions (POCs) remain largely unexplored. The aim of this study was to investigate the features of CNVs less than 3 Mb in POCs and their potential clinical significance in pregnancy loss/fetal death. Methods: CNV data were extracted from a cohort in our institution and 19 peer-reviewed publications, and only those CNVs less than 3 Mb detected in euploid pregnancy loss/fetal death were included. We conducted a CNV map to analyze the distribution of CNVs in chromosomes using R packages karyoploteR_1. 10.5. Gene names and annotated gene types covered by those CNVs were mined from the human Release 19 reference genome file and GENECODE database. We assessed the expression patterns and the consequences of murine knock-out of those genes using TiGER and Mouse Genome Informatics (MGI) databases. Functional enrichment and pathway analysis for genes in CNVs were performed using clusterProfiler V3.12. 0. Result: Breakpoints of 564 CNVs less than 3 Mb were obtained from 442 euploid POCs, with 349 gains and 185 losses. The CNV map showed that CNVs were distributed in all chromosomes, with the highest frequency detected in chromosome 22 and the lowest frequency in chromosome Y, and CNVs showed a higher density in the pericentromeric and sub-telomeric regions. A total of 5,414 genes mined from the CNV regions (CNVRs), Gene Ontology (GO), and pathway analysis showed that the genes were significantly enriched in multiple terms, especially in sensory perception, membrane region, and tight junction. A total of 995 protein-coding genes have been reported to present mammalian phenotypes in MGI, and 276 of them lead to embryonic lethality or abnormal embryo/placenta in knock-out mouse models. CNV located at 19p13.3 was the most common CNV of all POCs. Conclusion: CNVs less than 3 Mb in euploid POCs distribute unevenly in all chromosomes, and a higher density was seen in the pericentromeric and sub-telomeric regions. The genes in those CNVRs are significantly enriched in biological processes and pathways that are important to embryonic/fetal development. CNV in 19p13.3 and the variations of ARID3A and FSTL3 might contribute to pregnancy loss.
The Ecological View of Selective Attention

Accumulating evidence is supporting the hypothesis that our selective attention is a manifestation of mechanisms that evolved early in evolution and are shared by many organisms from different taxa. This surge of new data calls for the re-examination of our notions about attention, which have been dominated mostly by human psychology. Here, we present an hypothesis that challenges, based on evolutionary grounds, a common view of attention as a means to manage limited brain resources. We begin by arguing that evolutionary considerations do not favor the basic proposition of the limited brain resources view of attention, namely, that the capacity of the sensory organs to provide information exceeds the capacity of the brain to process this information. Moreover, physiological studies in animals and humans show that mechanisms of selective attention are highly demanding of brain resources, making it paradoxical to see attention as a means to release brain resources. Next, we build on the above arguments to address the question why attention evolved in evolution. We hypothesize that, to a certain extent, limiting sensory processing is adaptive irrespective of brain capacity. We call this hypothesis the ecological view of attention (EVA) because it is centered on interactions of an animal with its environment rather than on internal brain resources. In its essence is the notion that inherently noisy and degraded sensory inputs serve the animal’s adaptive, dynamic interactions with its environment. Attention primarily functions to resolve behavioral conflicts and false distractions. Hence, we evolved to focus on a particular target at the expense of others, not because of internal limitations, but to ensure that behavior is properly oriented and committed to its goals. Here, we expand on this notion and review evidence supporting it. We show how common results in human psychophysics and physiology can be reconciled with an EVA and discuss possible implications of the notion for interpreting current results and guiding future research.
Fusion Protein Cleavage Site Containing Three Basic Amino Acids Attenuates Newcastle Disease Virus in Chicken Embryos: Use as an in ovo Vaccine

In ovo vaccination is an attractive immunization strategy for the poultry industry. However, although most live Newcastle disease virus (NDV) vaccine strains, such as LaSota and V4, can be used after hatching, they are pathogenic to chicken embryos when administered in ovo. We have previously reported that NDV strain TS09-C is a safe in ovo vaccine in specific-pathogen-free and commercial chicken embryos because it is attenuated in chicken embryos. However, the molecular basis of its attenuation is poorly understood. In this study, we firstly evaluated the safety of chimeric NDV strains after exchanging genes between strains TS09-C and LaSota as in ovo vaccines, and demonstrated that the attenuation of NDV in chicken embryos was dependent upon the origin of the fusion (F) protein. Next, by comparing the F protein sequences of TS09-C strain with those of LaSota and V4 strain, the R115 in cleavage site and F379 were found to be unique to TS09-C strain. The mutant viruses were generated by substituting one or two amino acids at position 115 and 379 in the F protein, and their safety as in ovo vaccine was evaluated. Mutation in residue 379 did not affect the viral embryonic pathogenicity. While the mutant virus rTS-2B (R115G mutation based on the backbone of TS09-C strain) with two basic amino acids in F cleavage site, was pathogenic to chicken embryos and similar with rLaSota in its tissue tropism, differing markedly from rTS09-C with three basic amino acids in F cleavage site. Together, these findings indicate that the F protein cleavage site containing three basic amino acids is the crucial determinant of the attenuation of TS09-C in chicken embryos. This study extends our understanding of the pathogenicity of NDV in chicken embryos and should expedite the development of in ovo vaccines against NDV.
Pharmacodynamic Parameters of Pharmacokinetic/Pharmacodynamic (PK/PD) Integration Models

Pharmacokinetic/pharmacodynamic (PK/PD) integration models are used to investigate the antimicrobial activity characteristics of drugs targeting pathogenic bacteria through comprehensive analysis of the interactions between PK and PD parameters. PK/PD models have been widely applied in the development of new drugs, optimization of the dosage regimen, and prevention and treatment of drug-resistant bacteria. In PK/PD analysis, minimal inhibitory concentration (MIC) is the most commonly applied PD parameter. However, accurately determining MIC is challenging and this can influence the therapeutic effect. Therefore, it is necessary to optimize PD indices to generate more rational results. Researchers have attempted to optimize PD parameters using mutant prevention concentration (MPC)-based PK/PD models, multiple PD parameter-based PK/PD models, kill rate-based PK/PD models, and others. In this review, we discuss progress on PD parameters for PK/PD models to provide a valuable reference for drug development, determining the dosage regimen, and preventing drug-resistant mutations.
Affective Mobile Language Tutoring System for Supporting Language Learning

Students often face difficulties and experience negative emotions toward second language learning. The affective tutoring system (ATS) is a next-generation learning approach that can detect the affective status of learning to increase performance. Therefore, for the purposes of this study, an innovative affective mobile language tutoring system (AMLTS) was designed to support Japanese language learning. The effects of AMLTS, along with asynchronous discussion, that were intended to improve performance, were examined using a triangulation method. To investigate the effect on emotion, the proposed AMLTS provides a virtual emotion agent that can interact with users and record emotional events, learning assessments, and the results of the interaction into a database. Learning effectiveness evaluations were conducted via two experiments: prototype evaluation and final evaluation. Sixty-three students, all beginners, were invited to use the AMLTS to learn Japanese. The research results show that the proposed AMLTS affective interaction design significantly improves learner engagement and performance. In the emotion feedback analysis and learning process, AMLTS helped students deepen their understanding of the content, enabled them to clearly understand the content, and to engage in peer interaction and experience positive emotions. In the evaluation of system usability, AMLTS reveals good usability for foreign language acquisition.
Environmental Change at Deep-Sea Sponge Habitats Over the Last Half Century: A Model Hindcast Study for the Age of Anthropogenic Climate Change

Deep-sea sponges inhabit multiple areas of the deep North Atlantic at depths below 250 m. Living in the deep ocean, where environmental properties below the permanent thermocline generally change slowly, they may not easily acclimatize to abrupt changes in the environment. Until now consistent monitoring timeseries of the environment at deep sea sponge habitats are missing. Therefore, long-term simulation with coupled bio-physical models can shed light on the changes in environmental conditions sponges are exposed to. To investigate the variability of North Atlantic sponge habitats for the past half century, the deep-sea conditions have been simulated with a 67-year model hindcast from 1948 to 2014. The hindcast was generated using the ocean general circulation model HYCOM, coupled to the biogeochemical model ECOSMO. The model was validated at known sponge habitats with available observations of hydrography and nutrients from the deep ocean to evaluate the biases, errors, and drift in the model. Knowing the biases and uncertainties we proceed to study the longer-term (monthly to multi-decadal) environmental variability at selected sponge habitats in the North Atlantic and Arctic Ocean. On these timescales, these deep sponge habitats generally exhibit small variability in the water-mass properties. Three of the sponge habitats, the Flemish Cap, East Greenland Shelf and North Norwegian Shelf, had fluctuations of temperature and salinity in 4–6 year periods that indicate the dominance of different water masses during these periods. The fourth sponge habitat, the Reykjanes Ridge, showed a gradual warming of about 0.4°C over the simulation period. The flux of organic matter to the sea floor had a large interannual variability, that, compared to the 67-year mean, was larger than the variability of primary production in the surface waters. Lateral circulation is therefore likely an important control mechanism for the influx of organic material to the sponge habitats. Simulated oxygen varies interannually by less than 1.5 ml/l and none of the sponge habitats studied had oxygen concentrations below hypoxic levels. The present study establishes a baseline for the recent past deep conditions that future changes in deep sea conditions from observations and climate models can be evaluated against.
Neuroinflammation, Sleep, and Circadian Rhythms

Molecules involved in innate immunity affect sleep and circadian oscillators and vice versa. Sleep-inducing inflammatory molecules are activated by increased waking activity and pathogens. Pathologies that alter inflammatory molecules, such as traumatic brain injury, cancer, cardiovascular disease, and stroke often are associated with disturbed sleep and electroencephalogram power spectra. Moreover, sleep disorders, such as insomnia and sleep disordered breathing, are associated with increased dysregulation of inflammatory processes. Inflammatory molecules in both the central nervous system and periphery can alter sleep. Inflammation can also modulate cerebral vascular hemodynamics which is associated with alterations in electroencephalogram power spectra. However, further research is needed to determine the interactions of sleep regulatory inflammatory molecules and circadian clocks. The purpose of this review is to: 1) describe the role of the inflammatory cytokines interleukin-1 beta and tumor necrosis factor-alpha and nucleotide-binding domain and leucine-rich repeat protein-3 inflammasomes in sleep regulation, 2) to discuss the relationship between the vagus nerve in translating inflammatory signals between the periphery and central nervous system to alter sleep, and 3) to present information about the relationship between cerebral vascular hemodynamics and the electroencephalogram during sleep.