Miracle-dz/UniFAR-FTUs huggingface dataset:
TRPV1 Supports Axogenic Enhanced Excitability in Response to Neurodegenerative Stress

Early progression in neurodegenerative disease involves challenges to homeostatic processes, including those controlling axonal excitability and dendritic organization. In glaucoma, the leading cause of irreversible blindness, stress from intraocular pressure (IOP) causes degeneration of retinal ganglion cells (RGC) and their axons which comprise the optic nerve. Previously, we discovered that early progression induces axogenic, voltage-gated enhanced excitability of RGCs, even as dendritic complexity in the retina reduces. Here, we investigate a possible contribution of the transient receptor potential vanilloid type 1 (TRPV1) channel to enhanced excitability, given its role in modulating excitation in other neural systems. We find that genetic deletion of Trpv1 (Trpv1−/−) influences excitability differently for RGCs firing continuously to light onset (αON-Sustained) vs. light offset (αOFF-Sustained). Deletion drives excitability in opposing directions so that Trpv1−/− RGC responses with elevated IOP equalize to that of wild-type (WT) RGCs without elevated IOP. Depolarizing current injections in the absence of light-driven presynaptic excitation to directly modulate voltage-gated channels mirrored these changes, while inhibiting voltage-gated sodium channels and isolating retinal excitatory postsynaptic currents abolished both the differences in light-driven activity between WT and Trpv1−/− RGCs and changes in response due to IOP elevation. Together, these results support a voltage-dependent, axogenic influence of Trpv1−/− with elevated IOP. Finally, Trpv1−/− slowed the loss of dendritic complexity with elevated IOP, opposite its effect on axon degeneration, supporting the idea that axonal and dendritic degeneration follows distinctive programs even at the level of membrane excitability.
An Integrated Transcriptome Analysis Reveals IGFBP7 Upregulation in Vasculature in Traumatic Brain Injury

Vasculature plays critical roles in the pathogenesis and neurological repair of traumatic brain injury (TBI). However, how vascular endothelial cells respond to TBI at the molecular level has not been systematically reviewed. Here, by integrating three transcriptome datasets including whole cortex of mouse brain, FACS-sorted mouse brain endothelial cells, and single cell sequencing of mouse brain hippocampus, we revealed the key molecular alteration of endothelial cells characterized by increased Myc targets and Epithelial-Mesenchymal Transition signatures. In addition, immunofluorescence staining of patients’ samples confirmed that IGFBP7 was up-regulated in vasculature in response to TBI. TGFβ1, mainly derived from microglia and endothelial cells, sufficiently induces IGFBP7 expression in cultured endothelial cells, and is significantly upregulated in response to TBI. Our results identified IGFBP7 as a potential biomarker of vasculature in response to TBI, and indicate that TGFβ signaling may contribute to the upregulation of IGFBP7 in the vasculature.
Extracellular Vesicle-Derived microRNA-410 From Mesenchymal Stem Cells Protects Against Neonatal Hypoxia-Ischemia Brain Damage Through an HDAC1-Dependent EGR2/Bcl2 Axis

Hypoxia-ischemia brain damage (HIBD) is a neurological disorder occring in neonates, which is exacerbated by neuronal apoptosis. Mesenchymal stem cells (MSCs)-derived extracellular vesicles (EVs) have been proposed as a promising strategy for treating or preventing ischemia-related diseases. However, their mechanisms in HIBD remain unclear. Thus, we aimed to address the role of EV-derived microRNA (miR)-410 in HIBD. Neonatal HIBD mouse model was constructed using HI insult, from which neurons were isolated, followed by exposure to oxygen glucose deprivation (OGD). EVs were isolated from human umbilical cord (hUC)-derived MSCs. In silico analyses, dual-luciferase reporter gene and chromatin immunoprecipitation assays were adopted to determine relationships among miR-410, histone deacetylase 1 (HDAC1), early growth response protein 2 (EGR2), and B cell lymphoma/leukemia 2 (Bcl2). The functional roles of EV-derived miR-410 were determined using loss- and gain-of functions experiments, and by evaluating neuronal viability, cell-cycle distribution and neuronal apoptosis in vitro as well as modified neurological severity score (mNSS), edema formation, and cerebral infarction volume in vivo. hUC-MSCs-derived EVs protected against HIBD in vivo and inhibited the OGD-induced neuronal apoptosis in vitro. miR-410 was successfully delivered to neurons by hUC-MSCs-EVs and negatively targeted HDAC1, which inversely mediated the expression of EGR2/Bcl2. Upregulation of EV-derived miR-410 promoted the viability but inhibited apoptosis of neurons, which was reversed by HDAC1 overexpression. EV-derived miR-410 elevation reduced mNSS, edema formation, and cerebral infarction volume by increasing EGR2/Bcl2 expression through downregulating HDAC1 expression in vivo. In summary, EV-derived miR-410 impeded neuronal apoptosis by elevating the expression of EGR2/Bcl2 via HDAC1 downregulation, thereby providing a potential strategy for treating or preventing HIBD.
Compassion As an Intervention to Attune to Universal Suffering of Self and Others in Conflicts: A Translational Framework

As interpersonal, racial, social, and international conflicts intensify in the world, it is important to safeguard the mental health of individuals affected by them. According to a Buddhist notion “if you want others to be happy, practice compassion; if you want to be happy, practice compassion,” compassion practice is an intervention to cultivate conflict-proof well-being. Here, compassion practice refers to a form of concentrated meditation wherein a practitioner attunes to friend, enemy, and someone in between, thinking, “I’m going to help them (equally). ” The compassion meditation is based on Buddhist philosophy that mental suffering is rooted in conceptual thoughts that give rise to generic mental images of self and others and subsequent biases to preserve one’s egoism, blocking the ultimate nature of mind. To contextualize compassion meditation scientifically, we adopted a Bayesian active inference framework to incorporate relevant Buddhist concepts, including mind (buddhi), compassion (karuna), aggregates (skandhas), suffering (duhkha), reification (samaropa), conceptual thoughts (vikalpa), and superimposition (prapañca). In this framework, a person is considered a Bayesian Engine that actively constructs phenomena based on the aggregates of forms, sensations, discriminations, actions, and consciousness. When the person embodies rigid beliefs about self and others’ identities (identity-grasping beliefs) and the resulting ego-preserving bias, the person’s Bayesian Engine malfunctions, failing to use prediction errors to update prior beliefs. To counter this problem, after recognizing the causes of sufferings, a practitioner of the compassion meditation aims to attune to all others equally, friends and enemies alike, suspend identity-based conceptual thoughts, and eventually let go of any identity-grasping belief and ego-preserving bias that obscure reality. We present a brain model for the Bayesian Engine of three components: (a) Relation-Modeling, (b) Reality-Checking, and (c) Conflict-Alarming, which are subserved by (a) the Default-Mode Network (DMN), (b) Frontoparietal Network (FPN) and Ventral Attention Network (VAN), and (c) Salience Network (SN), respectively. Upon perceiving conflicts, the strengthening or weakening of ego-preserving bias will critically depend on whether the SN up-regulates the DMN or FPN/VAN, respectively. We propose that compassion meditation can strengthen brain regions that are conducive for suspending prior beliefs and enhancing the attunements to the counterparts in conflicts.
Consumer Decision-Making Creativity and Its Relation to Exploitation–Exploration Activities: Eye-Tracking Approach

Modern consumers face a dramatic rise in web-based technological advancements and have trouble making rational and proper decisions when they shop online. When they try to make decisions about products and services, they also feel pressured against time when sorting among all of the unnecessary items in the flood of information available on the web. In this sense, they need to use consumer decision-making creativity (CDMC) to make rational decisions. However, unexplored research questions on this subject remain. First, in what ways do task difficulty and time constraints affect visual attention on exploitative and exploratory activities differently? Second, how does the location of the reference (i.e., hints) influence the level of visual attention to exploitative and exploratory activities depending on affordance theory? Third, how do exploratory and exploitative activities affect CDMC? Eye-tracking experiments were conducted with 70 participants to obtain relevant metrics such as total fixation duration (TFD), fixation count (FC), and visit count (VC) to answer these research questions. Our findings suggest that task difficulty influences exploitative activity, whereas time constraint is related to the exploratory activity. The result of the location of hints aligns with the affordance theory for the exploitative activity. Besides, exploratory activity positively affected CDMC, but exploitative activity did not show any effect.
Dysregulated H3K27 Acetylation Is Implicated in Fatty Liver Hemorrhagic Syndrome in Chickens

Epigenetic regulation of gene expression has been reported in the pathogenesis of metabolic disorders such as diabetes and liver steatosis in humans. However, the molecular mechanisms of fatty liver hemorrhagic syndrome (FLHS) in chickens have been rarely studied. H3K27ac chromatin immunoprecipitation coupled with high-throughput sequencing and high-throughput RNA sequencing was performed to compare genome-wide H3K27ac profiles and transcriptomes of liver tissue between healthy and FLHS chickens. In total, 1,321 differential H3K27ac regions and 443 differentially expressed genes were identified (| log2Fold change| ≥ 1 and P-value ≤ 0.05) between the two groups. Binding motifs for transcription factors involved in immune processes and metabolic homeostasis were enriched among those differential H3K27ac regions. Differential H3K27ac peaks were associated with multiple known FLHS risk genes, involved in lipid and energy metabolism (PCK1, APOA1, ANGPTL4, and FABP1) and the immune system (FGF7, PDGFRA, and KIT). Previous studies and our current results suggested that the high-energy, low-protein (HELP) diet might have an impact on histone modification and chromatin structure, leading to the dysregulation of candidate genes and the peroxisome proliferator-activated receptor (PPAR) signaling pathway, which causes excessive accumulation of fat in the liver tissue and induces the development of FLHS. These findings highlight that epigenetic modifications contribute to the regulation of gene expression and play a central regulatory role in FLHS. The PPAR signaling pathway and other genes implicated in FLHS are of great importance for the development of novel and specific therapies for FLHS-susceptible commercial laying hens.
Introducing a Controlled Outdoor Environment Impacts Positively in Cat Welfare and Owner Concerns: The Use of a New Feline Welfare Assessment Tool

There is much debate over the pros and cons of allowing cats to roam freely as opposed to keeping them confined indoors. We surveyed owners who implemented a commercial physical containment system to the outdoors to evaluate their characteristics and the apparent impact of this system on cat welfare and owner perceptions. As part of the latter aim, we also developed a new feline welfare assessment tool based on the mathematical relationship between different measures. The survey was circulated to customers over the preceding 2 years of ProtectaPet® between May and June 2019 and gathered 446 responses. Univariate analyses compared changes following installation on factors such as the amount of time the cat spent outside, other cats entering the owner's garden and owners' concerns about their cat outside. Principal component analysis was used to reduce 21 potential indicators of feline welfare into fewer variables. This resulted in 4 subscales, 2 relating to positive welfare and 2 relating to negative welfare. The effects of installation of the containment system and significant predictors of these four welfare subscales were assessed. The majority of respondents lived in an urban environment with a relatively small garden, had multiple cats and a history of feline trauma associated with a road traffic accident. As expected, the time spent outside significantly increased, while the frequency of other cats entering the garden and owner concern about leaving their cats outside significantly decreased. The 4 welfare subscales grouped into positivity, maintenance behaviors, health issues and fearfulness; installation of the system was associated with significant improvements across all of these. Time spent outside after installation had a significant effect on positivity and, to a lesser extent, maintenance behaviors. Overall, installation was associated with positive changes in both owner and cat quality of life, which seem to be particularly associated with an increased sense of security. This suggests that housing cats within a controlled outside environment with physical barriers can provide a practical solution for many of the problems associated with cats being allowed out.
To Reveal or Not to Reveal? Observation of Social Outcomes Facilitates Reward Processing

Motivation is a key topic that comprises considerable theoretical and practical implications, and its study is gaining increasing traction in recent years. Employing both behavioral and neural techniques, previous studies examined the extent to which intrinsic and extrinsic motivations collectively shape individual decision making. Investigations found that both processes play indispensable and interactive roles in choice behavior. However, despite its importance, little is known respecting the role of extrinsic social factors in contributing to individual variations in intrinsic motivation. Toward elucidating the role of extrinsic social factors in motivated decision making, the current study implements the stop watch task, combined with hyper-recording electrophysiological measurements. With the electrophysiological toolkit, our goal is to bring to light how extrinsic social signals impact intrinsic motivation and shape the reward processing over success and failure at the succeeding stage. Empirically, we show that, following social outcome presentation, there is an increased divergent feedback-related negativity (FRN), which reflects the failure/success discrepancy at the outcome stage of choice behavior. In summary, this study demonstrates the saliency of social information in intrinsic motivational processes that underpin success-failure outcomes.
UPLC-ESI-MRM/MS for Absolute Quantification and MS/MS Structural Elucidation of Six Specialized Pyranonaphthoquinone Metabolites From Ventilago harmandiana

Pyranonaphthoquinones (PNQs) are important structural scaffolds found in numerous natural products. Research interest in these specialized metabolites lies in their natural occurrence and therapeutic activities. Nonetheless, research progress has thus far been hindered by the lack of analytical standards and analytical methods for both qualitative and quantitative analysis. We report here that various parts of Ventilago harmandiana are rich sources of PNQs. We developed an ultraperformance liquid chromatography–electrospray ionization multiple reaction monitoring/mass spectrometry method to quantitatively determine six PNQs from leaves, root, bark, wood, and heartwood. The addition of standards in combination with a stable isotope of salicylic acid-D6 was used to overcome the matrix effect with average recovery of 82% ± 1% (n = 15). The highest concentration of the total PNQs was found in the root (11,902 μg/g dry weight), whereas the lowest concentration was found in the leaves (28 μg/g dry weight). Except for the root, PNQ-332 was found to be the major compound in all parts of V. harmandiana, accounting for ∼48% of the total PNQs quantified in this study. However, PNQ-318A was the most abundant PNQ in the root sample, accounting for 27% of the total PNQs. Finally, we provide novel MS/MS spectra of the PNQs at different collision induction energies: 10, 20, and 40 eV (POS and NEG). For structural elucidation purposes, we propose complete MS/MS fragmentation pathways of PNQs using MS/MS spectra at collision energies of 20 and 40 eV. The MS/MS spectra along with our discussion on structural elucidation of these PNQs should be very useful to the natural products community to further exploring PNQs in V. harmandiana and various other sources.
Cytologic and Molecular Diagnostics for Vitreoretinal Lymphoma: Current Approaches and Emerging Single-Cell Analyses

Vitreoretinal lymphoma (VRL) is a rare ocular malignancy that manifests as diffuse large B-cell lymphoma. Early and accurate diagnosis is essential to prevent mistreatment and to reduce the high morbidity and mortality associated with VRL. The disease can be diagnosed using various methods, including cytology, immunohistochemistry, cytokine analysis, flow cytometry, and molecular analysis of bulk vitreous aspirates. Despite these options, VRL diagnosis remains challenging, as samples are often confounded by low cellularity, the presence of debris and non-target immunoreactive cells, and poor cytological preservation. As such, VRL diagnostic accuracy is limited by both false-positive and false-negative outcomes. Missed or inappropriate diagnosis may cause delays in treatment, which can have life-threatening consequences for patients with VRL. In this review, we summarize current knowledge and the diagnostic modalities used for VRL diagnosis. We also highlight several emerging molecular techniques, including high-resolution single cell-based analyses, which may enable more comprehensive and precise VRL diagnoses.
Deciphering the Subtype Differentiation History of SARS-CoV-2 Based on a New Breadth-First Searching Optimized Alignment Method Over a Global Data Set of 24,768 Sequences

SARS-CoV-2 has caused a worldwide pandemic. Existing research on coronavirus mutations is based on small data sets, and multiple sequence alignment using a global-scale data set has yet to be conducted. Statistical analysis of integral mutations and global spread are necessary and could help improve primer design for nucleic acid diagnosis and vaccine development. Here, we optimized multiple sequence alignment using a conserved sequence search algorithm to align 24,768 sequences from the GISAID data set. A phylogenetic tree was constructed using the maximum likelihood (ML) method. Coronavirus subtypes were analyzed via t-SNE clustering. We performed haplotype network analysis and t-SNE clustering to analyze the coronavirus origin and spread. Overall, we identified 33 sense, 17 nonsense, 79 amino acid loss, and 4 amino acid insertion mutations in full-length open reading frames. Phylogenetic trees were successfully constructed and samples clustered into subtypes. The COVID-19 pandemic differed among countries and continents. Samples from the United States and western Europe were more diverse, and those from China and Asia mainly contained specific subtypes. Clades G/GH/GR are more likely to be the origin clades of SARS-CoV-2 compared with clades S/L/V. Conserved sequence searches can be used to segment long sequences, making large-scale multisequence alignment possible, facilitating more comprehensive gene mutation analysis. Mutation analysis of the SARS-CoV-2 can inform primer design for nucleic acid diagnosis to improve virus detection efficiency. In addition, research into the characteristics of viral spread and relationships among geographic regions can help formulate health policies and reduce the increase of imported cases.
Transcriptomic Profiling of Buffalo Spermatozoa Reveals Dysregulation of Functionally Relevant mRNAs in Low-Fertile Bulls

Although, it is known that spermatozoa harbor a variety of RNAs that may influence embryonic development, little is understood about sperm transcriptomic differences in relation to fertility, especially in buffaloes. In the present study, we compared the differences in sperm functional attributes and transcriptomic profile between high- and low-fertile buffalo bulls. Sperm membrane and acrosomal integrity were lower (P < 0.05), while protamine deficiency and lipid peroxidation were higher (P < 0.05) in low- compared to high-fertile bulls. Transcriptomic analysis using mRNA microarray technology detected a total of 51,282 transcripts in buffalo spermatozoa, of which 4,050 transcripts were differentially expressed, and 709 transcripts were found to be significantly dysregulated (P < 0.05 and fold change >1) between high- and low-fertile bulls. Majority of the dysregulated transcripts were related to binding activity, transcription, translation, and metabolic processes with primary localization in the cell nucleus, nucleoplasm, and in cytosol. Pathways related to MAPK signaling, ribosome pathway, and oxidative phosphorylation were dysregulated in low-fertile bull spermatozoa. Using bioinformatics analysis, we observed that several genes related to sperm functional attributes were significantly downregulated in low-fertile bull spermatozoa. Validation of the results of microarray analysis was carried out using real-time qPCR expression analysis of selected genes (YBX1, ORAI3, and TFAP2C). The relative expression of these genes followed the same trend in both the techniques. Collectively, this is the first study to report the transcriptomic profile of buffalo spermatozoa and to demonstrate the dysregulation of functionally relevant transcripts in low-fertile bull spermatozoa. The results of the present study open up new avenues for understanding the etiology for poor fertility in buffalo bulls and to identify fertility biomarkers.
Fungal and Bacterial Diversity Patterns of Two Diversity Levels Retrieved From a Late Decaying Fagus sylvatica Under Two Temperature Regimes

Environmental fluctuations are a common occurrence in an ecosystem, which have an impact on organismic diversity and associated ecosystem services. The aim of this study was to investigate how a natural and a species richness-reduced wood decaying community diversity were capable of decomposing Fagus sylvatica dead wood under a constant and a fluctuating temperature regime. Therefore, microcosms with both diversity levels (natural and species richness-reduced) were prepared and incubated for 8 weeks under both temperature regimes. Relative wood mass loss, wood pH, carbon dioxide, and methane emissions, as well as fungal and bacterial community compositions in terms of Simpson‘s diversity, richness and evenness were investigated. Community interaction patterns and co-occurrence networks were calculated. Community composition was affected by temperature regime and natural diversity caused significantly higher mass loss than richness-reduced diversity. In contrast, richness-reduced diversity increased wood pH. The bacterial community composition was less affected by richness reduction and temperature regimes than the fungal community composition. Microbial interaction patterns showed more mutual exclusions in richness-reduced compared to natural diversity as the reduction mainly reduced abundant fungal species and disintegrated previous interaction patterns. Microbial communities reassembled in richness-reduced diversity with a focus on nitrate reducing and dinitrogen-fixing bacteria as connectors in the network, indicating their high relevance to reestablish ecosystem functions. Therefore, a stochastic richness reduction was followed by functional trait based reassembly to recover previous ecosystem productivity.