Miracle-dz/UniFAR-FTUs huggingface dataset:
Three month inhalation exposure to low-level PM2.5 induced brain toxicity in an Alzheimer’s disease mouse model

Although numerous epidemiological studies revealed an association between ambient fine particulate matter (PM2.5) exposure and Alzheimer’s disease (AD), the PM2.5-induced neuron toxicity and associated mechanisms were not fully elucidated. The present study assessed brain toxicity in 6-month-old female triple-transgenic AD (3xTg-AD) mice following subchronic exposure to PM2.5 via an inhalation system. The treated mice were whole-bodily and continuously exposed to real-world PM2.5 for 3 months, while the control mice inhaled filtered air. Changes in cognitive and motor functions were evaluated using the Morris Water Maze and rotarod tests. Magnetic resonance imaging analysis was used to record gross brain volume alterations, and tissue staining with hematoxylin and eosin, Nissl, and immunohistochemistry methods were used to monitor pathological changes in microstructures after PM2.5 exposure. The levels of AD-related hallmarks and the oxidative stress biomarker malondialdehyde (MDA) were assessed using Western blot analysis and liquid chromatography-mass spectrometry, respectively. Our results showed that subchronic exposure to environmental levels of PM2.5 induced obvious neuronal loss in the cortex of exposed mice, but without significant impairment of cognitive and motor function. Increased levels of phosphorylated-tau and MDA were also observed in olfactory bulb or hippocampus after PM2.5 exposure, but no amyloid pathology was detected, as reported in previous studies. These results revealed that a relatively lower level of PM2.5 subchronic exposure from the environmental atmosphere still induced certain neurodegenerative changes in the brains of AD mice, especially in the olfactory bulb, entorhinal cortex and hippocampus, which is consistent with the nasal entry and spreading route for PM exposure. Systemic factors may also contribute to the neuronal toxicity. The effects of PM2.5 after a more prolonged exposure period are needed to establish a more comprehensive picture of the PM2.5-mediated development of AD.
An irradiated marrow niche reveals a small non-collagenous protein mediator of homing, dermatopontin.

Hematopoietic cell homing after hematopoietic cell transplant (HCT) is governed by several pathways involving marrow niche cells that are evoked after pre-HCT conditioning. To understand the factors that play a role in homing, we performed expression analysis on the zebrafish marrow niche cells following conditioning. We determined that the non-collagenous protein extracellular matrix related protein dermatopontin (Dpt) was upregulated seven-fold in response to irradiation. Studies in mice revealed DPT induction both with radiation and lipopolysaccharide exposure. Interestingly, we found that co-incubation of zebrafish or murine hematopoietic cells with rDPT impedes hematopoietic stem and progenitor cell homing by 50% and 86%, respectively. Similarly, this translated into a 24% reduction in long term engraftment (versus control, p = 0.01). We found DPT to interact with VLA-4 and block hematopoietic - endothelial cell adhesion and transendothelial migration. Finally, a DPT knockout mouse displayed a 60% increase in homing of hematopoietic cells versus wildtype (p = 0.03) with slight improvement in long-term LSK-SLAM engraftment (2-fold, p = 0.04). These data show that the extracellular matrix (ECM)-related protein DPT increases with radiation and transiently impedes the transendothelial migration of hematopoietic cells to the marrow.
A Visual Encoding Model Based on Contrastive Self-Supervised Learning for Human Brain Activity along the Ventral Visual Stream

Visual encoding models are important computational models for understanding how information is processed along the visual stream. Many improved visual encoding models have been developed from the perspective of the model architecture and the learning objective, but these are limited to the supervised learning method. From the view of unsupervised learning mechanisms, this paper utilized a pre-trained neural network to construct a visual encoding model based on contrastive self-supervised learning for the ventral visual stream measured by functional magnetic resonance imaging (fMRI). We first extracted features using the ResNet50 model pre-trained in contrastive self-supervised learning (ResNet50-CSL model), trained a linear regression model for each voxel, and finally calculated the prediction accuracy of different voxels. Compared with the ResNet50 model pre-trained in a supervised classification task, the ResNet50-CSL model achieved an equal or even relatively better encoding performance in multiple visual cortical areas. Moreover, the ResNet50-CSL model performs hierarchical representation of input visual stimuli, which is similar to the human visual cortex in its hierarchical information processing. Our experimental results suggest that the encoding model based on contrastive self-supervised learning is a strong computational model to compete with supervised models, and contrastive self-supervised learning proves an effective learning method to extract human brain-like representations.
Impact of Cystic Fibrosis Transmembrane Conductance Regulator Therapy on Chronic Rhinosinusitis and Health Status: Deep Learning CT Analysis and Patient-reported Outcomes

Rationale Elexacaftor, tezacaftor, and ivacaftor (ETI) in triple combination improves pulmonary health for people with cystic fibrosis (PwCF). However, its impact on objective measures of sinus disease and health utility is unestablished. Objectives To evaluate the impact of ETI on chronic rhinosinusitis (CRS) and general health status incorporating computed tomography (CT), quality-of-life (QOL) and productivity loss. Methods Adult PwCF+CRS with CF transmembrane conductance regulator genotype F508del/F508del or F508del/minimal function who clinically initiated ETI participated in a prospective, observational study. The primary endpoint was change in percent sinus CT opacification (%SO) after 6 months of ETI assessed via deep learning-based methods. Secondary endpoints included changes in sinonasal QOL, health utility value and productivity loss, which were evaluated monthly via validated metrics. Results 30 PwCF provided baseline data; 25 completed the study. At baseline, the cohort had substantial CRS, with mean 22-question SinoNasal Outcome Test (SNOT-22) score 33.1 and mean sinus CT %SO 63.7%. At 6-month follow-up, %SO improved by mean 22.9% (P < 0.001). %SO improvement trended toward greater magnitude for those naïve to prior modulator therapy (P = 0.09). Mean SNOT-22 scores and health utility improved by 15.3 and 0.068 [6.8%] (all P ⩽ 0.007). Presenteeism, activity impairment and overall productivity loss improved (all P ⩽ 0.049). Improvements in SNOT-22 scores and health utility occurred by one month and remained improved over the study. Conclusions ETI is associated with substantial improvements in sinus CT opacification and productivity loss, and clinically meaningful improvements in sinonasal QOL and health utility. Most improvements were rapid, robust, and durable over the study.
Epigenetic Regulation of Circadian Clocks and Its Involvement in Drug Addiction

Based on studies describing an increased prevalence of addictive behaviours in several rare sleep disorders and shift workers, a relationship between circadian rhythms and addiction has been hinted for more than a decade. Although circadian rhythm alterations and molecular mechanisms associated with neuropsychiatric conditions are an area of active investigation, success is limited so far, and further investigations are required. Thus, even though compelling evidence connects the circadian clock to addictive behaviour and vice-versa, yet the functional mechanism behind this interaction remains largely unknown. At the molecular level, multiple mechanisms have been proposed to link the circadian timing system to addiction. The molecular mechanism of the circadian clock consists of a transcriptional/translational feedback system, with several regulatory loops, that are also intricately regulated at the epigenetic level. Interestingly, the epigenetic landscape shows profound changes in the addictive brain, with significant alterations in histone modification, DNA methylation, and small regulatory RNAs. The combination of these two observations raises the possibility that epigenetic regulation is a common plot linking the circadian clocks with addiction, though very little evidence has been reported to date. This review provides an elaborate overview of the circadian system and its involvement in addiction, and we hypothesise a possible connection at the epigenetic level that could further link them. Therefore, we think this review may further improve our understanding of the etiology or/and pathology of psychiatric disorders related to drug addiction.
Magnesium oxide modified with various iodine‐containing compounds––Surface studies

The activity of iodine‐modified MgO in transfer hydrogenation of acrolein with alcohols can be significantly higher than that of unmodified MgO. Data from literature and our previous studies indicate that the initial source of a halide influences the surface properties and hence the activity of the obtained catalytic system. The aim of this paper is to present a systematic study on the influence of the initial source of a halide on the activity and surface properties of MgO‐based catalysts. For the sake of comparison, results for an MgO sample subjected to the same procedure as the iodine‐modified catalysts (MgO‐CH3OH) are included in the manuscript. The following order of activity was observed: MgO‐I2 > MgO‐MgI2 > MgO‐HI >> MgO‐KI > MgO = MgO‐CH3OH. The second part of the study consisted of characterization studies aimed at determining the strengths of Brønsted basic and acidic sites, total concentrations of acidic and basic sites, topography of the surfaces, elemental composition, differences in the chemical environment of the surface ions, as well as relative amounts of different bands in an attenuated total reflectance–Fourier transform infrared spectrum, which correspond to the bonds present on the surface of the samples. Some parameters were independent of the iodine precursor used (eg, the breadth of the Mg 2p signal), whereas others strongly varied from one sample to another (eg, the range of strengths of the Brønsted acidic and basic sites). The ratio of 2 carbonate bands of the attenuated total reflectance–Fourier transform infrared spectra of the modified catalysts shows a trend which corresponds to the order of activity.
Population Genomics Reveals Gene Flow and Adaptive Signature in Invasive Weed Mikania micrantha

A long-standing and unresolved issue in invasion biology concerns the rapid adaptation of invaders to nonindigenous environments. Mikania micrantha is a notorious invasive weed that causes substantial economic losses and negative ecological consequences in southern China. However, the contributions of gene flow, environmental variables, and functional genes, all generally recognized as important factors driving invasive success, to its successful invasion of southern China are not fully understood. Here, we utilized a genotyping-by-sequencing approach to sequence 306 M. micrantha individuals from 21 invasive populations. Based on the obtained genome-wide single nucleotide polymorphism (SNP) data, we observed that all the populations possessed similar high levels of genetic diversity that were not constrained by longitude and latitude. Mikania micrantha was introduced multiple times and subsequently experienced rapid-range expansion with recurrent high gene flow. Using FST outliers, a latent factor mixed model, and the Bayesian method, we identified 38 outlier SNPs associated with environmental variables. The analysis of these outlier SNPs revealed that soil composition, temperature, precipitation, and ecological variables were important determinants affecting the invasive adaptation of M. micrantha. Candidate genes with outlier signatures were related to abiotic stress response. Gene family clustering analysis revealed 683 gene families unique to M. micrantha which may have significant implications for the growth, metabolism, and defense responses of M. micrantha. Forty-one genes showing significant positive selection signatures were identified. These genes mainly function in binding, DNA replication and repair, signature transduction, transcription, and cellular components. Collectively, these findings highlight the contribution of gene flow to the invasion and spread of M. micrantha and indicate the roles of adaptive loci and functional genes in invasive adaptation.
Quantifying Accelerations and Decelerations in Elite Women Soccer Players during Regular In-Season Training as an Index of Training Load

Accelerations (ACC) and decelerations (DEC) are important and frequent actions in soccer. We aimed to investigate whether ACC and DEC were good indicators of the variation of training loads in elite women soccer players. Changes in the training load were monitored during two different selected weeks (considered a “low week” and a “heavy week”) during the in-season. Twelve elite soccer women playing in the French first division wore a 10-Hz Global Positioning System unit recording total distance, distance within speed ranges, sprint number, ACC, DEC, and a heart rate monitor during six soccer training sessions and rated their perceived exertion (RPE). They answered the Hooper questionnaire (sleep, stress, fatigue, DOMS) to get an insight of their subjective fitness level at the start (Hooper S) and at the end of each week (Hooper E). A countermovement jump (CMJ) was also performed once a week. During the heavy week, the training load was significantly greater than the low week when considering number of ACC >2 m·s−2 (28.2 ± 11.9 vs. 56.1 ± 10.1, p < 0.001) and number of DEC < −2 m·s−2 (31.5 ± 13.4 vs. 60.9 ± 14.4, p < 0.001). The mean heart rate percentage (HR%) (p < 0.05), RPE (p < 0.001), and Hooper E (p < 0.001) were significantly greater during the heavy week. ACC and DEC showed significant correlations with most outcomes: HR%, total distance, distance per min, sprint number, Hooper index of Hooper E, DOMS E, Fatigue E, RPE, and session RPE. We concluded that, for elite women soccer players, quantifying ACC and DEC alongside other indicators seemed to be essential for a more complete training load monitoring. Indeed, it could lead to a better understanding of the reasons why athletes get fatigued and give insight into neuromuscular, rather than only energetic, fatigue.
Cellular Models in Schizophrenia Research

Schizophrenia (SZ) is a prevalent functional psychosis characterized by clinical behavioural symptoms and underlying abnormalities in brain function. Genome-wide association studies (GWAS) of schizophrenia have revealed many loci that do not directly identify processes disturbed in the disease. For this reason, the development of cellular models containing SZ-associated variations has become a focus in the post-GWAS research era. The application of revolutionary clustered regularly interspaced palindromic repeats CRISPR/Cas9 gene-editing tools, along with recently developed technologies for cultivating brain organoids in vitro, have opened new perspectives for the construction of these models. In general, cellular models are intended to unravel particular biological phenomena. They can provide the missing link between schizophrenia-related phenotypic features (such as transcriptional dysregulation, oxidative stress and synaptic dysregulation) and data from pathomorphological, electrophysiological and behavioural studies. The objectives of this review are the systematization and classification of cellular models of schizophrenia, based on their complexity and validity for understanding schizophrenia-related phenotypes.
Parenteral Nutrition and Oxidant Load in Neonates

Neonates with preterm, gastrointestinal dysfunction and very low birth weights are often intolerant to oral feeding. In such infants, the provision of nutrients via parenteral nutrition (PN) becomes necessary for short-term survival, as well as long-term health. However, the elemental nutrients in PN can be a major source of oxidants due to interactions between nutrients, imbalances of anti- and pro-oxidants, and environmental conditions. Moreover, neonates fed PN are at greater risk of oxidative stress, not only from dietary sources, but also because of immature antioxidant defences. Various interventions can lower the oxidant load in PN, including the supplementation of PN with antioxidant vitamins, glutathione, additional arginine and additional cysteine; reduced levels of pro-oxidant nutrients such as iron; protection from light and oxygen; and proper storage temperature. This narrative review of published data provides insight to oxidant molecules generated in PN, nutrient sources of oxidants, and measures to minimize oxidant levels.
Small Structural Proteins E and M Render the SARS-CoV-2 Pseudovirus More Infectious and Reveal the Phenotype of Natural Viral Variants

The SARS-CoV-2 pseudovirus is a commonly used strategy that mimics certain biological functions of the authentic virus by relying on biological legitimacy at the molecular level. Despite the fact that spike (S), envelope (E), and membrane (M) proteins together wrap up the SARS-CoV-2 virion, most of the reported pseudotype viruses consist of only the S protein. Here, we report that the presence of E and M increased the virion infectivity by promoting the S protein priming. The S, E, and M (SEM)-coated pseudovirion is spherical, containing crown-like spikes on the surface. Both S and SEM pseudoviruses packaged the same amounts of viral RNA, but the SEM virus bound more efficiently to cells stably expressing the viral receptor human angiotensin-converting enzyme II (hACE2) and became more infectious. Using this SEM pseudovirus, we examined the infectivity and antigenic properties of the natural SARS-CoV-2 variants. We showed that some variants have higher infectivity than the original virus and that some render the neutralizing plasma with lower potency. These studies thus revealed possible mechanisms of the dissemination advantage of these variants. Hence, the SEM pseudovirion provides a useful tool to evaluate the viral infectivity and capability of convalescent sera in neutralizing specific SARS-CoV-2 S dominant variants.
Role of Matrix Gla Protein in the Complex Network of Coronary Artery Disease: A Comprehensive Review

Coronary artery disease (CAD) is widely recognized as one of the most important clinical entities. In recent years, a large body of accumulated data suggest that coronary artery calcification, a process highly prevalent in patients with CAD, occurs via well-organized biologic processes, rather than passively, as previously regarded. Matrix Gla protein (MGP), a vitamin K-dependent protein, emerged as an important inhibitor of both intimal and medial vascular calcification. The functionality of MGP hinges on two post-translational modifications: phosphorylation and carboxylation. Depending on the above-noted modifications, various species of MGP may exist in circulation, each with their respective level of functionality. Emerging data suggest that dysfunctional species of MGP, markedly, dephosphorylated-uncarboxylated MGP, might find its application as biomarkers of microvascular health, and assist in clinical decision making with regard to initiation of vitamin K supplementation. Hence, in this review we summarized the current knowledge with respect to the role of MGP in the complex network of vascular calcification with concurrent inferences to CAD. In addition, we discussed the effects of warfarin use on MGP functionality, with concomitant implications to coronary plaque stability.
The Effect of Polyethylene Glycol Addition on Wettability and Optical Properties of GO/TiO2 Thin Film

Modification has been made to TiO2 thin film to improve the wettability and the absorption of light. The sol-gel spin coating method was successfully used to synthesize GO/TiO2 thin films using a titanium (IV) isopropoxide (TTIP) as a precursor. Different amounts of polyethylene glycol (PEG) (20 to 100 mg) were added into the parent sol solution to improve the optical properties and wettability of the GO/TiO2 thin film. The effect of different amounts of PEG was characterized using X-ray diffraction (XRD) for the phase composition, scanning electron microscopy (SEM) for microstructure observation, atomic force microscopy (AFM) for the surface topography, ultraviolet–visible spectrophotometry (UV-VIS) for the optical properties and wettability of the thin films by measuring the water contact angle. The XRD analysis showed the amorphous phase. The SEM and AFM images revealed that the particles were less agglomerated and surface roughness increases from 1.21 × 102 to 2.63 × 102 nm when the amount of PEG increased. The wettability analysis results show that the water contact angle of the thin film decreased to 27.52° with the increase of PEG to 80 mg which indicated that the thin film has hydrophilic properties. The optical properties also improved significantly, where the light absorbance wavelength became wider and the band gap was reduced from 3.31 to 2.82 eV with the presence of PEG.
GSK3 as a Regulator of Cytoskeleton Architecture: Consequences for Health and Disease

Glycogen synthase kinase 3 (GSK3) was initially isolated as a critical protein in energy metabolism. However, subsequent studies indicate that GSK-3 is a multi-tasking kinase that links numerous signaling pathways in a cell and plays a vital role in the regulation of many aspects of cellular physiology. As a regulator of actin and tubulin cytoskeleton, GSK3 influences processes of cell polarization, interaction with the extracellular matrix, and directional migration of cells and their organelles during the growth and development of an animal organism. In this review, the roles of GSK3–cytoskeleton interactions in brain development and pathology, migration of healthy and cancer cells, and in cellular trafficking of mitochondria will be discussed.
INTRODUCTIONAND HISTORICAL NOTES EXCITOTOXICITY IN NEUROLOGIC DISEASES

Excitotoxicity refers to neuronal death caused by activation of excitatory amino acid receptors. Several lines of evidence have linked excitotoxic cell death to the pathogenesis of both acute and chronic neurologic diseases. The initial observation that glutamate was neurotoxic was that of Lucas and Newhouse, who found that administration of glutamate to mice resulted in retinal degeneration (Lucas and Newhouse, 1957). Subsequent studies of Olney and colleagues linked neurotoxicity to the activation of excitatory amino acid receptors , and the term "excitotoxin" was coined (Olney, 1969). Further advances were those of Rothman linking release of excitatory amino acids to anoxic cell death in hippocampal cultures (Rothman, 1984), and ofChoi linking calcium influx to delayed cell death caused by excitatory amino acids (Choi, 1987). More work has linked activation of excitatory amino acid receptors to free radical generation and nitric oxide, both of which may lead to oxidative stress (Dawson et al., 1991: Lafon -Cazal et al., 1993).