Miracle-dz/UniFAR-FTUs huggingface dataset:
A Novel Variation in the Mitochondrial Complex I Assembly Factor NDUFAF5 Causes Isolated Bilateral Striatal Necrosis in Childhood

Background: Bilateral striatal necrosis (BSN) is characterized by symmetrical degeneration, predominantly of the caudate and putamen nucleus, in the basal ganglia. It is associated with numerous acquired and hereditary neuro-developmental and motor dysfunction-related pathological conditions. BSN results in high morbidity and mortality among infants and children, and its diagnosis is clinically challenging due to several overlapping disease phenotypes. Therefore, a precise genetic diagnosis is urgently needed for accurate genetic counseling and improved prognostic outcomes as well. Objective: To identify novel missense mutations in the NDUFAF5 gene as a cause of childhood BSN in members of a Chinese family and summarize the clinical characteristics of patients with the NDUFAF5 gene mutations. Methods: This study included a large family living in a remote northwestern area of China. Three siblings developed a neurological disorder characterized by generalized dystonia within the first decade of their lives. Cerebral computed tomography (CT) and magnetic resonance imaging (MRI) showed bilateral lesions of the putamen. Biochemical and genetic approaches were used to identify the cause of BSN. Results: Sequence analysis showed no pathogenic variation in PANK2, SLC25A19, SLC19A3, and NUP62 genes and in the entire mitochondrial genome as well. Whole-exome sequencing revealed compound heterozygous mutations consisting of NDUFAF5:c.425A > C(p.E142A) and c.836T > G (p.M279R). The father, a healthy sister, and a healthy brother of the affected siblings carried the c.836T > G mutation, and the mother carried the c.425A > C mutation. These variants were absent in 100 ethnically matched non-BSN controls. In silico analysis demonstrated that the E142A and M279R mutations in NDUFAF5 protein significantly perturbed the normal conformation of the protein due to alterations in the hydrogen bonding patterns around the evolutionarily conserved catalytic domains, leading to its loss of function in the early stage of mitochondrial complex I assembly. Conclusions: We identified a novel compound heterozygous mutation (c.425A > C and c.836T > G) in the NDUFAF5 gene as the potential cause of autosomal recessive childhood BSN, which extended the pathogenic variation spectrum of the NDUFAF5 gene. This study provides substantial evidence for further improvement of genetic counseling and better clinical management of BSN affected individuals.
Regulation of Free Fatty Acid Receptor 4 on Inflammatory Gene Induced by LPS in Large Yellow Croaker (Larimichthys crocea)

Free fatty acid receptor 4 (FFAR4) plays a key role in regulating the inflammatory response in mammals. The present study aimed to investigate the function of large yellow croaker FFAR4 on inflammation. In the present study, ffar4 was widely expressed in 10 tissues of large yellow croaker including gill, head kidney and spleen. Further studies showed that treatment of head kidney macrophages with agonists (TUG891 or GSK137647A) or overexpression of ffar4 reduced the mRNA expression of pro-inflammatory genes induced by LPS, and increased the expression of pparγ. Treatment of macrophages with antagonist AH7614 increased the mRNA expression of pro-inflammatory genes induced by LPS, and decreased the mRNA expression of pparγ. In order to verify the immunomodulatory effect of PPARγ, PPARγ was overexpressed in macrophages which significantly reduced the mRNA expression of pro-inflammatory genes il6, il1β, il8, tnfα and cox2. Moreover, results of dual-luciferase assays showed that PPARγ downregulated the transcriptional activity of il6 and il1β promoters. In conclusion, FFAR4 showed anti-inflammatory effects on LPS-induced inflammation in large yellow croaker.
SARS-CoV-2 ORF8 Forms Intracellular Aggregates and Inhibits IFNγ-Induced Antiviral Gene Expression in Human Lung Epithelial Cells

Infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19, a disease that involves significant lung tissue damage. How SARS-CoV-2 infection leads to lung injury remains elusive. The open reading frame 8 (ORF8) protein of SARS-CoV-2 (ORF8SARS-CoV-2) is a unique accessory protein, yet little is known about its cellular function. We examined the cellular distribution of ORF8SARS-CoV-2 and its role in the regulation of human lung epithelial cell proliferation and antiviral immunity. Using live imaging and immunofluorescent staining analyses, we found that ectopically expressed ORF8SARS-CoV-2 forms aggregates in the cytosol and nuclear compartments of lung epithelial cells. Using in silico bioinformatic analysis, we found that ORF8SARS-CoV-2 possesses an intrinsic aggregation characteristic at its N-terminal residues 1-18. Cell culture did not reveal any effects of ORF8SARS-CoV-2 expression on lung epithelial cell proliferation and cell cycle progression, suggesting that ORF8SARS-CoV-2 aggregates do not affect these cellular processes. Interestingly, ectopic expression of ORF8SARS-CoV-2 in lung epithelial cells suppressed basal expression of several antiviral molecules, including DHX58, ZBP1, MX1, and MX2. In addition, expression of ORF8SARS-CoV-2 attenuated the induction of antiviral molecules by IFNγ but not by IFNβ in lung epithelial cells. Taken together, ORF8SARS-CoV-2 is a unique viral accessory protein that forms aggregates when expressing in lung epithelial cells. It potently inhibits the expression of lung cellular anti-viral proteins at baseline and in response to IFNγ in lung epithelial cells, which may facilitate SARS-CoV-2 escape from the host antiviral innate immune response during early viral infection. In addition, it seems that formation of ORF8SARS-CoV-2 aggregate is independent from the viral infection. Thus, it would be interesting to examine whether any COVID-19 patients exhibit persistent ORF8 SARS-CoV-2 expression after recovering from SARS-CoV-2 infection. If so, the pathogenic effect of prolonged ORF8SARS-CoV-2 expression and its association with post-COVID symptoms warrant investigation in the future.
Did You Enjoy It? The Role of Intensity-Trait Preference/Tolerance in Basic Psychological Needs and Exercise Enjoyment

Promoting exercise regimens that aim at enhancing the quality of individuals’ subjective exercise experience can be challenging. Given the recent theoretical contributions regarding the possible interaction of exercise intensity-traits and several motivational variables, as well as their potential value for exercise adherence, the objective of this study was to examine the mediation role of basic psychological needs in the relationship between preference for and tolerance of exercise intensity and enjoyment. This cross-sectional study comprised a total of 160 exercisers (Mage = 34.12, SD = 9.23, 73 males) enrolled in several health clubs. All analyses were performed using SPSS v. 23.0/PROCESS v. 3.4. The results indicate that intensity-traits presented positive associations with enjoyment, and negative associations with all of needs frustration variables. A mediation role of needs frustration emerged in the intensity-traits and enjoyment associations that was analyzed according to relatable theoretical considerations.
Inhouse Bridging Thrombolysis Is Associated With Improved Functional Outcome in Patients With Large Vessel Occlusion Stroke: Findings From the German Stroke Registry

Background: Endovascular treatment (EVT) for large vessel occlusion stroke (LVOS) is highly effective. To date, it remains controversial if intravenous thrombolysis (IVT) prior to EVT is superior compared with EVT alone. The aim of our study was to specifically address the question, whether bridging IVT directly prior to EVT has additional positive effects on reperfusion times, successful reperfusion, and functional outcomes compared with EVT alone. Methods: Patients with LVOS in the anterior circulation eligible for EVT with and without prior IVT and direct admission to endovascular centers (mothership) were included in this multicentric, retrospective study. Patient data was derived from the German Stroke Registry (an open, multicenter, and prospective observational study). Outcome parameters included groin-to-reperfusion time, successful reperfusion [defined as a Thrombolysis in Cerebral Infarction (TICI) scale 2b-3], change in National Institute of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS), and mortality at 90 days. Results: Of the 881 included mothership patients with anterior circulation LVOS, 486 (55.2%) received bridging therapy with i.v. -rtPA prior to EVT, and 395 (44.8%) received EVT alone. Adjusted, multivariate linear mixed effect models revealed no difference in groin-to-reperfusion time between the groups (48 ± 36 vs. 49 ± 34 min; p = 0.299). Rates of successful reperfusion (TICI ≥ 2b) were higher in patients with bridging IVT (fixed effects estimate 0.410, 95% CI, 0.070; 0.750, p = 0.018). There was a trend toward a higher improvement in the NIHSS during hospitalization [ΔNIHSS: bridging-IVT group 8 (IQR, 9.8) vs. 4 (IQR 11) points in the EVT alone group; fixed effects estimate 1.370, 95% CI, −0.490; 3.240, p = 0.149]. mRS at 90 days follow-up was lower in the bridging IVT group [3 (IQR, 4) vs. 4 (IQR, 4); fixed effects estimate −0.350, 95% CI, −0.680; −0.010, p = 0.041]. There was a non-significantly lower 90 day mortality in the bridging IVT group compared with the EVT alone group (22.4% vs. 33.6%; fixed effects estimate 0.980, 95% CI −0.610; 2.580, p = 0.351). Rates of any intracerebral hemorrhage did not differ between both groups (4.1% vs. 3.8%, p = 0.864). Conclusions: This study provides evidence that bridging IVT might improve rates of successful reperfusion and long-term functional outcome in mothership patients with anterior circulation LVOS eligible for EVT.
Antimicrobial Peptides Human Beta-Defensin-2 and -3 Protect the Gut During Candida albicans Infections Enhancing the Intestinal Barrier Integrity: In Vitro Study

The intestinal mucosa is composed of a monolayer of epithelial cells, which is highly polarized and firmly united to each other thanks to the presence of proteins complexes, called Tight junctions (TJs). Alteration of the mucus layer and TJs causes an increase in intestinal permeability, which can lead to a microbial translocation and systemic disorders. Candida albicans, in addition to its role of commensal, is an opportunistic pathogen responsible for disseminated candidiasis, especially in immunocompromised subjects where the dysbiosis leads to damage of the intestinal mucosal barrier . In this work, we used a line of intestinal epithelial cells able to stably express the genes that encodes human beta defensin-2 (HBD-2) and -3 (HBD-3) to monitor the invasion of C. albicans in vitro. Defensins are a group of antimicrobial peptides (AMPs) found in different living organisms, and are involved in the first line of defense in the innate immune response against pathogens. The results obtained show that the presence of antimicrobial peptides improves the expression of TJs and increases the Trans Epithelial Electrical Resistence value. In addition, the invasive ability of C. albicans in transfected cells is significantly reduced, as well as the expression levels of genes involved in the apoptotic pathway. Through the study of interaction between antimicrobial peptides and microbiota we will be able in the future to better understand the mechanisms by which they exert the host defense function against intestinal pathogens.
The Inhibitory Effect of Lysophosphatidylcholine on Proangiogenesis of Human CD34+ Cells Derived Endothelial Progenitor Cells

Increasing evidence reveals that lysophosphatidylcholine (LPC) is closely related to endothelial dysfunction. The present study aimed to investigate the mechanism of LPC in inhibiting the proangiogenesis and vascular inflammation of human endothelial progenitor cells (EPCs) derived from CD34+ cells. The early EPCs were derived from CD34+ hematopoietic stem cells whose purity was identified using flow cytometry analysis. The surface markers (CD34, KDR, CD31; VE-cadherin, vWF, eNOS) of EPCs were examined by flow cytometry analysis and immunofluorescence. RT-qPCR was used to detect the mRNA expression of inflammatory cytokines (CCL2, IL-8, CCL4) and genes associated with angiogenesis (VEGF, ANG-1, ANG-2) in early EPCs after treatment of LPC (10 μg/ml) or phosphatidylcholine (PC, 10 μg/ml, control). The angiogenesis of human umbilical vein endothelial cells (HUVECs) incubated with the supernatants of early EPCs was detected by a tube formation assay. The mRNA and protein levels of key factors on the PKC pathway (phosphorylated PKC, TGF-β1) were measured by RT-qPCR and western blot. The localization of PKC-β1 in EPCs was determined by immunofluorescence staining. We found that LPC suppressed the expression of CCL2, CCL4, ANG-1, ANG-2, promoted IL-8 expression and had no significant effects on VEGF expression in EPCs. EPCs promoted the angiogenesis of HUVECs, which was significantly inhibited by LPC treatment. Moreover, LPC was demonstrated to promote the activation of the PKC signaling pathway in EPCs. In conclusion, LPC inhibits proangiogenesis of human endothelial progenitor cells derived from CD34+ hematopoietic stem cells.
Contribution of CT-Scan Analysis by Artificial Intelligence to the Clinical Care of TBI Patients

The gold standard to diagnose intracerebral lesions after traumatic brain injury (TBI) is computed tomography (CT) scan, and due to its accessibility and improved quality of images, the global burden of CT scan for TBI patients is increasing. The recent developments of automated determination of traumatic brain lesions and medical-decision process using artificial intelligence (AI) represent opportunities to help clinicians in screening more patients, identifying the nature and volume of lesions and estimating the patient outcome. This short review will summarize what is ongoing with the use of AI and CT scan for patients with TBI.
Vacuum-Ultraviolet Absorption Spectra of Icy C2H4 at 13–60 K

The thermal variation of absorption spectra of icy ethene in wavelength range 105–220 nm was measured from 13 to 100 K using a synchrotron as light source. Sublimation of icy ethene began above 62 K, resulting in decreasing absorption. The absorption of icy ethene increased at wavelengths less than about 150 nm with increasing temperature from 13 to 60 K, but decreased beyond above 150 nm. According to detailed examination, the absorption spectra of icy ethene intersected at isosbestic point 147.0 nm from 13 to 17 K, whereas those varied absorption profiles crossed at another point, 150.6 nm, from 23 to 60 K. These results indicate that ethene ices might exhibit three structures within temperature range 13–60 K. This work enhances our understanding of the spectra of icy ethene at low temperatures and our knowledge of its astrochemistry and astrophysics in cold astro-environments.
Using Virtual Reality to Assess Reading Fluency in Children

Here we provide a proof-of-concept for the use of virtual reality (VR) goggles to assess reading behavior in beginning readers. Children performed a VR version of a lexical decision task that allowed us to record eye-movements. External validity was assessed by comparing the VR measures (lexical decision RT and accuracy, gaze durations and refixation probabilities) to a gold standard reading fluency test—the One-Minute Reading test. We found that the VR measures correlated strongly with the classic fluency measure. We argue that VR-based techniques provide a valid and child-friendly way to study reading behavior in a school environment. Importantly, they enable not only the collection of a richer dataset than standard behavioral assessments but also the possibility to tightly control the environment.
Comparing the Performance of a Remotely Operated Vehicle, a Drop Camera, and a Trawl in Capturing Deep-Sea Epifaunal Abundance and Diversity

Deep-sea ecosystems provide services such as food, minerals, and nutrient recycling, yet baseline data on their structure is often lacking. Our limited knowledge of vulnerable deep-sea ecosystems presents a challenge for effective monitoring and mitigation of increasing anthropogenic threats, including destructive fishing and climate change. Using data from two stations differing in total epifaunal abundance and taxonomic composition, we compared the use of imagery collected by two non-invasive tools [remotely operated vehicle (ROV) and drop camera] and data collected with a trawl system, commonly used to quantify epibenthic megafauna in the deep sea. Imagery and trawl data captured different epifaunal patterns, the former being more efficient for capturing epifauna, particularly Pennatulacean recruits. The image-based methods also caused less disturbance, had higher position accuracy, and allow for analyses of spatial structure and species associations; fine-scale distributions could not be elucidated with a trawl. Abundance was greater for some taxa, and diversity accumulated faster with increasing sample size for the drop camera than the ROV at one station. However, there are trade-offs between these tools, including continuous and discrete sampling for the ROV and drop camera, respectively, which can affect follow-up analyses. Our results can be used to inform monitoring frameworks on the use of appropriate sampling tools. We recommend further research into tool sampling biases and biometric relationships to help integrate datasets collected with different tools.
Application of CRISPR/Cas9 System for Plasmid Elimination and Bacterial Killing of Bacillus cereus Group Strains

The CRISPR-Cas system has been widely applied in prokaryotic genome editing with its high efficiency and easy operation. We constructed some “scissors plasmids” via using the temperature-sensitive pJOE8999 shuttle plasmid, which carry the different 20nt (N20) guiding the Cas9 nuclease as a scissors to break the target DNA. We successfully used scissors plasmids to eliminate native plasmids from Bacillus anthracis and Bacillus cereus, and specifically killed B. anthracis. When curing pXO1 and pXO2 virulence plasmids from B. anthracis A16PI2 and A16Q1, respectively, we found that the plasmid elimination percentage was slightly higher when the sgRNA targeted the replication initiation region (96–100%), rather than the non-replication initiation region (88–92%). We also tried using a mixture of two scissors plasmids to simultaneously eliminate pXO1 and pXO2 plasmids from B. anthracis, and the single and double plasmid-cured rates were 29 and 14%, respectively. To our surprise, when we used the scissor plasmid containing two tandem sgRNAs to cure the target plasmids pXO1 and pXO2 from wild strain B. anthracis A16 simultaneously, only the second sgRNA could guide Cas9 to cleave the target plasmid with high efficiency, while the first sgRNA didn't work in all the experiments we designed. When we used the CRISPR/cas9 system to eliminate the pCE1 mega-virulence plasmid from B. cereus BC307 by simply changing the sgRNA, we also obtained a plasmid-cured isogenic strain at a very high elimination rate (69%). The sterilization efficiency of B. anthracis was about 93%, which is similar to the efficiency of plasmid curing, and there was no significant difference in the efficiency of among the scissors plasmids containing single sgRNA, targeting multi-sites, or single-site targeting and the two tandem sgRNA. This simple and effective curing method, which is applicable to B. cereus group strains, provides a new way to study these bacteria and their virulence profiles.
Interplay Between Exercise and Gut Microbiome in the Context of Human Health and Performance

Gut microbiota and exercise have recently been shown to be interconnected. Both moderate and intense exercise are typically part of the training regimen of endurance athletes, but they exert different effects on health. Moderate exercise has positive effects on the health of average athletes, such as a reduction in inflammation and intestinal permeability and an improvement in body composition. It also induces positive changes in the gut microbiota composition and in the microbial metabolites produced in the gastrointestinal tract. Conversely, intense exercise can increase gastrointestinal epithelial wall permeability and diminish gut mucus thickness, potentially enabling pathogens to enter the bloodstream. This, in turn, may contribute to the increase in inflammation levels. However, elite athletes seem to have a higher gut microbial diversity, shifted toward bacterial species involved in amino acid biosynthesis and carbohydrate/fiber metabolism, consequently producing key metabolites such as short-chain fatty acids. Moreover, rodent studies have highlighted a bidirectional relationship, with exercise impacting the gut microbiota composition while the microbiota may influence performance. The present review focuses on gut microbiota and endurance sports and how this interconnection depends upon exercise intensity and training. After pointing out the limits of the studies so far available, we suggest that taking into account the microbiota composition and its metabolic contribution to human host health could help in monitoring and modulating athletes' health and performance. Such an integrated approach should help in the design of microbiome-based solutions for health or performance.
Construction and Validation of a Reliable Six-Gene Prognostic Signature Based on the TP53 Alteration for Hepatocellular Carcinoma

Background The high mutation rate of TP53 in hepatocellular carcinoma (HCC) makes it an attractive potential therapeutic target. However, the mechanism by which TP53 mutation affects the prognosis of HCC is not fully understood. Material and Approach This study downloaded a gene expression profile and clinical-related information from The Cancer Genome Atlas (TCGA) database and the international genome consortium (ICGC) database. We used Gene Set Enrichment Analysis (GSEA) to determine the difference in gene expression patterns between HCC samples with wild-type TP53 (n=258) and mutant TP53 (n=116) in the TCGA cohort. We screened prognosis-related genes by univariate Cox regression analysis and Kaplan–Meier (KM) survival analysis. We constructed a six-gene prognostic signature in the TCGA training group (n=184) by Lasso and multivariate Cox regression analysis. To assess the predictive capability and applicability of the signature in HCC, we conducted internal validation, external validation, integrated analysis and subgroup analysis. Results A prognostic signature consisting of six genes (EIF2S1, SEC61A1, CDC42EP2, SRM, GRM8, and TBCD) showed good performance in predicting the prognosis of HCC. The area under the curve (AUC) values of the ROC curve of 1-, 2-, and 3-year survival of the model were all greater than 0.7 in each independent cohort (internal testing cohort, n = 181; TCGA cohort, n = 365; ICGC cohort, n = 229; whole cohort, n = 594; subgroup, n = 9). Importantly, by gene set variation analysis (GSVA) and the single sample gene set enrichment analysis (ssGSEA) method, we found three possible causes that may lead to poor prognosis of HCC: high proliferative activity, low metabolic activity and immunosuppression. Conclusion Our study provides a reliable method for the prognostic risk assessment of HCC and has great potential for clinical transformation.