Miracle-dz/UniFAR-FTUs huggingface dataset:
A Novel MicroRNA and the Target Gene TAB2 Can Regulate the Process of Sucking Blood in and the Spawn Rate of Hyalomma asiaticum (Acari: Ixodidae) Ticks

Ticks are blood-sucking parasites that are harmful to humans and animals. MicroRNAs are a class of conserved small noncoding RNAs that play regulatory roles in the expression of many genes at the posttranscriptional level. Here, a novel miRNA (nov-miR-17) was identified from a small RNA data library of Hyalomma asiaticum by next-generation sequencing. PCR was used to obtain precursor nov-miR-17 by RACE using mature loop primers. The secondary structure was predicted with UNAFold. The interaction of nov-miR-17 with its target gene TAB2 was predicted using RNAhybrid software and identified in vitro by luciferase assays. Moreover, the interaction was confirmed in vivo by phenotype rescue experiments in which dsTAB2 was used for RNA interference (RNAi) and an antagomir of nov-miR-17 was used for miRNA silencing. The expression levels of nov-miR-17 and TAB2 in ticks at different developmental stages and the expression of nov-miR-17 in different tissues were analyzed by real-time qPCR. All data were analyzed using GraphPad Prism version 5. Results: The results showed that TAB2 was a target gene of nov-miR-17. When the blood-sucking process of larval, nymph and adult ticks was prolonged, the expression of nov-miR-17 was decreased, and TAB2 expression was increased. However, the level of nov-miR-17 in the midgut of engorged ticks was highest at all stages. Therefore, nov-miR-17 plays an important role in the blood-sucking process. The overexpression of nov-miR-17 indicated that this miRNA affected the engorged weight (P < 0.001) and spawn rate (P < 0.001) of female ticks. RNAi of TAB2 also had the same effect. dsRNA not only impacted the weight (P < 0.01) but also reduced the spawn rate (P < 0.001) of the ticks. Furthermore, significant recovery was observed in nov-miR-17-silenced ticks after TAB2 silencing by RNAi. nov-miR-17 silencing by antagomir not only impacted the engorged weight of the female ticks (P < 0.001) but also the number of days that the females needed to progress from engorgement to spawning (P < 0.001). The study showed that nov-miR-17, as a new miRNA, plays an important role along with its target gene TAB2 in the blood-sucking and spawning processes in female ticks.
CCR5 as a Prognostic Factor in Lower-Grade Glioma is Involved in the Remodeling of the Tumor Microenvironment

Background: Lower-grade gliomas (LGGs) carry a high risk of malignant transformation, leading to severe neurologic deterioration and ultimately, death. The tumor microenvironment (TME) plays an essential role in tumor maintenance, progression, and immunotherapy resistance. Therefore, the LGG TME deserves comprehensive exploration for a novel therapeutic target. Methods: The ESTIMATE algorithm was used to estimate infiltrating stromal and immune cells of LGG patients obtained from the Cancer Genome Atlas (TCGA) database. Kaplan–Meier analysis was performed to classify survival differences. TME-related differentially expressed genes were identified between the low- and high-immune/stromal groups. Hub genes were screened by constructing protein–protein interaction networks and performing the Cox regression analysis. Differential analysis, survival analysis, gene set enrichment analysis, and clinical relevance analysis specific to hub genes were evaluated by using the TCGA and the Chinese Glioma Genome Atlas datasets, and the results were validated by qRT-PCR, Western blotting, and immunohistochemistry in tissues from LGG patients. Results: The immune and stromal components in TME were negatively related to patient prognosis. Differentially expressed genes sharing immune score and stromal score were mainly involved in the immune response. C-C chemokine receptor type 5 (CCR5), as only a hub gene, was significantly higher in LGG patients than normal patients and negatively correlated with the prognosis of patients. High-expression CCR5 was positively related to immune-related and tumor progression pathways. CCR5 protein expression was higher in LGG with isocitrate dehydrogenase wildtype. Validated results showed that CCR5 was upregulated in LGG tissues at mRNA and protein levels and could affect immune cell infiltration. These results suggested that CCR5 was a potential indicator for the status of TME. Conclusion: Glioma cells remodel the immune microenvironment through the high expression of CCR5 and lead to a poor prognosis in patients with LGG. The inhibition of CCR5 may contribute to the efficacy of LGG immunotherapy.
Efficiently Enumerating Unimodular Mappings

Unimodular matrices are often used as (unimodular) time/space-mappings in loop parallelization because they map iteration domains to convex regions. Some methods to automatically parallelize a given loop nest enumerate many different possible mappings and choose the best of these according to some heuristic. This technical report discusses methods to efficientyly enumerate unimodular mappings. Furthermore, methods are developed to enumerate unimodular matrices having a given scheduling vector and a given projection vector. These two vectors can be supplied by some parallelization heuristics not in the scope of this report.
Phylogenetic Classification and Functional Review of Autotransporters

Autotransporters are the core component of a molecular nano-machine that delivers cargo proteins across the outer membrane of Gram-negative bacteria. Part of the type V secretion system, this large family of proteins play a central role in controlling bacterial interactions with their environment by promoting adhesion to surfaces, biofilm formation, host colonization and invasion as well as cytotoxicity and immunomodulation. As such, autotransporters are key facilitators of fitness and pathogenesis and enable co-operation or competition with other bacteria. Recent years have witnessed a dramatic increase in the number of autotransporter sequences reported and a steady rise in functional studies, which further link these proteins to multiple virulence phenotypes. In this review we provide an overview of our current knowledge on classical autotransporter proteins, the archetype of this protein superfamily. We also carry out a phylogenetic analysis of their functional domains and present a new classification system for this exquisitely diverse group of bacterial proteins. The sixteen phylogenetic divisions identified establish sensible relationships between well characterized autotransporters and inform structural and functional predictions of uncharacterized proteins, which may guide future research aimed at addressing multiple unanswered aspects in this group of therapeutically important bacterial factors.
Efficacy of Cerebrolysin Treatment as an Add-On Therapy to Mechanical Thrombectomy in Patients With Acute Ischemic Stroke Due to Large Vessel Occlusion: Study Protocol for a Prospective, Open Label, Single-Center Study With 12 Months of Follow-Up

This study is designed to determine the efficacy of Cerebrolysin treatment as an add-on therapy to mechanical thrombectomy (MT) in reducing global disability in subjects with acute ischemic stroke (AIS). We have planned a single center, prospective, open-label, single-arm study with a 12-month follow-up of 50 patients with moderate to severe AIS, with a small established infarct core and with good collateral circulation who achieve significant reperfusion following MT and who receive additional Cerebrolysin within 8 h of stroke onset compared to 50 historical controls treated with MT alone, matched for age, clinical severity, occlusion location, baseline perfusion lesion volume, onset to reperfusion time, and use of iv thrombolytic therapy. The primary outcome measure will be the overall proportion of subjects receiving Cerebrolysin compared to the control group experiencing a favorable functional outcome (by modified Rankin Scale 0–2) at 90 days, following stroke onset. The secondary objectives are to determine the efficacy of Cerebrolysin as compared to the control group in reducing the risk of symptomatic secondary hemorrhagic transformation, improving neurological outcomes (NIHSS 0–2 at day 7, day 30, and 90), reducing mortality rates (over the 90-day and 12 months study period), and improving: activities of daily living (by Barthel Index), health-related quality of life (EQ-5D-5L) assessed at day 30, 90, and at 12 months. The other measures of efficacy in the Cerebrolysin group will include: assessment of final stroke volume and penumbral salvage (measured by CT/CTP at 30 days) and its change compared to baseline volume, changes over time in language function (by the 15-item Boston Naming Test), hemispatial neglect (by line bisection test), global cognitive function (by The Montreal Cognitive Assessment), and depression (by Hamilton Depression Rating Scale) between day 30 and day 90 assessments). The patients will receive 30 ml of Cerebrolysin within 8 h of AIS stroke onset and continue treatment once daily until day 21 (first cycle) and they will receive a second cycle of treatment (30 ml/d for 21 days given in the Outpatient Department or Neurorehabilitation Clinic) from day 69 to 90.
Different Dimensions of Grit as the Predictor of Job-Search Intensity and Clarity

Job-search is considered as a developmental task for college students to move from campus to workplace. Based on the self-determination theory, 859 Chinese college students were selected as the study sample and hierarchical regression analysis was used to explore the effects of perseverance per severance of effort and consistency of interest on job-search intensity and clarity. The survey showed that the perseverance of effort has a significant positive effect on the job-search intensity, while it has no significant positive effect on job-search clarity. Consistency of interest has a significant negative effect on job-search intensity and a significant positive effect on job-search clarity. Theoretical and practical implications are discussed and the directions for future research are outlined in this study.
AMPK Activation Alleviates Myocardial Ischemia-Reperfusion Injury by Regulating Drp1-Mediated Mitochondrial Dynamics

Mitochondrial dysfunction is a salient feature of myocardial ischemia/reperfusion injury (MIRI), while the potential mechanism of mitochondrial dynamics disorder remains unclear. This study sought to explore whether activation of Adenosine monophosphate-activated protein kinase (AMPK) could alleviate MIRI by regulating GTPase dynamin-related protein 1 (Drp1)-mediated mitochondrial dynamics. Isolated mouse hearts in a Langendorff perfusion system were subjected to ischemia/reperfusion (I/R) treatment, and H9C2 cells were subjected to hypoxia /reoxygenation (H/R) treatment in vitro. The results showed that AICAR, the AMPK activator, could significantly improve the function of left ventricular, decrease arrhythmia incidence and myocardial infarction area of isolated hearts. Meanwhile, AICAR increased superoxide dismutase (SOD) activity and decreased malondialdehyde (MDA) content in myocardial homogenate. Mechanistically, AICAR inhibited the phosphorylation of Drp1 at Ser 616 while enhanced phosphorylation of Drp1 at Ser 637. In addition, AICAR reduced the expression of inflammatory cytokines including TNF-ɑ, IL-6, and IL-1β, as well as mitochondrial fission genes Mff and Fis1, while improved the expression of mitochondrial fusion genes Mfn1 and Mfn2. Similar results were also observed in H9C2 cells. AICAR improved mitochondrial membrane potential (MMP), reduced reactive oxygen species (ROS) production, and inhibited mitochondrial damage. To further prove if Drp1 regulated mitochondrial dynamics mediated AMPK protection effect, the mitochondrial fission inhibitor Mdivi-1 was utilized. We found that Mdivi-1 significantly improved MMP, inhibited ROS production, reduced the expression of TNF-a, IL-6, IL-1β, Fis1, and Mff, and improved the expression of Mfn1 and Mfn2. However, the protection effect of Mdivi-1 was not reversed by AMPK inhibitor Compound C. In conclusion, this study confirmed that activation of AMPK exerted the protective effects on MIRI, which were largely dependent on the inhibition of Drp1-mediated mitochondrial fission.
Advancing Key Gaps in the Knowledge of Plasmodium vivax Cryptic Infections Using Humanized Mouse Models and Organs-on-Chips

Plasmodium vivax is the most widely distributed human malaria parasite representing 36.3% of disease burden in the South-East Asia region and the most predominant species in the region of the Americas. Recent estimates indicate that 3.3 billion of people are under risk of infection with circa 7 million clinical cases reported each year. This burden is certainly underestimated as the vast majority of chronic infections are asymptomatic. For centuries, it has been widely accepted that the only source of cryptic parasites is the liver dormant stages known as hypnozoites. However, recent evidence indicates that niches outside the liver, in particular in the spleen and the bone marrow, can represent a major source of cryptic chronic erythrocytic infections. The origin of such chronic infections is highly controversial as many key knowledge gaps remain unanswered. Yet, as parasites in these niches seem to be sheltered from immune response and antimalarial drugs, research on this area should be reinforced if elimination of malaria is to be achieved. Due to ethical and technical considerations, working with the liver, bone marrow and spleen from natural infections is very difficult. Recent advances in the development of humanized mouse models and organs-on-a-chip models, offer novel technological frontiers to study human diseases, vaccine validation and drug discovery. Here, we review current data of these frontier technologies in malaria, highlighting major challenges ahead to study P. vivax cryptic niches, which perpetuate transmission and burden.
Copeptin as a Diagnostic and Prognostic Biomarker in Cardiovascular Diseases

Copeptin is the carboxyl-terminus of the arginine vasopressin (AVP) precursor peptide. The main physiological functions of AVP are fluid and osmotic balance, cardiovascular homeostasis, and regulation of endocrine stress response. Copeptin, which is released in an equimolar mode with AVP from the neurohypophysis, has emerged as a stable and simple-to-measure surrogate marker of AVP and has displayed enormous potential in clinical practice. Cardiovascular disease (CVD) is currently recognized as a primary threat to the health of the population worldwide, and thus, rapid and effective approaches to identify individuals that are at high risk of, or have already developed CVD are required. Copeptin is a diagnostic and prognostic biomarker in CVD, including the rapid rule-out of acute myocardial infarction (AMI), mortality prediction in heart failure (HF), and stroke. This review summarizes and discusses the value of copeptin in the diagnosis, discrimination, and prognosis of CVD (AMI, HF, and stroke), as well as the caveats and prospects for the application of this potential biomarker.
N400 Indexing the Motion Concept Shared by Music and Words

The two event-related potentials (ERP) studies investigated how verbs and nouns were processed in different music priming conditions in order to reveal whether the motion concept via embodiment can be stimulated and evoked across categories. Study 1 (Tasks 1 and 2) tested the processing of verbs (action verbs vs. state verbs) primed by two music types, with tempo changes (accelerating music vs. decelerating music) and without tempo changes (fast music vs. slow music) while Study 2 (Tasks 3 and 4) tested the processing of nouns (animate nouns vs. inanimate nouns) in the same priming condition as adopted in Study 1. During the experiments, participants were required to hear a piece of music prior to judging whether an ensuing word (verb or noun) is semantically congruent with the motion concept conveyed by the music. The results show that in the priming condition of music with tempo changes, state verbs and inanimate nouns elicited larger N400 amplitudes than action verbs and animate nouns, respectively in the anterior regions and anterior to central regions, whereas in the priming condition of music without tempo changes, action verbs elicited larger N400 amplitudes than state verbs and the two categories of nouns revealed no N400 difference, unexpectedly. The interactions between music and words were significant only in Tasks 1, 2, and 3. Taken together, the results demonstrate that firstly, music with tempo changes and music without tempo prime verbs and nouns in different fashions; secondly, action verbs and animate nouns are easier to process than state verbs and inanimate nouns when primed by music with tempo changes due to the shared motion concept across categories; thirdly, bodily experience differentiates between music and words in coding (encoding and decoding) fashion but the motion concept conveyed by the two categories can be subtly extracted on the metaphorical basis, as indicated in the N400 component. Our studies reveal that music tempos can prime different word classes, favoring the notion that embodied motion concept exists across domains and adding evidence to the hypothesis that music and language share the neural mechanism of meaning processing.
A Simple Indoor Localization Methodology for Fast Building Classification Models Based on Fingerprints

Indoor localization has received tremendous attention in the last two decades due to location-aware services being highly demanded. Wireless networks have been suggested to solve this problem in many research works, and efficient algorithms have been developed with precise location and high accuracy. Nevertheless, those approaches often have high computational and high energy consumption. Hence, in temporary environments, such as emergency situations, where a fast deployment of an indoor localization system is required, those methods are not appropriate. In this manuscript, a methodology for fast building of an indoor localization system is proposed. For that purpose, a reduction of the data dimensionality is achieved by applying data fusion and feature transformation, which allow us to reduce the computational cost of the classifier training phase. In order to validate the methodology, three different datasets were used: two of them are public datasets based mainly on Received Signal Strength (RSS) from different Wi-Fi access point, and the third is a set of RSS values gathered from the LED lamps in a Visible Light Communication (VLC) network. The simulation results show that the proposed methodology considerably amends the overall computational performance and provides an acceptable location estimation error.
The Hepatoprotective and Hepatotoxic Roles of Sex and Sex-Related Hormones

Most liver diseases, including acute liver injury, drug-induced liver injury, viral hepatitis, metabolic liver diseases, and end-stage liver diseases, are strongly linked with hormonal influences. Thus, delineating the clinical manifestation and underlying mechanisms of the “sexual dimorphism” is critical for providing hints for the prevention, management, and treatment of those diseases. Whether the sex hormones (androgen, estrogen, and progesterone) and sex-related hormones (gonadotrophin-releasing hormone, luteinizing hormone, follicle-stimulating hormone, and prolactin) play protective or toxic roles in the liver depends on the biological sex, disease stage, precipitating factor, and even the psychiatric status. Lifestyle factors, such as obesity, alcohol drinking, and smoking, also drastically affect the involving mechanisms of those hormones in liver diseases. Hormones deliver their hepatic regulatory signals primarily via classical and non-classical receptors in different liver cell types. Exogenous sex/sex-related hormone therapy may serve as a novel strategy for metabolic liver disease, cirrhosis, and liver cancer. However, the undesired hormone-induced liver injury should be carefully studied in pre-clinical models and monitored in clinical applications. This issue is particularly important for menopause females with hormone replacement therapy (HRT) and transgender populations who want to receive gender-affirming hormone therapy (GAHT). In conclusion, basic and clinical studies are warranted to depict the detailed hepatoprotective and hepatotoxic mechanisms of sex/sex-related hormones in liver disease. Prolactin holds a promising perspective in treating metabolic and advanced liver diseases.
Impact of Dark Triad on Anxiety Disorder: Parallel Mediation Analysis During Pandemic

The current study aimed to investigate the mediating role of loneliness, ASMR, on the relationship between narcissism, Machiavellianism, and psychopathy and anxiety disorder. The population of the study was professionals working in public and private sector organizations. Non-probability snowball technique was used. Data was collected from 512 professionals. A total of 653 questionnaires were distributed and 512 were used in the analysis yielding a response rate of 78.4%. PLS-SEM was used to analyze the data. Measurement and structural models were developed to test the reliability, and validity of the scales as well as hypotheses. Findings of the measurement model revealed that scales were reliable and valid while results of the structural model revealed that narcissism, psychopathy, COVID loneliness, and ASMR have a significant direct impact on anxiety disorder but Machiavellianism does not have a significant effect on anxiety disorder. In addition, COVID loneliness and ASMR mediated between narcissism and psychopathy but do not significantly mediate between Machiavellianism and anxiety disorder. The current study has extended the body of knowledge by bridging the two theories theory of attachment and cognitive dissonance theory. The current study has provided the primary evidence that COVID loneliness increases anxiety while ASMR (audio-visual) tingling sensations help to reduce anxiety disorder.
Isolation and Characterization of vB_kpnM_17-11, a Novel Phage Efficient Against Carbapenem-Resistant Klebsiella pneumoniae

Phages and phage-encoded proteins exhibit promising prospects in the treatment of Carbapenem-Resistant Klebsiella pneumoniae (CRKP) infections. In this study, a novel Klebsiella pneumoniae phage vB_kpnM_17-11 was isolated and identified by using a CRKP host. vB_kpnM_17-11 has an icosahedral head and a retractable tail. The latent and exponential phases were 30 and 60 minutes, respectively; the burst size was 31.7 PFU/cell and the optimal MOI was 0.001. vB_kpnM_17-11 remained stable in a wide range of pH (4-8) and temperature (4-40°C). The genome of vB_kpnM_17-11 is 165,894 bp, double-stranded DNA (dsDNA), containing 275 Open Reading Frames (ORFs). It belongs to the family of Myoviridae, order Caudovirales, and has a close evolutionary relationship with Klebsiella phage PKO111. Sequence analysis showed that the 4530 bp orf022 of vB_kpnM_17-11 encodes a putative depolymerase. In vitro testing demonstrated that vB_kpnM_17-11 can decrease the number of K. pneumoniae by 105-fold. In a mouse model of infection, phage administration improved survival and reduced the number of K. pneumoniae in the abdominal cavity by 104-fold. In conclusion, vB_kpnM_17-11 showed excellent in vitro and in vivo performance against K. pneumoniae infection and constitutes a promising candidate for the development of phage therapy against CRKP.