Miracle-dz/UniFAR-FTUs huggingface dataset:
Neuropeptides and G-Protein Coupled Receptors (GPCRs) in the Red Palm Weevil Rhynchophorus ferrugineus Olivier (Coleoptera: Dryophthoridae)

The red palm weevil Rhynchophorus ferrugineus is a devastating, invasive pest that causes serious damages to palm trees, and its invasiveness depends on its strong ability of physiological and behavioral adaptability. Neuropeptides and their receptors regulate physiology and behavior of insects, but these protein partners have not been identified from many insects. Here, we systematically identified neuropeptide precursors and the corresponding receptors in the red palm weevil, and analyzed their tissue expression patterns under control conditions and after pathogen infection. A total of 43 putative neuropeptide precursors were identified, including an extra myosuppressin peptide was identified with amino acid substitutions at two conserved sites. Forty-four putative neuropeptide receptors belonging to three classes were also identified, in which neuropeptide F receptors and insulin receptors were expanded compared to those in other insects. Based on qRT-PCR analyses, genes coding for several neuropeptide precursors and receptors were highly expressed in tissues other than the nervous system, suggesting that these neuropeptides and receptors play other roles in addition to neuro-reception. Some of the neuropeptides and receptors, like the tachykinin-related peptide and receptor, were significantly induced by pathogen infection, especially sensitive to Bacillus thuringiensis and Metarhizium anisopliae. Systemic identification and initial characterization of neuropeptides and their receptors in the red palm weevil provide a framework for further studies to reveal the functions of these ligand- and receptor-couples in regulating physiology, behavior, and immunity in this important insect pest species.
The Significance of Negative Lymph Nodes in Esophageal Cancer After Curative Resection: A Retrospective Cohort Study

Objective The impact of negative lymph nodes (NLNs) count on prognosis in esophageal cancer (EC) was analyzed using two institutions surgical database. Methods We conducted a retrospective study of 768 EC patients treated by surgical resection between January 2010 and December 2012. The effects of the NLNs count on prognosis was analyzed. Cox regression model was conducted to determine the significant prognostic elements. Results The number of NLNs was studied as a categorical variable based on the quartiles (Q1: ≤15, Q2: 16–21, Q3: 22–30, Q4: ≥31). And a better overall survival (OS) was observed with increasing number of NLNs (HR= 0.762; 95% CI, 0.596–0.974 for Q2, HR= 0.666; 95% CI, 0.516–0.860 for Q3 and HR= 0.588; 95% CI, 0.450–0.768 for Q4) (all P<0.05). Multivariate regression analysis revealed that the NLNs count was an independent prognostic factor. Besides, for patients in T2 or T3 stage, a high number of NLNs was found to be significantly associated with a favorable OS (log rank P<0.001). Conclusion A higher number of NLNs is independently related to the better OS in EC patients after surgical resection.
Long Non-Coding RNA TMPO-AS1 Promotes Cell Migration and Invasion by Sponging miR-140-5p and Inducing SOX4-Mediated EMT in Gastric Cancer

Background Mounting evidence show that long non-coding RNAs (lncRNAs) play critical roles in the progression of various human cancers, including gastric cancer (GC), a common gastrointestinal tumor. In this study, the biological functions of lncRNA TMPO-AS1 in GC were studied. Methods TMPO-AS1 and miR-140-5p expression levels were detected in GC tissues and cell lines by RT-qPCR analysis. Knockdown or overexpression of TMPO-AS1 was conducted to evaluate the effects of TMPO-AS1 on the malignant behaviors of GC cells. Bioinformatic prediction and dual-luciferase reporter assay were performed to investigate the direct interaction between TMPO-AS1 and miR-140-5p in GC. Results We observed that TMPO-AS1 was up-regulated in GC tissues, and high TMPO-AS1 expression in GC patients was closely correlated with aggressive clinicopathologic characteristics and poor overall survival. Functionally, gain- and loss-of-function studies showed that TMPO-AS1 overexpression enhanced the proliferation, migration, invasion and EMT of GC cells in vitro, whereas knockdown of TMPO-AS1 inhibited these malignant traits. Importantly, we demonstrated that TMPO-AS1 could function as a competing endogenous RNA (ceRNA) by sponging miR-140-5p in GC cells, thereby diminishing the inhibition on SOX4, an EMT regulator. Conclusion Our findings indicated that TMPO-AS1 promotes GC progression partly by regulating miR-140-5p/SOX4 axis, and may serve as a novel therapeutic target for GC.
International Health Practices: A Multidisciplinary Approach to Therapeutic Mediations With an Artistic Medium Based on the Model of Play

This article, corresponding to a part of the restitution of a financed international research project between France, Brazil, Canada, Italy and Belgium, aims to offer a modelisation and qualitative evaluation of mediation care settings based on an original methodological tool that involves identifying the typical games at the foundations of creativity, following a multidisciplinary perspective. Therapeutic mediations are settings or devices organized around a “pliable medium,” often artistic, like painting, modeling, writing and theater, which are very widespread in institutional practices, both in France and abroad. The scientific objectives of this research consist in a multi-disciplinary exploration (anthropology, criminology, neuroscience, clinical psychology) of the process of creative symbolization understood as a process of transformation involving play. According to this orientation, play can be defined as a psychic process whereby a subjective experience can be explored with pleasure, and consequently symbolized and appropriated. Our fundamental and original hypothesis is that play is at the source of the creative process, conceived as a work of metabolization by the psyche of playful experiences during the different stages of life. The review of the understanding of play in psychoanalysis, anthropology, criminology and neuroscience emphasizes the richness of this model and the importance of reflecting on the typical games in the field of psychic care. A clinical example of treatment in a pictorial therapeutic mediation setting of a child with psychotic disorders makes it possible to identify a number of typical games as well as the modalities of interpretation of the therapists through play. These multidisciplinary studies lead to the presentation of a general table of typical games, and these first results highlight the richness of identifying typical games in clinical settings. Ultimately, the multidisciplinary approach shows the interest of the model of play in the evaluation of therapeutic mediation settings, with a convergence of the different disciplines emphasizing the pertinence of this model. The scientific impact of this research overlaps with its societal impact, through the development of innovative tools for evaluating therapeutic mediations, in order to take account of the evolution of the different forms of social expression of psychic suffering.
Inhibition of Rho-associated protein kinase improves the survival of human induced pluripotent stem cell-derived cardiomyocytes after dissociation

Heart disease remains the leading cause of morbidity and mortality worldwide. Induced pluripotent stem cells (iPSCs) have the ability to differentiate into cardiomyocytes (CMs), rendering this cell type to be a promising pre-cursor of cardiomyocytes for cell-based cardiac regeneration. Obtaining CMs with a high yield and purity coupled with improved subsequent survival could prove to be invaluable for the future cell replacement therapeutic strategies. Rho-associated protein kinase (ROCK) is involved in a wide range of fundamental cellular functions and serves significant roles in cardiac physiology. In the present study, human (h)iPSC-CMs were generated from iPSCs by including glycogen synthase kinase 3β and Wnt inhibitors in the basal culture media. The possible effect of Y27632, a ROCK inhibitor, on hiPSC-CMs was then investigated. hiPSC-CMs of high purity were harvested with >96% of cells expressing cardiac troponin T. Additionally, treatment with 10 µM Y27632 significantly improved the viability of dissociated hiPSC-CMs. The effects of ROCK inhibitors Y27632 and fasudil, on the proliferation and apoptosis of hiPSC-CMs were also examined. Treatment with ROCK inhibitors markedly enhanced hiPSC-CM proliferation, by up to 2.5-fold, whilst Y27632 treatment reduced apoptosis in hiPSC-derived CMs under serum starvation and suspension by suppressing the expression of caspase-3. Taken together, data from the present study indicated that ROCK kinase inhibitors effectively improved the cultural system of hiPSC-derived CMs.
Group Guided Fused Laplacian Sparse Group Lasso for Modeling Alzheimer's Disease Progression

As the largest cause of dementia, Alzheimer's disease (AD) has brought serious burdens to patients and their families, mostly in the financial, psychological, and emotional aspects. In order to assess the progression of AD and develop new treatment methods for the disease, it is essential to infer the trajectories of patients' cognitive performance over time to identify biomarkers that connect the patterns of brain atrophy and AD progression. In this article, a structured regularized regression approach termed group guided fused Laplacian sparse group Lasso (GFL-SGL) is proposed to infer disease progression by considering multiple prediction of the same cognitive scores at different time points (longitudinal analysis). The proposed GFL-SGL simultaneously exploits the interrelated structures within the MRI features and among the tasks with sparse group Lasso (SGL) norm and presents a novel group guided fused Laplacian (GFL) regularization. This combination effectively incorporates both the relatedness among multiple longitudinal time points with a general weighted (undirected) dependency graphs and useful inherent group structure in features. Furthermore, an alternating direction method of multipliers- (ADMM-) based algorithm is also derived to optimize the nonsmooth objective function of the proposed approach. Experiments on the dataset from Alzheimer's Disease Neuroimaging Initiative (ADNI) show that the proposed GFL-SGL outperformed some other state-of-the-art algorithms and effectively fused the multimodality data. The compact sets of cognition-relevant imaging biomarkers identified by our approach are consistent with the results of clinical studies.
Patient-Reported Outcome in Two Chronic Diseases: A Comparison of Quality of Life and Response Profiles in Severe Migraine and Severe Asthma

Introduction Migraine and asthma are two frequent, disabling, chronic disorders with a major impact on patient well-being. The objectives of this study were to compare subjective well-being between patients with severe forms of migraine or asthma using a panel of PROs. Methods Adult patients were recruited during routine consultations with chest physicians or neurologists. Patients with severe migraine (reporting headaches on ≥8 days/month and having failed ≥2 prophylactic treatments) and patients with severe asthma (according to the 2017 GINA definition: requiring Step 4 or 5 treatment or presenting uncontrolled symptoms) were eligible. Each patient completed the EuroQol Questionnaire (EQ-5D-5L), the Work Productivity and Activity Impairment Questionnaire (WPAI) and the Hospital Anxiety and Depression scale (HAD). Patients with severe migraine the 6-item Headache Impact Test (HIT-6) and those with severe asthma completed the Asthma Control Test (ACT). Results 249 patients with severe migraine and 96 with severe asthma were enrolled. Mean EQ-5D-5L utility scores were significantly higher in the severe migraine group than in the severe asthma group (0.75±0.25 vs 0.68±0.26; p<0.01). Low EQ-5D-5L utility scores were associated with frequent (≥15 headache days/month) or disabling (HIT-6 score ≥60) headaches and with poor asthma control. Patients with severe migraine more frequently presented a HAD depression score ≥11 (23.0% in severe migraine; 7.5% in severe asthma; p<0.01), whereas those with severe asthma more frequently reported problems with mobility, self-care and usual activities. Absenteeism (percent worktime missed) was similar in both groups (severe migraine: 9.0%±19.1%; severe asthma: 13.8%±22.9%) but work impairment was higher in the severe migraine group (44.3% vs 28.4%; p<0.01). Conclusion Quality of life, work activity and psychological distress are all deteriorated in both severe migraine and severe asthma. Different aspects are affected in the two diseases: a greater impact on psychological aspects in severe migraine and a greater impact on physical aspects in severe asthma.
FTO Facilitates Lung Adenocarcinoma Cell Progression by Activating Cell Migration Through mRNA Demethylation

Background The fat mass and obesity-associated protein (FTO) was identified as a critical demethylase involved in regulating cellular mRNA stability by removing N6-methyladenosine (m6A) residues from mRNA. Emerging evidence has revealed that FTO is deeply implicated in lung cancer. However, knowledge of the function of FTO in lung adenocarcinoma (LUAC) is limited. Methods FTO and FTO R96Q (R96Q), an FTO missense mutant lacking demethylase activity, were ectopically overexpressed, and FTO was knocked down via siRNA in A549 and H1299 cells. The relationships between FTO with cell characteristics and mRNA m6A levels were explored. Furthermore, RNA sequencing was performed on A549 cells. Results FTO overexpression enhanced the proliferation, migration, and invasion ability of A549 and H1299 cells, decreased mRNA m6A levels. Interestingly, overexpression of R96Q, blunted the effects of FTO overexpression on cell proliferation and invasion. Through RNA sequencing analysis of A549 cells overexpressing FTO or R96Q and control A594 cells, 45 genes were identified as affected by m6A mRNA demethylation. Most of these genes were related to lung cancer, such as laminin γ2, thrombospondin 1, nerve growth factor inducible, integrin alpha11, and proprotein convertase subtilisin/kexin type 9. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses suggested that these genes are fundamental to cancer development processes, such as cell migration and extracellular matrix organization. Conclusion Our research shows that FTO facilitates LUAC cell progression by activating cell migration through m6A demethylation; however, further research on the mechanism underlying FTO activity in LUAC is necessary.
Sialic Acid-Siglec-E Interactions During Pseudomonas aeruginosa Infection of Macrophages Interferes With Phagosome Maturation by Altering Intracellular Calcium Concentrations

Pseudomonas aeruginosa (PA) is commonly associated with nosocomial and chronic infections of lungs. We have earlier demonstrated that an acidic sugar, sialic acid, is present in PA which is recognized and bound by sialic acid binding immunoglobulin type lectins (siglecs) expressed on neutrophils. Here, we have tried to gain a detailed insight into the immunosuppressive role of sialic acid-siglec interactions in macrophage-mediated clearance of sialylated PA (PA+Sia). We have demonstrated that PA+Sia shows enhanced binding (~1.5-fold) to macrophages due to additional interactions between sialic acids and siglec-E and exhibited more phagocytosis. However, internalization of PA+Sia is associated with a reduction in respiratory burst and increase in anti-inflammatory cytokines secretion which is reversed upon desialylation of the bacteria. Phagocytosis of PA+Sia is also associated with reduced intracellular calcium ion concentrations and altered calcium-dependent signaling which negatively affects phagosome maturation. Consequently, although more PA+Sia was localized in early phagosomes (Rab5 compartment), only fewer bacteria reach into the late phagosomal compartment (Rab7). Possibly, this leads to reduced phagosome lysosome fusion where reduced numbers of PA+Sia are trafficked into lysosomes, compared to PA−Sia. Thus, internalized PA+Sia remain viable and replicates intracellularly in macrophages. We have also demonstrated that such siglec-E-sialic acid interaction recruited SHP-1/SHP-2 phosphatases which modulate MAPK and NF-κB signaling pathways. Disrupting sialic acid-siglec-E interaction by silencing siglec-E in macrophages results in improved bactericidal response against PA+Sia characterized by robust respiratory burst, enhanced intracellular calcium levels and nuclear translocation of p65 component of NF-κB complex leading to increased pro-inflammatory cytokine secretion. Taken together, we have identified that sialic acid-siglec-E interactions is another pathway utilized by PA in order to suppress macrophage antimicrobial responses and inhibit phagosome maturation, thereby persisting as an intracellular pathogen in macrophages.
Formulation and Characterization of Solid Lipid Nanoparticles Loading RF22-c, a Potent and Selective 5-LO Inhibitor, in a Monocrotaline-Induced Model of Pulmonary Hypertension

Pulmonary arterial hypertension (PAH) is a rare but fatal disease characterized by persistent elevated blood pressure in the pulmonary circulation, due to increased resistance to blood flow, through the lungs. Advances in the understanding of the pathobiology of PAH clarify the role of leukotrienes (LTs) that appear to be an exciting new target for disease intervention. Over the years, our group has long investigated this field, detecting the 1,2-benzoquinone RF-22c as the most powerful and selective competitive inhibitor of the enzyme 5-lipoxygenase (5-LO). With the aim to improve the bioavailability of RF-22c and to confirm the role of 5-LO as therapeutic strategy for PAH treatment, we developed a solid lipid nanoparticle (SLN) loaded with drug. Therefore, in monocrotaline (MCT) rat model of PAH, the role of 5-LO has been investigated through the formulation of RF-22c-SLN. The rats were randomly grouped into control group, MCT group, and MCT + RF22-c group. After 21 days, all the animals were sacrificed to perform functional and histological evaluations. RF22-c-SLN treatment was able to significantly reduce the mean pulmonary arterial pressure (mPAP) and precapillary resistance (R-pre) compared to the MCT group. The MCT induced rise in medial wall thickness of pulmonary arterioles, and the cardiomyocytes width were significantly attenuated by RF22-c-SLN formulation upon treatment. The results showed that the selective inhibition of 5-LO improved hemodynamic parameters as well as vascular and cardiac remodeling by preventing induced pulmonary hypertension. The improved sustained release properties and targeting abilities achieved with the innovative nanotechnological approach may be therapeutically beneficial for PAH patients as a consequence of the increase of pharmacological effects and of the possible reduction and/or optimization of the drug frequency of administration.
Enhanced Electromagnetic Absorption Properties of Commercial Ni/MWCNTs Composites by Adjusting Dielectric Properties

In this manuscript, we constructed a Ni/MWCNTs absorber and properly adjusted the permittivity resulted from absorber content in the PVDF to optimize impedance matching properties. Both ε′ and ε″ increase obviously with the increasing content of Ni/MWCNTs in PVDF, demonstrating that dielectric properties are dependent on the conductivity. Moderate dielectric properties and excellent impedance matching can be obtained for the filler content of 20 wt% Ni/MWCNTs. Reasonable impedance matching allows electromagnetic waves to propagate into the materials and finally realize energy dissipation through dielectric loss and interfacial polarization. As expected, the minimum reflection loss (RL) of −46.85 dB at 6.56 GHz with a low filler loading (20 wt%) and wide effective bandwidth (RL<-10 dB) of 14.0 GHz in the thickness range of 1.5–5.0 mm was obtained for the commercial Ni/MWCNTs composites, which is promising for mass production in industrial applications. Our findings offer an effective and industrialized way to design high-performance material to facilitate the research in microwave absorption.
Intraoperative Floppy Iris Syndrome: Updated Perspectives

Abstract Almost fifteen years since its initial description, intraoperative floppy iris syndrome (IFIS) during phacoemulsification surgery remains a challenge for cataract surgeons in all its key aspects that include the stratification of the preoperative risk, preoperative prophylaxis treatment, surgery design and intraoperative management. Since its original association with tamsulosin intake, IFIS has been positively correlated with a plethora of risk factors which include: gender, age, hypertension, other a1-adrenergic receptor antagonists, finasteride, angiotensin II receptor inhibitors, benzodiazepines, antipsychotics, hypertension drugs and decreased dilated pupil diameter. The assessment and stratification of the preoperative risk is pivotal in screening patients prone to develop IFIS. For these patients, it is essential that preoperative prophylaxis, employment of necessary measures and surgical technique modifications are considered. A multidisciplinary approach of IFIS is a mandate, thus ophthalmologists, urologists and sometimes other specialties should cooperate to “educate” each other about the risks of their respective fields. They both must be aware of the joint statement on IFIS by the American Academy of Ophthalmology and the American Society of Cataract and Refractive Surgery which suggests either the initiation of tamsulosin after phacoemulsification or the use of a non-selective a1-ARA for benign prostatic hyperplasia treatment. In conclusion, awareness of the risk factors associated with IFIS and their detailed preoperative documentation is crucial in addressing IFIS. The lack of such an awareness can turn a routine, uneventful surgery into one with significant visual morbidity.