Miracle-dz/UniFAR-FTUs huggingface dataset:
Lipoproteins Cause Bone Resorption in a Mouse Model of Staphylococcus aureus Septic Arthritis

Septic arthritis, most often caused by Staphylococcus aureus, is a rapidly progressive and destructive joint disease with substantial mortality and morbidity. Staphylococcus aureus lipoproteins (Lpps) are known to induce arthritis and bone destruction. Here, we aimed to investigate the bone resorptive effect of S. aureus Lpps in a murine arthritis model by intra-articular injection of purified S. aureus Lpps, synthetic lipopeptides, and live S. aureus strains. Analyses of the bone mineral density (BMD) of the distal femur bone were performed. Intra-articular injection of both live S. aureus and purified S. aureus Lpps were shown to significantly decrease total- and trabecular BMD. Liquid chromatography–mass spectrometry analyses revealed that the Lpps expressed by S. aureus SA113 strain contain both diacyl and triacyl lipid moieties. Interestingly, synthetic diacylated lipopeptide, Pam2CSK4, was more potent in inducing bone resorption than synthetic triacylated lipopeptide, Pam3CSK4. Modified lipoproteins lacking the lipid moiety were deprived of their bone resorptive abilities. Monocyte depletion by clodronate liposomes fully abrogated the bone resorptive capacity of S. aureus lipoproteins. Our data suggest that S. aureus Lpps induce bone resorption in locally-induced murine arthritis, an effect mediated by their lipid-moiety through monocytes/macrophages.
Elastic Net avec gestion des interactions et débiaisage

Résumé. Nous présentons quelques résultats statistiques pour un modèle de régression pénalisée et dé-biaisée pour ajuster, en grande dimension, un modèle linéaire parcimonieux avec interactions. L’analyse statistique s’intéresse à l’approche proposée par Bascou et al. (2020), notamment afin d’illustrer le fonctionnement du débiaisage. De plus, on montre qu’il permet de sélectionner moins de variables que le modèle sans débiaisage sur données simulées et réelles.
Craniopharyngioma and Metabolic Syndrome: A 5-Year Follow-Up Single-Center Experience

Patients with craniopharyngioma often have comorbidities, such as obesity and hypopituitarism. These two conditions affect each other and worsen the quality of life of patients, which lead to a higher risk of morbidity and mortality. In addition, abdominal obesity, measured as waist circumference (WC), is together with other parameters [arterial hypertension, hyperglycemia, hypertriglyceridemia, and reduced levels of high-density lipoprotein (HDL) cholesterol], one of the components of metabolic syndrome (MS). Each one of these morbidities occurs in patients with craniopharyngioma more frequently than in the remaining population. On these bases, we evaluated metabolic parameters in patients with craniopharyngioma at the time of diagnosis and after a 5-year follow-up, which compares these data with those of age-, gender-, WC-, and body mass index (BMI)-matched controls. In addition, we evaluated the prevalence of MS according to IDF criteria (MS-IDF) and the prevalence of MS according to ATP III (MS-ATPIII) criteria in patients and controls at baseline and after 5 years. We recruited 20 patients with craniopharyngioma (age 38.5 ± 15 years, 10 M) and 20 age-, gender-, WC- and BMI-matched controls (age 34.16 ± 13.19 years, 10 M). In all patients and controls, we evaluated the following: anthropometric features [height, weight, BMI, WC, hip circumference (HC) and waist-to-hip ratio (WHR)], systolic blood pressure (SBP) and diastolic blood pressure (DBP), lipid profile [total cholesterol (TC), HDL, low-density lipoprotein (LDL) cholesterol, triglycerides (TG)], and blood glucose at baseline and after 5 years. The prevalence of MS, according to IDF and ATPIII criteria, was calculated in the two groups at baseline and after 5 years. According to our results, at baseline, patients with craniopharyngioma had a worse metabolic profile than controls and a higher prevalence of MS. Besides, at a 5-year follow-up, patients still had impaired metabolic characteristics and more frequent MS (according to IDF and ATPIII criteria) when compared to controls. These data confirm that MS in patients with craniopharyngioma is unresponsive to life-changing interventions and to a common pharmacological approach. Other factors may be involved in the evolution of these conditions; so, further studies are needed to establish the correct management of these patients.
The Lipid-Lowering Effect of Dietary Taurine in Orange-Spotted Groupers (Epinephelus coioides) Involves Both Bile Acids and Lipid Metabolism

An 8-week feeding trial was conducted to investigate how dietary taurine supplementation attenuates the lipid deposition induced by dietary high lipid in juvenile orange-spotted grouper (Epinephelus coioides). Three isonitrogenous (47% crude protein) semipurified diets were formulated to contain two levels of lipid and termed as 10% lipid diet, 15% lipid diet, and 15% lipid with 1% taurine (namely, diet 10L, diet 15L, and diet 15L + T, respectively). Groupers fed diet 15L + T showed higher weight gain and feed efficiency compared with diet 15L. Groupers fed diet 15L showed higher liver lipid contents, plasma total cholesterol (TC), and leptin contents vs. those fed diet 10L. Diet 15L + T decreased hepatosomatic index, liver lipid content, and plasma TC and adiponectin contents, and increased liver 3-hydroxy-3-methy1 glutary1 coenzyme A reductase content compared with diet 15L. Fish fed diet 15L had higher contents of chenodeoxycholic acid, deoxycholic acid, and lithocholic acid, and lower contents of glycodeoxycholic acid (GDCA), glycolithocholic acid, glycoursodeoxycholic acid, taurodeoxycholic acid (TDCA), and β-, γ-, and ω-muricholic acid (MCA) when compared with fish fed diet 10L. Diet 15L + T downregulated the contents of glycocholic acid, glycochenodeoxycholic acid, taurohyodeoxycholic acid, tauromuricholic acid, TDCA, ursodeoxycholic acid, GDCA, and β-MCA vs. diet 15L. Diet 15L upregulated expression of peroxisome proliferator-activated receptor α (pparα) gene but downregulated expression of acyl-CoA carboxylase (acc), fatty acid synthase (fas), and glucose-6-phosphate dehydrogenase (g6pd) genes in comparison with diet 10L. The gene expression level of fas and 6pgd was downregulated and the pparα gene expression level was upregulated in fish fed diet 15L + T compared with those in fish fed diet 15L. Overall, this study indicated that dietary taurine supplementation can attenuate the liver lipid deposition of groupers caused by feeding 15% lipid through accelerating lipid absorption of taurine-conjugated bile acids and fatty acid β-oxidation and inhibiting lipogenesis.
Application of Magnetically Assisted Reactors for Modulation of Growth and Pyocyanin Production by Pseudomonas aeruginosa

Pseudomonas aeruginosa is a producer of desired secondary metabolites, including pyocyanin. Potential uses of this pigment urge a search for improved production methods. Recent trends in bioprocessing show the potential of the use of electromagnetic fields (EMFs) to influence the growth of microorganisms and even modulate the concentration of bioproducts. Here, we aimed at assessing the influence of rotating magnetic field (RMF) and static magnetic field (SMF) on pyocyanin production, growth rate, and respiration of P. aeruginosa. Moreover, exposure time to EMFs (2, 6, and 12 h) and culture volume (10 and 50 ml) were initially assessed. P. aeruginosa was cultivated in magnetically assisted reactors with 5 and 50 Hz RMF (magnetic induction of 24.32 and 42.64 mT, respectively) and SMF (−17.37 mT). Growth kinetics was assessed with Gompertz equation. The viability was tested using resazurin assay, whereas pyocyanin production by chloroform-HCl methodology. The growth of P. aeruginosa was slightly stimulated by exposure to a RMF with 50 Hz (108% related to the control) and significantly by SMF (132% related to the control), while RMF 5 Hz exposure prolonged the time of inflection (in comparison to RMF 50 Hz and SMF). The 6-h exposure to EMFs resulted in the highest pyocyanin production in comparison to the control, indicating a relationship between exposure time and product concentration. Moreover, cultures led in smaller volumes produced more pyocyanin. Our findings show that the use of different EMF types, frequency, and exposition time and volume could be used interchangeably to obtain different bioprocess aims.
Molecular Dynamics Simulation of the Nanoindentation of Coal Vitrinite

Coal deformation is closely correlated with the distribution of organic maceral groups, however, molecular dynamics (MD) simulations of vitrinite nanoindentation have rarely been conducted. In this study, the vitrinite substrate for indentation was constructed utilizing polymer consistent force field (PCFF), and a spherical ghost indenter was used for loading. The results showed that: 1) In the indentation process, some of the vitrinite atoms overcame the energy barrier to move, with the most important deformation mechanism including the sliding, bending, and reorientation of vitrinite molecular chains, leading to the formation of a shearing transformation zone (STZ), which was also found to contain structural defects and stacking of aromatic structures. 2) The distribution of atomic displacements in the vitrinite substrate could be subdivided into distinct regions, with slippage at the region boundaries producing shear bands. 3) The surface morphology and mechanical properties obtained from the nanoindentation simulation were similar to experimental results from the literature, indicating that MD simulations are a powerful tool for studying coal nanoindentation. The results from this study increase the current scientific understanding of the mechanical properties of vitrinite by providing a new perspective that elucidates the nanoscale structural evolution occurring during the indentation process.
Exogenous Melatonin Alleviates Alkaline Stress by Removing Reactive Oxygen Species and Promoting Antioxidant Defence in Rice Seedlings

Saline-alkali stress seriously restricts rice growth, development, and production in northern China. The damage of alkaline stress on rice is much greater than that of salt due to ion toxicity, osmotic stress, and especially high pH. As a signal molecule, melatonin (N-acetyl-5-methoxytryptamine, MT) mediates many physiological processes in rice and participates in protecting rice from abiotic stress. The potential mechanism of exogenous melatonin-mediated alkaline stress tolerance is still largely unknown. In this study, the effects of melatonin on the morphological change, physiological property, and corresponding genes expression in rice seedlings were analyzed under alkaline stress (20 mmol L−1, pH 9.55). The results showed that the expression levels of MT synthesis genes (TDC2, T5H, SNAT, ASMT1, and ASMT2) were induced by both exogenous MT and alkaline stress treatment. The cell membrane was protected by MT, and the MT furtherly play role in scavenging reactive oxygen species (ROS), reducing lipoxygenase (LOX) activity, and malondialdehyde (MDA) content. The scavenging of ROS by melatonin is attributed to the coupling of the improvement of redox homeostasis and the enhancement of antioxidant enzyme activity and antioxidant content by upregulating the transcriptional levels of antioxidase genes. In the meantime, MT pretreatment promoted the accumulation of free proline, sucrose, and fructose by regulating the OsP5CS, OsSUS7, and OsSPS1 gene expression level and increased chlorophyll content upregulating the expression of chlorophyll synthesis-related genes. Ultimately, the alleviating effect of exogenous melatonin on alkaline stress was reflected in increasing the leaf relative water content (RWC) and root-shoot ratio and reducing the leaf tip wilt index (TWI) through a series of physiological and biochemical changes. Melatonin pretreatment changed the expression level of MT synthesis genes which might contribute to MT synthesis in rice, consequently, activated the ROS scavenging system and alleviating the damage of alkaline stress on rice seedlings. Our study comprehensively understands the alleviating effect of exogenous melatonin on rice under alkaline stress.
Optimizing a bi-objective inventory model for a two-echelon supply chain management using a tuned meta-heuristic algorithm

Since vendor-managed inventory strategy plays an important role to reduce total inventory costs, the focus of this paper is to develop an economic order quantity model presented for a two-echelon supply chain management including one vendor and one retailer. In this bi-objective model, the vendor delivers several products to the retailer while shortages are allowed. The aim of this paper is to determine order sizes and maximum backorder levels for each product to simultaneously minimize total inventory costs and a storage space. Moreover, two main constraints, namely budget and the number of orders, are considered to simulate real-world operating conditions for the proposed model. Since the presented model belongs to integer non-linear programming problems, a meta-heuristic algorithm, particle swarm optimization (PSO), is employed to optimize it. In addition, because the quality of solutions depends on the values of parameters of meta-heuristics, the parameters of PSO are tuned using the Taguchi method. Then, the proposed algorithm is compared to branch and bound method.
miR-145-5p Inhibits Neuroendocrine Differentiation and Tumor Growth by Regulating the SOX11/MYCN Axis in Prostate cancer

Recent studies have shown that the downregulation of miR-145-5p in prostate cancer (PCa) is significantly associated with poor differentiation and prognosis. We aimed to investigate the biological role of miR-145-5p in the neuroendocrine differentiation (NED) of PCa. In this study, TheCancer Genome Atlas was used to identify the association of miR-145-5p with PCa. The functions of miR-145-5p were evaluated using the Cell Counting Kit-8 (CCK-8) assay and cell cycle analysis. We validated changes in cell cycle control by testing the expression of cyclin-related genes by western blot. The luciferase reporter assay was performed to test miR-145-5p-targeting genes and direct transcriptional targets of SOX11. The expression of miR-145-5p was found to be significantly downregulated in castration-resistant PCa, and this was correlated with higher Gleason score and prostate-specific antigen. We confirmed these results using PC3 and LNCaP cell lines depicted a gradual decline of miR-145-5p while the cells were cultured under androgen depletion conditions. Moreover, the knockdown of miR-145-5p significantly promoted NED and proliferation of LNCaP cells, whereas overexpression of miR-145-5p significantly inhibited NED and proliferation of LNCaP cells. Mechanistically, we found that SOX11 was a direct target of miR-145-5p, which regulates MYCN might mediate induction of NED and proliferation of LNCaP cells. Furthermore, knockdown of miR-145-5p promoted tumor growth in vivo. Our findings suggest that miR-145-5p can inhibit NED and tumor growth by targeting SOX11, which regulates the expression of MYCN, and that this could be a novel therapeutic strategy for preventing the progression of PCa.
Uncoupling the Vicious Cycle of Mechanical Stress and Inflammation in Calcific Aortic Valve Disease

Calcific aortic valve disease (CAVD) is a common acquired valvulopathy, which carries a high burden of mortality. Chronic inflammation has been postulated as the predominant pathophysiological process underlying CAVD. So far, no effective medical therapies exist to halt the progression of CAVD. This review aims to outline the known pathways of inflammation and calcification in CAVD, focussing on the critical roles of mechanical stress and mechanosensing in the perpetuation of valvular inflammation. Following initiation of valvular inflammation, dysregulation of proinflammatory and osteoregulatory signalling pathways stimulates endothelial-mesenchymal transition of valvular endothelial cells (VECs) and differentiation of valvular interstitial cells (VICs) into active myofibroblastic and osteoblastic phenotypes, which in turn mediate valvular extracellular matrix remodelling and calcification. Mechanosensitive signalling pathways convert mechanical forces experienced by valve leaflets and circulating cells into biochemical signals and may provide the positive feedback loop that promotes acceleration of disease progression in the advanced stages of CAVD. Mechanosensing is implicated in multiple aspects of CAVD pathophysiology. The mechanosensitive RhoA/ROCK and YAP/TAZ systems are implicated in aortic valve leaflet mineralisation in response to increased substrate stiffness. Exposure of aortic valve leaflets, endothelial cells and platelets to high shear stress results in increased expression of mediators of VIC differentiation. Upregulation of the Piezo1 mechanoreceptor has been demonstrated to promote inflammation in CAVD, which normalises following transcatheter valve replacement. Genetic variants and inhibition of Notch signalling accentuate VIC responses to altered mechanical stresses. The study of mechanosensing pathways has revealed promising insights into the mechanisms that perpetuate inflammation and calcification in CAVD. Mechanotransduction of altered mechanical stresses may provide the sought-after coupling link that drives a vicious cycle of chronic inflammation in CAVD. Mechanosensing pathways may yield promising targets for therapeutic interventions and prognostic biomarkers with the potential to improve the management of CAVD.
Plasmodium falciparum-Specific Memory B-Cell and Antibody Responses Are Associated With Immunity in Children Living in an Endemic Area of Kenya

Identifying the mechanism of naturally acquired immunity against Plasmodium falciparum malaria could contribute to the design of effective malaria vaccines. Using a recently developed multiplexed FluoroSpot assay, we assessed cross-sectional pre-existing memory B-cells (MBCs) and antibody responses against six well known P. falciparum antigens (MSP-119, MSP-2 (3D7), MSP-2 (FC27), MSP-3, AMA-1 and CSP) and measured their associations with previous infections and time to clinical malaria in the ensuing malaria season in Kenyan children. These children were under active weekly surveillance for malaria as part of a long-term longitudinal malaria immunology cohort study, where they are recruited from birth. After performing Cox regression analysis, we found that children with a breadth of three or more antigen-specific MBC or antibody responses at the baseline had a reduced risk for malaria in the ensuing P. falciparum transmission season. Specifically, MBC responses against AMA-1, MSP-2 (3D7) and MSP-3, as well as antibody responses to MSP-2 (3D7) and MSP-3 were prospectively associated with a reduced risk for malaria. The magnitude or breadth of MBC responses were however not correlated with the cumulative number of malaria episodes since birth. We conclude that increased breadth for merozoite antigen-specific MBC and antibody responses is associated with protection against malaria.
Pneumocystis Jirovecii Pneumonia Diagnosis via Metagenomic Next-Generation Sequencing

The incidence of non-HIV-infected Pneumocystis Jirovecii Pneumonia (PJP) is increasing. The prognosis for non-HIV PJP is poor and diagnostic tests are of lower sensitivity in non-HIV patients. Metagenomic next-generation sequencing (mNGS) was compared with routine detection assays, including Gomori methenamine silver (GMS) stain and polymerase chain reaction (PCR) technique. Specimens of 4 bronchoalveolar lavages (BAL) and 1 lung tissue samples were obtained from 4 non-HIV patients from our hospitals. Although both GMS and mNGS were positive for P. jirovecii with PCR as positive control, the testing time of mNGS was obviously shorter than GMS. Compared with the traditional GMS method, mNGS has absolute advantages. However, the issue with PJP presentations having atypical symptoms and ambiguous imaging features persists. Hence, the disease can easily be ignored. Secondly, PJP progresses rapidly in non-HIV-infected patients and can cause severe respiratory failure with unfavorable prognosis. This study affirms that mNGS can be used to quickly and accurately diagnose PJP, but a combination of clinical judgement of symptoms, laboratory testing, and imaging examination is required to make a comprehensive judgment along with mNGS test results.
The Physiologic Mechanisms of Paced QRS Narrowing During Left Bundle Branch Pacing in Right Bundle Branch Block Patients

Left bundle branch pacing (LBBP) is a physiological pacing technique that captures the left bundle branch (LBB) directly, causing the left ventricle (LV) to be excited earlier than the right ventricle (RV), resulting in a “iatrogenic” right bundle branch block (RBBB) pacing pattern. Several studies have recently shown that permanent LBBP can completely or partially narrow the wide QRS duration of the intrinsic RBBB in most patients with bradycardia, although the mechanisms by which this occurs has not been thoroughly investigated. This article presents a review of the LBBP in patients with intrinsic RBBB mentioned in current case reports and clinical studies, discussing the technique, possible mechanisms, future clinical explorations, and the feasibility of eliminating the interventricular dyssynchronization accompanied with LBBP.
Linking High School Students’ Achievement Goal Orientations With Their Competence Beliefs and Their Perception of Teachers’ Emotional Support During the COVID-19 Pandemic

Due to the COVID-19 pandemic, adolescents have experienced limitations in their everyday activities. Consequently, their mental health has become an area of concern. However, there has been much less of a focus on the factors and mechanisms contributing to how they have approached their various academic activities during the pandemic. The current study fills this gap by investigating associations between adolescents’ competence beliefs and perception of teachers’ emotional support and their achievement goals (mastery, performance, and work avoidance) at the onset of the second wave of this pandemic in Canada. Participants were 90 Canadian high school adolescents in grades 9 and 10 and they were surveyed in November of 2020. Data were analyzed using multiple regression and mediation analyses. Among the most salient results, competence beliefs were found to predict achievement goals, above and beyond teachers’ emotional support, and these beliefs were significantly and positively associated with mastery and performance orientation, and marginally and negatively associated with work avoidance orientation. Results also showed that competence beliefs mediated the association between teachers’ emotional support and the mastery goal orientation. These findings are discussed in light of relevant pre-pandemic evidence about the role of competence beliefs and teachers’ emotional support on achievement goal orientations.