Miracle-dz/UniFAR-FTUs huggingface dataset:
The ubiquitination ligase SMURF2 reduces aerobic glycolysis and colorectal cancer cell proliferation by promoting ChREBP ubiquitination and degradation

The glucose-responsive transcription factor carbohydrate response element–binding protein (ChREBP) critically promotes aerobic glycolysis and cell proliferation in colorectal cancer cells. It has been reported that ubiquitination may be important in the regulation of ChREBP protein levels and activities. However, the ChREBP-specific E3 ligase and molecular mechanism of ChREBP ubiquitination remains unclear. Using database exploration and expression analysis, we found here that levels of the E3 ligase SMURF2 (Smad-ubiquitination regulatory factor 2) negatively correlate with those of ChREBP in cancer tissues and cell lines. We observed that SMURF2 interacts with ChREBP and promotes ChREBP ubiquitination and degradation via the proteasome pathway. Interestingly, ectopic SMURF2 expression not only decreased ChREBP levels but also reduced aerobic glycolysis, increased oxygen consumption, and decreased cell proliferation in colorectal cancer cells. Moreover, SMURF2 knockdown increased aerobic glycolysis, decreased oxygen consumption, and enhanced cell proliferation in these cells, mostly because of increased ChREBP accumulation. Furthermore, we identified Ser/Thr kinase AKT as an upstream suppressor of SMURF2 that protects ChREBP from ubiquitin-mediated degradation. Taken together, our results indicate that SMURF2 reduces aerobic glycolysis and cell proliferation by promoting ChREBP ubiquitination and degradation via the proteasome pathway in colorectal cancer cells. We conclude that the SMURF2–ChREBP interaction might represent a potential target for managing colorectal cancer.
Modelling the effects of age and sex on the resistive and viscoelastic components of the work of breathing during exercise

What is the central question of this study? What is the effect of age and sex on the resistive and viscoelastic components of work of breathing (Wb) during exercise? What is the main finding and its importance? The resistive and viscoelastic components of Wb were higher in older adults, regardless of sex. The resistive, but not viscoelastic, component of Wb was higher in females than in males, regardless of age. These findings contribute to improving our understanding of the effects of ageing and sex on the mechanical ventilatory response to exercise.
Shaping Magnetite with Poly-l-arginine and pH: From Small Single Crystals to Large Mesocrystals

Control over particle size, size distribution, and colloidal stability are central aims in producing functional nanomaterials. Recently, biomimetic approaches have been successfully used to enhance control over properties in the synthesis of those materials. Magnetotactic bacteria produce protein-stabilized magnetite away from its thermodynamic equilibrium structure. Mimicking the bacteria’s proteins using poly-l-arginine we show that by simply increasing the pH, the dimensions of magnetite increase and a single- to mesocrystal transformation is induced. Using synchrotron X-ray diffraction and transmission electron microscopy, we show that magnetite nanoparticles with narrow size distributions and average diameters of 10 ± 2 nm for pH 9, 20 ± 2 nm for pH 10, and up to 40 ± 4 nm for pH 11 can be synthesized. We thus selectively produce superparamagnetic and stable single-domain particles merely by controlling the pH. Remarkably, while an increase in pH brings about a thermodynamically driven decrease in size for magnetite without additives, this dependency on pH is inverted when poly-l-arginine is present.
Melatonin receptor activation protects against low potassium‐induced ventricular fibrillation by preserving action potentials and connexin‐43 topology in isolated rat hearts

Hypokalemia prolongs the QRS and QT intervals, deteriorates intercellular coupling, and increases the risk for arrhythmia. Melatonin preserves gap junctions and shortens action potential as potential antiarrhythmic mechanisms, but its properties under hypokalemia remain unknown. We hypothesized that melatonin protects against low potassium‐induced arrhythmias through the activation of its receptors, resulting in action potential shortening and connexin‐43 preservation. After stabilization in Krebs‐Henseleit solution (4.5 mEq/L K+), isolated hearts from Wistar rats underwent perfusion with low‐potassium (1 mEq/L) solution and melatonin (100 μmol/L), a melatonin receptor blocker (luzindole, 5 μmol/L), melatonin + luzindole or vehicle. The primary endpoint of the study was the prevention of ventricular fibrillation. Electrocardiography was used, and epicardial action potentials and heart function were measured and analyzed. The ventricular expression, dephosphorylation, and distribution of connexin‐43 were examined. Melatonin reduced the incidence of low potassium‐induced ventricular fibrillation from 100% to 59%, delayed the occurrence of ventricular fibrillation and induced a faster recovery of sinus rhythm during potassium restitution. Melatonin prevented QRS widening, action potential activation delay, and the prolongation of action potential duration at 50% of repolarization. Other ECG and action potential parameters, the left ventricular developed pressure, and nonsustained ventricular arrhythmias did not differ among groups. Melatonin prevented connexin‐43 dephosphorylation and its abnormal topology (lateralization). Luzindole abrogated the protective effects of melatonin on electrophysiological properties and connexin‐43 misdistribution. Our results indicate that melatonin receptor activation protects against low potassium‐induced ventricular fibrillation, shortens action potential duration, preserves ventricular electrical activation, and prevents acute changes in connexin‐43 distribution. All of these properties make melatonin a remarkable antifibrillatory agent.
Dual effects of an anti-CD147 antibody for Esophageal cancer therapy

ABSTRACT Background: Esophageal cancer is a highly aggressive neoplasm. Targeted therapy has been proven to be a promising way for cancer therapy. Here, we report a novel anti-CD147 antibody for esophageal cancer therapy, which is a chimeric antibody with modified glycoform in Fc region. Methods: ADCC assay was used to explore the antitumor efficacy of Metuzumab against esophageal cancer in vitro. Wound healing assay and Boyden Chamber invasion assay were performed to explore whether Metuzumab could inhibit migration and invasion of esophageal cancer in vitro. Insulin-like growth factors 1 (IGF-1) and PI3k/Akt was assayed for elaborating antagonistic mechanism of Metuzumab in migration and invasion of esophageal cancer cells. Subcutaneous xenograft nude mouse model was used to investigate the antitumor efficacy of Metuzumab against esophageal cancer in vivo. The esophageal cancer tissue microarrays (TMA) was examined for identification of association of CD147 with lymph node metastasis, and the footpad xenograft nude mouse model was used to explore whether Metuzumab could inhibit lymph node metastasis of esophageal cancer in vivo. Results: The results showed that Metuzumab exhibited higher ADCC compared to the wild type antibody cHAb18. Metuzumab inhibited migration and invasion of esophageal cancer through blockade of CD147 in vitro. The results of Western blot showed Metuzumab might inhibit migration and invasion of esophageal cancer cells through suppressing activation of PI3k/Akt and expression of IGF-1. Experiments in vivo showed that Metuzumab exhibited significant antitumor efficacy and inhibited lymph node metastasis of esophageal cancer in xenograft models. The immunochemical staining of TMA showed CD147 was high-expressed on various kinds of esophageal cancer tissues and associated with the grade of lymph node-metastasis. Conclusions: The in vitro and in vivo study demonstrated dual effects of Metuzumab in effectively mediating ADCC by activating effector cells, and inhibiting metastasis of esophageal cancer through blockade the function of CD147, providing justification for moving Metuzumab forward to clinical development in esophageal cancer.
One-Volt, Solution-Processed Organic Transistors with Self-Assembled Monolayer-Ta2O5 Gate Dielectrics

Low-voltage, solution-processed organic thin-film transistors (OTFTs) have tremendous potential to be key components in low-cost, flexible and large-area electronics. However, for these devices to operate at low voltage, robust and high capacitance gate dielectrics are urgently needed. Herein, the fabrication of OTFTs that operate at 1 V is reported. These devices comprise a solution-processed, self-assembled monolayer (SAM) modified tantalum pentoxide (Ta2O5) as the gate dielectric. The morphology and dielectric properties of the anodized Ta2O5 films with and without n-octadecyltrichlorosilane (OTS) SAM treatment have been studied. The thickness of the Ta2O5 film was optimized by varying the anodization voltage. The results show that organic TFTs gated with OTS-modified tantalum pentoxide anodized at 3 V (d ~7 nm) exhibit the best performance. The devices operate at 1 V with a saturation field-effect mobility larger than 0.2 cm2 V−1 s−1, threshold voltage −0.55 V, subthreshold swing 120 mV/dec, and current on/off ratio in excess of 5 × 103. As a result, the demonstrated OTFTs display a promising performance for applications in low-voltage, portable electronics.
Poly(trimethylene carbonate-co-L-lactide) electrospun scaffolds for use as vascular grafts

Currently, there is great clinical need for suitable synthetic grafts that can be used in vascular diseases. Synthetic grafts have been successfully used in medium and large arteries, however, their use in small diameter vessels is limited and presents a high failure rate. In this context, the aim of this study was to develop tissue engineering scaffolds, using poly(trimethylene carbonate-co-L-lactide) (PTMCLLA), for application as small diameter vascular grafts. For this, copolymers with varying trimethylene carbonate/lactide ratios – 20/80, 30/70, and 40/60 – were submitted to electrospinning and the resulting scaffolds were evaluated in terms of their physicochemical and biological properties. The scaffolds produced with PTMCLLA 20/80, 30/70, and 40/60 showed smooth fibers with an average diameter of 771±273, 606±242, and 697±232 nm, respectively. When the degradation ratio was evaluated, the three scaffold groups had a similar molecular weight (M w) on the final day of analysis. PTMCLLA 30/70 and 40/60 scaffolds exhibited greater flexibility than the PTMCLLA 20/80. However, the PTMCLLA 40/60 scaffolds showed a large wrinkling and their biological properties were not evaluated. The PTMCLLA 30/70 scaffolds supported the adhesion and growth of mesenchymal stem cells (MSCs), endothelial progenitor cells, and smooth muscle cells (SMCs). In addition, they provided a spreading of MSCs and SMCs. Given the results, the electrospun scaffolds produced with PTMCLLA 30/70 copolymer can be considered promising candidates for future applications in vascular tissue engineering.
Towards osteogenic differentiation of human dental pulp stem cells on PCL-PEG-PCL/zeolite nanofibrous scaffolds

Abstract Presently, tissue engineering has been developed as an effective option in the restoration and repair of tissue defects. One of the tissue engineering strategies is to use both biodegradable scaffolds and stimulating factors for enhancing cell responses. In this study, the effect of zeolite was assessed on cell viability, proliferation, osteo/odontogenic differentiation, and mineralization of human dental pulp stem cells (hDPSCs) cultured on poly (ε-coprolactone) – poly (ethylene glycol)-poly (ε-caprolactone) (PCL-PEG-PCL) nanofibers. For this purpose, PCL-PEG-PCL nanofibrous scaffolds incorporated with zeolite were prepared via electrospinning. Both PCL-PEG-PCL and PCL-PEG-PCL/Zeolite nanofibrous scaffolds revealed bead-less constructions with average diameters of 430 nm and 437 nm, respectively. HDPSCs were transferred to PCL-PEG-PCL nanofibrous scaffolds containing zeolite nanoparticles. Cell adhesion and proliferation of hDPSCs and their osteo/odontogenic differentiation on these scaffolds were evaluated using MTT assay, Alizarin red S staining, and qRT-PCR assay. The results revealed that PCL-PEG-PCL/Zeolite nanofibrous scaffolds could support better cell adhesion, proliferation and osteogenic differentiation of hDPSCs and as such is expected to be a promising scaffold for bone tissue engineering applications.
Structural diversity and efficacy of culturable cellulose decomposing bacteria isolated from rice–pulse resource conservation practices

The diversity of cellulolytic bacteria from the rice–pulse system can be sourced for identification of efficient cellulose decomposing microbial strains. In the present study, the abundance, structural diversity, and cellulolytic potential of the culturable bacterial community were studied in 5‐year old rice–pulse system under different resource conservation technologies. Higher cellulose (68% more) and xylanase (35% more) activities were observed under zero tilled soil. The populations of cellulolytic bacteria were significantly higher (44%) in zero tillage (ZT) treatment than those of conventional practice. Results revealed that the cellulolytic bacterial diversity was found to be significantly higher under ZT practice, but the present population may not be sufficient for effective recycling of organic wastes in this system. Out of 290 bacterial isolates, 20 isolates had significantly higher cellulolytic activities, of which the top three superior isolates were received from ZT practice. The cellulolytic bacterial diversity based on 16S rDNA sequencing data revealed that the Firmicutes was the most dominant phyla and the Bacillus spp. were the common genus, the observation also showed that there were 17 different haplotypes were recorded among 20 isolates of cellulolytic bacteria. The present findings indicated that long‐term ZT in the rice–pulse system could be a unique source for efficient cellulose decomposing bacteria and further the efficient bacterial strains isolated from this system can be used as efficient bioinoculants for in situ as well as ex‐situ decomposition of rice straw particularly in conservation agriculture.
Bone Stress Injuries Are Associated With Differences in Bone Microarchitecture in Male Professional Soldiers

Bone stress injuries are commonly due to repetitive loading, as often described in competitive athletes or military recruits. The underlying pathophysiology of bone stress injuries is multifactorial. The present cross‐sectional study investigated (i) cortical and trabecular bone microstructure as well as volumetric bone mineral density in subjects with bone stress injuries at the tibial diaphysis, measured at the distal tibia and the distal radius by means of high‐resolution peripheral quantitative computed tomography (CT), (ii) areal bone mineral density using dual‐energy X‐ray absorptiometry as well as calcaneal dual X‐ray absorptiometry and laser, and (iii) the influence on bone turnover markers of formation and resorption at the early phase after injury. A total of 26 Caucasian male professional soldiers with post‐training bone stress injury at the tibial diaphysis were included (case group). A total of 50 male, Caucasian professional soldiers from the same military institution served as controls (control group). High‐resolution peripheral quantitative CT revealed a higher total area at the radius within the case group. Cortical bone mineral density was reduced at the radius and tibia within the case group. The trabecular number and trabecular thickness were reduced at the tibia in the case group. The trabecular network was more inhomogeneous at the radius and tibia within the case group. Calcaneal dual X‐ray absorptiometry and laser was significantly reduced in the case group. This study quantified differences in bone microstructure among otherwise healthy individuals. Differences in bone microarchitecture may impair the biomechanical properties by increasing the susceptibility to sustain bone stress injuries. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2516–2523, 2019
The effects of ROCK inhibition on mesenchymal stem cell chondrogenesis are culture model dependent.

Rho-associated protein kinase (ROCK) signaling correlates with cell shape, with decreased cell spreading accompanied by decreased ROCK activity. However, how cell shape and ROCK activity impact chondrogenesis of mesenchymal stem cells (MSCs) remains inconclusive. Here we examine the effects of ROCK inhibition on human MSC chondrogenesis in four different culture models including 3D microribbon (μRB) scaffolds, 2D hydrogel substrates, 3D hydrogels, and pellet. For each culture model involving biomaterials, four polymers were compared including gelatin, chondroitin sulfate, hyaluronic acid, and polyethylene glycol. ROCK inhibition decreased MSC chondrogenesis in μRB model, enhanced chondrogenesis in pellet, and had minimal effect in 2D or 3D hydrogel models. Furthermore, we demonstrate that MSC chondrogenesis cannot be predicted using ROCK signaling alone. While varying biomaterial composition can impact the amount or phenotype of resulting cartilage, varying biomaterials did not change the chondrogenic response to ROCK inhibition within each culture model. Regardless of culture model or ROCK expression, increased cartilage formation was always accompanied by enhanced N-cadherin expression and production, suggesting N-cadherin is a robust marker to select culture conditions that promote chondrogenesis. Together, the results from this study may be used to enhance MSC-based cartilage regeneration in different culture models.
Transient enhancement of p53 activity protects from radiation-induced gastrointestinal toxicity

Significance Gastrointestinal (GI) failure is a serious dose-limiting side effect observed in patients undergoing lower-abdominal radiotherapy with no approved protective measure/cure. Here, we show that increased p53-induced p21 activity protects against radiation-induced GI toxicity in a genetically engineered mouse model. This radioprotection can be recapitulated in wild-type mice by pretreating them with RG7112, a pharmacological compound that enhances p53 activity by disrupting p53–Mdm2 interaction. These results signify that transient enhancement of wild-type p53 activity by pharmacological means could be exploited as a potential prophylactic strategy to alleviate GI toxicity issues in patients undergoing radiotherapy in the clinic. Gastrointestinal (GI) syndrome is a serious side effect and dose-limiting toxicity observed in patients undergoing lower-abdominal radiotherapy. Previous mouse studies show that p53 gene dosage determines susceptibility to GI syndrome development. However, the translational relevance of p53 activity has not been addressed. Here, we used a knock-in mouse in which the p53–Mdm2 negative feedback loop is genetically disrupted. These mice retain biallelic p53 and thus, normal basal p53 levels and activity. However, due to the lack of p53-mediated Mdm2 transcription, irradiated Mdm2P2/P2 mice exhibit enhanced acute p53 activity, which protects them from GI failure. Intestinal crypt cells residing in the +4 and higher positions exhibit decreased apoptosis, increased p21 expression, and hyperproliferation to reinstate intestinal integrity. Correspondingly, pharmacological augmentation of p53 activity in wild-type mice with an Mdm2 inhibitor protects against GI toxicity without affecting therapeutic outcome. Our results suggest that transient disruption of the p53–Mdm2 interaction to enhance p53 activity could be a viable prophylactic strategy for alleviating GI syndrome in patients undergoing radiotherapy.
Study of safety culture in healthcare institutions: case of an Algerian hospital.

PURPOSE For many years, the concept of safety culture has attracted researchers from all over the world, and more particularly in the area of healthcare services. The purpose of this paper is to measure safety culture dimensions in order to improve and promote healthcare in Algeria. DESIGN/METHODOLOGY/APPROACH The used approach consists of getting a better understanding of healthcare safety culture (HSC) by measuring the perception of healthcare professionals in order to guide promotion actions. For this, the Hospital Survey on Patient Safety Culture questionnaire was used in a pilot hospital setting where it was distributed on a number of 114 health professionals chosen by stratified random sampling. FINDINGS The results showed that the identified priority areas for HSC improvement help in establishing a trust culture and a non-punitive environment based on the system and not on the individual. ORIGINALITY/VALUE Safety is recognized as a key aspect of service quality, thus measuring the HSC can help establish an improvement plan. In Algerian health facilities, this study is considered the first to examine perceptions in this particular area. The current results provide a baseline of strengths and opportunities for healthcare safety improvement, allowing the managers of this type of facilities to take steps that are more effective.
Association between hippocampal volume change and change in memory following electroconvulsive therapy in late‐life depression

Electroconvulsive therapy (ECT)‐induced hippocampal volume change (HVC) has been repeatedly described in recent years. The similar time course of HVC and ECT‐related cognitive effects suggest a relation, that is to date, understudied. This study investigates whether HVC following ECT predicts the change in memory performance six months after the end of the ECT treatment.
Molecular Insight into the Interaction between Epigenetics and Leptin in Metabolic Disorders

Nowadays, it is well-known that the deregulation of epigenetic machinery is a common biological event leading to the development and progression of metabolic disorders. Moreover, the expression level and actions of leptin, a vast adipocytokine regulating energy metabolism, appear to be strongly associated with epigenetics. Therefore, the aim of this review was to summarize the current knowledge of the epigenetic regulation of leptin as well as the leptin-induced epigenetic modifications in metabolic disorders and associated phenomena. The collected data indicated that the deregulation of leptin expression and secretion that occurs during the course of metabolic diseases is underlain by a variation in the level of promoter methylation, the occurrence of histone modifications, along with miRNA interference. Furthermore, leptin was proven to epigenetically regulate several miRNAs and affect the activity of the histone deacetylases. These epigenetic modifications were observed in obesity, gestational diabetes, metabolic syndrome and concerned various molecular processes like glucose metabolism, insulin sensitivity, liver fibrosis, obesity-related carcinogenesis, adipogenesis or fetal/early postnatal programming. Moreover, the circulating miRNA profiles were associated with the plasma leptin level in metabolic syndrome, and miRNAs were found to be involved in hypothalamic leptin sensitivity. In summary, the evidence suggests that leptin is both a target and a mediator of epigenetic changes that develop in numerous tissues during metabolic disorders.