The synthesis of a metal–organic framework (UiO‐67) functionalised simultaneously with two different transition metal complexes (Ir and Pd or Rh) through a one‐pot procedure is reported for the first ...time. This has been achieved by an iterative modification of the synthesis parameters combined with characterisation of the resulting materials using different techniques, including X‐ray absorption spectroscopy (XAS). The method also allows the first synthesis of UiO‐67 with a very wide range of loadings (from 4 to 43 mol %) of an iridium complex (IrCp*(bpydc)(Cl)Cl2−; bpydc=2,2′‐bipyridine‐5,5′‐dicarboxylate, Cp*=pentamethylcyclopentadienyl) through a pre‐functionalisation methodology.
MOFs with dual metal complexes: An efficient and straightforward one‐pot synthesis of a metal–organic framework (UiO‐67) functionalised simultaneously with two different transition metal complexes (of Ir and Pd or Rh; see scheme) is reported. This has been achieved by optimisation of the synthesis parameters assisted by characterisation techniques. Additionally, a controlled synthesis of UiO‐67 with a wide range of loadings of an iridium complex (from 4 to 43 mol %), achieved in a pre‐functionalisation fashion, is reported.
Background and Aims
Liver cancer stem cells (CSCs) could be involved in the carcinogenesis, recurrence, metastasis and chemoresistance of hepatocellular carcinoma (HCC). The aim of this study was to ...explore the role of lncRNA‐H19 as a biomarker for liver cancer.
Methods
LncRNA‐H19 expression levels and the functional assays were conducted in EpCAM+CD133+ CSCs and C57BL/6J mice fed with a high‐fat high‐cholesterol carbohydrate (HFHCC) or standard diet for 52 weeks. Liver tissue and plasma samples from patients with cirrhosis, with or without HCC, were used for the analyses of gene expression and circulating lncRNA‐H19 levels in an estimation and validation cohort.
Results
EpCAM+CD133+ cells showed a stem cell‐like phenotype, self‐renewal capacity, upregulation of pluripotent gene expression and overexpressed lncRNA‐H19 (p < .001). Suppression of lncRNA‐H19 by antisense oligonucleotide treatment significantly reduced the self‐renewal capacity (p < .001). EpCAM, CD133 and lncRNA‐h19 expression increased accordingly with disease progression in HFHCC‐fed mice (p < .05) and also in liver tissue from HCC patients (p = .0082). Circulating lncRNA‐H19 levels were significantly increased in HCC patients in both cohorts (p = .013; p < .0001). In addition, lncRNA‐H19 levels increased accordingly with BCLC staging (p < .0001) and decreased after a partial and complete therapeutic response (p < .05). In addition, patients with cirrhosis who developed HCC during follow‐up showed higher lncRNA‐H19 levels (p = .0025).
Conclusion
LncRNA‐H19 expression was increased in CSCs, in liver tissue and plasma of patients with HCC and decreased after partial/complete therapeutic response. Those patients who developed HCC during the follow‐up showed higher levels of lncRNA‐H19. LncRNA‐H19 could constitute a new biomarker of HCC.
Noncoding RNAs (ncRNAs) control cellular programs by affecting protein-coding genes, but evidence increasingly points to their involvement in a network of ncRNA-ncRNA interactions. Here, we show that ...a long ncRNA, Uc.283+A, controls pri-miRNA processing. Regulation requires complementarity between the lower stem region of the pri-miR-195 transcript and an ultraconserved sequence in Uc.283+A, which prevents pri-miRNA cleavage by Drosha. Mutation of the site in either RNA molecule uncouples regulation in vivo and in vitro. We propose a model in which lower-stem strand invasion by Uc.283+A impairs microprocessor recognition and efficient pri-miRNA cropping. In addition to identifying a case of RNA-directed regulation of miRNA biogenesis, our study reveals regulatory networks involving different ncRNA classes of importance in cancer.
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•The lncRNA Uc.283+A negatively regulates the production of miR-195•Uc.283+A RNA binds to the lower stem region on pri-miR-195 transcript•This direct RNA:RNA interaction hinders DGCR8 binding and microprocessor activity
miRNA biogenesis is a multistep process that affects the final amount of mature, functional miRNA. Liz et al. find that a noncoding RNA transcribed from an ultraconserved region base pairs with a pri-miRNA to inhibit pri-mRNA cleavage by the microprocessor.
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Pancreatic cancer is an aggressive and devastating disease characterized by invasiveness, rapid progression and profound resistance to treatment. Despite years of intense ...investigation, the prognosis of this type of cancer is poor and there is no efficacious treatment to overcome the disease. Using human PANC-1 and MIA PaCa-2 cells, we demonstrate that the bioactive sphingolipid ceramide 1-phosphate (C1P) increases pancreatic cancer cell migration and invasion. Treatment of these cells with selective inhibitors of phosphatidylinositol 3-kinase (PI3K), Akt1, or mammalian target of rapamycin 1 (mTOR1), or with specific siRNAs to silence the genes encoding these kinases, resulted in potent inhibition of C1P-induced cell migration and invasion. Likewise, the extracellularly regulated kinases 1 and 2 (ERK1-2), and the small GTPase RhoA, which regulates cytoskeleton reorganization, were also found to be implicated in C1P-stimulated ROCK1-dependent cancer cell migration and invasion. In addition, pre-treatment of the cancer cells with pertussis toxin abrogated C1P-induced cell migration, suggesting the intervention of a Gi protein-coupled receptor in this process. Pancreatic cancer cells engineered to overexpress ceramide kinase (CerK), the enzyme responsible for C1P biosynthesis in mammalian cells, showed enhanced spontaneous cell migration that was potently blocked by treatment with the selective CerK inhibitor NVP-231, or by treatment with specific CerK siRNA. Moreover, overexpression of CerK with concomitant elevations in C1P enhanced migration of pancreatic cancer cells. Collectively, these data demonstrate that C1P is a key regulator of pancreatic cancer cell motility, and suggest that targeting CerK expression/activity and C1P may be relevant factors for controlling pancreatic cancer cell dissemination.
Cooperative learning and Project-Based Learning are methodologies that can promote learning environments and improve learning, school achievement, and social and emotional competencies.
A mixed ...combination of these two methodologies called Cooperative Project-Based Learning was designed, and a quasi-experimental evaluation study with a pre-test and a post-test was conducted with a sample of 156 students from Primary Education. Literacy competence and social and emotional competencies, including empathy, were analyzed and compared between experimental and control groups.
The intervention effectively increased scores on literacy competence, social and emotional competencies, and empathy in the experimental group, significantly more than in the control group. The girls in the experimental group exhibited greater improvement than the controls in literacy competence, social and emotional competencies and empathy. However, the boys in the experimental group were only different from the boys in the control group in literacy competence, but not in the other two variables.
These results have implications for school practice and curriculum planning in Primary Education. New lines of future research are also being opened based on the impact of Cooperative Project-Based Learning on other key competencies and on the prevention of antisocial behaviors.
With the rapid proliferation of Internet of things (IoT) devices across various sectors, ensuring robust cybersecurity practices has become paramount. The complexity and diversity of IoT ecosystems ...pose unique security challenges that traditional educational approaches often fail to address comprehensively. Current curricula may provide theoretical knowledge but typically lack the practical components necessary for students to engage with real-world cybersecurity scenarios. This gap hinders the development of proficient cybersecurity professionals capable of securing complex IoT infrastructures. To bridge this educational divide, a remote online laboratory was developed, allowing students to gain hands-on experience in identifying and mitigating cybersecurity threats in an IoT context. This virtual environment simulates real IoT ecosystems, enabling students to interact with actual devices and protocols while practicing various security techniques. The laboratory is designed to be accessible, scalable, and versatile, offering a range of modules from basic protocol analysis to advanced threat management. The implementation of this remote laboratory demonstrated significant benefits, equipping students with the necessary skills to confront and resolve IoT security issues effectively. Our results show an improvement in practical cybersecurity abilities among students, highlighting the laboratory’s efficacy in enhancing IoT security education.
Abstract
Aim
This study aimed to assess technical aspects and clinical results of a new minimally invasive technique in parastomal hernia (PSH) repair, full endoscopic retromuscular access, after 2 ...years of follow‐up.
Methods
Data from consecutive patients requiring minimally invasive ventral PSH repair were collected from 2019 to 2022. The inclusion criteria were patients aged between 18 and 80 years old with symptomatic PSH. Demographics and perioperative and postoperative data were collected. Postoperative pain and functional recovery were compared with preoperative data.
Results
Twelve patients with symptomatic PSH were included. The mean PSH defect area was 16.2 cm
2
and the mean midline defect was 8.7 cm
2
. No intra‐operative complications or conversion to open surgery were detected. One patient (8%) required postoperative readmission due to partial bowel obstruction symptoms that required catheterization of the stoma. Pain significantly worsened after the first postoperative day compared to preoperative data but improved after the first postoperative month compared to the first postoperative week and after the 90th postoperative day compared to the first postoperative month, with significant differences. Significant restriction improvement was identified when 30 days after surgery data were compared to preoperative data and when the 180th postoperative day results were compared to 30 days after surgery. The average follow‐up was 29 months. During the follow‐up no clinical or radiological recurrence was observed.
Conclusion
This paper shows low rate of intra‐ and postoperative complications with significant improvement in terms of pain activities restriction compared to preoperatory. After 29 months follow‐up, no recurrence was identified, confirming that this approach offers good mid‐term results.
This paper presents a wireless fault detection system for industrial motors that combines vibration, motor current and temperature analysis, thus improving the detection of mechanical faults. The ...design also considers the time of detection and further possible actions, which are also important for the early detection of possible malfunctions, and thus for avoiding irreversible damage to the motor. The remote motor condition monitoring is implemented through a wireless sensor network (WSN) based on the IEEE 802.15.4 standard. The deployed network uses the beacon-enabled mode to synchronize several sensor nodes with the coordinator node, and the guaranteed time slot mechanism provides data monitoring with a predetermined latency. A graphic user interface offers remote access to motor conditions and real-time monitoring of several parameters. The developed wireless sensor node exhibits very low power consumption since it has been optimized both in terms of hardware and software. The result is a low cost, highly reliable and compact design, achieving a high degree of autonomy of more than two years with just one 3.3 V/2600 mAh battery. Laboratory and field tests confirm the feasibility of the wireless system.
Abstract Background Oral anticoagulation reduces the risk of mortality in atrial fibrillation (AF), but examination of the causes of death is essential to design new strategies to further reduce the ...high mortality rates observed in this population. Objectives The authors sought to analyze and compare causes of death in patients receiving direct oral anticoagulants (DOAC) or warfarin for prevention of stroke and systemic embolism (SE) in AF. Methods The authors systematically searched for randomized trials of DOAC versus warfarin for prevention of stroke/SE in AF. The main outcome was mortality and independently adjudicated specific causes of death. The authors used the random effects model of meta-analysis to combine the studies. Results 71,683 patients from 4 trials were included (134,046 patient-years of follow-up). A total of 6,206 patients (9%) died during follow-up. Adjusted mortality rate was 4.72%/year (95% confidence interval CI: 4.19 to 5.28). Cardiac deaths accounted for 46% of all deaths, whereas nonhemorrhagic stroke/SE and hemorrhage-related deaths represented 5.7% and 5.6% of the total mortality, respectively. Compared with patients who were alive, those who died had more frequent history of heart failure (odds ratio OR: 1.75; 95% CI: 1.25 to 2.44), permanent/persistent AF (OR: 1.38; 95% CI: 1.25 to 1.52) and diabetes (OR: 1.37; 95% CI: 1.11 to 1.68); were more frequently male (OR: 1.24; 95% CI: 1.13 to 1.37) and older (mean difference 3.2 years; 95% CI: 1.6 to 4.8); and had a lower creatinine clearance (−9.9 ml/min; 95% CI: −11.3 to −8.4). There was a small, but significant, reduction in all-cause mortality with the DOAC versus warfarin (difference −0.42%/year; 95% CI: −0.66 to −0.18), mainly driven by a reduction in fatal bleedings. Conclusions In contemporary AF trials, most deaths were cardiac-related, whereas stroke and bleeding represented only a small subset of deaths. Interventions beyond anticoagulation are needed to further reduce mortality in AF.
Quercetin is a natural flavonoid, which has been shown to have anti hepatitis C virus (HCV) properties. However, the exact mechanisms whereby quercetin impacts the HCV life cycle are not fully ...understood. We assessed the effect of quercetin on different steps of the HCV life cycle in Huh-7.5 cells and primary human hepatocytes (PHH) infected with HCVcc. In both cell types, quercetin significantly decreased i) the viral genome replication; ii) the production of infectious HCV particles and iii) the specific infectivity of the newly produced viral particles (by 85% and 92%, Huh7.5 and PHH respectively). In addition, when applied directly on HCV particles, quercetin reduced their infectivity by 65%, suggesting that it affects the virion integrity. Interestingly, the HCV-induced up-regulation of diacylglycerol acyltransferase (DGAT) and the typical localization of the HCV core protein to the surface of lipid droplets, known to be mediated by DGAT, were both prevented by quercetin. In conclusion, quercetin appears to have direct and host-mediated antiviral effects against HCV.
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