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Background: Colorectal cancer (CRC) is one of the major causes of cancer-related death worldwide. Aerobic glycolysis precedes obtainment of oncogenic mutations and loss of tumor suppressors, promoting the progress of CRC. Although numerous biomarkers have been identified to be associated with prognosis and survival, a glycolysis-related gene signature in CRC has not been explored. Methods: mRNA expression profiling data in a group of CRC patients (n = 540) was extracted from the Cancer Genome Atlas (TCGA). Gene set enrichment analysis (GESA) was performed to identify gene sets that were significantly different between CRC tissues and normal tissues. Cox proportional hazards regression models were used to identify genes significantly associated with overall survival. Multivariate Cox regression analysis was used to establish a prognostic risk parameter formula. Kaplan–Meier survival estimates and the log-rank test were used to validate the significance of risk parameters for prognosis prediction. Results: Five glycolysis-related genes (ENO3, GPC1, P4HA1, IDUA, ANKZF1) were identified to be significantly associated with overall survival (AUC=0.754). Based on the five‑gene signature, patients with CRC were divided into high and low‑risk subgroups. CRC patients with a low-risk score had better survival benefits than those with a high one (P < 0.001). Conclusions: A five-gene signature associated with glycolysis for predicting the outcome of CRC patients was generated, serving as a valuable prognosis model with high efficiency and potential targeted therapy of CRC patients.
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Tumeurs colorectales , TumeursRésumé
The uterine leiomyoma is the most common benign tumor in women of childbearing age. It may lead to problem of conception or complications during gestational period. The methods of treatment can be surgical (myomectomy and hysterectomy, embolization of arteries) and therapeutic treatment (Ulipristal acetate, Leuprolide acetate, Cetrorelix, Goserelin, Mifeprestone). Both approaches are efficient, but are incompatible with pregnancy planning. Therefore, there is a call for medical practice in developing therapeutical means of preventing leiomyoma onset in patients planning on pregnant. Based on the analysis of GWAS data on the search for mononucleotide polymorphisms associated with the risk of leiomyoma, meta-transcriptomic and meta-methylomic studies, target proteins have been proposed. Prospective therapeuticals of leiomyoma may be based on chemical compounds, humanized recombinant antibodies, vaccines based on markers of the uterine leiomyoma cells that are absent in the adult organism, DNA and RNA preparations. Three different nosological forms of the disease associated with driver mutations in the MED12, HMGA2 and FH genes should be considered when developing or prescribing drugs. E.g. synthetic inhibitors and vaccines based on matrix metalloproteinases MMP11 and MMP16 are expected to be effective only for the prevention of the occurrence of MED12-dependent nodules.
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Léiomyome , TumeursRésumé
The aim of this study was to investigate the parameters affecting the extraction of positive molecules such as chlorogenic acids and antioxidants, as well as potentially carcinogenic substances such as acrylamide, in different coffee brewing methods. Three coffee varieties, each assigned to different roasting degree, were used to prepare coffee brews following eight diverse preparation methods. Acrylamide was quantified by HPLC-MS/MS instrument while chlorogenic acids and caffeine by HPLC-DAD system. Three spectrophotometric analyses were also performed (DPPH, TFC and TPC) to evaluate antioxidant activity as well. The results showed that the main brewing parameters, that have the greatest influence on the final content of these compounds were the volume of water used, more specifically the brewing ratio (coffee to water ratio), the extraction time and the particle size of the coffee powder.
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This review article explores the convergence of virtual reality (VR) and architectural design from an inclusive lens. It underscores the crucial role of virtual reality (VR) in serving as a catalyst for the incorporation of social and cultural sustainability principles in architectural projects. The exploration is guided by inclusive design principles, which encompass several aspects such as accessibility, cultural sensitivity, diversity and inclusivity, user-centered design, and empathy. These concepts serve as the basis for further investigation into the potential of virtual reality (VR) technology to enhance and heighten these features within architectural design, therefore promoting the progress of social and cultural sustainability. The review article highlights the profound impact that virtual reality (VR) may have, going beyond mere visualisation to generate architectural experiences that are immersive, interactive, and empathetic. These experiences are designed to take into account diverse perspectives and needs.
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Inspired by the process of bone formation in living organisms, many studies have been conducted to develop organic-inorganic composite materials by generating calcium phosphate crystals within solutions or dispersions of polymers with appropriate functional groups. Bones are composite materials consisting of organic polymers (mainly Type I collagen), carbonated apatite, and water, with volume fractions 35-45%, 35-45%, 15-25%, respectively. Carbonated apatite in bone contributes to rigidity, while organic polymers and water contribute to toughness. The inorganic crystal, carbonated apatite, is a plate-shaped crystal with dimensions of 50 nm × 25 nm × 1-4 nm, generating a significant organic-inorganic interface due to its nanoscale size. This interface is believed to absorb externally applied forces to dissipate mechanical energy to thermal energy. Creating such nanometer-scale structures using top-down approaches is challenging, making bottom-up methods like co-precipitation of polymer and inorganic crystals more suitable. In this account, efforts to develop eco-friendly mechanical materials using biomass such as cellulose and starch based on the bottom-up approach to bone-like composites are described.
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Raideur musculaireRésumé
In this work, Al-Mo-B(CN) thin coatings were deposited by magnetron sputtering using composite metal-ceramic Al-Mo-B4C target. A metal-ceramic composite target for magnetron sputtering was fabricated by a robotic complex for detonation spraying of coatings equipped with a multi-chamber detonation accelerator. The powder composition (30Mo-30Al-40B4C) was sprayed onto the copper plate base of the composite target-cathode. The obtained cathode target with Al-Mo-B4C coating (thickness 280-300 μm) was used to deposit the Al-Mo-B(CN) coating (DC mode) on flat specimens of AISI 316 steels and silicon using equipment for magnetron sputtering UNICOAT 200. The Al-Mo-B4C coating has a lamella-type structure with inclusions of boron car-bide particles the elemental composition is evenly distributed in the material. The structure and morphology of coatings were studied using methods of optical, scanning electron microscopy (SEM), atomic force microscopy (AFM), X-ray analysis (XRD), and X-ray photoelectron spectros-copy (XPS). Mechanical and tribological properties of the Al-Mo-B(CN) thin coatings were determined using methods of nanoindentation, scratch testing, and tribological testing under fluid-free friction regime at room temperature. The Al-Mo-B(CN) coating (thickness ~ 1 μm) exhibited a dense uniform fine-grained structure with no columnar elements and were well-adherent to the substrates after deposition. Al-Mo-B(CN) coating has a amorphous structure. XPS analysis confirmed the formation of the MoB2 and AlN phase with an admixture of oxygen in the form of aluminum oxide, molybdenum oxide and boron oxide. Al-Mo-B(CN) coating possess hardness of 13 GPa, elasticity modulus of 114 GPa, elastic recovery of 45%, and friction coefficient of 0.8 against steel 100 Cr6 ball. The failure mode occurring in the tested coatings was fatigue and abrasive. The adhesion strength of Al-Mo-B(CN) coating amounted to about 11 N, and the failure mode was cohesive associated with plastic deformation and formation of fatigue cracks in the coating material.
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Maladies ostéomusculaires , Syndrome pulmonaire à hantavirus , FatigueRésumé
Due to the imbalance between the supply and demand of oxygen, the oxygen system of iron- and steel-making enterprises in China has problems with high oxygen emission and high pressure in the pipelines, resulting in the energy consumption of oxygen production being high. To relieve this problem, using a large-scale iron- and steel-making mill as a case study, the research on demand forecasting and optimal scheduling of the oxygen system was carried out. The ARIMA model and the GABP model are employed to forecast oxygen demand. Based on the forecast results, an optimal scheduling model for the oxygen system was developed to conduct optimal scheduling. The case study shows that based on the oxygen demand forecast and the optimal scheduling, the oxygen emission and the pipeline pressure in the studied iron- and steel-making enterprise can be significantly reduced, thereby achieving considerable energy-saving effects and economic benefits. Specifically, the following conclusions are obtained: (1) For the oxygen demand forecast, the prediction accuracy of the GABP model is better than that of the ARIMA model. The average MAPE of the 12 sets of data of the ARIMA and GABP models are 23.8% and 20.2%, respectively. (2) By comparing the scheduling results and the field data, it is found that after the scheduling, the amount of oxygen emission has decreased by 6.32%, the pipeline pressure has decreased by 0.61%, and the energy consumption of oxygen compression has decreased by 1.6%. Considering both the oxygen emission loss and the energy consumption of oxygen compression, the total power consumption of the oxygen system is reduced by 1.38%, which saves the electricity cost of about 9.03 million RMB per year.
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Aims: To date, precision medicine plays a pivotal role in the clinical administration of solid tumor patients. In this scenario, a rapidly increasing number of predictive biomarkers have been approved in diagnostic practice or are currently investigated in clinical trials. A pitfall in the molecular tests is the diagnostic routine sample available to analyze predictive biomarkers; scant tissue sample often represents the only diagnostical source of nucleic acids to assess molecular analysis. At the sight of these critical issues, Next Generation Sequencing (NGS) platforms emerged as referral testing strategy for molecular analysis of predictive biomarkers in routine practice but high-skilled personnel, extensive working-time drastically impact on the widespread diffusion of this technology in diagnostic setting. Here, we technically validate a fully integrated NGS platform on diagnostic routine tissue samples previously tested with NGS based diagnostic workflow by a referral institution. Methods: A retrospective series of n=64 samples (n=32 DNA, n=32 RNA samples), previously tested using a customized NGS assay (SiRe™ and SiRe fusion) were retrieved from internal archive of University of Naples Federico II. Each sample was tested by adopting Oncomine Precision Assay (OPA), able to detect 2769 molecular actionable alterations [hot spot mutations, copy number variations (CNV) and gene fusions on fully integrated NGS platform (Genexus, Thermofisher Scientifics. (26,27) Concordance rate between these technical approaches was carried out. Results: Genexus system successfully carried out molecular analysis in all instances. A concordance rate of 96.9% (31 out of 32) was observed between OPA and SiRe™ panel both for DNA and RNA based analysis. A negative predictive value of 100% and a positive predictive value of 96.9% (62 out of 64) was assessed. Conclusions: Fully automatized Genexus system combined with OPA (Thermofisher Scientifics) may be considered a technically valuable, saving time sequencing platform to test predictive biomarkers in diagnostic routine practice.
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TumeursRésumé
Introduction: Bystander CPR rates have increase from 15% to 30% in many countries over the last 20 years. However, these gains are at risk of being lost in the face of fear of transmission of the SARS-COV-2 virus given the global COVID-19 pandemic. This survey study was designed to examine the opinions and perceptions of the Canadian public on bystanderism as it relates to out-of-hospital cardiac arrest during the COVID-19 pandemic with a view to understanding the implications of those opinions on our expectations of bystanders during, and after the pandemic. Methods: In order to capture a pan-Canadian sample of the general public, we engaged with a well-established public opinion polling vendor, IPSOS (www.ipsos.com), to conduct a robust survey on public willingness to do bystander CPR in the context of the global COVID-19 pandemic. Results: A total of n=1,000 surveys were completed by Canadian adults using the IPSOS eNation Canadian Online Omnibus survey platform.In summary there were five key findings from this pan-Canadian survey: 1) the ability to recognize cardiac arrest remains a point of confusion for the lay public, 2) at the time of the survey only about half of respondents said they would respond to someone having cardiac arrest, 3) the majority of respondents said the pandemic has changed their willingness to respond to someone in cardiac arrest, 4) willingness to use an AED is low and the greatest barrier was reported as lack of experience, and lastly 5) most Canadians say it is important to be certified in CPR and are willing to take a CPR training course, however only half are willing to pay for it. Conclusion: Bystander CPR is an out-of-hospital cardiac arrest victim’s best chance of survival and so our understanding of how we encourage more citizens to respond given the current realities is more crucial than ever. Wider dissemination of the growing evidence on the safety of CPR in the context of COVID-19 and resuscitation training courses implemented with specific CPR maneuvers to reduce the risk of infection should be implemented to continued uncertainty and erosion in bystander CPR culture.
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COVID-19 , Arrêt cardiaque , Confusion , Maladie de ParkinsonRésumé
Objective The aim of this study was to explore the prognosis and influencing factors of recurrent ependymoma in children. Methods PubMed, Embase, Cochrane Library, and Web of Science were searched to collect studies on survival outcomes and influencing factors of recurrent ependymoma in children. The search time frame was from the establishment of the database to September 2023. Two evaluators independently screened the literature, extracted data, and evaluated the quality of the included studies. Meta-analysis was performed using RevMan 5.4 software. Results A total of 11 studies involving 1120 patients were included. The integrated results of mOS from the 11 studies showed significant heterogeneity (I2 = 92%). Therefore, a random-effects model was used for merging, and the results showed statistically significant differences (P < 0.00001). In all the studies, the pooled estimate of median OS from the time of recurrence was 15.54 months (95% CI 8.80-27.45; P < 0.00001), and the combined median progression-free survival (PFS) from the time of first recurrence was 6.7 months (95% CI 5.59-7.64; P < 0.0001). The median OS for patients who underwent surgery at the time of recurrence was 20.7 months (95% CI 12.40–34.72; P < 0.00001), while the mOS for patients who received radiation therapy was 29.5 months (95% CI 18.97–46.00; P < 0.0001), and for patients who received chemotherapy mOS was 18.0 months (95% CI 8.62–37.75; P < 0.00001). The mOS for patients under 3 years old at the time of recurrence was 20.1 months (95% CI 1.98-204.50; P < 0.00001), while for patients over 3 years old at the time of recurrence mOS was 16.6 months (95% CI 9.40-29.35; P < 0.00001). Conclusion The results of the study show poor prognosis for children with recurrent ependymoma, and there are significant differences in these results. The influencing factors include patient age, tumor recurrence location, and treatment methods. These findings can further guide clinical research on new treatment methods and strategies to improve the prognosis of this population.
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Épendymome , TumeursRésumé
In this paper, an adaptive technology and the interconnection and damping assignment passivity-based control method are combined to solve the stabilization problem for underactuated mechanical systems with uncertainties (including matched and unmatched). Uncertainties include unknown friction coefficients and unknown terms in kinetic energy and potential energy. A novel adaptive interconnection and damping assignment passivity-based control scheme is proposed and an adaptive stabilization controller is designed to make the closed-loop system locally stable. Verification is conducted on the ball and beam system, taking into account uncertainties of friction coefficients, kinetic energy, and potential energy. The locally asymptotic stability is demonstrated using the LaSalle’s invariance principle and approximate linearization. The effectiveness of the proposed control law is verified through numerical simulations.
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The paper proposes an innovative solution for managing and ensuring high energy efficiency of power supply systems at high non-linear loads. This is realized by maintaining optimal value of reliability indicators and high quality of power supply. The validation is carried out using analyzes and tests of quality of electromagnetic compatibility (EMC) for increased number of powered frequency converters. It has been proven that the effective use and reduction of energy consumption can be achieved thanks to the unique technological features of the employed electrical devices. This enables a normal operation of the system with decreased power and adequate control of energy processes. The problem of predicting power losses under changing conditions in a decentralized electrical network has been solved based on the theory of electromagnetic compatibility. The influence of the mains mode parameters and the indices of instantaneous distortion of current and voltage waveforms caused by the operation of converters on the resonance phenomena in power supply systems were investigated. Recommendations were developed for the selection of proper parameters of compensators for 6-10 kV and 0.4-0.66 kV circuits based on the analysis of the optimization problem when minimizing active power losses. Results of our findings may aid parties involved in designing and maintaining power networks in various applications, such as mines, etc.
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Treatment regimens are regularly evolving, together with novel therapies and drugs. Such evolution is necessary to circumvent resistance mechanisms and to give patients the best possible health care. When dealing with cancer, most regimens involve multiple treatments (surgery, radiation therapy, chemotherapy, immunotherapy, etc.). The purpose of this study was to associate in a single compound metal-based drugs and photosensitizers to combine chemotherapy and photodynamic therapy. Two arene-ruthenium tetrapyridylporphyrin compounds (2H-TPyP-arene-Ru and Zn-TPyP-arene-Ru) have been synthesized and evaluated on two colorectal cancer cell lines (HCT116 and HT-29). The cytotoxicity and phototoxicity have been evaluated. In addition, the anticancer mechanism and the cell death process mediated by the two compounds were studied. The results showed that the two arene-ruthenium photosensitizer-containing complexes have a strong phototoxic effect after photoactivation. The 2H-TPyP-arene-Ru induced outstanding cytotoxicity when compared to the Zn-TPyP-arene-Ru analogue. Moreover, under light, these two arene-ruthenium photosensitizers induce an apoptotic process in human colorectal cancer cell lines.
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Effets secondaires indésirables des médicaments , Dermatite phototoxique , Tumeurs colorectales , TumeursRésumé
Neutrophils are the principal trouper of innate immune system. Activated neutrophils undergo a noble cell death termed NETosis and release a mesh-like structure called neutrophil extracellular traps (NETs) as a part of their defensive strategy against microbial pathogen attack. This web-like architecture includes a DNA backbone embedded with antimicrobial proteins like myeloperoxidase (MPO), neutrophil elastase (NE), histones etc. and deploys in the entrapment and clearance of encountered pathogens. Thus NETs play an inevitable beneficial role in the host's protection. However, recent accumulated evidence shows that dysregulated and enhanced NET formation has various pathological aspects including promotion of sepsis, pulmonary, cardiovascular, hepatic, nephrological, thrombotic, autoimmune, pregnancy, cancer diseases etc. and the list is increasing gradually. In this review, we summarize NETs mediated pathophysiology of different diseases, focus on some updated potential therapeutic approaches against NETs and share our future perspectives.
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Sepsie , Thrombose , Troubles chronobiologiques , TumeursRésumé
Vitamin C is an essential enzyme cofactor and antioxidant with pleiotropic roles in human physiology. Circulating vitamin C concentrations are lower in people with diabetes mellitus suggesting a higher dietary requirement for the vitamin. We interrogated the NHANES 2017/2018 and EPIC-Norfolk datasets to compare vitamin C requirements between those with and without diabetes mellitus using dose-concentration relationships fitted with sigmoidal (four parameter logistic) curves. The NHANES cohort (n=2828 non-supplementing adults) comprised 488 (17%) participants with diabetes (self-reported or HbA1c ≥6.5%). The participants with diabetes had a lower vitamin C status (median [IQR]) than those without (38 [17, 52] µmol/L vs 44 [25, 61] µmol/L, p<0.0001), despite comparable dietary intakes between the two groups (51 [26, 93] mg/d vs 53 [24, 104] mg/d, p=0.5). Dose-concentration relationships indicated that the group without diabetes reached adequate vitamin C concentrations (50 µmol/L) with an intake of 81 (72, 93) mg/d, whilst the those with diabetes required an intake of 166 (126, NA) mg/d. In the EPIC-Norfolk cohort, comprising 20692 non-supplementing adults, 475 (2.3%) had self-reported diabetes at baseline. The EPIC cohort had lower a BMI than the NHANES cohort (26 [24, 28] kg/m2 vs 29 [25, 34] kg/m2, respectively). Correspondingly, the EPIC participants without diabetes required a lower vitamin C intake of 64 (63, 65) mg/d while those with diabetes required 129 (104, NA) mg/d to reach adequate circulating vitamin C status. C-reactive protein concentrations were strongly correlated with body weight and BMI and provided a surrogate biomarker for vitamin C requirements. In conclusion, people with diabetes have 1.4- to 1.6-fold higher requirements for vitamin C than those without diabetes. This corresponds to additional daily vitamin C intake requirements of ~30-40 mg for people with diabetes.
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DiabèteRésumé
Germanium films were grown on c-plane sapphire with a 10 nm AlAs buffer layer using molecular beam epitaxy. The effects of Ge film thickness on the surface morphology and crystal structure were investigated by ex-situ characterization techniques. The nucleation of Ge proceeds by forming (111) oriented three-dimensional islands with two rotational twin domains about the growth axis. The boundaries between the twin grains are the origin of 0.2% strain and tilt grains. The transition to a single-grain orientation reduces the strain and results in a better-quality Ge buffer. Understanding the role of thickness on material quality during the Ge(111)/Al2O3(0001) epitaxy is vital for achieving device quality when using group IV material on the sapphire platform.
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Inbreeding depression is expected to be more pronounced in fitness-related traits, such as pig litter size. Recent studies have suggested that the genetic determinism of inbreeding depression may be heterogeneous across the genome. Therefore, the objective of this study is to conduct a genomic scan across the pig autosomal genome to detect the genomic regions that control inbreeding depression for litter size in two varieties of Iberian pigs (Entrepelado and Retinto). The datasets consist of 2,069 (338 sows) and 2,028 (327 sows) records for litter size (Total Number Born and Number Born Alive) for the Entrepelado and Retinto varieties. All sows were genotyped using the Geneseek GGP PorcineHD 70 K. We employed the Unfavorable Haplotype Finder software to extract runs of homozygosity (ROHs) and conducted a mixed model analysis to identify highly significant differences between homozygous and heterozygous sows for each specific ROH. A total of 8 genomic regions located on SSC2, SSC5, SSC7, SSC8, and SSC13, were significantly associated with inbreeding depression, housing some relevant genes such as FSHR, LHCGR, CORIN, AQP6, and CEP120.
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Trouble dépressifRésumé
The flow field around a delta wing is substantially altered by the impact of the active flow control technique. The present study involves the sharp-edged delta wing of 65 deg sweep angle with different active flow control configurations. The blowing was employed as an active flow control method on the airfoil surface. The various configurations considered are the baseline delta wing, delta wing with blowing holes located at 1.62%, 3.24% and 4.86% of root chord from the leading edge to the centre of the blowing holes. The computation is performed using the commercial software ANSYS Fluent. Unsteady, incompressible Reynolds-averaged Navier-Stokes equation and the shear-stress transport k-ω turbulence model are employed. The angles of attack varied in the range of 0 deg. < α < 35 deg. and Reynolds number is 2.64 x10^6 and the jet momentum coefficient is fixed at 0.05. The blowing of air from the injection region enhances the strength of the leading-edge vortices resulting in the delay of the vortex breakdown. The performance of the delta wing is greatly improved while using the blowing method specifically for the blowing holes located at 3.24% of root chord from the leading edge as compared to without the blowing method.
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Ambitious biodiversity goals to protect 30% or more of the Earth’s surface by 2030 to prevent the most likely and imminent extinctions require strategic near-term targets. We propose Conservation Imperatives, spanning 164 Mha across 16,825 unprotected sites harboring rare and threatened species. These sites should be prioritized for conservation action over the next three to five years as part of a broader strategy to expand the global protected area network. The expansion of global protected areas between 2018–2023 incorporated only 7% of sites harboring range-limited and threatened species, highlighting a renewed urgency to conserve these habitats. Permanently protecting only 0.74% of land found in the tropics, where Conservation Imperatives sites are concentrated, at a cost of US$34 to $56 billion per year over the next 3-5 years, could prevent the majority of predicted near-term extinctions once adequately resourced. Multiple approaches could achieve this goal: providing rights and title to Indigenous Peoples and Local Communities (IPLCs) conserving traditional lands, government designation of new protected areas on federal and state lands; or land purchase and long-term leasing of privately held lands.
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Sustainable energy development (SED) is a crucial component of the Sustainable Development Goals (SDG), aiming to maintain economic and social progress while protecting the environment and mitigating climate change's effects. SED serves as a transition paradigm for sustainable development, providing a blueprint for energy peace and prosperity for people and all uses. This article identifies 10 interlinked themes of SED and explores 2 of them, which are the least studied in existing SED reviews. These two themes include energy financing and the need for 100% renewable energy (RE), a part of the decarbonization strategy towards the 1.5 – 2.0° C Scenario. The study suggests that the current G20 countries' contributions, if done continuously per annum, in addition to 80% more funding from private investment of the same amount in the 1.5°C scenario financial requirement for clean energy, is sufficient to limit global warming. In addition to the present drive for 100% RE, the article also emphasizes addressing other issues, such as energy storage options, developing countries' development agenda, and regional security stability to prevent energy wars. Emerging SED decarbonization strategies are presented across power, transport, building, and industrial sectors. The study concludes with progress and directions for future research, mainly the need for re-defining National Determined Contribution (NDC) through a centralized global or regional stock-taking strategy for greenhouse gas emissions reduction.