Proteomic Analysis Reveals Trilaciclib-Induced Senescence

\ua9 2024 THE AUTHORS. Published by Elsevier Inc on behalf of American Society for Biochemistry and Molecular Biology.Trilaciclib, a cyclin-dependent kinase 4/6 inhibitor, was approved as a myeloprotective agent for protecting bone marrow from chemotherapy-induced damage in extensive-stage small cell lung cancer. This is achieved through the induction of a temporary halt in the cell cycle of bone marrow cells. While it has been studied in various cancer types, its potential in hematological cancers remains unexplored. This research aimed to investigate the efficacy of trilaciclib in hematological cancers. Utilizing mass spectrometry-based proteomics, we examined the alterations induced by trilaciclib in the chronic myeloid leukemia cell line, K562. Interestingly, trilaciclib promoted senescence in these cells rather than cell death, as observed in acute myeloid leukemia, acute lymphoblastic leukemia, and myeloma cells. In K562 cells, trilaciclib hindered cell cycle progression and proliferation by stabilizing cyclin-dependent kinase 4/6 and downregulating cell cycle–related proteins, along with the concomitant activation of autophagy pathways. Additionally, trilaciclib-induced senescence was also observed in the nonsmall cell lung carcinoma cell line, A549. These findings highlight trilaciclib\u27s potential as a therapeutic option for hematological cancers and underscore the need to carefully balance senescence induction and autophagy modulation in chronic myeloid leukemia treatment, as well as in nonsmall cell lung carcinoma cell line

Steel waste valorisation Steel Slag Waste Effect on Concrete Shrinkage

The concept of sustainability is becoming widespread every day in society, enterprises and institutions. Defining something as sustainable means that the relationship that it establishes with the environment does not represent an aggression or a threat to the latter neither when it is being utilized nor when it stops performing the function for which was designed. To make this happen we need a system in which the main priority is recycling. Everything mentioned above is related to what is called the “Circular Economy”. Concrete is one of the most widely used construction materials in the world. However, the production of portland cement, an essential constituent of concrete, leads to the release of significant amounts of CO22. The global production of concrete represents more than 5% of the anthropogenic emissions of carbon dioxide every year, mainly from the production of cement. The replacement of cement by fly ash and other industrial waste, such as steel slags, is a good example of how resource conservation can be improved and contamination can be reduced. On the other hand, future trends are predicted to increase demand for steel worldwide. Mainly due to the expected improvement in the living standards and demands of underdeveloped populations. The steelmaking process produces a by-product called slag ranging from 10 to 15% per tonne of steel, where reuse is still reduced and much of it is deposited in a landfill. This study presents laboratory test results on the total and autogenous shrinkage of medium strength concrete with partial replacement of cement by slags. Two different slags were tested, namely ladle furnaces slags (LFS) and ground granulated blast furnace slags (GGBFS). The results show the concrete shrinkage behavior when 25% of substitution are used. These data are important to predict future behavior and show that for the substitution dosages used there are no significant divergences for the shrinkage.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Wave attenuation model for dephasing and measurement of conditional times

Inelastic scattering induces dephasing in mesoscopic systems. An analysis of previous models to simulate inelastic scattering in such systems is presented and also a relatively new model based on wave attenuation is introduced. The problem of Aharonov-Bohm(AB) oscillations in conductance of a mesoscopic ring is studied. We have shown that conductance is symmetric under flux reversal and visibility of AB oscillations decay to zero as function of the incoherence parameter, signalling dephasing. Further wave attenuation is applied to a fundamental problem in quantum mechanics, i.e., the conditional(reflection/transmission) times spent in a given region of space by a quantum particle before scattering off from that region.Comment: 8 pages, 6 figures. Based on presentations by A. M. J and C. B at the 2nd Winter Institute on Foundations of Quantum theory, Quantum Optics and QIP held at S N Bose National Centre for Basic Sciences, Kolkata, India, from January 2-11, 200

Psychosocial developmental milestones in men with classic galactosemia

Patients with classic galactosemia suffer from several long term effects of their disease. Research in a group of mainly female patients has shown that these patients may also have a developmental delay with regard to their social aptitude. To study if male galactosemia patients achieve psychosocial developmental milestones more slowly than male peers from the general Dutch population, we assessed their development with the Course of Life Questionnaire (CoLQ). A total of 18 male galactosemia patients participated in this study (response rate 69%): 11 Dutch patients and seven American patients. We found severe delays in the social and psychosexual scales of this questionnaire, but not on the autonomy axis. These results are comparable to an earlier study with a limited number of male patients. The observed delays could be secondary to less developed social skills, cognitive dysfunction, or disrupted language development. We strongly recommend screening of galactosemia patients for developmental delays, to ensure early intervention through social skills training

The Evershed Flow and the Brightness of the Penumbra

The Evershed flow is a systematic motion of gas that occurs in the penumbra of all sunspots. Discovered in 1909, it still lacks a satisfactory explanation. We know that the flow is magnetized, often supersonic, and that it shows conspicuous fine structure on spatial scales of 0.2"-0.3", but its origin remains unclear. The hope is that a good observational understanding of the relation between the flow and the penumbral magnetic field will help us determine its nature. Here I review advances in the characterization of the Evershed flow and sunspot magnetic fields from high-resolution spectroscopic and spectropolarimetric measurements. Using this information as input for 2D heat transfer simulations, it has been demonstrated that hot Evershed upflows along nearly horizontal field lines are capable of explaining one of the most intriguing aspects of sunspots: the surplus brightness of the penumbra relative to the umbra. They also explain the existence of penumbral filaments with dark cores. These results support the idea that the Evershed flow is largely responsible for the transport of energy in the penumbra.Comment: 18 pages, to appear in "Magnetic Coupling between the Interior and the Atmosphere of the Sun", eds. S.S. Hasan and R.J. Rutten, Astrophysics and Space Science Proceedings, Springer, Heidelberg, 200

Oral direct anticoagulants in the treatment of nonvalvular atrial fibrillation. Results of the daily clinical practice.

Atrial fibrillation (AF) is the most common arrhythmia. It leads to significant morbidity and mortality. The new oral anticoagulants (NOAC) represent an improvement compared with standard treatment (vitamin K antagonists (AVK)) in the prevention of thromboembolic complications in patients with non-valvular AF.N

Bio-nanotechnology application in wastewater treatment

The nanoparticles have received high interest in the field of medicine and water purification, however, the nanomaterials produced by chemical and physical methods are considered hazardous, expensive, and leave behind harmful substances to the environment. This chapter aimed to focus on green-synthesized nanoparticles and their medical applications. Moreover, the chapter highlighted the applicability of the metallic nanoparticles (MNPs) in the inactivation of microbial cells due to their high surface and small particle size. Modifying nanomaterials produced by green-methods is safe, inexpensive, and easy. Therefore, the control and modification of nanoparticles and their properties were also discussed

The D-score: a metric for interpreting the early development of infants and toddlers across global settings

Introduction: Early childhood development can be described by an underlying latent construct. Global comparisons of children’s development are hindered by the lack of a validated metric that is comparable across cultures and contexts, especially for children under age 3 years. We constructed and validated a new metric, the Developmental Score (D-score), using existing data from 16 longitudinal studies. / Methods: Studies had item-level developmental assessment data for children 0–48 months and longitudinal outcomes at ages >4–18 years, including measures of IQ and receptive vocabulary. Existing data from 11 low-income, middle-income and high-income countries were merged for >36 000 children. Item mapping produced 95 ‘equate groups’ of same-skill items across 12 different assessment instruments. A statistical model was built using the Rasch model with item difficulties constrained to be equal in a subset of equate groups, linking instruments to a common scale, the D-score, a continuous metric with interval-scale properties. D-score-for-age z-scores (DAZ) were evaluated for discriminant, concurrent and predictive validity to outcomes in middle childhood to adolescence. / Results: Concurrent validity of DAZ with original instruments was strong (average r=0.71), with few exceptions. In approximately 70% of data rounds collected across studies, DAZ discriminated between children above/below cut-points for low birth weight (<2500 g) and stunting (−2 SD below median height-for-age). DAZ increased significantly with maternal education in 55% of data rounds. Predictive correlations of DAZ with outcomes obtained 2–16 years later were generally between 0.20 and 0.40. Correlations equalled or exceeded those obtained with original instruments despite using an average of 55% fewer items to estimate the D-score. / Conclusion: The D-score metric enables quantitative comparisons of early childhood development across ages and sets the stage for creating simple, low-cost, global-use instruments to facilitate valid cross-national comparisons of early childhood development

Bench-to-bedside review : targeting antioxidants to mitochondria in sepsis

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