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The adult heart is made up of cardiomyocytes (CMs) that maintain pump function but are unable to divide and form new myocytes in response to myocardial injury. In contrast, the developmental cardiac tissue is made up of proliferative CMs that regenerate injured myocardium. In mammals, CMs during development are diploid and mononucleated. In response to cardiac maturation, CMs undergo polyploidization and binucleation associated with CM functional changes. The transition from mononucleation to binucleation coincides with unique metabolic changes and shift in energy generation. Recent studies provide evidence that metabolic reprogramming promotes CM cell cycle reentry and changes in ploidy and nucleation state in the heart that together enhances cardiac structure and function after injury. This review summarizes current literature regarding changes in CM ploidy and nucleation during development, maturation and in response to cardiac injury. Importantly, how metabolism affects CM fate transition between mononucleation and binucleation and its impact on cell cycle progression, proliferation and ability to regenerate the heart will be discussed. [ABSTRACT FROM AUTHOR]

The study aimed at investigating the correlations among the physical and bulk properties of carrier based dry powder inhaler formulations and the performance of the powder inhaler device estimated by in-vitro tests for a specific active pharmaceutical ingredient (API), and at obtaining predictive models for the in-vitro performance. Samples from scale-up process batches having different formulations, process settings and bulk size, were characterized by rheological, density and particle size tests. In vitro performance was evaluated by several parameters obtained by a dosage unit sampling apparatus (DUSA) and a next generation impactor (NGI). Correlations between powder properties and performance properties were established using partial least square (PLS) regression analysis. Variable importance in projection (VIP) was used in order to assess the most influential powder characterization variables to estimate the analytical ones. Particle size, density and rate of flowability are significant for modeling the Delivered Dose of the API and the total quantity of powder related to each dose. Powder characterization variables, describing the degree of cohesiveness and the flow properties of powder, are related to the total amount of the active ingredient for different formulations. DUSA test variables were satisfactory predicted on the basis of powder characterization variables, while NGI performance variables were predicted with higher error. [ABSTRACT FROM AUTHOR]

Radon, a radioactive inert gas that comes from the decay of naturally occurring radioactive species, poses a substantial health risk due to its involvement in lung cancer carcinogenesis. This work proposes a metrological approach for determining radon exhalation rates from diverse building materials. This methodology employs an electrostatic collection chamber for alpha spectrometry of radon isotopic decay products. Experimental evaluations were conducted particularly focusing on volcanic gray tuff from Sant'Agata de' Goti (Campania region, Italy), a material commonly utilized in construction, to assess radon exhalation rates. The study aligns with Legislative Decree 101/2020, a transposition of European Directive 59/2013/Euratom, highlighting the need to identify materials with a high risk of radon exhalation. Moreover, this work supports the goals of the Italian National Radon Action Plan related to the aforementioned decree, aiming to develop methodologies for estimating radon exhalation rates from building materials and improving radioprotection practices. [ABSTRACT FROM AUTHOR]

The article discusses Estrogen receptor (ER)–positive, human epidermal growth factor receptor 2 (HER2)–negative (ER+/HER2−), the most common subtype of breast cancer, accounting for up to 70% of all cases diagnosed. Mentions estrogen drives cell proliferation by inducing the expression of cyclin D1 and activating the cyclin-dependent kinase 4/6 (CDK4/6) pathway, in ER+ breast cancer. Informs relapses of ER+/ HER2- breast cancer remain a major problem, comprising 60% of metastatic breast cancer.

The primary forms of cell death seen in ischemic stroke are of two major types: a necrotic/necroptotic form, and an apoptotic form that is frequently seen in penumbral regions of injury. Typically apoptotic versus necroptotic programmed cell death is described as competitive in nature, where necroptosis is often described as playing a backup role to apoptosis. In the present study, we examined the relationship between these two forms of cell death in a murine endothelin-1 model of ischemia–reperfusion injury in wildtype and caspase-3 null mice with and without addition of the pharmacologic RIPK1 phosphorylation inhibitor necrostatin-1. Analyses of ischemic brain injury were performed via both cellular and volumetric assessments, electron microscopy, TUNEL staining, activated caspase-3 and caspase-7 staining, as well as CD11b and F4/80 staining. Inhibition of caspase-3 or RIPK1 phosphorylation demonstrates significant neural protective effects which are non-additive and exhibit significant overlap in protected regions. Interestingly, morphologic analysis of the cortex demonstrates reduced apoptosis following RIPK1 inhibition. Consistent with this, RIPK1 inhibition reduces the levels of both caspase-3 and caspase-7 activation. Additionally, this protection appears independent of secondary inflammatory mediators. Together, these observations demonstrate that the necroptotic protein RIPK1 modifies caspase-3/-7 activity, ultimately resulting in decreased neuronal apoptosis. These findings thus modify the traditional exclusionary view of apoptotic/necroptotic signaling, revealing a new form of interaction between these dominant forms of cell death. [ABSTRACT FROM AUTHOR]