Pulmonary hypertension (PH) is a serious pulmonary vascular disease characterized by vascular remodeling. Circular RNAs (CircRNAs) play important roles in pulmonary hypertension, but the mechanism of PH is not fully understood, particularly the roles of circRNAs located in the nucleus. Circ-calmodulin 4 (circ-calm4) is expressed in both the cytoplasm and the nucleus of pulmonary arterial smooth muscle cells (PASMCs). This study aimed to investigate the role of endonuclear circ-calm4 in PH and elucidate its underlying signaling pathway in ferroptosis. Immunoblotting, quantitative real-time polymerase chain reaction (PCR), malondialdehyde (MDA) assay, immunofluorescence, iron assay, dot blot, and chromatin immunoprecipitation (ChIP) were performed to investigate the role of endonuclear circ-calm4 in PASMC ferroptosis. Increased endonuclear circ-calm4 facilitated ferroptosis in PASMCs under hypoxic conditions. We further identified the cartilage oligomeric matrix protein (COMP) as a downstream effector of circ-calm4 that contributed to the occurrence of hypoxia-induced ferroptosis in PASMCs. Importantly, we confirmed that endonuclear circ-calm4 formed circR-loops with the promoter region of the COMP gene and negatively regulated its expression. Inhibition of COMP restored the phenotypes related to ferroptosis under hypoxia stimulation combined with antisense oligonucleotide (ASO)-circ-calm4 treatment. We conclude that the circ-calm4/COMP axis contributed to hypoxia-induced ferroptosis in PASMCs and that circ-calm4 formed circR-loops with the COMP promoter in the nucleus and negatively regulated its expression. The circ-calm4/COMP axis may be useful for the design of therapeutic strategies for protecting cellular functionality against ferroptosis and pulmonary hypertension.

Global energy consumption is expected to reach 911 BTU by the end of 2050 as a result of rapid urbanization and industrialization. Hydrogen is increasingly recognized as a clean and reliable energy vector for decarbonization and defossilization across various sectors. Projections indicate a significant rise in global demand for hydrogen, underscoring the need for sustainable production, efficient storage, and utilization. In this state-of-the-art review, we explore hydrogen production methods, compare their environmental impacts through life cycle analysis, delve into geological storage options, and discuss hydrogen\'s potential as a future transportation fuel. Combining electrolysis to make hydrogen and storing it in porous underground materials like salt caverns and geological reservoirs looks like a good way to balance out the variable supply of renewable energy and meet the demand at peak times. Hydrogen is a key component of our sustainable economy, and this article gives a broad overview of the process from production to consumption, touching on technical, economic, and environmental concerns along the way. We have made an attempt in this paper to compile different methods for the production of hydrogen and its storage, the challenges faced by current methods in the manufacturing of hydrogen gas, and the role of hydrogen in the future. This review paper will serve as a very good reference for hydrogen system engineering applications. The paper concludes with some suggestions for future research to help improve the technological efficiency of certain production methods, all with the goal of scaling up the hydrogen economy.

Estrogens exert effects on cognition by acting on estrogen receptors (ER) including ERα. Activation of nuclear ERα results in classical genomic signaling leading to transcriptional changes that occur over hours to days. In contrast, activation of ERα localized to the membrane results in rapid signaling with effects occurring in seconds to minutes. The goal of the current study was to determine the role of membrane ERα in spatial memory. Female wildtype (WT) and transgenic mice that lack membrane ERα and express nuclear only ERα (NOER) were trained on an eight-arm radial-maze task. Following training, mice were tested on delay trials, in which delays ranging from 30 min to 5 h were inserted between the 4th and 5th arm choices. Performance was measured by number of proactive and retroactive errors. Proactive errors are short-term working memory errors defined by reentries into arms previously visited during the post-delay period or errors made during the pre-delay period. Retroactive errors are delay-dependent memory errors, defined as reentries into arms during the post-delay that were previously visited during the pre-delay. Consistent with a role for membrane ERα in rapid signaling, NOER mice made more proactive errors than WTs across all delays. NOER mice made more retroactive errors than WTs only after the 5-h delay. WT and NOER mice performed similarly on elevated plus maze and open field tests indicating no effects of membrane ERα on anxiety-related behavior or locomotor activity. Results reveal that membrane ERα plays important roles in both short-term and longer-term delay-dependent memory either directly or potentially indirectly through a role in the regulation of estradiol levels via the hypothalamic-pituitary-gonadal axis.

Cardiac ischemia results in anaerobic metabolism and lactic acid accumulation and with time, intracellular and extracellular acidosis. Ischemia and subsequent reperfusion injury (IRI) lead to various forms of programmed cell death. Necroptosis is a major form of programmed necrosis that worsens cardiac function directly and also promotes inflammation by the release of cellular contents. Potential effects of increasing acidosis on programmed cell death and their specific components have not been well studied. While apoptosis is caspase-dependent, in contrast, necroptosis is mediated by the receptor-interacting protein kinases 1 and 3 (RIPK1/3). In our study, we observed that at physiological pH = 7.4, caspase-8 inhibition did not prevent TNFα-induced cell death in mouse cardiac vascular endothelial cells (MVECs) but promoted necroptotic cell death. As expected, necroptosis was blocked by RIPK1 inhibition. However, at pH = 6.5, TNFα induced an apoptosis-like pattern which was inhibited by caspase-8 inhibition. Interestingly phosphorylation of necroptotic molecules RIPK1, RIPK3, and mixed lineage kinase domain-like protein (MLKL) was enhanced in an acidic pH environment. However, RIPK3 and MLKL phosphorylation was self-limited which may have limited their participation in necroptosis. In addition, an acidic pH promoted apoptosis-inducing factor (AIF) cleavage and nuclear translocation. AIF RNA silencing inhibited cell death, supporting the role of AIF in this cell death. In summary, our study demonstrated that the pH of the micro-environment during inflammation can bias cell death pathways by altering the function of necroptosis-related molecules and promoting AIF-mediated cell death. Further insights into the mechanisms by which an acidic cellular micro-environment influences these and perhaps other forms of regulated cell death, may lead to therapeutic strategies to attenuate IRI.

After the first atomic bomb test in Alamogordo in July 1945, followed by the Hiroshima and Nagasaki bombs in August 1945, radioecology became recognized as a branch of ecology in response to the radioactive fallout associated with the subsequent proliferation of atmospheric nuclear weapons testing which continued throughout the Cold War. In parallel, environmental radiochemistry emerged in the 70s to understand the chemical behavior of possible nuclear contaminants of the environment. In this discussion we stress the need to crosslink radioecology and chemical speciation, where radiochemistry and radioecology should meet to go beyond the present state of the art. Accordingly, we are seeking a methodology that calls for several angles of investigation: speciation (chemistry), toxicology (physiology and biology), accumulation data (environmental studies), distribution (geochemistry).

Quantifying an imaging modality\'s ability to reproduce results is important for establishing its utility. In magnetic resonance spectroscopic imaging (MRSI), new acquisition protocols are regularly introduced which improve upon their precursors with respect to signal-to-noise ratio (SNR), total acquisition duration, and nominal voxel resolution. This study has quantified the within-subject and between-subject reproducibility of one such new protocol (reduced-field-of-view density-weighted concentric ring trajectory (rFOV-DW-CRT) MRSI) by calculating the coefficient of variance of data acquired from a test-retest experiment. The posterior cingulate cortex (PCC) and the right superior corona radiata (SCR) were selected as the regions of interest (ROIs) for grey matter (GM) and white matter (WM), respectively. CVs for between-subject and within-subject were consistently around or below 15% for Glx, tCho, and Myo-Ins, and below 5% for tNAA and tCr.

Filtration media used to quantify particulate and gaseous releases have been collected from Hartlepool Power Station in the United Kingdom and measured using high-sensitivity gamma-spectrometry systems. Radionuclides that are relevant to the monitoring regime of the Comprehensive Nuclear-Test-Ban Treaty (CTBT) have been detected. Results are reported and compared to detections recorded on the International Monitoring System (IMS). Time series activity plots have been produced and results interpreted with respect to known plant activities. The reported results improve the understanding of trace-level radionuclide emissions from Advanced Gas-cooled Reactors (AGRs) and aid interpretation of IMS measurements. This work is being performed as part of the Xenon Environmental Nuclide Analysis at Hartlepool (XENAH) collaboration between the Atomic Weapons Establishment (AWE, UK), EDF Energy (UK), Pacific Northwest National Laboratory (PNNL, US) and the Swedish Defence Agency (FOI, Sweden).

Kinetoplastid parasites are \"living bridges\" in the evolution from prokaryotes to higher eukaryotes. The near-intronless genome of the kinetoplastid Leishmania exhibits polycistronic transcription which can facilitate R-loop formation. Therefore, to prevent such DNA-RNA hybrids, Leishmania has retained prokaryotic-like DNA Topoisomerase IA (LdTOPIA) in the course of evolution. LdTOPIA is an essential enzyme that is expressed ubiquitously and is adapted for the compartmentalized eukaryotic form in harboring functional bipartite nuclear localization signals. Although exhibiting greater homology to mycobacterial TOPIA, LdTOPIA could functionally complement the growth lethality of Escherichia coli TOPIA null GyrB ts strain at non-permissive temperatures. Purified LdTOPIA exhibits Mg2+-dependent relaxation of only negatively supercoiled DNA and preference towards single-stranded DNA substrates. LdTOPIA prevents nuclear R-loops as conditional LdTOPIA downregulated parasites exhibit R-loop formation and thereby parasite killing. The clinically used tricyclic antidepressant, norclomipramine could specifically inhibit LdTOPIA and lead to R-loop formation and parasite elimination. This comprehensive study therefore paves an avenue for drug repurposing against Leishmania.

Neutrons interact with the magnetic moment of the atomic shell of an atom, as is common for X-rays, but mainly they interact directly with the nucleus. Therefore, the atomic number and the related number of electrons does not play a role in the strength of an interaction. Instead, hydrogen that is nearly invisible for X-rays has a higher attenuation for neutrons than most of the metals, e.g., zirconium, and thus would be visible through dark contrast in neutron images. Consequently, neutron imaging is a precise, non-destructive method to quantify the amount of hydrogen in materials with low attenuation. Because nuclear fuel cladding tubes of light water reactors are made of zirconium (98%), the hydrogen amount and distribution in metallic claddings can be investigated. Even hydrogen concentrations smaller than 10 wt.ppm can be determined locally with a spatial resolution of less than 10 μm (with a high-resolution neutron microscope). All in all, neutron imaging is a very fast and precise method for several applications. This article explains the basics of neutron imaging and provides samples of investigation possibilities, e.g., for hydrogen in zirconium alloy cladding tubes or in situ investigations of hydrogen diffusion in metals.

BACKGROUND: Characterizing lens thickness (LT) in patients with cataracts is important for better understanding the lens aging process and for designing new intraocular lens power formulas. This study aimed to analyze the influence of common senile cataract formation on the LT, anterior (ACS) and posterior (PCS) cortex space, and nuclear thickness (NT), controlling for sex, age, and axial length.
METHODS: A cross-sectional study was performed. A consecutive sample of 603 volunteers (403 women, 200 men) aged 59.1 ± 18.8 years was recruited. The standardized Lens Opacification Classification System (LOCS)-III was used to classify eyes (randomly selected) into cataractous and non-cataractous groups. Also, they were classified according to the cataract location (presence or absence of cortical, nuclear, or posterior subcapsular cataract). Optical biometry was performed to measure LT, ACS, NT, and PCS. Propensity score was used to match participants one-to-one for sex, age, and axial length. Groups were compared using the Student\'s t test or Yuen\'s test.
RESULTS: The four classifications divided unmatched eyes into: 361 cataractous lenses and 242 non-cataractous, 226 cortical and 377 non-cortical cataractous, 313 nuclear and 290 non-nuclear cataractous and 242 subcapsular and 361 non-subcapsular cataractous. Before matching, cataractous eyes showed significantly higher LT (4.52 ± 0.39 vs. 3.94 ± 0.46 mm, p < 0.001), ACS (0.75 ± 0.20 vs. 0.58 ± 0.23 mm, p < 0.001), NT (3.34 ± 0.23 vs. 3.18 ± 0.25 mm, p < 0.001) and PCS (0.42 ± 0.19 vs. 0.37 ± 0.19 mm, p = 0.003). Matched lens, cortical, nuclear, and subcapsular cataract samples comprised 146, 258, 182, and 226 eyes, respectively. After matching, no significant differences were observed in LT (4.34 ± 0.37 vs. 4.33 ± 0.36 mm, p = 0.94), ACS (0.72 ± 0.20 vs. 0.76 ± 0.19 mm, p = 0.08), NT (3.31 ± 0.22 vs. 3.30 ± 0.23 mm, p = 0.24) and PCS (0.42 ± 0.19 vs. 0.43 ± 0.16 mm, p = 0.79).
CONCLUSIONS: The presence of senile cortical, nuclear, and posterior subcapsular cataract have no effect on LT, ACS, NT, and PCS. Confounding factors should be controlled for when measuring LT and its main components.