-
Scientific Reports Jun 2024Despite of excellent thermal properties and high sputtering resistance, pure tungsten cannot fully satisfy the requirements for plasma facing materials in future...
Despite of excellent thermal properties and high sputtering resistance, pure tungsten cannot fully satisfy the requirements for plasma facing materials in future high-duty cycle nuclear fusion reactions due to the coupled extreme environments, including the high thermal loads, plasma exposure, and radiation damage. Here, we demonstrated that tungsten-based composite materials fabricated using spark-plasma sintering (SPS) present promising solutions to these challenges. Through the examination of two model systems, i.e., tungsten-zirconium composite for producing porous tungsten near the surface and dispersoid-strengthened tungsten, we discussed both the strengths and limitations of the SPS-fabricated materials. Our findings point towards the need for future studies aimed at optimizing the SPS process to achieve desired microstructures and effective control of oxygen impurities in the tungsten-based composite materials.
PubMed: 38879710
DOI: 10.1038/s41598-024-64614-3 -
Scientific Reports Jun 2024Acute kidney injury (AKI) is a systemic disease that affects energy metabolism in various remote organs in murine models of ischemic AKI. However, AKI-mediated effects...
Acute kidney injury (AKI) is a systemic disease that affects energy metabolism in various remote organs in murine models of ischemic AKI. However, AKI-mediated effects in the liver have not been comprehensively assessed. After inducing ischemic AKI in 8-10-week-old, male C57BL/6 mice, mass spectrometry metabolomics revealed that the liver had the most distinct phenotype 24 h after AKI versus 4 h and 7 days. Follow up studies with in vivo [C]-glucose tracing on liver and kidney 24 h after AKI revealed 4 major findings: (1) increased flux through glycolysis and the tricarboxylic (TCA) cycle in both kidney and liver; (2) depleted hepatic glutathione levels and its intermediates despite unchanged level of reactive oxygen species, suggesting glutathione consumption exceeds production due to systemic oxidative stress after AKI; (3) hepatic ATP depletion despite unchanged rate of mitochondrial respiration, suggesting increased ATP consumption relative to production; (4) increased hepatic and renal urea cycle intermediates suggesting hypercatabolism and upregulation of the urea cycle independent of impaired renal clearance of nitrogenous waste. Taken together, this is the first study to describe the hepatic metabolome after ischemic AKI in a murine model and demonstrates that there is significant liver-kidney crosstalk after AKI.
Topics: Animals; Acute Kidney Injury; Liver; Glutathione; Energy Metabolism; Kidney; Male; Mice; Mice, Inbred C57BL; Ischemia; Metabolomics; Disease Models, Animal; Oxidative Stress; Glycolysis; Metabolome
PubMed: 38879688
DOI: 10.1038/s41598-024-64586-4 -
Scientific Reports Jun 2024The problem of cadmium pollution and its control is becoming increasingly severe issue in the world. Banana straw is an abundant bio raw material, but its burning or...
The problem of cadmium pollution and its control is becoming increasingly severe issue in the world. Banana straw is an abundant bio raw material, but its burning or discarding in field not only causes pollution but also spreads fusarium wilt. The objective of this paper is to utilize biochar derived from the wilt-infected banana straw for remediation of Cd(II) pollution while to eliminate the pathogen. The activity of wilt pathogen in biochar was determined by PDA petri dish test. The Cd(II) adsorption of the biochar was determined by batch adsorption experiments. The effects of KOH concentration (0.25, 0.5 and 0.75 M) on the physicochemical characteristics of the biochar were also observed by BET, SEM, FTIR, XRD and XPS. Results showed that pristine banana straw biochar (PBBC) did not harbor any pathogen. The specific surface area (SSA) and Cd(II) adsorption capacity of 0.75 M KOH modified banana straw biochar (MBBC) were increased by 247.2% and 46.1% compared to that of PBBC, respectively. Cd(II) adsorption by MBBC was suitable to be described by the pseudo-second-order kinetic model and Freundlich isotherm. After Cd(II) adsorption, the CdCO were confirmed by XRD and observed through SEM. The weakness and shift of oxygen-containing functional groups in MBBC after Cd(II) adsorption implied that those groups were complexed with Cd(II). The results showed that pyrolysis could not only eliminate banana fusarium wilt, but also prepare porous biochar with the wilt-infected banana straw. The porous biochar possessed the potential to adsorb Cd(II) pollutants.
Topics: Musa; Charcoal; Fusarium; Cadmium; Adsorption; Porosity; Water Pollutants, Chemical; Plant Diseases; Environmental Restoration and Remediation; Kinetics
PubMed: 38879683
DOI: 10.1038/s41598-024-63954-4 -
Scientific Reports Jun 2024Exoplanet atmospheres are expected to vary significantly in thickness and chemical composition, leading to a continuum of differences in surface pressure and atmospheric...
Exoplanet atmospheres are expected to vary significantly in thickness and chemical composition, leading to a continuum of differences in surface pressure and atmospheric density. This variability is exemplified within our Solar System, where the four rocky planets exhibit surface pressures ranging from 1 nPa on Mercury to 9.2 MPa on Venus. The direct effects and potential challenges of atmospheric pressure and density on life have rarely been discussed. For instance, atmospheric density directly affects the possibility of active flight in organisms, a critical factor since without it, dispersing across extensive and inhospitable terrains becomes a major limitation for the expansion of complex life. In this paper, we propose the existence of a critical atmospheric density threshold below which active flight is unfeasible, significantly impacting biosphere development. To qualitatively assess this threshold and differentiate it from energy availability constraints, we analyze the limits of active flight on Earth, using the common fruit fly, Drosophila melanogaster, as a model organism. We subjected Drosophila melanogaster to various atmospheric density scenarios and reviewed previous data on flight limitations. Our observations show that flies in an N-enriched environment recover active flying abilities more efficiently than those in a helium-enriched environment, highlighting behavioral differences attributable to atmospheric density vs. oxygen deprivation.
PubMed: 38879676
DOI: 10.1038/s41598-024-64114-4 -
Cell Death Discovery Jun 2024Peroxisomal L-bifunctional enzyme (EHHADH) plays a role in the classic peroxisomal fatty acid β-oxidation pathway; however, the relationship between EHHADH expression...
Peroxisomal L-bifunctional enzyme (EHHADH) plays a role in the classic peroxisomal fatty acid β-oxidation pathway; however, the relationship between EHHADH expression and diabetic kidney disease has not been well understood. Here, we found that endogenous EHHADH levels were strongly correlated with the progression and severity of diabetic nephropathy in T2D patients. EHHADH knockout mice exhibited worsened renal tubular injury in diabetic mice. Furthermore, EHHADH is a modulator of pexophagy. In renal tubular epithelial cells (RTECs) in vitro, the knockdown of EHHADH induced a dramatic loss of peroxisomes. The loss of peroxisomes in EHHADH-deficient RTECs was restored by either an autophagic inhibitor 3-methyladenine or bafilomycin A1 both in vitro and in vivo. NBR1 was required for pexophagy in EHHADH-knockdown cells, where the level of reactive oxygen species (ROS) was increased, while inhibition of ROS blocked pexophagy. In summary, our findings revealed EHHADH deficiency accelerated renal injury in DKD as a modulator of pexophagy.
PubMed: 38879653
DOI: 10.1038/s41420-024-02066-4 -
Nature Communications Jun 2024Hydrogen borrowing is an attractive and sustainable strategy for carbon-carbon bond formation that enables alcohols to be used as alkylating reagents in place of alkyl...
Hydrogen borrowing is an attractive and sustainable strategy for carbon-carbon bond formation that enables alcohols to be used as alkylating reagents in place of alkyl halides. However, despite intensive efforts, limited functional group tolerance is observed in this methodology, which we hypothesize is due to the high temperatures and harsh basic conditions often employed. Here we demonstrate that room temperature and functional group tolerant hydrogen borrowing can be achieved with a simple iridium catalyst in the presence of substoichiometric base without an excess of reagents. Achieving high yields necessitates the application of anaerobic conditions to counteract the oxygen sensitivity of the catalytic iridium hydride intermediate, which otherwise leads to catalyst degradation. Substrates containing heteroatoms capable of complexing the catalyst exhibit limited room temperature reactivity, but the application of moderately higher temperatures enables extension to a broad range of medicinally relevant nitrogen rich heterocycles. These newly developed conditions allow alcohols possessing functional groups that were previously incompatible with hydrogen borrowing reactions to be employed.
PubMed: 38879563
DOI: 10.1038/s41467-024-49249-2 -
Nature Communications Jun 2024Hepatocellular carcinoma frequently recurs after surgery, necessitating personalized clinical approaches based on tumor avatar models. However, location-dependent oxygen...
Hepatocellular carcinoma frequently recurs after surgery, necessitating personalized clinical approaches based on tumor avatar models. However, location-dependent oxygen concentrations resulting from the dual hepatic vascular supply drive the inherent heterogeneity of the tumor microenvironment, which presents challenges in developing an avatar model. In this study, tissue samples from 12 patients with hepatocellular carcinoma are cultured directly on a chip and separated based on preference of oxygen concentration. Establishing a dual gradient system with drug perfusion perpendicular to the oxygen gradient enables the simultaneous separation of cells and evaluation of drug responsiveness. The results are further cross-validated by implanting the chips into mice at various oxygen levels using a patient-derived xenograft model. Hepatocellular carcinoma cells exposed to hypoxia exhibit invasive and recurrent characteristics that mirror clinical outcomes. This chip provides valuable insights into treatment prognosis by identifying the dominant hepatocellular carcinoma type in each patient, potentially guiding personalized therapeutic interventions.
Topics: Carcinoma, Hepatocellular; Humans; Liver Neoplasms; Animals; Mice; Oxygen; Tumor Microenvironment; Cell Line, Tumor; Male; Female; Xenograft Model Antitumor Assays; Middle Aged; Lab-On-A-Chip Devices
PubMed: 38879551
DOI: 10.1038/s41467-024-49386-8 -
NPJ Microgravity Jun 2024Iron is essential for cell respiration, muscle metabolism, and oxygen transport. Recent research has shown that simulated microgravity rapidly affects iron metabolism in...
Iron is essential for cell respiration, muscle metabolism, and oxygen transport. Recent research has shown that simulated microgravity rapidly affects iron metabolism in men. However, its impact on women remains unclear. This study aims to compare iron metabolism alterations in both sexes exposed to 5 days of dry immersion. Our findings demonstrate that women, similarly to men, experience increased systemic iron availability and elevated serum hepcidin levels, indicative of iron misdistribution after short-term exposure to simulated microgravity.
PubMed: 38879550
DOI: 10.1038/s41526-024-00399-z -
Chinese Medicine Jun 2024Resident microglia- and peripheric macrophage-mediated neuroinflammation plays a predominant role in the occurrence and development of ischemic stroke. Microglia undergo...
BACKGROUND
Resident microglia- and peripheric macrophage-mediated neuroinflammation plays a predominant role in the occurrence and development of ischemic stroke. Microglia undergo polarization to M1/M2-like phenotype under stress stimulation, which mediates intracellular inflammatory response. β-elemene is a natural sesquiterpene and possesses potent anti-inflammatory activity. This study aimed to investigate the anti-inflammatory efficacy and mechanism of β-elemene in ischemic stroke from the perspective of balancing microglia M1/M2-like polarization.
METHODS
The middle cerebral artery occlusion (MCAO) model and photothrombotic stroke model were established to explore the regulation effect of β-elemene on the cerebral ischemic injury. The LPS and IFN-γ stimulated BV-2 cells were used to demonstrate the anti-inflammatory effects and potential mechanism of β-elemene regulating M1/M2-like polarization in vitro.
RESULTS
In C57BL/6 J mice subjected to MCAO model and photothrombotic stroke model, β-elemene attenuated neurological deficit, reduced the infarction volume and neuroinflammation, thus improving ischemic stroke injury. β-elemene promoted the phenotype transformation of microglia from M1-like to M2-like, which prevented neurons from oxygen and glucose deprivation/reoxygenation (OGD/R) injury by inhibiting inflammatory factor release, thereby reducing neuronal apoptosis. Mechanically, β-elemene prevented the activation of TLR4/NF-κΒ and MAPK signaling pathway and increased AKT/mTOR mediated-autophagy, thereby promoting M2-like polarization of microglia.
CONCLUSIONS
These results indicated that β-elemene improved cerebral ischemic injury and promoted the transformation of microglia phenotype from M1-like to M2-like, at least in part, through AKT/mTOR-mediated autophagy. This study demonstrated that β-elemene might serve as a promising drug for alleviating ischemic stroke injury.
PubMed: 38879549
DOI: 10.1186/s13020-024-00946-6 -
Cell Death & Disease Jun 2024Tamoxifen has been the mainstay therapy to treat early, locally advanced, and metastatic estrogen receptor-positive (ER + ) breast cancer, constituting around 75% of...
Tamoxifen has been the mainstay therapy to treat early, locally advanced, and metastatic estrogen receptor-positive (ER + ) breast cancer, constituting around 75% of all cases. However, the emergence of resistance is common, necessitating the identification of novel therapeutic targets. Here, we demonstrated that long-noncoding RNA LINC00152 confers tamoxifen resistance by blocking tamoxifen-induced ferroptosis, an iron-mediated cell death. Mechanistically, inhibiting LINC00152 reduces the mRNA stability of phosphodiesterase 4D (PDE4D), leading to activation of the cAMP/PKA/CREB axis and increased expression of the TRPC1 Ca channel. This causes cytosolic Ca overload and generation of reactive oxygen species (ROS) that is, on the one hand, accompanied by downregulation of FTH1, a member of the iron sequestration unit, thus increasing intracellular Fe levels; and on the other hand, inhibition of the peroxidase activity upon reduced GPX4 and xCT levels, in part by cAMP/CREB. These ultimately restore tamoxifen-dependent lipid peroxidation and ferroptotic cell death which are reversed upon chelating Ca or overexpressing GPX4 or xCT. Overexpressing PDE4D reverses LINC00152 inhibition-mediated tamoxifen sensitization by de-activating the cAMP/Ca/ferroptosis axis. Importantly, high LINC00152 expression is significantly correlated with high PDE4D/low ferroptosis and worse survival in multiple cohorts of tamoxifen- or tamoxifen-containing endocrine therapy-treated ER+ breast cancer patients. Overall, we identified LINC00152 inhibition as a novel mechanism of tamoxifen sensitization via restoring tamoxifen-dependent ferroptosis upon destabilizing PDE4D, increasing cAMP and Ca levels, thus leading to ROS generation and lipid peroxidation. Our findings reveal LINC00152 and its effectors as actionable therapeutic targets to improve clinical outcome in refractory ER+ breast cancer.
Topics: Humans; Tamoxifen; Breast Neoplasms; Ferroptosis; Female; RNA, Long Noncoding; Cyclic AMP; Calcium; Drug Resistance, Neoplasm; Cell Line, Tumor; Animals; Receptors, Estrogen; Mice; Reactive Oxygen Species; MCF-7 Cells
PubMed: 38879508
DOI: 10.1038/s41419-024-06814-3