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Acute kidney injury (AKI) is a serious health concern with high morbidity and high mortality worldwide. Recently, sexual dimorphism has become increasingly recognized as a factor influencing the severity of the disease. This study explores the gender-specific renoprotective pathways in αMUPA transgenic mice subjected to AKI. αMUPA transgenic male and female mice were subjected to ischemia–reperfusion (I/R)-AKI in the presence or absence of orchiectomy, oophorectomy, and L-NAME administration. Blood samples and kidneys were harvested 48 h following AKI for the biomarkers of kidney function, renal injury, inflammatory response and intracellular pathway sensing of or responding to AKI. Our findings show differing responses to AKI, where female αMUPA mice were remarkably protected against AKI as compared with males, as was evident by the lower SCr and BUN, normal renal histologically and attenuated expression of NGAL and KIM-1. Moreover, αMUPA females did not show a significant change in the renal inflammatory and fibrotic markers following AKI as compared with wild-type (WT) mice and αMUPA males. Interestingly, oophorectomized females eliminated the observed resistance to renal injury, highlighting the central protective role of estrogen. Correspondingly, orchiectomy in αMUPA males mitigated their sensitivity to renal damage, thereby emphasizing the devastating effects of testosterone. Additionally, treatment with L-NAME proved to have significant deleterious impacts on the renal protective mediators, thereby underscoring the involvement of eNOS. In conclusion, gender-specific differences in the response to AKI in αMUPA mice include multifaceted and keen interactions between the sex hormones and key biochemical mediators (such as estrogen, testosterone and eNOS). These novel findings shed light on the renoprotective pathways and mechanisms, which may pave the way for development of therapeutic interventions. [ABSTRACT FROM AUTHOR]

Climate change significantly impacts global forests, leading to tree decline and dieback. To cope with climate change, trees develop several functional traits, such as intra-annual density fluctuations (IADFs) in tree rings. The formation of these traits facilitates trees to optimize resource allocation, allowing them to withstand periods of stress and eventually recover when the conditions become favourable again. This study focuses on a Pinus pinaster Aiton forest in a warm, drought-prone Mediterranean area, comparing two growing seasons with different weather patterns. The innovative continuous monitoring approach used in this study combines high-resolution monitoring of sap flow (SF), analysis of xylogenesis and quantitative wood anatomy. Our results revealed the high plasticity of P. pinaster in water use and wood formation, shedding light on the link between IADFs and tree conductance. Indeed, the capacity to form large cells in autumn (as IADFs) improves the total xylem hydraulic conductivity of this species. For the first time, a continuous SF measurement system captured the dynamics of bimodal SF during the 2022 growing season in conjunction with the bimodal growth pattern observed through xylogenesis monitoring. These results highlight the intricate interplay between environmental conditions, water use, wood formation and tree physiology, providing valuable insights into the acclimation mechanisms employed by P. pinaster to cope with weather fluctuations. [ABSTRACT FROM AUTHOR]

Metachrony is defined as coordinated asynchronous movement throughout multiple appendages, such as the cilia of cells and swimmerets of crustaceans. Used by species of crustaceans and microscopic cells to move through fluid, the process of metachronal propulsion was investigated. A rigid crustacean model with paddles moving in symmetric strokes was created to simulate metachronal movement. Coupled with the surrounding fluid domain, the immersed boundary method was employed to analyze the fluid–structure interactions. To explore the effect of a nonlinear morphology on the efficiency of metachronal propulsion, a range of crustacean body shapes was generated and simulated, from upward curves to downward curves. The highest propulsion velocity was found to be achieved when the crustacean model morphology was a downward curve, specifically a parabola of leading coefficient k = −0.4. This curved morphology resulted in a 4.5% higher velocity when compared to the linear model. As k deviated from −0.4, the propulsion velocity decreased with increasing magnitude, forming a concave downward trend. The impact of body shape on propulsion velocity is shown by how the optimal velocity with k = −0.4 is 71.5% larger than the velocity at k = 1. Overall, this study suggests that morphology has a significant impact on metachronal propulsion. [ABSTRACT FROM AUTHOR]

Background: Non-alcoholic fatty liver disease affects up to 30% of adults in the USA, and is associated with a higher incidence of chronic liver morbidity and mortality. Several molecular pathways are involved in the pathology of liver steatosis, including lipid uptake, lipogenesis, lipolysis, and beta-oxidation. The enzyme heparanase has been implicated in liver steatosis. Herein, we investigated the effect of heparanase inhibition on liver steatosis in E0 mice. Methods: In vivo experiments: Male wild-type mice fed with either chow diet (n = 4) or high-fat diet (n = 6), and male E0 mice fed with chow diet (n = 8) or high-fat diet (n = 33) were included. Mice on a high-fat diet were treated for 12 weeks with PG545 at low dose (6.4 mg/kg/week, ip, n = 6) or high dose (13.3 mg/kg/week, ip, n = 7), SST0001 (1.2 mg/mouse/day, ip, n = 6), or normal saline (control, n = 14). Animals were sacrificed two days after inducing peritonitis. Serum was analyzed for biochemical parameters. Mouse peritoneal macrophages (MPMs) were harvested and analyzed for lipid content. Livers were harvested for histopathological analysis of steatosis, lipid content, and the expression of steatosis-related factors at the mRNA level. In vitro experiments: MPMs were isolated from untreated E0 mice aged 8–10 weeks and were cultured and treated with either PG545 or SST0001, both at 50 µg/mL for 24 h, followed by assessment of mRNA expression of steatosis related factors. Results: Heparanase inhibition significantly attenuated the development of liver steatosis, as was evident by liver histology and lipid content. Serum analysis indicated lowering of cholesterol and triglycerides levels in mice treated with heparanase inhibitors. In liver tissue, assessment of mRNA expression of key factors in lipid uptake, lipolysis, lipogenesis, and beta-oxidation exhibited significant downregulation following PG545 treatment and to a lesser extent when SST0001 was applied. However, in vitro treatment of MPMs with PG545, but not SST0001, resulted in increased lipid content in these cells, which is opposed to their effect on MPMs of treated mice. This may indicate distinct regulatory pathways in the system or isolated macrophages following heparanase inhibition. Conclusion: Heparanase inhibition significantly attenuates the development of liver steatosis by decreasing tissue lipid content and by affecting the mRNA expression of key lipid metabolism regulators.

Isotopes of meteoric 10Be, 137Cs, 239+240Pu have been proposed as a soil redistribution tracer and applied worldwide as an alternative method to classical field-related techniques (e.g., sediment traps). Meteoric 10Be provides information about long-term soil redistribution rates (millennia), while 137Cs and 239+240Pu give medium-term rates (decades). A significant progress in developing new models and approaches for the calculation of erosion rates has been made; thus, we provide a global review (n = 59) of research articles to present these three isotopes (meteoric 10Be, 239+240Pu and 137Cs) as soil erosion markers in different environments and under different land-use types. Understanding the dynamics and behaviours of isotopes in the soil environment is crucial to determine their usefulness as soil erosion tracers; thus, we discuss the chemical–physical behaviour of meteoric 10Be, 137Cs and 239+240Pu in soils. The application of these isotopes sometimes has strong limitations, and we give suggestions on how to overcome them or how to adapt them to a given situation. This review also shows where these isotopic methods can potentially be applied in the future. A lack in knowledge about soil redistribution rates exists particularly in loess-dominated areas where the tillage system has changed or in areas with strong wind erosion.

Most comparisons of Thomas Hobbes and Baruch Spinoza focus on the difference in understanding of natural right. We argue that Hobbes also places more weight on a rudimentary and exclusive education of the public by the state. We show that the difference is related to deeper disagreements over the prospect of Enlightenment. Hobbes is more sanguine than Spinoza about using the state to make people rational. Spinoza considers misguided an overemphasis on publicly educating everyone out of superstition—public education is important, but modes of superstition may remain and must be offset by institutions and a civil religion. The differences are confirmed by Spinoza’s interest in the philosopher who stands apart and whose flourishing may be protected, but not simply brought about, by rudimentary public education. Spinoza’s openness to a wisdom-loving elite in a democracy also sets up an interesting parallel with Thomas Jefferson’s own commitment to the natural aristocracy needed to sustain republicanism. In demonstrating the 17th century philosopher’s skepticism toward using the state exclusively to promote rationality, even as he recognizes the importance of a sovereign pedagogical role and the protection of philosophy, we move to suggest that Spinoza is relevant to contemporary debates about public education and may reinvigorate moral and political discourse in a liberal democracy.

Oysters and shrimp are abundant and commonly consumed seafood by the indigenous population of the Kongo central region of the Democratic Republic of the Congo (DRC). Literature reviews suggest that no data were available for the metal concentrations in these species. Consequently, the purpose of this study is to determine the metal concentrations in tissues of oysters (Egeria congica) and shrimp (Macrobrachium spp., Parapenaeus spp., Penaeus spp.) collected in November 2017 from the Atlantic Ocean Coast of DRC in the territory of Muanda. Metal levels in the seafood species studied here were put into context using international regulation for human consumption set by the Food and Agriculture Organization (FAO), Canadian Food Inspection Agency (CFIA), European Union (EU), and World Health Organization (WHO). Our results demonstrated that the concentration of heavy metals varied considerably between sampling sites and analyzed species (P < 0.05), with the values (in mg kg1) ranged between 0.05-0.41, 0.03–2.25,

Abstract Background Histone deacetylase inhibitors (HDACi) suppress cytokine production in immune and stromal cells of patients with rheumatoid arthritis (RA). Here, we investigated the effects of the HDACi givinostat (ITF2357) on the transcriptional and post-transcriptional regulation of inflammatory markers in RA fibroblast-like synoviocytes (FLS). Methods The effects of ITF2357 on the expression and messenger RNA (mRNA) stability of IL-1β-inducible genes in FLS were analyzed using array-based qPCR and Luminex. The expression of primary and mature cytokine transcripts, the mRNA levels of tristetraprolin (TTP, or ZFP36) and other AU-rich element binding proteins (ARE-BP) and the cytokine profile of fibroblasts derived from ZFP36 +/+ and ZFP36 −/− mice was measured by qPCR. ARE-BP silencing was performed by small interfering RNA (siRNA)-mediated knockdown, and TTP post-translational modifications were analyzed by immunoblotting. Results ITF2357 reduced the expression of 85% of the analyzed IL-1β-inducible transcripts, including cytokines (IL6, IL8), chemokines (CXCL2, CXCL5, CXCL6, CXCL10), matrix-degrading enzymes (MMP1, ADAMTS1) and other inflammatory mediators. Analyses of mRNA stability demonstrated that ITF2357 accelerates IL6, IL8, PTGS2 and CXCL2 mRNA degradation, a phenomenon associated with the enhanced transcription of TTP, but not other ARE-BP, and the altered post-translational status of TTP protein. TTP knockdown potentiated cytokine production in RA FLS and murine fibroblasts, which in the latter case was insensitive to inhibition by ITF2357 treatment. Conclusions Our study identifies that regulation of cytokine mRNA stability is a predominant mechanism underlying ITF2357 anti-inflammatory properties, occurring via regulation of TTP. These results highlight the therapeutic potential of ITF2357 in the treatment of RA.

Debates about judicial review and departmentalism have continued to rage, and in the wake of the last three Supreme Court appointments and current Presidential Commission on the Court, only look to intensify. Should the US adopt a notwithstanding or override provision, of the kind that exits in Canada and Israel? These countries take a departmentalist approach to allow the legislature to override the Court, “notwithstanding” its ruling. Although America is a presidential framework, a paradox emerges: evidence exists that its system already makes possible the equivalent of a notwithstanding clause. This consists of Congress and the President together “overruling” the Supreme Court. In another sense, however, this is not an accepted practice—large parts of the legal community hold that the US Constitution establishes judicial supremacy. To better understand this dynamic, we consider two kinds of power: formal and authorized (potestas) as well as direct and concrete (potentia). The contrast between the positions on both power and sovereignty of Thomas Hobbes (associated with potestas) and Baruch Spinoza (linked to potentia) helps clarify these issues in a contemporary context. It turns out that a robust departmentalist equivalent of the notwithstanding clause already exists in the US, as a matter of Hobbesian potestas but not of Spinozist potentia. Another term for the latter is pouvoir constituant. Spinoza’s perspective on political activity further clarifies the in-between nature of the American override capacity: the active or passive character of a multitude is not binary, but is a matter of degree. Without making an institutional recommendation, we note that Spinoza’s understanding of power also allows for dynamic interaction between potentia and potestas: formal authorization can contribute to the expression of direct power. It is, therefore, conceivable that additional codification of the existing American override capacity, either through a joint declaration of Congress and the Presidency or a Constitutional Amendment, can strengthen the effective sovereignty of the American people in relation to the courts.