Polycystic ovary syndrome (PCOS) is a prevalent disorder that affects women of reproductive age, and patients struggle with hormonal, metabolic, and reproductive disorders. Lauric acid (LA) has beneficial effects on metabolism. However, its effect on PCOS remain unclear. This study aimed to investigate the effect of LA in a PCOS model induced by letrozole (LET), an aromatase inhibitor. Forty adult female mice were divided into four groups (n = 10): 1) normal control, 2) LA 150 mg/kg, 3) LET 6 mg/kg, and 4) LET + LA. PCOS was induced by administering LET for 21 days, followed by a 15-day treatment with LA. After sacrificing the animals, blood, ovarian, and white adipose tissues were collected for biochemical and histological analyses. The results showed that LA treatment restored irregular estrous cycles, improved fasting blood glucose and insulin resistance, and elevated glucagon-like peptide-1 levels. LA also normalizes hormonal imbalances associated with PCOS, including low FSH, estrogen and high LH and testosterone levels. Additionally, LA improved lipid profiles. It increased adiponectin and peroxisome proliferator-activated receptor gamma gene expression in the white adipose tissue of LET-treated mice. LET decreased CYP19a1 activity and increased androgen receptor expression in the ovary, which was significantly reversed by LA treatment. LA also enhanced the Sirtuin 1/AMP-activated protein kinase signaling pathway activity in the ovary, which was suppressed by LET. Finally, LA treatment significantly improved LET-induced ovarian cysts. LA can potentially improve metabolic and reproductive symptoms in LET-induced PCOS mice by enhancing metabolism-related pathways.
Immunosuppression is a prominent risk factor for infections following severe illness, trauma, or surgery. Understanding its underlying mechanisms could lead to novel strategies to reduce infection-related morbidity and mortality. This study systematically assessed the immune response to a Pseudomonas aeruginosa infection following an immune-weakening challenge. Male C57BL/6J mice underwent cecal ligation and puncture (CLP) or sham surgery followed by intranasal Pseudomonas aeruginosa instillation (1 × 10 6 , 1 × 10 7 , 5 × 10 7 , or 1 × 10 8 colony-forming units [CFU]) 4 days later. Consistent with previous findings, sublethal (mortality rate < 6%) systemic inflammation was induced, evidenced by elevated circulating TNFα, IL-6, and MCP-1 levels 4 h post-CLP. Twenty hours post- Pseudomonas challenge, CLP mice exposed to 5 × 10 7 CFU displayed persistently elevated Clinical Severity Scores, although pulmonary Pseudomonas burden did not significantly differ between groups. Lower inocula resulted in limited infection, whereas 1 × 10 8 CFU resulted in 100% mortality. We further demonstrated that, following a secondary ex vivo LPS challenge, spleen-derived macrophages and adherent bone marrow cells from CLP control animals showed lower TNFα and IL-6, but higher IL-10 release compared to sham controls. Lung macrophage responses were similarly suppressed, with reduced pulmonary levels of cytokines (TNFα, IL-6) and chemokines (CXCL9, CXCL10, CCL22) after a secondary in vivo Pseudomonas aeruginosa infection. The diminished pro-inflammatory macrophage response was partially restored ex vivo by rice-derived arabinoxylan preparations. In conclusion, pro-inflammatory lung, spleen, and bone marrow macrophage responses are suppressed following an immune-weakening challenge, potentially contributing to increased clinical severity during Pseudomonas aeruginosa -associated pneumonia. Rice-derived arabinoxylans, by boosting macrophage responsiveness ex vivo, emerge as potential therapeutic agents to enhance immune defense against opportunistic infections.
Communities in the central Andes of Peru rely on ethnobotanical plants for their primary health care, consuming them mainly as herbal teas. These plants are exposed to heavy metal contamination from both geogenic and anthropogenic sources. The extent of heavy metal contamination and the associated risks to human health in the Mantaro River Valley are not yet fully understood. The objective of this study was to assess the concentrations and risks to human health of six target elements (As, Cr, Cu, Zn, Co, and Pb) in the leaves of five widely used medicinal species (Matricaria chamomilla, Aloysia citrodora, Eucalyptus globulus, Schinus molle, and Minthostachys mollis) in the agricultural districts of Chupuro and Pucará, in the Mantaro River Valley, Peru. The analyses were performed using inductively coupled plasma mass spectrometry (ICP-MS). The results showed that the leaves of E. globulus and M. mollis from the Pucará district had the highest mean concentrations of Zn (11.99 mg/kg) and Cu (5.27 mg/kg), and of As (0.30 mg/kg) and Co (0.24 mg/kg), respectively. The leaves of E. globulus and M. mollis plants from the Chupuro district contained the highest mean concentrations of Cr (0.98 mg/kg) and Pb (0.49 mg/kg), respectively. Regarding the assessment of risk to human health, the individual hazard quotients (HQ) and the cumulative hazard index (HI), which assess non-carcinogenic health risk, were below the safety threshold (HQ < 1 and HI < 1) for all plant species. The estimated total carcinogenic risk (TR), averaged over a 70-year lifetime, was found to be driven primarily by Cr and As, reaching a maximum of 1.14 × 10−6 (E. globulus, Chupuro), the only value marginally above the precautionary reference target of 1 × 10−6. Overall, these results indicate a low level of potential risk, supporting the need for periodic monitoring to ensure the long-term safety of ethnobotanical plants rather than suggesting an immediate threat to human health.
The increasing share of intermittent renewable energy sources supports energy system decarbonization but increases flexibility requirements. Biogas, a low-carbon and dispatchable energy source, can significantly enhance flexibility. However, European and national regulations mainly reduce barriers and costs without promoting flexible biogas power plant operation. With carbon prices at unprecedented levels despite the crisis following the Russian attack on Ukraine, a key question arises: Should flexible operation of biogas plants be incentivized through subsidies, carbon pricing, or both? This study extends an established European energy system model by incorporating biogas and heat storage, as well as flexible combined heat and power units. Gas storage enables short-term flexibility by temporally shifting electricity and heat production, while heat storage decouples heat supply from electricity generation. Two mechanisms are analyzed: CO2 pricing and a market-oriented subsidy combining bonus and malus payments. Results demonstrate that higher CO2 prices and the proposed subsidy effectively incentivize flexible operation, improving system efficiency. CO2 pricing increases price variability, favoring flexibility, while the subsidy rewards market-aligned production. We recommend higher CO2 prices to support low-carbon technologies and a targeted subsidy to accelerate the shift from inflexible to flexible biogas plant operation.
