Nrf2/FSP1/CoQ10 axis-mediated ferroptosis is involved in sodium aescinate-induced nephrotoxicity.

Sodium aescinate (SA), an active compound found in horse chestnut seeds, is widely used in clinical practice. Recently, the incidence of SA-induced adverse events, particularly renal impairment, has increased. Our previous work demonstrated that SA causes severe nephrotoxicity via nephrocyte ferroptosis; however, the underlying mechanism remains to be fully elucidated. In the current study, we investigated additional molecular pathways involved in SA-induced nephrotoxicity. Our results showed that SA inhibited cell viability, disrupted cellular membrane integrity, and enhanced reactive oxygen species (ROS), ferrous iron (Fe2+), and malondialdehyde (MDA) levels, as well as lipid peroxidation in rat proximal renal tubular epithelial cell line (NRK-52E) cells. SA also depleted coenzyme Q10 (CoQ10, ubiquinone) and nicotinamide adenine dinucleotide (NADH) and reduced ferroptosis suppressor protein 1 (FSP1) and polyprenyltransferase (coenzyme Q2, COQ2) activity, triggering lipid peroxidation and ROS accumulation in mouse kidneys and NRK-52E cells. The overexpression of COQ2, FSP1, or CoQ10 (ubiquinone) supplementation effectively attenuated SA-induced ferroptosis, whereas iFSP1 or 4-formylbenzoic acid (4-CBA) pretreatment exacerbated SA-induced nephrotoxicity. Additionally, SA decreased nuclear factor-erythroid-2-related factor 2 (Nrf2) levels and inhibited Nrf2 binding to the -1170/-1180 bp ARE site in FSP1 promoter, resulting in FSP1 suppression. Overexpression of Nrf2 or its agonist dimethyl fumarate (DMF) promoted FSP1 expression, thereby improving cellular antioxidant capacity and alleviating SA-induced ferroptosis. These results suggest that SA-triggers renal injury through oxidative stress and ferroptosis, driven by the suppression of the Nrf2/FSP1/CoQ10 axis.

Matrine induces cardiotoxicity by promoting ferroptosis through the Nrf2 antioxidant system in H9c2 cells.

Matrine (MT) has shown promising efficacy in various cancers and chronic hepatitis; however, its clinical application is limited because of its side effects. Our previous studies have indicated that MT can induce severe hepatotoxicity and nephrotoxicity. The current study aimed to investigate its cardiotoxicity and potential underlying mechanisms in H9c2 cells. Our results showed that MT induced H9c2 cell death and disrupted the cellular membrane integrity. Moreover, MT decreased glutathione (GSH) and cysteine (Cys) levels, and increased Fe2+, lipid peroxidation, reactive oxygen species (ROS), and MDA levels, ultimately leading to ferroptosis. Interestingly, these phenomena were alleviated by the ferroptosis inhibitor Fer-1, whereas MT-induced ferroptosis was exacerbated by the ferroptosis agonist RSL3. In addition, MT significantly reduced FTH, Nrf2, xCT, GPX4, and FSP1 protein levels and inhibited the transcriptional activity of Nrf2 while increasing TFR1 protein levels. Supplementation with Nrf2 agonist (Dimethyl fumarate, DMF) or selenium (Sodium selenite, SS) and CoQ10 alleviated MT-induced cytotoxic effects in H9c2 cells. These results suggest that ferroptosis, which is mediated by an imbalance in the Nrf2 antioxidant system, is involved in MT-induced cardiac toxicity.

Sodium Selenite Prevents Matrine-Induced Nephrotoxicity by Suppressing Ferroptosis via the GSH-GPX4 Antioxidant System.

Matrine (MT), an active ingredient derived from Sophor flavescens Ait, is used as a therapeutic agent to treat liver disease and cancer. However, the serious toxic effects of MT, including nephrotoxicity, have limited its clinical application. Here, we explored the involvement of ferroptosis in MT-induced kidney injury and evaluated the potential efficacy and underlying mechanism of sodium selenite (SS) in attenuating MT-induced nephrotoxicity. We found that MT not only disrupts renal structure in mice but also induces the death of NRK-52E cells. Additionally, MT treatment resulted in significant elevations in ferrous iron, reactive oxygen species (ROS) and lipid peroxidation levels, accompanied by decreases in glutathione (GSH) and glutathione peroxidase (GPx) levels. SS effectively mitigated the alterations in ferroptosis-related indicators caused by MT and prevented MT-induced nephrotoxicity as effectively as Fer-1 in vivo and in vitro. SS also reversed the MT-induced reduction in GPX4, CTH and xCT protein levels. However, the glutathione peroxidase 4 (GPX4) inhibitor RSL3 and knockdown of GPX4, CTH, or xCT via siRNA abolished the protective effect of SS against MT-induced nephrotoxicity, indicating that SS exhibited antiferroptotic effects via the GSH-GPX4 antioxidant system. Overall, MT-induced ferroptosis triggers nephrotoxicity, and SS is a promising therapeutic drug for alleviating MT-induced renal injury by activating the GSH-GPX4 axis.

Blood glucose variance measured by continuous glucose monitors across the menstrual cycle.

Past studies on how blood glucose levels vary across the menstrual cycle have largely shown inconsistent results based on limited blood draws. In this study, 49 individuals wore a Dexcom G6 continuous glucose monitor and a Fitbit Sense smartwatch while measuring their menstrual hormones and self-reporting characteristics of their menstrual cycles daily. The average duration of participation was 79.3 ± 21.2 days, leading to a total of 149 cycles and 554 phases in our dataset. We use periodic restricted cubic splines to evaluate the relationship between blood glucose and the menstrual cycle, after which we assess phase-based changes in daily median glucose level and associated physiological parameters using mixed-effects models. Results indicate that daily median glucose levels increase and decrease in a biphasic pattern, with maximum levels occurring during the luteal phase and minimum levels occurring during the late-follicular phase. These trends are robust to adjustments for participant characteristics (e.g., age, BMI, weight) and self-reported menstrual experiences (e.g., food cravings, bloating, fatigue). We identify negative associations between each of daily estrogen level, step count, and low degrees of fatigue with higher median glucose levels. Conversely, we find positive associations between higher food cravings and higher median glucose levels. This study suggests that blood glucose could be an important parameter for understanding menstrual health, prompting further investigation into how the menstrual cycle influences glucose fluctuation.

Anisotropic thermal analyses of a high efficiency Tm:YAP slab laser and its intra-cavity pumping for Ho lasers.

We evaluate the thermal effects of a c-cut Tm:YAP slab laser by considering the anisotropic properties of the biaxial YAP crystal. Significant improvements in thermal stress were demonstrated by selecting the crystallographic a-axis, which possesses higher thermal conductivity and thermal expansion, as the direction of the slab thickness. A maximum laser power of 30 W (E//a) at 2 µm was obtained under an incident LD power of 55 W with an optical conversion efficiency of 55.4% and slope efficiency of 61.8% using the a-slab. The slab laser was then used for realizing compact Ho lasers via intra-cavity pumping, resulting in a 0.8 W Ho:YAG laser and a 5.5 W Ho:YAP laser (E//b) at 2.12 µm and 2.13 µm, respectively.

A chemical-bond-driven edge reconstruction of Sb nanoribbons and their thermoelectric properties from first-principles calculations.

We present a theoretical study on the potential thermoelectric performance of antimony nanoribbons (SNRs). Based on density functional theory and the semiclassical transport model, the thermoelectric figure of merit ZT was calculated for various Sb nanoribbon sizes and different chiralities. The results indicated that the chemical-bond-driven edge reconstruction of nanoribbons (denoted as SNRs-recon) eliminated all of the dangling bonds and passivated all of the boundary antimony atoms with 3-fold coordination. SNRs-recon are the most energy favorable compared to the ribbons with unsaturated edge atoms. Semimetal to semiconductor transition occurred in SNRs-recon. The band gap was width-dependent in armchair SNRs (denoted as ASNRs-recon), whereas it was width-independent in zigzag SNRs (ZSNRs-recon). After nanolization and reconstruction, the TE properties of SNRs were enhanced due to higher Seebeck coefficient and lower thermal conductivity. The thermoelectric properties of n-doped ASNRs-recon and p-doped ZSNRs-recon showed width-dependent odd-even oscillation and eventually resulted in ZT values of 0.75 and 0.60, respectively. Upon increasing the ribbon width, ZT of n-doped ASNRs-recon decreased and approached a constant value of about 0.85. However, n-doped ZSNRs-recon exhibited poor TE performance compared with the others. Importantly, the ZT value could be optimized to as high as 1.91 at 300 K, which was larger than those of Sb-based bulk materials and 100 times that of thin Sb films. These optimizations make the materials promising room-temperature high-performance thermoelectric materials. Furthermore, the proposed new concept of chemical-bond-driven edge reconstruction may be useful for many other related systems.

Manipulating the wavelength-drift of a Tm laser for resonance enhancement in an intra-cavity pumped Ho laser.

We demonstrate an enhancement mechanism and thermal model for intra-cavity pumped lasers, where resonance enhancement in intra-cavity pumped Ho laser was achieved by manipulating the wavelength-drift nature of the Tm laser for the first time. Optical conversion efficiency of 37.5% from an absorbed 785 nm diode laser to a Ho laser was obtained with a maximum output power of 7.51 W at 2122 nm, which is comparable to the conversion efficiency in 1.9 µm LD pumped Ho lasers. Meanwhile, more severe thermal effects in the Ho-doped gain medium than the Tm-doped one at high power operation were verified based on the built thermal model. This work benefits the design or evaluation of intra-cavity pumped lasers, and the resonance enhancement originated from the difference in reabsorption loss between stark levels at the lasing manifolds of quasi-three-level rare-earth ions has great interest to improve the existing intra-cavity pumped lasers or explore novel lasers.

(Cs6Cl)6Cs3[Ga53Se96]: A Unique Long Period-Stacking Structure of Layers Made from Ga2Se6 Dimers via Cis or Trans Intralayer Linking.

The new compound (Cs6Cl)6Cs3[Ga53Se96] with its own structure type has been discovered by high-temperature solid-state reactions. The compound features a unique long period-stacking structure of layers that are built by the commonly observed dimeric Ga2Se6 unit extending in cis or trans intralayer linking. Single-crystal X-ray diffraction analyses show the trigonal space group R3̅m (No. 166) and a = 11.990(5) Å, c = 50.012(4) Å, and V = 6226.5(6) Å(3). The UV-vis-near-IR spectrum reveals a wide band gap of 2.74 eV that agrees well with the electronic structure calculation.

Superionic adjustment leading to weakly temperature-dependent ZT values in bulk thermoelectrics.

Thermoelectric (TE) materials are of worldwide interest for energy sustainability through direct waste-heat-to-electricity conversion. Practically, a TE power generator requires a large working temperature gradient; to achieve high efficiency, key TE materials with high ZT values are necessary and, furthermore, their ZT values should decline as little as possible over the imposed temperature range. Unfortunately, sharp ZT declines in all of the known materials are inevitable. Here we found the bulk superionic α-Ag(1-x)CuSe material exhibits unusual weakly temperature-dependent ZT values in the range of 480-693 K with the smallest ZT-T slope known to date. These result from the Seebeck coefficient balance of the countercontributions of holes and electrons and the weakly temperature-dependent thermal conductivity.