Activation of SIRT3 by Tanshinone IIA ameliorates renal fibrosis by suppressing the TGF-ß/TSP-1 pathway and attenuating oxidative stress.

Although doxorubicin (DOX) is a common chemotherapeutic drug, the serious nephrotoxicity caused by DOX-induced renal fibrosis remains a considerable clinical problem. Tanshinone IIA (Tan IIA), a compound extracted from Salvia miltiorrhiza, has been reported to have an anti-fibrotic effect. Therefore, this study investigated the molecular pathway whereby Tan IIA protects the kidneys from DOX administration. DOX (3 mg/kg body weight) was intraperitoneally administered every 3 d for a total of 7 injections (cumulative dose of 21 mg/kg) to induce nephrotoxicity. Then, Tan IIA (5 or 10 mg/kg/d) was administered by intraperitoneal injection for 28 d. In an in vitro study, 293 T cells were cultured and treated with DOX and Tan IIA for 24 h. Tan IIA reduced the blood urea nitrogen levels elevated by DOX while increasing superoxide dismutase activity, down-regulating reactive oxygen species, ameliorating renal-tubule thickening, and rescuing mitochondrial morphology. Additionally, Tan IIA reduced the renal collagen deposition, increased ATP production and complex-I activity, down-regulated transforming growth factor-ß1 (TGF-ß1) and thrombospondin-1 (TSP-1), and up-regulated sirtuin 3 (SIRT3). Tan IIA significantly increased cell viability. Additionally, RNA interference was employed to silence the expression of SIRT3, which eliminated the effect of Tan IIA in suppressing the expression of TGF-ß1 and TSP-1. In conclusion, Tan IIA ameliorated DOX-induced nephrotoxicity by attenuating oxidative injury and fibrosis. The Tan IIA-induced rescue of mitochondrial morphology and function while alleviating renal fibrosis may be associated with the activation of SIRT3 to suppress the TGF-ß/TSP-1 pathway.

Global terrestrial drought and its projected socioeconomic implications under different warming targets.

Droughts are increasingly frequent as the Earth warms, presenting adaptation challenges for ecosystems and human communities worldwide. A strategic environmental assessment (SEA) and the integration of adaptation strategies into policies, plans, and programs (PPP) are two important approaches for enhancing climate resilience and fostering sustainable development. This study developed an innovative approach to strengthen the SEA of droughts by quantifying the impacts of future temperature increases. A novel method for projecting drought events was integrated into the SEA process by leveraging multiple data sources, including atmospheric reanalysis, reconstructions, satellite-based observations, and model simulations. We identified drought conditions using terrestrial water storage (TWS) anomalies and applied a random forest (RF) model for disentangling the drivers behind drought events. We then set two global warming targets (2.0 °C and 2.5 °C) and analyzed drought changes under three shared socioeconomic pathways (SSP126, SSP370, SSP585). In a 2.0 °C warming world, over 50 % of the global surface will face increased drought risk. With an additional 0.5 °C increase, >60 % of the land will be prone to further drought escalation. We utilized copulas to build the joint distribution for drought duration and severity, estimating the joint return periods (JRP) for bivariate drought hazard. In tropical and subtropical regions, JRP reductions exceeding half are projected for >33 % of the regional land surface under 2.0 °C warming and for >50 % under 2.5 °C warming. Finally, we projected the impacts of drought events on population and gross domestic product (GDP). Among the three SSPs, under SSP370, population exposure is highest and GDP exposure is minimal under 2.0 °C warming. Global GDP and population risks from drought are projected to increase by 37 % and 24 %, respectively, as warming continues. This study enhances the accuracy of SEA in addressing drought risks and vulnerabilities, supporting climate-resilient planning and adaptive strategies.

Puncture and Drainage Surgery for Intracerebral Hemorrhage Guided by 3D Printing Puncture Guide Plate.

OBJECTIVES: Accurate puncture is the key to ensure the effect of puncture and drainage surgery for intracerebral hemorrhage. It usually uses CT to guide the drainage tube to reach the center of the hematoma cavity, which has the problems of inaccurate positioning using 2D images and high requirements for surgeon's experience in brain anatomy and imaging diagnosis. The aim of this study was to use a 3D printing puncture guide plate to guide the puncture and drainage surgery for intracerebral hemorrhage. METHODS: The CT images were imported into 3D Slicer software to reconstruct 3D models of the head skin and intracerebral hematoma. The target was set in the center of the hematoma and the puncture path from the target to the entry point was designed, the 3D model of puncture guide plate was constructed and saved as stereolithography format file, which was imported into 3D printer to print. During surgery, the drainage tube was placed in the center of the hematoma guided by the 3D printing puncture guide plate, and the blood clot was extracted by the suction syringe. RESULTS: Eight patients with hypertensive intracerebral hemorrhage were treated with puncture and drainage surgery guided by 3D printing puncture guide plate. The average operation time of the 8 surgeries was 17.63 minutes. The drainage tubes were all precisely placed in the center of the hematoma, and the blood clots were all successfully extracted. The positioning errors of the 8 drainage tubes were between 1.76 mm and 2.68 mm, and the mean value was 2.10±0.32 mm. The hematoma clearance rate of the 8 patients was between 74.18% and 96.73%, and the mean value was 85.14±6.71%. CONCLUSIONS: The puncture and drainage surgery for intracerebral hemorrhage guided by 3D printing puncture guide plate helps to quickly and effortlessly localize intracerebral hematoma and achieves satisfactory hematoma clearance rate.