Novel use for old drugs: The emerging role of artemisinin and its derivatives in fibrosis.

Artemisinin and its derivatives are a family of anti-malarial drugs with known clinical safety and efficacy. Apart from its anti-malarial effect, artemisinin has also been reported to show anti-cancer, anti-viral, anti-parasitosis, anti-inflammatory properties in vitro and in vivo. An increasing number of studies report that artemisinin can impact the fibrotic process through various ways, such as TGF-ß, MAPK, Wnt/ß-catenin, PI3K/AKT/mTRO, FRX and Notch signaling pathways, as well as regulation of BMP-7 and cell autophagy. Moreover, the anti-inflammatory properties of artemisinin also contribute to the anti-fibrotic process. The present review summarizes the related studies on artemisinin treatment in fibrosis and elucidates the underlying mechanisms. We believe that this review can explain the potential anti-fibrotic value of artemisinin, outlining its potential use in the development of a safe and effective therapeutic method to alleviate fibrosis in the future.

Neoformation and summer arrest are common sources of tree plasticity in response to water stress of apple cultivars.

BACKGROUND AND AIMS: Depending on the species, water stress affects different growth and developmental processes, mainly due to changes in hydraulic properties and hormonal signalling. This study compared the impact of water stress on tree development and organ growth in three apple cultivars. METHODS: Trees were differentially irrigated to induce water stress or to provide well-watered conditions in their second and third years of growth. Effects of water stress were evaluated at tree scale by shoot number and proportions of the different types of shoots, and at shoot scale by metamer appearance rate, growth duration and arrest time, as well as organ size. KEY RESULTS: Water stress promoted early growth cessation, prolonged summer arrests and decreased growth resumptions, thus modifying within-tree shoot demography in favour of short shoots. Growth cessations occurred in mild water stress conditions before any difference in stem water potential appeared. No major impact was observed on organ size. Consistently with tree ontogeny, the number of shoots that resumed growth after summer arrest decreased with years, but more in water-stressed than well-watered conditions. CONCLUSIONS: Even though the impact of water stress differed slightly among cultivars, the reduction in neoformation and increase in summer arrest played a common role in apple tree morphological responses and led to stress avoidance by early reduction of tree leaf area.

Bioavailable electron donors from ultrasound-treated biomass for stimulating denitrification.

Finding low-cost electron donors to drive denitrification is an important target for many municipal wastewater treatment plants (MWTPs). Excess sludge (biomass) potentially is a low-cost electron donor generated internally to the MWTP, but it has to be made more bioavailable. Aerobic and anoxic biomasses were treated with ultrasound, and their supernatants were used as electron donors for stimulating denitrification. The supernatant from ultrasound-treated anoxic biomass achieved 54% faster nitrate-N removal than did supernatant from the treated aerobic biomass, and the supernatant of untreated biomass was ineffective as an electron donor. UV illumination of the supernatants further enhanced the rates, with increments of 19% and 14%, respectively for the aerobic and anoxic supernatants. Sodium acetate at a range of initial concentrations was compared as a readily bioavailable electron donor to gauge the acceleration impact of the supernatants as equivalent bioavailable chemical oxygen demand (COD). The total chemical oxygen demand (TCOD) of the supernatant harvested from anoxic biomass without UV illumination was 76% bioavailable, while its bioavailable TCOD was 78% after UV illumination. For the supernatant from the aerobic biomass, the bioavailable fractions were, respectively, 56% and 58% without and with UV illumination. The greatest impact for converting excess biomass into a source of bioavailable electron donor to drive denitrification came from ultrasound treatment of the biomass, which disrupted the biomass to form particulate chemical oxygen demand (PCOD) that was bioavailable. PCOD was at least 51% bioavailable, and it contributed no less than 82% of the bioavailable COD.

The role of ultrasound-treated sludge for accelerating quinoline mono-oxygenation.

Activated sludge treated by ultrasound was tested as a source of exogenous electron donor to accelerate quinoline mono-oxygenation, which requires an intracellular electron donor (2H). The quinoline-removal rate was proportional to the amount of treated or untreated sludge added in flask experiments, but the best biodegradation kinetics was obtained with a mixture of 25% untreated sludge plus 75% treated sludge. The treated sludge primarily provided exogenous electron donor, while the untreated sludge provided active biomass. A biofilm system also showed the same beneficial effect of treated sludge, and the soluble fraction of the treated sludge had the greatest impact. Using treated sludge instead of a purchased electron donor provides an economic advantage for accelerating the biodegradation of contaminants whose biodegradation is initiated by an oxygenation reaction, such as quinoline.

Ferroptosis: A New Research Direction of Artemisinin and Its Derivatives in Anti-Cancer Treatment.

Ferroptosis, an iron-dependent cell death mechanism driven by an accumulation of lipid peroxides on cellular membranes, has emerged as a promising strategy to treat various diseases, including cancer. Ferroptosis inducers not only exhibit cytotoxic effects on multiple cancer cells, including drug-resistant cancer variants, but also hold potential as adjuncts to enhance the efficacy of other anti-cancer therapies, such as immunotherapy. In addition to synthetic inducers, natural compounds, such as artemisinin, can be considered ferroptosis inducers. Artemisinin, extracted from Artemisia annua L., is a poorly water-soluble antimalarial drug. For clinical applications, researchers have synthesized various water-soluble artemisinin derivatives such as dihydroartemisinin, artesunate, and artemether. Artemisinin and artemisinin derivatives (ARTEs) upregulate intracellular free iron levels and promote the accumulation of intracellular lipid peroxides to induce cancer cell ferroptosis, alleviating cancer development and resulting in strong anti-cancer effects in vitro and in vivo. In this review, we introduce the mechanisms of ferroptosis, summarize the research on ARTEs-induced ferroptosis in cancer cells, and discuss the clinical research progress and current challenges of ARTEs in anti-cancer treatment. This review deepens the current understanding of the relationship between ARTEs and ferroptosis and provides a theoretical basis for the clinical anti-cancer application of ARTEs in the future.

Ferroptosis, necroptosis, and pyroptosis in cancer: Crucial cell death types in radiotherapy and post-radiotherapy immune activation.

Tumor cell death and antitumor immune activation induced by radiotherapy are extensively well-studied. While radiotherapy is believed to mainly induce tumor cell necrosis and apoptosis, recent studies have shown that it can also induce ferroptosis, necroptosis, and pyroptosis in tumor cells. However, studies on the role of ferroptosis, necroptosis, and pyroptosis in radiotherapy and post-radiotherapy immune activation are limited. In this review, we summarize the comprehensive literature on the molecular mechanisms and more recent research progress related to radiotherapy-induced ferroptosis, necroptosis, and pyroptosis in tumor cells. Further, we discuss the role of tumor cells undergoing these types of cell death in immune activation after radiotherapy. In addition, we highlight some unresolved questions on the association of radiotherapy with ferroptosis, necroptosis, and pyroptosis. This review can improve our current understanding of the relationship between radiotherapy and different cell death pathways and provide a theoretical framework to improve the therapeutic effect of tumor radiotherapy in the future.

Comparison of immunotherapy combined with stereotactic radiotherapy and targeted therapy for patients with brain metastases: A systemic review and meta-analysis.

Advances in brain imaging have led to a higher incidence of brain metastases (BM) being diagnosed. Stereotactic radiotherapy (SRS), systemic immunotherapy, and targeted drug therapy are commonly used for treating BM. In this study, we summarized the differences in overall survival (OS) between several treatments alone and in combination. We carried out a systematic literature search on Pubmed, EMBASE, and Cochrane Library. Differences in OS associated with Immune checkpoint inhibitors (ICI) alone versus targeted therapy alone and SRS + ICI or ICI alone were evaluated. This analysis was conducted on 11 studies involving 4,154 patients. The comprehensive results of fixed effect model showed that the OS of SRS + ICI group was longer than that of the ICI group (hazard ratio, 1.72; 95% CI: 1.41-2.11; P = 0.22; I 2 = 30%). The combined fixed-effect model showed that the OS time of ICI was longer than that of targeted therapy (hazard ratio, 2.09; 95% CI: 1.37-3.20; P = 0.21; I 2 = 35%). The study had a low risk of bias. In conclusion, our analysis confirmed that immunotherapy alone showed a higher OS benefit in BM patients than targeted therapy alone. The total survival time of patients with SRS combined with ICI was higher than that of patients with single ICI.

Comprehensive analysis of the migration and transformation of nutrients between sediment and overlying water in complex habitat systems.

Under the influence of environmental change, disturbance and other external conditions, sediments release internal nutrients to the overlying water and become a contamination source in the lake. Complex habitat systems provide a unique opportunity for determining the influences of environmental changes in lakes. In this study, Baiyangdian Lake (BYDL) was divided into different habitat systems (connected water areas, river courses, reed fields, lotus ponds, fishponds, farmland, and thorps) based on the influence of natural and artificial activities. The physical and chemical properties of overlying water and sediment in different habitat systems were investigated. In addition, statistical analytical methods were used to analyze the relationship between sediment characteristics and overlying water parameters in different habitat systems. The results showed that nitrogen and phosphorus in the overlying water could accumulate in the sediments, while disturbance was one of the main factors affecting the release of nutrients from sediments. Disturbance promoted the suspension of sediments and increased the oxygen content, thereby facilitating the internal release of nutrients. However, there were also some differences in the process of internal release of nutrients between the habitat systems. Nitrogen in the overlying water was closely related to the source of organic matter (r > 0.950), especially in the ponds (including lotus ponds, reed fields, and fishponds), and phosphorus was mainly influenced by turbidity (r > 0.870). In the river course (p = 0.198, n = 26), the disturbance and increase in pH promoted the internal release of nutrients from the sediments (contributions of 35.2 % and 25.1 %, respectively). In the ponds, the aquatic macrophytes reduced the release of nitrogen and phosphorus in sediments. Overall, this study provides more information on the migration and transformation of nutrients between sediment and overlying water in lakes with multiple habitats.

Experimental study of mulching effects on water restoration of deep, desiccated soil in a loess hilly region.

Drought climate and human activity have led to serious soil desiccation in the loess hilly region. Mulching measures can effectively increase rainfall infiltration and reduce evaporation, thus improving soil moisture status. The objective of this study was to explore the characteristics of water restoration of deep desiccated soil under different mulching measures and determine a promising mulching measure. We built large-scale simulation desiccated soil columns in the field (soil columns with an 0.8-m diameter and 10-m depth). Six kinds of treatments were tested: film mulching, gravel mulching, branch mulching, planting of jujube tree (Ziziphus jujuba Mill.) and robinia (Robinia pseudoacacia L.), and bare land as the control. The results showed that different mulching measures can increase soil water storage and alleviate the soil drying phenomenon to different degrees. Compared with other treatments, film mulching is more effective, with larger increment of soil water storage, deeper restoration of soil dry layer, and simple to operate in loess hilly region. So, we recommend film mulching, which is a feasible method to improve the soil desiccation status in hilly loess areas.

Enrichment differences and source apportionment of nutrients, stable isotopes, and trace metal elements in sediments of complex and fragmented wetland systems.

Anthropogenic activities significantly influence the lake environment and are reflected by the element contents in sediments/soils. The lake fragmentation provides a unique opportunity for comparing the influences of natural/anthropogenic activities of different wetlands systems. In this study, a complex and fragmented lake was investigated, and sediment/soil samples were collected from different systems. The nutrient contents (C, N, and P), stable isotopic compositions (δ13C and δ15N), and trace metal contents (As, Cd, Cr, Cu, Ni, Pb, and Zn) in the sediments/soils were measured to determine the natural and anthropogenic influences and pollution sources. Lake fragmentation was caused by insufficient water input and long-term agricultural and aquacultural activities of local residents. Due to the effect of anthropogenic activities, the enrichment conditions of various elements differed significantly for different wetland systems. Industrial, agricultural, and biological sources significantly influenced the element enrichment in different systems. The results demonstrated that the anthropogenic activities significantly influenced the sediments/soils in wetland systems, and the lake fragmentation reduced the diffusion of the contaminants. These results provide accurate reference information for pollution control, lake management, and ecological restoration.