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.

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.

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.

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.

Relationship between the matrix metalloproteinase-9 gene polymorphisms and ischemic stroke.

BACKGROUND: In recent years, with the further research of human genome scanning, the relationship between matrix metalloproteinase-9 (MMP-9) gene polymorphisms and many diseases has aroused increased attention. But there is little research on the relationship between MMP-9 gene polymorphisms and ischemic stroke (IS). This study was conducted to evaluate the relationships between the rs3918242 and rs17577 polymorphisms in the MMP-9 gene and IS in a Chinese population. METHODS: 152 cases of IS patients and 152 healthy controls were enrolled in this study. All subjects were genotyped for the MMP-9 rs3918242 and rs17577 polymorphisms by polymerase chain reaction (PCR) coupled with restriction fragment length polymorphism (RFLP) and restriction analysis. RESULTS: Rs3918242 showed genotypes TT, TC, and CC, and rs17577 exhibited genotypes AA, AG, and GG. The MMP-9 polymorphisms rs3918242 and rs17577 exhibited complete linkage. Our study found there was no significant difference in genotype and allele between rs3918242 and rs17577 between patients and controls. The MMP-9 gene rs3918242 and rs17577 polymorphisms are not significantly correlated with IS risk. Genetic polymorphisms vary among ethnic and regional populations. CONCLUSION: Our results suggest that MMP-9 rs3918242 is completely linked to rs17577, while the rs3918242 and rs17577 polymorphisms are not significantly associated with the risk of IS. Genetic polymorphisms vary among ethnic and regional populations.

Comparison of drip, pipe and surge spring root irrigation for Jujube (Ziziphus jujuba Mill.) fruit quality in the Loess plateau of China.

Loess Plateau is a typical rain-fed farming region, facing the threat of drought. Irrigation method is among the most important factors affecting jujube quality. This study investigated the response of Ziziphus jujuba Mill. cv. Lizao quality to three different irrigation methods (drip-, pipe- and surge spring root irrigation) combining two water levels (20 m(3)/hm(2) and 120 m(3)/hm(2)). The effects of the trials were evaluated by taking into account the physical-chemical characteristics of jujubes and the antioxidant activity. Concomitant to this, the concentration of some taste-related (viz. glucose, fructose, TSS and malic acid) and health-related compounds/parameters (viz. catechin and epicatechin) were generally much greater in jujube fruit treated with drip irrigation (120 m(3)/hm(2)). Different irrigation treatments had no significant effects on antioxidant capacity, total phenolics and proanthocyanidins (except for pipe irrigation 20 m(3)/hm(2)). The best compromise between quality and irrigation of jujube fruit was achieved with drip irrigation (120 m(3)/hm(2)).

[Indoor simulation on dew formation on plant leaves].

Dew forming on plant leaves through water condensation plays a significant ecological role in arid and semi-arid areas as an ignorable fraction of water resources. In this study, an artificial intelligent climate chamber and an automatic temperature-control system for leaves were implemented to regulate the ambient temperature, the leaf surface temperature and the leaf inclination for dew formation. The impact of leaf inclination, ambient temperature and dew point-leaf temperature depression on the rate and quantity of dew accumulation on leaf surface were analyzed. The results indicated that the accumulation rate and the maximum volume of dew on leaves decreased with increasing the leaf inclination while increased with the increment of dew point-leaf temperature depression, ambient temperature and relative humidity. Under the horizontal configuration, dew accumulated linearly on leaf surface over time until the maximum volume (0.80 mm) was reached. However, dew would fall down after reaching the maximum volume when the leaf inclination existed (45 degrees or 90 degrees), significantly slowing down the accumulative rate, and the zigzag pattern for the dynamic of dew accumulation appeared.

[Water impounding characteristics of bamboo-shaped rainwater harvesting ditch in the hilly loess region].

Bamboo-shaped rainwater harvesting ditch (BRHD) is a new water harvesting and application technology being promoted in the hilly loess region of North Shannxi Province. This paper measured the soil moisture condition and water storage capacity of BRHDs filled with straw, branch or gravel through field and simulated rainfall experiments to evaluate the water holding and absorption capacity of different BRHD fillers. From May to October, the water storage of BRHDs showed a decrease trend at first and then increased in field experiment. The water storage depths within 30-200 cm profile of branch ditch (BD), gravel ditch (GD) and straw ditch (SD) were 186.76, 177.23 and 169.26 mm in May, respectively, and increased by 14.24, 20.28 and 21.23 mm in October, respectively. In contrast, the water storage depth of the level bench was reduced by 6.52 mm in October from 185.76 mm in May. The soil water restoration depth was different between BRHDs with different fillers and the level bench within 30-200 cm profile in October. The SD and BD had the deepest restoration depth (140 cm), followed by GD (110 cm), and the level bench was the minimum (80 cm). Through rainfall simulation experiment, the amount of water intercepted by BRHD was in the order of SD (99.5 L) > GD (91 L) > BD (71.5 L). The water-holding rate of straw and branch showed logarithmic function with soaking time, while the water-absorption rate followed a power function. Moreover, there was a negative logarithm correlation between water-holding rate and water-absorption rate. Straw showed a better water holding and absorption capacity than branch. Gravel had a weak water holding and absorption capacity which was almost not changed during soaking, while it displayed a negative liner correlation between water holding rate and absorption rate. The three kinds of BRHDs could be applied in the hilly loess region, and that filled with straw would exhibit the best capacity of water interception and holding.