Water quality characteristics and evaluation of Qilian Mountain National Park section in Heihe River Basin based on water quality indices and 3D fluorescence technology.

The water quality of the Heihe River Basin affects the life quality and health of tens of thousands of residents along it. However, there are relatively few studies that evaluate its water quality. In this study, we used principal component analysis (PCA), an improved comprehensive water quality index (WQI), and three-dimensional (3D) fluorescence technology to identify pollutants and evaluate water quality at nine monitoring sites in the Qilian Mountain National Park in Heihe River Basin. PCA was applied to concentrate the water quality indices into nine items. The analysis shows that the water quality in the study area is mainly polluted by organic matter, nitrogen, and phosphorus. According to the revised WQI model, the water quality of the study area is from moderate to good, while the water quality of Qinghai section is worse than that of Gansu section. According to the 3D fluorescence spectrum analysis of the monitoring sites, the organic pollution of water comes from vegetation decay, animal feces, and some human activities. This study can not only provide support and basis for water environment protection and management in the Heihe River Basin, but also promote the healthy development of the water environment in the Qilian Mountains.

Targeting the Akt/PI3K/mTOR signaling pathway for complete eradication of keloid disease by sunitinib.

Keloid disease is a nodular lesion, tumor-like but not cancerous, and characterized of excessive proliferation of fibroblasts and deposition of extracellular matrix (ECM) components. This condition often causes itching, pain and cosmetic disfigurement, significantly reducing patient quality of life. To date, no universally effective therapies are available, possibly due to inadequate understanding of keloid pathogenesis. As an oral small-molecule inhibitor of certain tyrosine kinase receptors, sunitinib has shown significant therapeutic effects in renal cell carcinoma (RCC) and gastrointestinal stromal tumor (GIST). However, it has never been tested if keloid therapy can be effective for the management of keloids. This study thus aims to explore the potential of sunitinib for keloid treatment. Keloid-derived fibroblasts (KFs) were successfully isolated and demonstrated proliferative advantage to normal skin-derived fibroblasts (NFs). Additionally, sunitinib showed specific cytotoxicity and inhibition of invasion, and induced cell cycle arrest and significant apoptosis in KFs. These effects were accompanied by complete suppression of ECM component expression, including collagen types 1 and 3, upregulation of autophagy-associated LC3B and significant suppression of the Akt/PI3K/mTOR pathway. Moreover, a keloid explant culture model was successfully established and used to test the therapeutic efficacy of sunitinib on keloid formation in nude mice. Sunitinib was found to induce complete regression of keloid explant fragments in nude mice, showing significantly higher therapeutic efficacy than the most commonly used intralesional drug triamcinolone acetonide (TAC). These data suggest that sunitinib effectively inhibits keloid development through suppression of the Akt/PI3K/mTOR pathway and thus can be potentially developed as a monotherapy or combination therapy for the effective treatment of keloid disease.

Responses of CO2 and CH4 in the alpine wetlands of the Tibetan Plateau to warming and nitrogen and phosphorus additions.

Wetland ecosystems store large amounts of carbon, and CO2 and CH4 fluxes from this ecosystem receive the double impact of climate change and human activities. Nonetheless, research on how multi-gradient warming and nitrogen and phosphorus additions affect these wetland greenhouse gas emissions is still limited, particularly in alpine wetland ecosystems. Therefore, we conducted a field experiment on the Tibetan Plateau wetlands, investigating the effects of warming and nitrogen and phosphorus additions on the CO2 and CH4 fluxes in alpine wetlands. Results indicated that warming enhanced the CO2 absorption and CH4 emission in the alpine meadow ecosystem, possibly related to changes in plant growth and microbial activity induced by warming, while we noticed that the promotion of CO2 uptake weakened with the increase in the magnitude of warming, suggesting that there may be a temperature threshold beyond which the ecosystem's capacity for carbon sequestration may be reduced. Nitrogen addition increased CH4 emission, with the effect on CO2 absorption shifting from inhibition to enhancement as the amount of applied nitrogen or phosphorus increased. The interaction between warming and nitrogen and phosphorus additions further influenced CH4 emission, exhibiting a synergistic enhancement effect. This study deepens our understanding of the greenhouse gas responses of alpine wetland ecosystems to warming and nitrogen and phosphorus additions, which is significant for predicting and managing ecosystem carbon balance under global change.

Ultrasound imaging tracking of mesenchymal stem cells intracellularly labeled with biosynthetic gas vesicles for treatment of rheumatoid arthritis.

Rationale: Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation and damage to articular tissues that can lead to irreversible joint damage and progressive disability. The multipotent mesenchymal stem cells (MSCs) play an important role in immune disorders and tissue regeneration. However, their immunosuppressive effects and the underlying mechanisms are largely unclear due to the lack of tools for real-time imaging of MSCs in vivo. Gas vesicles (GVs) are biosynthetic nanobubbles that are ejected from aquatic microbes, such as bacteria and archaea, and have an excellent ultrasound imaging capacity. Methods: We harvested MSCs from the bone marrow of Sprague Dawley (SD) rats. Then, GVs were synthesized and incubated with MSCs to obtain intracellularly labeled MSCs. We firstly tested the ultrasound imaging of GV@MSCs in vitro and in vivo and then explored the therapeutic effect of GV@MSCs combined with methotrexate (MTX) in RA rats. Results: These GV@MSCs showed significant contrast-enhanced ultrasound signals without a loss of viability and differentiation capacity. In addition, the GV@MSCs could be imaged in real-time for 5 days using ultrasound both in vitro and in vivo, making it possible to visually track their migration and homing to the joint cavity from the subcutaneous layer of lateral malleolus joints in the injected RA rats. Furthermore, GV@MSCs significantly enhanced the curative effect of methotrexate (MTX) against RA, resulting in decreased paw thickness, lower arthritis index score, reduced bone erosion and cartilage destruction, compared to the PBS, free MTX, and GV@MSCs groups. Conclusion: We developed a novel therapeutic strategy against RA using GVs-loaded MSCs that can be tracked in vivo in real-time.

EV-T synergizes with AZD5582 to overcome TRAIL resistance through concomitant suppression of cFLIP, MCL-1, and IAPs in hepatocarcinoma.

Hepatocellular carcinoma (HCC) is an aggressive malignancy, and its effective treatment has been hampered by drug resistance. Extracellular vesicle (EV) delivery of TNF-related apoptosis-inducing ligand (TRAIL) (EV-T) was demonstrated to be superior to recombinant TRAIL (rTRAIL) for cancer treatment previously. And AZD5582, a potent antagonist of inhibitors of apoptosis proteins (IAPs) can potentiate apoptosis-based cancer therapies. However, the combination of EV-T and AZD5582 has never been examined for their possible apoptosis inducing synergism in cancers. In this study, we proposed and tested the combination of EV-T and AZD5582 as a potential novel therapy for effective treatment of HCC. Two HCC lines Huh7 and HepG2 that are both resistant to rTRAIL were examined. The results confirmed that AZD5582 and EV-T are synergistic for apoptosis induction in some cancer lines including Huh7 and HepG2 while sparing normal cells. More importantly, this study revealed that TRAIL sensitization by AZD5582 is mediated through the concomitant suppression of anti-apoptotic factors including cFLIP, MCL-1, and IAPs (XIAP, Survivin and cIAP-1). Particularly the downregulation of cFLIP and IAP's appeared to be essential and necessary for the synergism between AZD5582 and TRAIL. In vivo, we first time demonstrated that the combined therapy with low doses of AZD5582 and EV-Ts triggered drastically enhanced apoptosis leading to the complete eradication of Huh7 tumor development without any apparent adverse side effects examined. We thus have unraveled the important molecular mechanism underlying TRAIL sensitization by AZD5582, rationalizing the next development of a combination therapy with AZD5582 and EV-T for HCC treatment. KEY MESSAGES: It confirmed the TRAIL sensitization by AZD5582, a potent antagonist of IAPs in hepatocarcinoma. It revealed that the sensitization is via the concomitant suppression of antiapoptotic factors including cFLIP, MCL-1, and IAPs. The downregulation of cFLIP and IAPs like Survivin appeared to be essential and necessary for the synergism between AZD5582 and nanosomal TRAIL. In vivo the combined therapy with AZD5582 and nanosomal TRAIL led to complete eradication of hepatocarcinoma tumors. This study has rationalized the next development of a combination therapy with AZD5582 and nanosomal TRAIL for cancer treatment.

[Chemical composition and daily variation of melt water during ablation season in monsoonal temperate Glacier region: a case study of Baishui Glacier No. 1].

Melt water samples collected continuously from 29 August to 3 September 2009 in the Baishui Glacier No. 1 at elevation of 4750 m were analyzed for pH, conductivity, delta18O and inorganic ions. The results showed that the pH had obvious diurnal variations and was increased slightly by the influence of precipitation. The dissolution of alkaline soluble salts in the dust was the main reason for the increase of melt water conductivity; the value of delta18O was relatively low in strong ablation period and high in slight ablation period. Different from other research areas, the concentrations of Na+, K+, which were influenced by lithological and marine water vapor, were higher than that of Mg2+ in the study area; HCO3- and Ca2+ accounted for more than 80% of total ions in snow and ice melt water, indicating that the ions mainly came from limestone and the melt water was a typical carbonate solution; The content of melt water had an obvious daily change with temperature change, but the response amplitudes were different; Monsoon transport, local rock lithology, human industrial and agricultural activities were the main sources of inorganic ions and the deciding factors of the ion composition in the Baishui Glacier No. 1.

[Character and sources of conventional anion in different water bodies on the summer in Yulong Snow Mountain area].

Different water samples were collected at Mt. Yulong Region located in lijiang city, Yunnan Province from July 22 to July 28 in 2005. The concentration of anion was measured by Dionex-3000 Ion chromatography and Dionex-600 ion chromatography, different water bodies anion composition and concentration in the study area were analyzed by applying approaches of cluster analysis sea salt iron tracer and typical backward trajectories analyze. The results show that the anion concentration of water of altitude higher than 3 180 m takes on natural state and the influence of human activities and foundation rock is less significant. However, human activities and foundation rock exert direct and decisive influence on the anion concentration of water of altitude lower than 3 180 m, with more significant effects than high altitude. Cluster analysis shows that at high altitude anion concentration and composition of water have strong consistency, the consistency of different water bodies in low altitude area anions is weak, indicating the influence factors is more complex in low altitude than high altitude. Sea salt tracer analysis indicates that the average proportion of nonmarine source of Cl- is 65%; NO3- is predominantly of continental origin; nonmarine sources proportion of SO4(2-) is 93.7%. Typical backward trajectories analyze found that the mostly vapor in the region mainly from the Indian Ocean, part of the vapors from the eastern Pacific, the west wind South Branch occasionally along Tibetan Plateau into the study area. SO4(2-) and NO3(-) which from mainly from Southeast Asia and South Asia input with the monsoon circulation.

[Chemical characteristic of water-soluble ions in total suspended particles (TSP) at Lijiang winter time].

25 total suspended particles (TSP) samples were collected at Lijiang city from Dec 2008 to Jan 2009. Analyzed results indicated that the concentration of CU-, NO3-, SO4(2-), Na+ , NH+, K+, Mg2+ and Ca2+ were 16.00, 14.95, 49.40, 3.12, 44.75, 8.65, 29.50 and 183.02 neq x m(-3) respectively. The average total aerosol loading was 349.39 neq x m(-3), and the average concentration of Ca2+ was 52.38% percent of average total concentration, indicated it was the dominant ion in this sampling. The average concentration of detected cations was 3.35 times of anions, suggested the sum of cations generally exceed the sum of anions in our samples, and the main anion was not detected. The average value of SO4(2-)/NO3- was 3.98, showing that the sustained sources have mainly influences on air. According to the correlation coefficients among ions and factor analysis, Ca2+ and Mg2+ in our samples were from dust, and the sources of NO3-, SO4(2-), NH4+ and K+ were related to various combustion processes by human activities. As a whole, the ions in our samples were mainly combined as CaCO3, (NH4)2SO4, MgCO3, KNO3 and a little CaSO4 and Ca(NO3)2.