Drug-loaded balloon with built-in NIR controlled tip-separable microneedles for long-effective arteriosclerosis treatment.

Drug-eluting balloon (DEB) angioplasty has emerged as an effective treatment for cardiovascular and cerebrovascular diseases. However, distal embolism and late lumen restenosis could be caused by drug loss during DEB handling and rapid drug metabolization. Here, a drug-loaded balloon equipped with tip-separable microneedles on the balloon surface (MNDLB) was developed. Inbuilt near-infrared (NIR) ring laser inside the catheter inner shaft was introduced to activate the biodegradable microneedle tips for the first time. The drug-loaded tips thus could be embedded in the vasculature and then released antiproliferative drug - paclitaxel slowly via polymer degradation for more than half a year. A significant increase in drug delivery efficiency and superior therapeutic effectiveness compared with the standard DEB were demonstrated using an atherosclerosis rabbit model.

Vaccinia-related kinase 2 drives pancreatic cancer progression by protecting Plk1 from Chfr-mediated degradation.

As a key cell cycle regulator, polo-like kinase 1 (Plk1) has been recognized as a crucial factor involved in the progression of pancreatic cancer (PC). However, its regulatory mechanism is poorly understood. Here, we present evidence that Plk1 is a novel substrate of vaccinia-related kinase 2 (VRK2), a serine-threonine kinase that is highly expressed and predicts poor prognosis in PC. VRK2 phosphorylates Plk1 at threonine 210 and protects it from ubiquitin-dependent proteasomal degradation. We showed that mechanistically complement factor H-related protein (CFHR), as a major E3 ligase, promotes Plk1 degradation by ubiquitinating it at lysine 209. Phosphorylation of Plk1 at threonine 210 by VRK2 interferes with the interaction of Chfr with Plk1 and antagonizes Plk1 ubiquitination, thereby stabilizing the Plk1 protein. Taken together, our data reveal a mechanism of Plk1 overexpression in PC and provide evidence for targeting VRK2 as a potential therapeutic strategy.

Vaccinia-related kinase 2 blunts sorafenib's efficacy against hepatocellular carcinoma by disturbing the apoptosis-autophagy balance.

Hepatocellular carcinoma (HCC) is a lethal malignancy with limited treatment options. Sorafenib is the only Food and Drug Administration (FDA)-approved first-line targeted drug for the treatment of advanced HCC. However, its effect on patient survival is limited. Recently, studies have demonstrated that the imbalance between apoptosis and autophagy plays a critical role in chemoresistance, and it is hypothesised that restoring the balance between these processes is a potential treatment strategy for improving chemoresistance in cancer. However, there is currently no evidence supporting this hypothesis. We aimed to investigate if vaccinia-related kinase 2 (VRK2), a serine/threonine protein kinase, confers sorafenib resistance in HCC cells. Here, we found that VRK2 was enriched in sorafenib-resistant HCC cells and patient-derived xenografts. Both in vivo and in vitro evidences showed that VRK2 blunts the efficacy of sorafenib against hepatocellular carcinoma by disturbing the balance between apoptosis and autophagy. Mechanistically, VRK2 promotes the phosphorylation of Bcl-2 by activating JNK1/MAPK8, thereby enhancing the dissociation of Bcl-2 from Beclin-1 and promoting the formation of the Beclin-1-Atg14-Vps34 complex, which facilitates autophagy. Furthermore, VRK2-induced phosphorylation of Bcl-2 promotes the interaction of Bcl-2 with BAX, thereby inhibiting apoptosis. In conclusion, targeting VRK2 for modulation of the balance between autophagy and apoptosis may be a novel strategy for overcoming sorafenib resistance in HCC.

Climate, Life Form and Family Jointly Control Variation of Leaf Traits.

Variation in leaf traits may represent differences in physiological processes and environmental adaptative strategies. Using multivariate analyses, we investigated 13 leaf traits to quantify the trade-off in these traits and the trait-climate/biome relationships based on the China Plant Trait Database, which contains morphometric and physiological character information on 1215 species for 122 sites, ranging from the north to the tropics, and from deserts and grasslands to woodlands and forests. Leaf traits across the dataset of Chinese plants showed different spatial patterns along longitudinal and latitudinal gradients and high variation. There were significant positive or negative correlations among traits; however, with the exception of the leaf 13C:12C stable isotope ratio, there were no significant correlations between leaf area and other traits. Climate, life form, and family jointly accounted for 68.4% to 95.7% of trait variance. Amongst these forms of variation partitioning, the most important partitioning feature was the family independence of climate and life form (35.6% to 57.2%), while the joint effect of family and climate was 4.5% to 26.2%, and the joint effect of family and life form was 2.4% to 21.6%. The findings of this study will enhance our understanding of the variation in leaf traits in Chinese flora and the environmental adaptative strategies of plants against a background of global climate change, and also may enrich and improve the leaf economics spectrum of China.

Validation of spectrophotometric determination of chlorogenic acid in fermentation broth and fruits.

A fast and accurate ultraviolet-visible (UV-vis) spectrophotometric method was established to determine the presence of chlorogenic acid (CGA) according to potassium ferricyanide-Fe (III) detection system. The reaction temperature and pH level greatly influenced the CGA absorption spectrum. Maximum UV-vis absorption wavelength occurred at 790 nm under the optimum conditions (at 25 °C and pH 7.0). The results of UV-vis were further assessed by comparing the results with those of high-performance liquid chromatography (HPLC). The proposed method showed a wide linear sensing range of 10.0-800.0 µg mL-1 (R2 = 0.9996) and a high degree of precision (%R.S.D. < 1.50) and recovery (%R.S.D. > 3.39). Results of CGA and HPLC methods correlated well with each other. The proposed accurate, rapid, sensitive, low-cost, and high-throughput method was successfully used to quantify CGA in fermentation broth and fruits (Mango). Therefore, it may be applied for measuring CGA in biological samples.

Spatial distribution of tree species in evergreen-deciduous broadleaf karst forests in southwest China.

Understanding the spatial distribution of tree species in subtropical evergreen-deciduous broadleaf karst forest is fundamental to studying species coexistence and karst species diversity. Here, complete spatial randomness and heterogeneous Poisson process models were used to analyze the spatial distribution patterns of 146 species with at least one individual per ha in a 25-ha plot in southwest China. We used canonical correspondence analysis (CCA) and the torus-translation test (TTT) to explain the distributions of observed species. Our results show that an aggregated distribution was the dominant pattern in Mulun karst forests; the percentage and intensity of aggregated decreased with increasing spatial scale, abundance, mean diameter at breast height (DBH), and maximum DBH. Rare species were more aggregated than intermediately abundant and abundant species. However, functional traits (e.g., growth form and phenological guild) had no significant effects on the distributions of species. The CCA revealed that the four analyzed topographic variables (elevation, slope, aspect, and convexity) had significant influences on species distributions. The TTT showed that not all species have habitat preferences and that 68.5% (100 out of 146 species) show a strongly positive or negative association with at least one habitat. Most species were inclined to grow on slopes and hilltops.

[Major Factors Influencing the Cd Content and Seasonal Dynamics in Different Land Cover Soils in a Typical Acid Rain Region].

Understanding the seasonal variations in active heavy metal components and sensitive impact factors is of importance for the ecological risk reduction during the agricultural production processes. Paddy fields, vegetable lands, and hilly forests were selected as three main land cover types to assess the seasonal characteristics of Cd bioavailability and reveal how or to what extent it was affected by the physiochemical parameters of soils, under different land-use types in a typical Cd-contaminated watershed in the middle and lower reaches of Xiangjiang River. One-year in situ monitoring results showed that natural rainfall pH in winter and spring was lower than in summer and autumn in the study region. The total Cd content of paddy soils was significantly higher than that of the vegetable soil, while the hilly forest soil showed the lowest total Cd value. Similar seasonal variations in total Cd content were found in three soil types with slightly lower summer and autumn concentrations than spring and winter values, but no obvious correlation was detected between the total and the available Cd components. The paddy soil available Cd concentration during the 5-9-month crop growth season was significantly lower than the other months of the year, while vegetable cultivation and hilly forest soils showed the opposite trend. Eh was the key factor that had a positive influence on the Cd activity in paddy soil. Soil TOC concentration was negatively correlated with soil activity in vegetable soil. TOC, water soluble organic carbon, showed a significant positive correlation with Cd effectiveness. The results provide scientific references for Cd contamination control and safe agricultural production.

[Cd Runoff Load and Soil Profile Movement After Implementation of Some Typical Contaminated Agricultural Soil Remediation Strategies].

Owing to the strong ability to immobilize and hyperaccumulate some toxic heavy metals in contaminated soils, the biochar, lime and such as hyperaccumulator ramie received increasing interests from crops and environment safety in recent years. Outdoor pot experiment was conducted to compare the impacts of lime and biochar addition in paddy rice treatment, hyperaccumulator ramie and ramie combined with EDTA of plant Phytoremediation methods on soil available Cd dynamics in rainfall runoff and the mobility along soil profile, under both natural acid precipitation and acid soil conditions. The results showed that, biochar addition at a 2% mass ratio application amount significantly increased soil pH, while ramie with EDTA application obviously decreased soil pH compared to ramie monoculture. Within the same rainfall events, water soluble Cd concentration in surface runoff of ramie treatments was significantly higher than those of waterlogged rice treatments, and Cd concentration in runoff was obviously increased after EDTA addition, whereas lime at a 0.3% mass ratio application amount as additive had no obvious impact on soil pH and Cd speciation change, which may be due to the low application amount. During the whole experimental period , water soluble Cd concentration of rainfall runoff in spring was higher than that in summer, showing the same seasonal characteristics in all treatments. Biochar addition could significantly decrease available Cd content in 0-20 cm soil layer and with certain preferable persistency effects, whereas EDTA addition treatment obviously increased available Cd of 0-20 cm soil layer compared to other treatments, and obvious Cd element activation phenomenon in 20-40 cm soil layer was observed after EDTA addition. In conclusion, lime and biochar as environmental and friendly alkaline Cd immobilization materials showed lower environment risk to surface and ground receiving water, but attention should be paid to phytoremediation enhanced with EDTA or other organic acid before promotion and field application for heavy metals removal from contaminated soils.

Study on nitrogen load reduction efficiency of agricultural conservation management in a small agricultural watershed.

Different crops can generate different non-point source (NPS) loads because of their spatial topography heterogeneity and variable fertilization application rates. The objective of this study was to assess nitrogen NPS load reduction efficiency by spatially adjusting crop plantings as an agricultural conservation management (ACM) measure in a typical small agricultural watershed in the black soil region in northeast China. The assessment was undertaken using the Soil and Water Assessment Tool (SWAT). Results showed that lowland crops produce higher nitrogen NPS loads than those in highlands. It was also found that corn gave a comparatively larger NPS load than soybeans due to its larger fertilization demand. The ACM assessed was the conversion of lowland corn crops into soybean crops and highland soybean crops into corn crops. The verified SWAT model was used to evaluate the impact of the ACM action on nitrogen loads. The results revealed that the ACM could reduce NO3-N and total nitrogen loads by 9.5 and 10.7%, respectively, without changing the area of crops. Spatially optimized regulation of crop planting according to fertilizer demand and geological landscapes can effectively decrease NPS nitrogen exports from agricultural watersheds.

[Non-point loads of soluble cadmium by in situ field experiment with different landuses, in central Hunan province mining area].

Non-point source loads of heavy metals from contaminated soil has increasingly become the major cause of heavy metal concentrations of rivers and lakes surpassed the limitation value, while only few studies had focused on quantitative monitoring of soil heavy metal transportation to water, in situ field conditions. As reported, agricultural farmland heavy metal contamination was the major contamination problem, especially for cadmium (Cd) pollution in middle and downstream of Xiangjiang River. This study selected the typical Cd polluted agricultural watershed for a case study, three typical landuse types of rice, dry farmland and unused grassland with three replicate quadrates were carried out for natural rainfall runoff hydrology processes monitoring, from 2011-2012. Results showed that, precipitation pH value increased from spring to summer, soluble Cd concentration of spring runoff was significantly higher than that of summer rainfall runoff, which presented an obviously seasonal heterogeneity and had a negative correlation with rainfall pH value, and rainfall pH value can obviously impact soil soluble Cd transportation into surface runoff charge. In the same rainfall event, soluble Cd concentration and non-point load of rice were significantly lower than those of dry land and unused grassland, while no obviously seasonal trend was found for non-point load of Cd from three typical landuse types because of the rainfall depth variance, which needs more researches and concerns in the future. These results can provide valuable data and scientific supports for watershed scale's heavy metal non-point source load quantitative estimation and water environment management and water quality diagnosis and early warning.

[Strategy of grain yield stability cooperated with harmonious water environment quality of small agricultural watershed].

This paper investigated the spatial variability of the correlations between grain yields and fertilization quantity within the selected agricultural watershed, in the typical black soil region, and then optimized the fertilization quantity at different landscape farmlands within the watershed based on the regression equations. Study simulated the surface runoff water quality before and after fertilization spatial adjustment with the achieved parameters by Soil and Water Assessment Tool (SWAT) model. The results showed that watershed scale fertilization adjustment is possible and necessary according to the spatial heterogeneity about fertilization and grain yields. Based on grain yield stability, spatial adjustment of fertilization reduced the whole watershed total N fertilization quantity by 1.88%, and the total non-point nutrients load reduction of NH4+ -N and NO3- -N was 9.7%, 5.6%, respectively.