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BACKGROUND : There have been cases reporting anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) and associated serious gastrointestinal (GI) adverse drug reactions (gastrointestinal obstruction, perforation, and ulceration). These adverse drug reactions are not in the drug package inserts, and the drug relationships are not proven in the literature. AIM: We aimed to examine the potential association between GI obstruction, perforation, and ulceration, and ALK-TKIs by data mining of the US FDA Adverse Event Reporting System (FAERS). METHOD : We conducted a disproportionality analysis of GI obstruction, perforation, and ulceration by estimating the reporting odds ratios (ROR) and the information component (IC) with 95% confidence intervals. RESULTS : A total of 279 cases of ALK-TKI-associated GI obstruction, perforation, and ulceration from January 1, 2011, to December 31, 2020, were identified. GI obstruction, perforation, and ulceration cause 16% of cases of death. A significantly increased reporting rate for GI obstruction [ROR 1.77 (1.45-2.15); IC 0.82 (0.53-2.03)] and perforation [ROR 1.61 (1.28-2.02); IC 0.68 (0.35-1.92)] was observed for ALK-TKIs as a drug class. The signal of GI ulceration was detected only in crizotinib [ROR 1.23 (1.01-1.50); IC 0.29 (0.01-1.51)]. A statistically significant ROR and IC emerged for the site of the esophagus. CONCLUSION : Overall, the pharmacovigilance study of the FAERS indicates slightly increased reporting of GI obstruction and perforation, which may cause severe or even fatal outcomes among ALK-TKIs users.

Cyclocarya paliurus is widely distributed in subtropical areas of China. Secondary metabolites in the leaves, including flavonoids and triterpenoids, provide protection against diseases such as hyperlipidemia, diabetes, hypertension, and hypoimmunity. In this study, 343 C. paliurus leaves were collected from 32 distinct populations covering most of the main distribution, to deduce the response of flavonoids and triterpenoids to seven environmental factors. Principal component analysis was performed using seven flavonoid and six triterpenoid compounds. The results show that altitude, latitude, and longitude significantly contributed to variations in total flavonoid and triterpenoid contents. In addition, the interaction of these metabolites was extensively correlated with environment changes, and therefore should be considered during selection and cultivation.

Land urbanization has reduced the amount of area for natural ecosystem assets. However, with the development of the social economy, will the quality of natural ecosystem assets be improved? If one comprehensively considers the changes in the area and quality of natural ecosystem assets, is the dominant impact of urbanization on natural ecosystem assets positive or negative? In this study, detailed research is conducted on the area, pattern, quality, and overall situation of the ecosystem assets in the Beijing–Tianjin–Hebei urban agglomeration during the rapid urbanization process. The impact of urbanization on the overall situation of ecosystem assets is also analyzed. The research methods used to generate statistics, accounting, and analysis of the ecosystem assets include ArcGIS, satellite remote sensing images, R language programming, and other data analysis tools. The research results show that: (1) The ecosystem area was dominated by degradation, and the landscape pattern became increasingly fragmented, with the exception of farmland and wetland areas. (2) However, the quality of the natural ecosystem assets was significantly improved, and the overall situation of the natural ecosystem assets was optimized. (3) In addition to the population urbanization rate, the growth in the population density, land urbanization rate, and GDP per unit area had a significant negative impact on the overall situation of natural ecosystem assets. This reminds people that the improvement in asset quality can compensate for the reduction in area to some extent, and, in addition to the population urbanization rate, the levels of population density, land urbanization, and economic density should be appropriately controlled.

The efficacy of Adoptive Cell Therapy (ACT) for solid tumor is still mediocre. This is mainly because tumor cells can hijack ACT T cells' immune checkpoint pathways to exert immunosuppression in the tumor microenvironment. Immune Checkpoint Inhibitors such as anti-PD-1 (aPD1) can counter the immunosuppression, but the synergizing effects of aPD1 to ACT was still not satisfactory. Here we demonstrate an approach to safely anchor aPD1-formed nanogels onto T cell surface via bio-orthogonal click chemistry before adoptive transfer. The spatial-temporal co-existence of aPD1 with ACT T cells and the responsive drug release significantly improved the treatment outcome of ACT in murine solid tumor model. The average tumor weight of the group treated by cell-surface anchored aPD1 was only 18 % of the group treated by equivalent dose of free aPD1 and T cells. The technology can be broadly applicable in ACTs employing natural or Chimeric Antigen Receptor (CAR) T cells.

Beginning in the 21st century, the world entered a stage of the rapid development of land urbanization. In general, land urbanization sacrifices ecosystem service value for economic value. Optimizing the spatial pattern of land urbanization is the best means of balancing economic development and ecosystem service value. Taking China as an example, through remote sensing and GIS methods, this paper studies the basic situation of regional land urbanization and the distribution of other types of ecosystems from 2000 to 2015, assessing the relationship between the characteristics of regional land urbanization and economic growth and the value cost of ecosystem services. The results show that the spatial differences of land urbanization practices in China is significant and that the extensive development of land urbanization is a serious issue; the urbanization speed of provinces and cities with a larger scale of land urbanization is faster; the intensive, economical and centralized utilization of land urbanization is an effective way to improve GDP per unit area; and the ecosystem service value cost of land urbanization varies significantly among different ecosystem types and regions. For example, the loss of the ecosystem service value of wetland ecosystems due to land urbanization is the greatest, and the cost of the ecosystem service value of Inner Mongolia per 100 million yuan of new GDP is 13.1-fold that of Shanghai. Therefore, to improve the GDP output per unit area and reduce the value cost of ecosystem services, this study draws a series of conclusions and puts forward corresponding policy suggestions that clarify the development mode and priority development area of land urbanization.

Cyclocarya paliurus is a valuable medicinal tree species in China. However, limited information is available on its genotype selection and cultivation for improvement of growth and health-promoting phytochemicals. To contribute to improved knowledge of the potential use of the species, 33 families of C. paliurus were assessed with respect to genotype on growth and flavonoid content in the leaves, and the relationship between growth and flavonoid accumulation was examined. Growth and flavonoid content varied significantly among different families, and isoquercitrin was the main component of the individual flavonoids, followed by kaempferol and quercetin. Both total and individual flavonoids showed seasonal variation, with the mean highest contents of quercetin and isoquercitrin in July but the highest kaempferol content in October. Correlation analysis showed that tree height and diameter at breast height of C. paliurus were negatively correlated with the contents of quercetin and kaempferol in the leaves,...

Cyclocarya paliurus is a highly valued and multiple function tree species. Its leaves have traditionally been used as a medicine or nutraceutical tea. However, limited information is available on its genotype selection and cultivation under a wide range of environmental conditions for growth and enhanced antioxidant activities. Twelve genotypes of C. paliurus at four sites were assessed with respect to genotype, environment and their interaction on growth and flavonoid accumulation, while adaptability and stability of each genotype to varying growth environments were also examined. Results indicated that genotype and growth environment significantly affected the growth and flavonoid accumulation of C. paliurus, with environmental effects being more predominant. Interactions between genotype and environment significantly influenced flavonoid accumulation, but not in growth. Across four sites, stability in tree height growth and total flavonoid content of leaves varied among 12 genotypes of C. paliurus. Hierarchical cluster analysis based on height growth and total flavonoid content of leaves indicated the 12 genotypes were classified into four distinct groups, and three genotypes (SC-4, HF-10 and KM-5) were recommended for flavonoid production in future. Techniques used in this paper would be valuable in identifying the best choice among current and future genotype of C. paliurus for use in flavonoid production.

Cyclocarya paliurus has been used commonly to treat diabetes in China. However, the effective components and the effect of plant origin remain unclear. In this study, C. paliurus leaves with different chemical compositions were selected from five geographical locations, and their effects on streptozotocin (STZ)-induced diabetic mice were evaluated with both ethanol and aqueous extracts. Glucose levels, lipid levels, and biomarkers of liver and kidney function were measured. The principal components of both C. paliurus ethanol and aqueous extracts from different geographical locations differed quantitatively and qualitatively. Results showed that C. paliurus extracts with better antihyperglycemic effects were characterized by higher contents of total flavonoids, especially quercetin-3-O-glucuronide and kaempferol-3-O-glucuronide. Furthermore, significantly negative correlations were found between triterpenoids contents and lipid levels. These results revealed the potential antihyperglycemic capacity of C. paliurus flavonoids and the antihyperlipidemic effect of C. paliurus triterpenoids. Thus, we suggest that the composition of C. paliurus compounds might help to design therapeutic alternatives for the treatment of diabetes mellitus. However, geographic origins and the extraction solvents can also affect the effectiveness of the treatment as these factors influence the chemical compositions and thereby the biological activities.

Cyclocarya paliurus is an edible and medicinal plant containing various bioactive components with significant health benefits. A combinative method using high-performance liquid chromatography (HPLC) fingerprint and quantitative analysis was developed and successfully applied for characterization and quality evaluation of C. paliurus leaves collected from 18 geographical locations of China. For the fingerprint analysis, 21 common peaks were observed among the 18 samples, and these peaks were identified by high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (HPLC–Q–TOF–MS), while a simultaneous quantification of 16 markers was conducted to interpret the variations of contents of these bioactive compounds among the C. paliurus leaves from different geographical locations. Quantification results showed that the contents of these sixteen investigated compounds varied greatly among the leaves from different locations. The developed new method would be a valuable reference for further study and development of this bioactive plant.

Natural gas infrastructure releases methane (CH4), a potent greenhouse gas, into the atmosphere. The estimated emission rate associated with the production and transportation of natural gas is uncertain, hindering our understanding of its greenhouse footprint. This study presents a new application of inverse methodology for estimating regional emission rates from natural gas production and gathering facilities in northeastern Pennsylvania. An inventory of CH4 emissions was compiled for major sources in Pennsylvania. This inventory served as input emission data for the Weather Research and Forecasting model with chemistry enabled, and atmospheric CH4 mole fraction fields were generated at 3 km resolution. Simulated atmospheric CH4 enhancements from WRF-Chem were compared to observations obtained from a three-week flight campaign in May 2015. Modelled enhancements from sources not associated with upstream natural gas processes were assumed constant and known and therefore removed from the optimization procedure, creating a set of observed enhancements from natural gas only. Simulated emission rates from unconventional production were then adjusted to minimize the mismatch between aircraft observations and model-simulated mole fractions for ten flights. To evaluate the method, an aircraft mass balance calculation was performed for four flights where conditions permitted its use. Using the model optimization approach, the weighted mean emission rate from unconventional natural gas production and gathering facilities in northeastern Pennsylvania approach is found to be 0.36 % of total gas production, with a 2σ confidence interval between 0.27–0.45 % of production. Similarly, the mean emission estimates using the aircraft mass balance approach is calculated to be 0.34 % of regional natural gas production, with a 2σ confidence interval between 0.06–0.62 % of production. These emission rates as a percent of production are lower than rates found in any other basin using a top-down methodology, and may be indicative of some characteristics of the basin that makes sources from the northeastern Marcellus region unique.

The extraction conditions of procyanidins (PC) from the Chinese hawthorn ( Crataegus pinnatifida Bge. var. major N.E.Br.) fruits were optimized by response surface methodology (RSM). Results showed that 93.4 ± 0.21% of the PC could be recovered. The crude extract was then purified by using a LSA-10 resin column, which showed excellent adsorption and desorption properties for PC purification. A fraction with PC content above 83.2% and mainly consisting of EC, a singly-charged dimer and trimer as identified by HPLC/MS, was obtained by isolation on LSA-10 resin. The antioxidant activity of hawthorn PC was tested in vitro with different systems. In solution systems, the OH and O 2 − scavenging ability of hawthorn PC were higher than vitamin C. In a liposome peroxidation system, hawthorn PC exhibited much higher antioxidant activity than vitamin E. In addition, hawthorn PC (0.02% w/v) was efficient to inhibit lipid peroxidation during enzymatic hydrolysis of porcine meat at 50 °C for 24 h.

Medical imaging in clinical diagnoses and treatment has been increasingly important, and CT scan has been applied more widely. It is important to extract blood vessels structure for improving planning and navigating in interventional procedures. However, the complexity of vascular structures and the limitation of angiography equipment make vessel segmentation from CT images more challenging. A method for extracting abdominal aorta from CT images is proposed based on vessel enhancing diffusion filters and three-dimensional region growing algorithm. In order to certify the proposed method, a group of clinical CT image series is used and the results show that the proposed method is an effective way for improving the accuracy of abdominal aorta segmentation.

Emodin, an anthraquinone derivative isolated from root and rhizome of Rheum palmatum, has been reported to have promising anti-diabetic activity. The present study was to explore the possible mechanism of emodin to ameliorate insulin resistance. Insulin resistance was induced by feeding a high fat diet to Sprague-Dawley rats. The blood glucose and lipid profiles in serum were measured by an enzymatic method, and a hyperinsulinaemic-euglycaemic clamp was used to evaluate insulin resistance. L6 cells were cultured and treated with palmitic acid and emodin. The lipid content was assayed in the soleus muscle and L6 cells by Oil Red O staining. Western blot, qRT-PCR, and immunohistochemical staining were used to detect the following in the rat soleus muscle and L6 cells: protein levels, mRNA levels of FATP1, FATP4, transporter fatty acid translocase (FAT/CD36), and plasma membrane-associated fatty acid protein (FABPpm). We found that blood glucose, triglyceride (TG), total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) were significantly decreased in the emodin group. Oil Red O staining and the level of TG in skeletal muscle and L6 cells confirmed that lipid deposition decreased after treatment with emodin. Furthermore, the protein levels and mRNA levels of FATP1 in skeletal muscle and in L6 cells of rats were significantly decreased, yet the protein levels and mRNA levels of FATP4, FAT/CD36 and FABPpm did not drop off significantly. The study suggest that emodin ameliorates insulin resistance by reducing FATP1-mediated skeletal muscle lipid accumulation in rats fed a high fat diet.

Type 2 diabetes mellitus (T2DM) is associated with an increased risk of macrovascular disease. Epidemiological studies suggest that plant polyphenol resveratrol (REV) is associated with reduced risk of cardiovascular diseases. Since chronic inflammatory and endotheliar cell activation play a critical role in vascular aging and atherogenesis, we evaluated whether REV can inhibit inflammatory-induced vascular injury in T2DM. We found that REV (50 mg/kg/d) can regulate glucose and lipid metabolism, improve insulin resistance and vascular permeability, and protect against the foam cells and cholesterol crystals formation in arterial vessel walls of T2DM rats. The protective effects of REV were consistent with the decrease in nuclear translocation of nuclear factor kappa B (NF-kappa B) and there down-regulation of interleukin-1 beta (IL-1β) and interleukin-6 (IL-6) levers in blood and tumor necrosis factor-alpha (TNF-α), intercellular adhesion molecule-1 (ICAM-1), and monocyte chemoattractant protein-1 (MCP-1) expressions in vascular wall. In addition, REV (10 and 100 nmol/L) treatment protected cultured endothelial cells against increases in the expression of TNF-α, ICAM-1, and MCP-1 mRNA and protein induced by high glucose via inhibiting nuclear translocation of NF-kappa B p65. The specific NF-kappa B inhibitor pyrrolidine dithiocarbamate- (PDTC-) or small interfering RNA directed against NF-kappa B p65-mediated downregulation of NF-kappa B p65 was further enhanced by REV (100 nmol/L) in the human endothelial cell line EZ.hy926. In conclusion, these observations suggest that chronic treatment of T2DM rats with REV attenuates the inflammatory injury of the vascular wall and the effects are associated with down-regulation of the NF-kappa B signal pathway.

In the single crystal BiSr ( Ca 0.35 Sr 0.15 Bi 0.40)2 Cu 2 O y a characteristic defect-superdislocation has been observed by TEM. The twist boundary resulted from the interaction of two sets of mutually perpendicular superdislocations has been analysed.