Cisplatin and doxorubicin chemotherapy alters gut microbiota in a murine osteosarcoma model.

The gut microbiota is closely associated with tumor progression and treatment in a variety of cancers. However, the alteration of the gut microbiota during the progression and chemotherapy of osteosarcoma remains poorly understood. This study aimed to explore the relationship between dysbiosis in the gut microbiota during osteosarcoma growth and chemotherapy treatment. We used BALB/c nude mice to establish osteosarcoma xenograft tumor models and administered cisplatin (CDDP) or doxorubicin (DOX) intraperitonially once every 2 days for a total of 5 times to establish effective chemotherapy models. Fecal samples were collected and processed for 16S rRNA sequencing to analyze the composition of the gut microbiota. We observed that the abundances of Colidextribacter, Lachnospiraceae_NK4A136_group, Lachnospiraceae_UCG-010, Lachnospiraceae_UCG-006, and Lachnoclostridium decreased, and the abundances of Alloprevotella and Enterorhabdus increased in the osteosarcoma mouse model group compared to those in the control group. In addition, genera, such as Lachnoclostridium and Faecalibacterium were more abundant in chemotherapy-treated mice than those in saline-treated mice. Additionally, we observed that alterations in some genera, including Lachnoclostridium and Colidextribacter in the osteosarcoma animal model group returned to normal after CDDP or DOX treatment. Furthermore, the function of the gut microbiota was inferred through PICRUSt2 (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States), which indicated that metabolism-related microbiota was highly enriched and significantly different in each group. These results indicate correlations between dysbiosis of the gut microbiota and osteosarcoma growth and chemotherapy treatment with CDDP or DOX and may provide novel avenues for the development of potential adjuvant therapies.

Environmental carrying capacity and ecological risk assessment of pesticides under different soil use types in the Central Plains Urban Agglomeration (CPUA), China.

Soil environmental safety has received much attention during the past few decades due to its significance in agricultural production and human health. Special attention is required for soil pesticide residues and ecological risks. This study examined 197 soil samples from industrial, residential and agricultural areas for the presence of 12 organophosphorus pesticides (OPPs) and 8 synthetic pyrethroids (SYPs) in the 16 cities in Henan Province, and the center of CPUA, based on the Central Plains Urban Agglomeration (CPUA) concept proposed by China. The total average concentrations of ∑12OPPs in industrial, residential and agricultural soils were 194, 217, 267 ng/g dry weight, and those of ∑8SYPs were 26.8, 35.7, 25.5 ng/g dry weight, respectively. The two pollutants with the greatest concentrations in the soils were malathion and fenpropathrin, respectively, the dominant components of OPPs and SYPs. The soil environmental carrying capacity (SECC) analysis, representing the maximum residual load that can be supported, shows that acephate and cyhalothrin were overloaded, with a predicted period of over 500 years. Among the 16 cities of CPUA, a higher frequency of high ecological risk could be observed only in Shangqiu. The OPPs in children had total non-carcinogenic risk values of more than 1.0. Similarly, the non-carcinogenic risks of SYPs in adults and children in the residential areas were more than 1.0. The study provides knowledge on how to effectively manage soil safety in Henan Province, which is the center of the CPUA, with a large population and grain province to protect ecosystems and reduce the risks of soil pesticide residues in humans.

Surface electromyogram, kinematic, and kinetic dataset of lower limb walking for movement intent recognition.

Surface electromyogram (sEMG) offers a rich set of motor information for decoding limb motion intention that serves as a control input to Intelligent human-machine synergy systems (IHMSS). Despite growing interest in IHMSS, the current publicly available datasets are limited and can hardly meet the growing demands of researchers. This study presents a novel lower limb motion dataset (designated as SIAT-LLMD), comprising sEMG, kinematic, and kinetic data with corresponding labels acquired from 40 healthy humans during 16 movements. The kinematic and kinetic data were collected using a motion capture system and six-dimensional force platforms and processed using OpenSim software. The sEMG data were recorded using nine wireless sensors placed on the subjects' thigh and calf muscles on the left limb. Besides, SIAT-LLMD provides labels to classify the different movements and different gait phases. Analysis of the dataset verified the synchronization and reproducibility, and codes for effective data processing are provided. The proposed dataset can serve as a new resource for exploring novel algorithms and models for characterizing lower limb movements.

Transcriptomics and metabolomics reveal changes in the regulatory mechanisms of osteosarcoma under different culture methods in vitro.

BACKGROUND: Recently, increasing attention has been drawn to the impact of the tumor microenvironment (TME) on the occurrence and progression of malignant tumors. A variety of 3D culture techniques have been used to simulate TME in vitro. The purpose of this study was to reveal the differences in transcriptional and metabolic levels between osteosarcoma (OS) 2D cells, 3D cells, 3D cell-printed tissue, isolated tissue, and transplanted tumor tissue in vivo. METHODS: We cultured the OS Saos-2 cell line under different culture methods as 2D cells, 3D cells, 3D cell-printed tissue and isolated tissue for 14 days and transplanted tumors in vivo as a control group. Through transcriptomic and metabonomic analyses, we determined the changes in gene expression and metabolites in OS tissues under different culture methods. RESULTS: At the transcriptional level, 166 differentially expressed genes were found, including the SMAD family, ID family, BMP family and other related genes, and they were enriched in the TGF-ß signaling pathway, complement and coagulation cascades, signaling pathways regulating pluripotency of stem cells, Hippo signaling pathway, ferroptosis, cGMP-PKG signaling pathway and other pathways. At the metabolic level, 362 metabolites were significantly changed and enriched in metabolic pathways such as the Fc Epsilon RI signaling pathway, histidine metabolism, primary bile acid biosynthesis, steroid biosynthesis, protein digestion and absorption, ferroptosis, and arachidonic acid metabolism. After integrating the transcriptome and metabolomics data, it was found that 44 metabolic pathways were changed, and the significantly enriched pathways were ferroptosis and pyrimidine metabolism. CONCLUSION: Different culture methods affect the gene expression and metabolite generation of OS Saos-2 cells. Moreover, the cell and tissue culture method in vitro cannot completely simulate TME in vivo, and the ferroptosis and pyrimidine metabolism pathways mediate the functional changes of OS Saos-2 cells in different microenvironments.

Polycyclic aromatic hydrocarbons in soils of Central Plains Urban Agglomeration, China: The bidirectional effects of urbanization and anthropogenic activities.

To investigate the variations in environmental behavior (levels, distribution, sources, and soil toxicity) of polycyclic aromatic hydrocarbons (PAHs) under the impact of anthropogenic activities during the urbanization process, we collected soil samples from 195 sites in the Central Plains Urban Agglomeration (CPUA), North China, and analyzed 16 U.S. Environmental Protection Agency (EPA) PAH priority pollutants. We divided the sampling sites into three groups (urban area, industrial area, and farmland) and collected soil samples (0-20 cm surface layer). ∑16PAHs concentrations in the soils of the urban area, industrial area, and farmland ranged from 24.2 to 4400 ng/g, 12.3-8780 ng/g, and 20.9-852 ng/g (the average value of 349, 634, and 186 ng/g), respectively. The 4 to 5 ring PAHs were dominant compounds in three soil types, accounting for 65-80% of the ∑16PAHs. The results of the source analysis showed that the PAHs in the soils of CPUA were mainly from energy consumption. PAH levels in urban and industrial soils had a potential low cancer risk. The impact of urbanization on PAHs in the soil was bidirectional. On the one hand, the level of PAHs in the farmland soil might increase due to burning coal and agricultural machinery, which releases diesel or petrol fumes. On the other hand, in the urbanization process, the PAH content in urban soil and industrial soil showed a downward trend due to the implementation of environmental protection policies in China, which have reduced the atmospheric input of PAHs into the soil.

Sources of ammonium enriched in groundwater in the central Yangtze River Basin: Anthropogenic or geogenic?

The occurrence of excessive ammonium in groundwater threatens human and aquatic ecosystem health across many places worldwide. As the fate of ammonium in groundwater systems is often affected by a complex mixture of transport and biogeochemical transformation processes, identifying the sources of groundwater ammonium is an important prerequisite for planning effective mitigation strategies. Elevated ammonium was found in both a shallow and an underlying deep groundwater system in an alluvial aquifer system beneath an agricultural area in the central Yangtze River Basin, China. In this study we develop and apply a novel, indirect approach, which couples the random forest classification (RFC) of machine learning method and fluorescence excitation-emission matrices with parallel factor analysis (EEM-PARAFAC), to distinguish multiple sources of ammonium in a multi-layer aquifer. EEM-PARAFAC was applied to provide insights into potential ammonium sources as well as the carbon and nitrogen cycling processes affecting ammonium fate. Specifically, RFC was used to unravel the different key factors controlling the high levels of ammonium prevailing in the shallow and deep aquifer sections, respectively. Our results reveal that high concentrations of ammonium in the shallow groundwater system primarily originate from anthropogenic sources, before being modulated by intensive microbially mediated nitrogen transformation processes such as nitrification, denitrification and dissimilatory nitrate reduction to ammonium (DNRA). By contrast, the linkage between high concentrations of ammonium and decomposition of soil organic matter, which ubiquitously contained nitrogen, suggested that mineralization of soil organic nitrogen compounds is the primary mechanism for the enrichment of ammonium in deeper groundwaters.

Gut microbiota and fecal metabolic signatures in rat models of disuse-induced osteoporosis.

Background: Assessing the correlation between gut microbiota (GM) and bone homeostasis has increasingly attracted research interest. Meanwhile, GM dysbiosis has been found to be associated with abnormal bone metabolism. However, the function of GM in disuse-induced osteoporosis (DIO) remains poorly understood. In our research, we evaluated the characteristics of GM and fecal metabolomics to explore their potential correlations with DIO pathogenesis. Methods: DIO rat models and controls (CON) underwent micro-CT, histological analyses, and three-point bending tests; subsequently, bone microstructures and strength were observed. ELISAs were applied for the measurement of the biochemical markers of bone turnover while GM abundance was observed using 16S rDNA sequencing. Metabolomic analyses were used to analyze alterations fecal metabolites. The potential correlations between GM, metabolites, and bone loss were then assessed. Results: In the DIO group, the abundance of GM was significantly altered compared to that in the CON group. Moreover, DIO significantly altered fecal metabolites. More specifically, an abnormally active pathway associated with bile acid metabolism, as well as differential bacterial genera related to bone/tissue volume (BV/TV), were identified. Lithocholic acid, which is the main secondary bile acid produced by intestinal bacteria, was then found to have a relationship with multiple differential bacterial genera. Alterations in the intestinal flora and metabolites in feces, therefore, may be responsible for DIO-induced bone loss. Conclusions: The results indicated that changes in the abundance of GM abundance and fecal metabolites were correlated with DIO-induced bone loss, which might provide new insights into the DIO pathogenesis. The detailed regulatory role of GM and metabolites in DIO-induced bone loss needs to be explored further.

Design of an Unpowered Ankle-Foot Exoskeleton Used for Walking Assistance.

Enhance human walking and running is much more difficult compared to build a machine to help someone with disability. Unpowered ankle-foot exoskeletons are the current development trend due to their lightweight, wearable, and energy-free features, but the huge recognition and energy control system still affects their practicability. To refine the recognition and control system, we designed an unpowered soft ankle-foot exoskeleton with a purely mechanical self-adaptiveness clutch, which can realize the collection and release of energy according to different gait stage. Through switching and closing of this clutch, energy is collected when the ankle is doing negative work and released when the ankle is doing positive work. Results shows the unpowered ankle-foot exoskeleton at the stiffness of 12000 N/m could relieve muscles' load, with reduction of force by 52.3 % and 5.2%, and of power by 44.2% and 7.0%, respectively for soleus and gastrocnemius in simulation.Clinical Relevance-The proposed Unpowered Ankle-Foot Exoskeleton can both reduce muscle forces and powers. Hence, it can be used to assist walking of the elderly, others with neurocognitive disorders or leg diseases.

Factors controlling iodine enrichment in a coastal plain aquifer in the North Jiangsu Yishusi Plain, China.

Iodine is an essential micronutrient in the human diet and an appropriate human iodine intake level is important for population health. Excessive iodine intake is often associated with high iodine groundwater which serves as an important drinking water source in many regions. This study aims to identify the source and key hydrogeochemical processes for iodine accumulation and mobility in the groundwaters of the Northern Jiangsu Yishusi Plain. Combined hydrogeochemical and statistical analyses, specifically random forest modeling and factor analysis, were used to explore the mechanisms affecting the spatial distribution of iodine. The concentration of iodine in the investigated groundwaters was found to vary widely and to range between 4.8 and 4750 µg/L, with 48.9% of the total samples (674) exceeding the threshold value of 100 µg/L for toxic exposure, as defined by the Chinese high­iodine standard guideline. High iodine concentrations are shown to mainly occur in the marine plain and the shallow aquifer associated with the floodplains of the Old Yellow River. The marine or lagoons-facies sediments were identified as the most plausible iodine source. In addition, mixing of groundwater with paleo-seawater might also have played a role in the coastal area. In contrast, the flood sediments of the Old Yellow River are shown to be an unlikely source. However, they serve as a cover layer that favored the development of reducing hydrogeochemical conditions that can trigger iodine mobilization via the reductive dissolution of iron oxides and the degradation of organic matter. Slow groundwater flow rates also appear to favor iodine release from sediments.

A Five-microRNA Signature as Risk Stratification System in Uterine Corpus Endometrial Carcinoma.

BACKGROUND: MicroRNAs (miRs) have been shown to play important roles in various cancers and may be a reliable prognostic marker. However, its prognostic value in endometrial carcinoma (UCEC) needs to be further explored. OBJECTIVES: The aim of this study was to create a miR-based signature to effectively predict the prognosis for patients with uterine corpus endometrial carcinoma (UCEC). METHODS: Using UCEC data set in TCGA, we identified differentially expressed miRs between UCEC and healthy endometrial tissues. The LASSO method was used to construct a miR-based signature prognosis index for predicting prognosis in the training cohort. The miR-based signature prognosis index was validated in an independent test cohort. MiRNet tool was applied to perform functional enrichment analysis of this miR-based signature. RESULTS: A total of 208 miRs were differentially expressed between UCEC and healthy endometrial tissues. Five miRs (miR-652, miR-3170, miR-195, miR-34a, and miR-934) were identified to generate a prognosis index (PI). The five-miR signature is a promising biomarker for predicting the 5-year-survival rate of UCEC with AUC = 0.730. The PI remained an independent prognostic factor adjusted by routine clinicopathologic factors. Using the PI, we could successfully identify the high-risk individuals, furthermore, it still worked in an independent test cohort. The five miRs involved in various pathways associated with cancer. CONCLUSION: We proposed and validated a five-miR signature that could serve as an independent prognostic predictor of UCECs.

Hydrogeological controls on ammonium enrichment in shallow groundwater in the central Yangtze River Basin.

The controlling processes of excessive ammonium in surface water and groundwater in the central Yangtze River Basin remain unclear. In this study, monitoring of water levels and temporal-spatial distributions of major N compounds were implemented at the large Jiangshan plain and at the local site scale in the central Yangtze River Basin. The results indicate that the recharge, movement and transformation of ammonium were controlled by hydrogeological conditions. Manure and sewage from anthropogenic activities were identified as the main source of nitrogen compounds. The nitrogen loading into aquifers were governed by water table and groundwater flow. After entering subsurface soils, nitrification and dissimilatory nitrate reduction to ammonium (DNRA) were proposed as the ammonium consumption and production mechanisms, respectively, by combining the concentrations of ammonium­nitrogen and nitrate­nitrogen with the corresponding isotopic compositions. These microbially mediated processes controlling transport and transformation of nitrogen compounds were influenced by the seasonally varying groundwater flow regime that changed the redox conditions in the aquifers. In the subsurface environments, ammonium was converted to nitrate when sufficient oxygen supply was available, and this process was reversed under anoxic conditions along the groundwater flow path. A conceptual model for the reactive transport of nitrogen compounds jointly controlled by the vertical groundwater flows and biogeochemical processes was proposed, which provides new insights into the genesis of high ammonium groundwater.

Shallow Groundwater Quality and Its Controlling Factors in the Su-Xi-Chang Region, Eastern China.

Understanding factors influencing groundwater quality is critical to the development of best management practices at the large watershed scale. In this study, the shallow groundwater (10-20 m depth) in the Su-Xi-Chang region, eastern China, was investigated as part of a monitoring program from 2007 to 2008 to analyze the regional groundwater quality as well as the hydrogeochemical processes and their controlling factors. Conventional physicochemical water parameters (pH, turbidity, electrical conductivity, dissolved oxygen, total phosphorus), major cations (Na+, Ca2+, Mg2+ and NH4+) and anions (Cl-, NO3- and SO42-) were measured. Hydrochemical methods and multivariate statistical methods were applied to analyze the hydrogeochemical signatures, origins, the similarities among the variables and to identify the main pollution sources in the groundwater. The results showed that (1) the concentrations of TDS (224.89-1086.70 mg/L) and turbidity (0.1-18.60 NTU) were higher than the class II groundwater quality standards in China and the WHO drinking water standards, (2) there were extremely high concentrations of ammonia (0.01-32.90 mg/L), with a mean value of 0.72 mg/L and (3) the nitrate concentrations (average value of 22.07 mg/L) exceeded the class III groundwater quality standards. The study also provided evidence that weathering, dissolution of carbonate, halite and silicate and cation exchange were the possible primary hydrogeochemical control mechanisms in the groundwater. The sources of ammonia, total phosphorus, sulfates and nitrates included rock-water interactions and anthropogenic activities. The groundwater administration of pollution sinks and sources, long-term legal frameworks and economic incentives should be improved to optimize watershed scale management in the context of rapid development in China.

Identification of key genes involved in the metastasis of clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is the most common and lethal renal malignant tumor in adults. The aim of the present study was to identify the key genes involved in ccRCC metastasis. Expression profiling data for ccRCC patients with metastasis and without metastasis were obtained from The Cancer Genome Atlas database. The datasets were used to identify differentially expressed genes (DEGs) between the metastasis group and the non-metastasis group using the DESeq2 package. Function enrichment analyses of DEGs were performed. The protein-protein interaction (PPI) network was constructed and analyzed using the Search Tool for the Retrieval of Interacting Genes and Cytoscape for further analysis of the identified hub genes. A total of 472 DEGs were identified, including 247 that were upregulated and 225 that were downregulated in the metastasis group. Gene Ontology enrichment analysis revealed that DEGs were mainly enriched in cell transmembrane movement and mitotic cell cycle process. Kyoto Encyclopedia of Genes Genomes pathway analysis revealed that the DEGs were mainly involved in the 'cell cycle' (hsa04110), 'collecting duct acid secretion' (hsa04966), 'complement and coagulation cascades' (hsa04610) and 'aldosterone-regulated sodium reabsorption' (hsa04960) pathways. Using the PPI network, 35 hub genes were identified, and the majority of them were upregulated in ccRCC tissue compared with normal kidney tissue. The expression levels of certain hub genes (CDKN3, TPX2, BUB1B, CDCA8, UBE2C, NDC80, RRM2, NCAPG, NCAPH, PTTG1, FAM64A, ANLN, KIF4A, CEP55, CENPF, KIF20A, ASPM and HJURP) were significantly associated with overall survival and recurrence-free survival in ccRCC. The present study has identified key genes associated with the metastasis of ccRCC.

eSHAFTS: Integrated and graphical drug design software based on 3D molecular similarity.

With the development of computer technology, computer-aided drug design (CADD) has become an important means for drug research and development, and its representative method is virtual screening. Various virtual screening platforms have emerged in an endless stream and play great roles in the field of drug discovery. With the increasing number of compound molecules, virtual screening platforms face two challenges: low fluency and low visibility of software operations. In this article, we present an integrated and graphical drug design software eSHAFTS based on three-dimensional (3D) molecular similarity to overcome these shortcomings. Compared with other software, eSHAFTS has four main advantages, which are integrated molecular editing and drawing, interactive loading and analysis of proteins, multithread and multimode 3D molecular similarity calculation, and multidimensional information visualization. Experiments have verified its convenience, usability, and reliability. By using eSHAFTS, various tasks can be submitted and visualized in one desktop software without locally installing any dependent plug-ins or software. The software installation package can be downloaded for free at http://lilab.ecust.edu.cn/home/resource.html. © 2019 Wiley Periodicals, Inc.

Effects of Mining Activities on the Release of Heavy Metals (HMs) in a Typical Mountain Headwater Region, the Qinghai-Tibet Plateau in China.

Understanding the heavy metal (HM) contamination in alpine mountain headwaters regions is important to maintaining the ecosystem stability of the basin. A total of 119 water samples and 104 sediment samples were collected along tributaries and the main course of Heihe River. The concentrations of eight heavy metals (As, Cd, Cr, Cu, Mn, Ni, Pb, and Zn) in water and sediment were measured to describe their spatial variability and to assess water quality. To identify the origins and pathways of HMs, anions, cations, and trace elements, as well as δD/δ18O stable isotopes in water samples were also measured. The results of water quality assessment suggested that tributaries were affected by local mining activity. Factor analysis in sediments showed that all HMs in sediments were inherited from the parent bedrock. Both natural weathering and mining contribute HMs. Cr and Ni were homologous with a source from the weathering of basic gabbro and serpentine at Yushigou. Mn appeared to be influenced more by artificial activities such as agriculture and grazing. Depending on the mining technique involved, two pathways for the release of HMs were distinguished in this area. For open-pit mining, mining promoted the release of HMs primarily via enhanced weathering. For underground mining, HMs might have contributed to greater acid mine discharge at high elevations due to the weak weathering processes. As the elevation decreases, precipitation increases, and a series of complex hydrological factor significantly affect leaching and runoff. The study results can be applied to improve water management efficiency.

Long non-coding RNA expression profile can predict early recurrence in hepatocellular carcinoma after curative resection.

AIM: The aim of this study was to develop a novel long non-coding RNA (lncRNA) expression signature to accurately predict early recurrence for patients with hepatocellular carcinoma (HCC) after curative resection. METHODS: Using expression profiles downloaded from The Cancer Genome Atlas database, we identified multiple lncRNAs with differential expression between early recurrence (ER) and non-early recurrence (non-ER) groups of patients with HCC. Least absolute shrinkage and selection operator for logistic regression models were used to develop an lncRNA-based classifier for predicting ER in the training set. An independent test set was used to validate the predictive value of this classifier. Furthermore, a co-expression network based on these lncRNAs and its highly related genes was constructed and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of genes in the network were carried out. RESULTS: We identified 10 differentially expressed lncRNAs, including three that were upregulated and seven that were downregulated in the ER group. The lncRNA-based classifier was constructed based on seven lncRNAs (AL035661.1, PART1, AC011632.1, AC109588.1, AL365361.1, LINC00861, and LINC02084), and its accuracy was 0.83 in the training set, 0.87 in the test set, and 0.84 in the total set. Receiver operating characteristic curve analysis showed the area under the curve was 0.741 in the training set, 0.824 in the test set, and 0.765 in the total set. A functional enrichment analysis suggested that the genes highly related to four lncRNAs are involved in the immune system. CONCLUSION: The expression profile of seven lncRNAs can effectively predict ER after surgical resection for HCC.

Fingerprint analysis and quality consistency evaluation of flavonoid compounds for fermented Guava leaf by combining high-performance liquid chromatography time-of-flight electrospray ionization mass spectrometry and chemometric methods.

Guava leaves are used in traditional herbal teas as antidiabetic therapies. Flavonoids are the main active of Guava leaves and have many physiological functions. However, the flavonoid compositions and activities of Guava leaves could change due to microbial fermentation. A high-performance liquid chromatography time-of-flight electrospray ionization mass spectrometry method was applied to identify the varieties of the flavonoids in Guava leaves before and after fermentation. High-performance liquid chromatography, hierarchical cluster analysis and principal component analysis were used to quantitatively determine the changes in flavonoid compositions and evaluate the consistency and quality of Guava leaves. Monascus anka Saccharomyces cerevisiae fermented Guava leaves contained 2.32- and 4.06-fold more total flavonoids and quercetin, respectively, than natural Guava leaves. The flavonoid compounds of the natural Guava leaves had similarities ranging from 0.837 to 0.927. The flavonoid compounds from the Monascus anka S. cerevisiae fermented Guava leaves had similarities higher than 0.993. This indicated that the quality consistency of the fermented Guava leaves was better than that of the natural Guava leaves. High-performance liquid chromatography fingerprinting and chemometric analysis are promising methods for evaluating the degree of fermentation of Guava leaves based on quality consistency, which could be used in assessing flavonoid compounds for the production of fermented Guava leaves.

Heavy Metals in Surface Soils in the Upper Reaches of the Heihe River, Northeastern Tibetan Plateau, China.

The upper reaches of the Heihe River have been regarded as a hotspot for phytoecology, climate change, water resources and hydrology studies. Due to the cold-arid climate, high elevation, remote location and poor traffic conditions, few studies focused on heavy metal contamination of soils have been conducted or reported in this region. In the present study, an investigation was performed to provide information regarding the concentration levels, sources, spatial distributions, and environmental risks of heavy metals in this area for the first time. Fifty-six surface soil samples collected from the study area were analyzed for Cr, Mn, Ni, Cu, Zn, As, Cd and Pb concentrations, as well as TOC levels. Basic statistics, concentration comparisons, correlation coefficient analysis and multivariate analyses coupled with spatial distributions were utilized to delineate the features and the sources of different heavy metals. Risk assessments, including geoaccumulation index, enrichment factor and potential ecological risk index, were also performed. The results indicate that the concentrations of heavy metals have been increasing since the 1990 s. The mean values of each metal are all above the average background values in the Qinghai Province, Tibet, China and the world, except for that of Cr. Of special note is the concentration of Cd, which is extremely elevated compared with all background values. The distinguished ore-forming conditions and well-preserved, widely distributed limestones likely contribute to the high Cd concentration. Heavy metals in surface soils in the study area are primarily inherited from parent materials. Nonetheless, anthropogenic activities may have accelerated the process of weathering. Cd presents a high background concentration level and poses a severe environmental risk throughout the whole region. Soils in Yinda, Reshui daban, Kekeli and Zamasheng in particular pose threats to the health of the local population, as well as that of livestock and wildlife.

In vitro investigation of self-assembled nanoparticles based on hyaluronic acid-deoxycholic acid conjugates for controlled release doxorubicin: effect of degree of substitution of deoxycholic acid.

Self-assembled nanoparticles based on a hyaluronic acid-deoxycholic acid (HD) chemical conjugate with different degree of substitution (DS) of deoxycholic acid (DOCA) were prepared. The degree of substitution (DS) was determined by titration method. The nanoparticles were loaded with doxorubicin (DOX) as the model drug. The human cervical cancer (HeLa) cell line was utilized for in vitro studies and cell cytotoxicity of DOX incorporated in the HD nanoparticles was accessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. In addition, cellular uptake of fluorescently labeled nanoparticles was also investigated. An increase in the degree of deoxycholic acid substitution reduced the size of the nanoparticles and also enhanced their drug encapsulation efficiency (EE), which increased with the increase of DS. A higher degree of deoxycholic acid substitution also lead to a lower release rate and an initial burst release of doxorubicin from the nanoparticles. In summary, the degree of substitution allows the modulation of the particle size, drug encapsulation efficiency, drug release rate, and cell uptake efficiency of the nanoparticles. The herein developed hyaluronic acid-deoxycholic acid conjugates are a good candidate for drug delivery and could potentiate therapeutic formulations for doxorubicin-mediated cancer therapy.

Low catalyst loadings in olefin metathesis: synthesis of nitrogen heterocycles by ring-closing metathesis.

A series of ruthenium catalysts have been screened under ring-closing metathesis (RCM) conditions to produce five-, six-, and seven-membered carbamate-protected cyclic amines. Many of these catalysts demonstrated excellent RCM activity and yields with as low as 500 ppm catalyst loadings. RCM of the five-membered carbamate series could be run neat, the six-membered carbamate series could be run at 1.0 M, and the seven-membered carbamate series worked best at 0.2-0.05 M.