Combining Cd and Pb isotope analyses for heavy metal source apportionment in facility agricultural soils around typical urban and industrial areas.

Facility agriculture enhances food production capabilities. However, concerns persist regarding heavy metal accumulation resulting from extensive operation of this type of farming. This study integrated the total content, five fractions, and isotope composition of Cd and Pb in intensively farmed soils in regions characterized by industrialization (Shaoguan, SG) and urbanization (Guangzhou, GZ), to assess the sources and mechanisms causing metals accumulation. We found significantly more severe Cd/Pb accumulation and potential mobility in SG than GZ. Cd displayed higher accumulation levels and potential mobility than Pb. The distinct isotopic signals in SG (-0.54 to 0.47‰ for δ114/110Cd and 1.1755 to 1.1867 for 206Pb/207Pb) and GZ (-0.86 to 0.12‰ for δ114/110Cd and 1.1914 to 1.2012 for 206Pb/207Pb) indicated significant differences in Cd/Pb sources. The Bayesian model revealed that industrial activities and related transportation accounted for over 40% and approximately 30%, respectively, of the average contributions of Cd/Pb in SG. While urban-related (26.6%) and agricultural-related (26.3%) activities primarily contributed to Cd in GZ. The integration of δ114/110Cd and 208Pb/206Pb has further enhanced the regional contrast in sources. The present study established a comprehensive tracing system for Cd-Pb, providing crucial insights into the accumulation and distribution of these metals in facility agricultural soils.

A third (booster) dose of the inactivated SARS-CoV-2 vaccine elicits immunogenicity and T follicular helper cell responses in people living with HIV.

Introduction: This study sought to explore the immunogenicity of a booster dose of an inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine in people living with human immunodeficiency virus (HIV) and identify the factors affecting the magnitude of anti-SARS-CoV-2 antibody levels. Materials and methods: A total of 34 people living with HIV (PLWH) and 34 healthy donors (HD) were administered a booster dose of the same SARS-CoV-2 vaccine. Anti-SARS-CoV-2 antibody and immunoglobulin G (IgG) levels were measured using the SARS-CoV-2 S protein neutralizing antibody Enzyme-Linked Immunosorbent Assay (ELISA) and 2019-nCov IgG Chemiluminescent Immunoassay Microparticles, respectively. Spearman correlation analysis was used to measure the correlation between laboratory markers and neutralizing antibody and IgG levels. Peripheral blood mononuclear cells (PBMCs) were extracted from each subject using density gradient centrifugation and the numbers of memory T and T follicular helper (Tfh) cells were determined using flow cytometry. Results: PLWH had a marked reduction in CD4 and B cell levels that was accompanied by a lower CD4/CD8 T cell ratio. However, those who received a supplementary dose of inactivated SARS-CoV-2 vaccines exhibited antibody positivity rates that were analogous to levels previously observed. The booster vaccine led to a reduction in IgG and neutralizing antibody levels and the amplitude of this decline was substantially higher in the PLWH than HD group. Correlation analyses revealed a strong correlation between neutralizing antibody levels and the count and proportion of CD4 cells. Anti-SARS-CoV-2 IgG antibody levels followed a similar trend. The expression of memory T and Tfh cells was considerably lower in the PLWH than in the HD group. Discussion: PLWH had an attenuated immune response to a third (booster) administration of an inactivated SARS-CoV-2 vaccine, as shown by lower neutralizing antibody and IgG levels. This could be attributed to the reduced responsiveness of CD4 cells, particularly memory T and cTfh subsets. CD4 and cTfh cells may serve as pivotal markers of enduring and protective antibody levels. Vaccination dose recalibration may be critical for HIV-positive individuals, particularly those with a lower proportion of CD4 and Tfh cells.

Lake Sediment Archive Reveals a Distinct Response to Anthropogenic Pb and Zn Deposition with Historical Periods: Pb-Zn Isotope Evidence.

Anthropogenic activities release large quantities of heavy metals into the atmosphere. In China, the input of these heavy metals through local and trans-boundary atmospheric deposition is poorly understood. To assess this issue, herein, we use Pb and Zn isotopes to constrain the sources of Pb and Zn in a 210Pb-dated sediment core collected from the enclosed lake in South China. We observed a progressive shift toward higher 208Pb/206Pb and Pb fluxes (0.79-4.02 µg·cm-2·a-1) from 1850 to 1950 and a consistent decrease in δ66ZnIRMM (as low as -0.097 ± 0.030‰) coupled with an increase in Pb (1.74-3.36 µg·cm-2·a-1) and Zn (8.07-10.44 µg·cm-2·a-1) fluxes after 1980. These distinguished isotopic signals and flux variations reveal the presence of trans-boundary Pb since 1900, with the addition of local industrial Pb and Zn pollution after 1980. Up to 72.3% of Pb deposited at our site can be attributed to long-distance transportation from previously industrialized countries, resulting in a noteworthy legacy of Pb in China since 1900. Despite the phasing out of leaded gasoline, Chinese gasoline still contributes an average of 20.9%. The contribution of China's mining and smelting activities to Pb has increased steadily since 1980 and remained stable at an average of 25.1% since 2000.

Integrated 16 S rRNA gene sequencing and serum metabolomics approaches to decipher the mechanism of Qingre Lidan decoction in the treatment of cholestatic liver injury.

BACKGROUND: Cholestasis is a commonly occurring disorder induced by impaired bile flow, for which there is no effective treatment so far. Qingre Lidan decoction (QRLD) is a clinically used herbal compound for the long-term treatment of bile circulation disorders arising from inflammation and obstruction in the gallbladder and bile ducts. The objective of this study was to investigate the protective effect of QRLD on cholestatic liver injury and its possible mechanism. METHODS: α-Naphthyl isothiocyanate (ANIT) was used to induce cholestatic liver injury in rats. Liver histopathology and serum biochemical markers were used to assess QRLD's protective impact. The possible biomarkers and mechanism of the therapeutic benefits of QRLD were investigated using a UHPLC-based Q-Exactive Orbitrap MS / MS untargeted serum metabolomics technique together with 16 S rRNA microbiota profiling. Afterwards, using RT-qPCR as well as Western Blot techniques, the expression of pertinent indicators was determined. RESULTS: The intervention effect of QRLD was stronger at medium and high dosages than at low doses, and it dramatically decreased the levels of serum biochemical markers in cholestatic rats reflecting alterations in liver function and relieving ANIT-induced abnormalities in the liver's histopathology. Serum metabolomics showed that QRLD could affect the metabolic profile of cholestatic rats, mainly related to glycerophospholipid metabolism, taurine and hypotaurine metabolism, alanine, aspartate and glutamate metabolism, and histidine metabolic pathway. Additionally, analysis of 16 S rRNA gene sequencing indicated that QRLD could moderate ANIT-induced microbiota disorders, particularly Romboutsia, Bifidobacterium, Fusicatenibacter, Prevotella_9, Prevotellaceae_NK3B31_group and Prevotella_1. Other experimental results showed that QRLD significantly upregulated the mRNA and protein expression of PPARα, CYP7A1 and NTCP in the liver, inhibited the expression of p-IκBα, p-p65 and TNFα while increasing the anti-inflammatory factor IL-10, and downregulated the expression of MDA (a peroxidation product) and D-lactic acid (an intestinal barrier indicator) while increasing the expression of SOD and GSH. CONCLUSIONS: QRLD can effectively regulate endogenous metabolites and microbiota disorders in cholestatic rats that are correlated with the attenuation of inflammation and oxidative stress.

Systemic administration of mesenchymal stem cells loaded with a novel oncolytic adenovirus carrying a bispecific T cell engager against hepatocellular carcinoma.

We previously established a hepatocellular carcinoma (HCC) targeting system of conditionally replicative adenovirus (CRAd) delivered by human umbilical cord-derived mesenchymal stem cells (HUMSCs). However, this system needed to be developed further to enhance the antitumor effect and overcome the limitations caused by the alpha-fetoprotein (AFP) heterogeneity of HCC. In this study, a bispecific T cell engager (BiTE) targeting programmed death ligand 1 controlled by the human telomerase reverse transcriptase promoter was armed on the CRAd of the old system. It was demonstrated on orthotopic transplantation model mice that the new system had a better anti-tumor effect with no more damage to extrahepatic organs and less liver injury, and the infiltration and activation of T cells were significantly enhanced in the tumor tissues of the model mice treated with the new system. Importantly, we confirmed that the new system eliminated the AFP-negative cells on AFP heterogeneous tumor models efficiently. Conclusion: Compared with the old system, the new system provided a more effective and safer strategy against HCC.

Mechanism and Active Components of Qingre Lidan Tablets Alleviate Intrahepatic Cholestasis by Activating the Farnesoid X Receptor.

Background: Qingre Lidan tablets (QLTs) are a compound preparation of Chinese medicine that have long been used clinically to treat poor bile circulation caused by the inflammation and obstruction of the gallbladder and bile duct and to relieve jaundice and other symptoms. However, its material basis and mechanism are still unclear. The purpose of this study was to investigate the mechanism and active components of QLTs for treating intrahepatic cholestasis (IHC) in rat models. Methods: In vivo experiments verified the effect of QLTs on alpha-naphthyl isothiocyanate (ANIT)-induced IHC models in rats. The mRNA and protein expression levels of farnesoid X receptor (FXR), bile salt export pump (BSEP), and multidrug-associated protein 2 (MRP2) in the rat liver were detected. UPLC/Q-TOF-MS was used to separate and identify the monomers in QLTs, and a dual-luciferase reporter assay was used to select effective the monomers that stimulate FXR. Among the selected monomers, baicalein was used as a representative to verify the effect on rat IHC models. Results: QLTs and baicalein significantly reduced the serum biochemical indicators reflecting the changes in liver function among IHC rats and remitted the ANIT-induced liver histopathological changes. The expression levels of FXR, BSEP, and MRP2 in the liver were significantly increased after QLT treatment in a dose-dependent manner. Moreover, six types of active components that activate FXR were selected in QLTs, namely baicalein, wogonin, baicalein II, emodin, dibutyl phthalate, and diisooctyl phthalate. Conclusions: QLTs and the active component, baicalein, can alleviate IHC in model rats.

Geochemical Fractionation and Source Identification of Pb and Cd in Riparian Soils and River Sediments from Three Lower Reaches Located in the Pearl River Delta.

Pb and Cd accumulation in riparian soils and river sediments in river basins is a challenging pollution issue due to the persistence and bioaccumulation of these two trace metals. Understanding the migration characteristics and input sources of these metals is the key to preventing metal pollution. This study was conducted to explore the contents, geochemical fractionation, and input sources of Pb and Cd in riparian soils and river sediments from three lower reaches of the Pearl River Delta located in the Guangdong-Hong Kong-Macao Greater Bay Area. The total concentration of all Pb and Cd values exceeded the background values to varying degrees, and the exchangeable fraction of Cd in riparian soils and river sediments accounted for the largest proportion, while that of Pb was dominated by the residual fraction. Geoaccumulation index calculations showed that in the riparian soils, the average accumulation degree of Pb (0.52) in the Beijiang River (BJR) was the highest, while that of Cd (2.04) in the Xijiang River (XJR) was the highest. Unlike that in riparian soils, the maximum accumulation of Pb (0.76) and Cd (3.01) in river sediments both occurred in the BJR. Furthermore, the enrichment factor results also showed that Pb and Cd in the riparian soils and river sediments along the BJR were higher than those in the XJR and Dongjiang River (DJR). The relationship between enrichment factors and nonresidual fractions further proved that the enrichment factors of Cd were significantly correlated with the nonresidual fractions of Cd, which may imply various anthropogenic sources of Cd in the three reaches. Moreover, source identification based on principal component analysis (PCA) and Pb isotope ratio analysis indicated that riparian soils and river sediments have inconsistent pollution source structures. The PCA results showed that Pb and Cd were homologous inputs in the DJR, and there were significant differences only in the riparian soils and river sediments. Pb isotope tracing results further showed that the bedrock of high geological background from upstream may be the main reason for Cd accumulation in the XJR. However, the ultrahigh accumulation of Cd in the BJR is mainly caused by the input of the upstream mining and metallurgy industry. The control of upstream input sources will be the key to the prevention of trace metal pollution in these regions.

Integrated network pharmacology and serum metabolomics approach deciphers the anti-colon cancer mechanisms of Huangqi Guizhi Wuwu Decoction.

Huangqi Guizhi Wuwu Decoction (HGWD), as a classic Chinese herbal decoction, has been widely used in treating various diseases for hundreds of years. However, systematically elucidating its mechanisms of action remains a great challenge to the field. In this study, taking advantage of the network pharmacology approach, we discovered a potential new use of HGWD for patients with colon cancer (CC). Our in vivo result showed that orally administered HGWD markedly inhibited the growth of CC xenografts in mice. The subsequent enrichment analyses for the core therapeutic targets revealed that HGWD could affect multiple biological processes involving CC growth, such as metabolic reprogramming, apoptosis and immune regulation, through inhibiting multiple cell survival-related signalings, including MAPK and PI3K-AKT pathways. Notably, these in silico analysis results were most experimentally verified by a series of in vitro assays. Furthermore, our results based on serum metabolomics showed that the lipid metabolic pathways, including fatty acid biosynthesis and cholesterol metabolism, play key roles in delivery of the anti-CC effect of HGWD on tumor-bearing mice, and that cytochrome P450 family 2 subfamily E member 1 (CYP2E1) is a potential therapeutic target. Together, our integrated approach reveals a therapeutic effect of HGWD on CC, providing a valuable insight into developing strategies to predict and interpret the mechanisms of action for Chinese herbal decoctions.

Flooding-drainage alternations impact mobilization and isotope fractionation of cadmium in soil-rice systems.

Sequential flooding and draining substantially alter Cd mobilization in paddy fields, primarily due to redox-driven changes in Fe-Mn (hydro)oxides and Cd-sulfides. However, the impacts of carbonates on Cd mobilization during flooding-drainage alternations remain poorly understood. In this study, Cd isotope compositions were analyzed in soils and plants at three growth stages, and the results show a pH-dependent Cd mobilization and isotope fractionation. Sequential extraction shows the Cd mainly binds to the exchangeable fraction and carbonates, and their amounts vary with pH. Exchangeable Cd with light isotopes coprecipitates into carbonates due to increased pH during flooding (tillering and panicle initiation). Whereas in drained soils (maturity), the carbonate-bound Cd releases with decreased pH. Light isotopes are enriched in rice compared with exchangeable Cd, but this enrichment is insignificant at maturity. This difference is mainly caused by the change in Cd isotope composition of exchangeable Cd pool due to carbonate coprecipitation during flooding. Limited isotope fractionation between roots and aboveground tissues is found at tillering, whereas significant isotope fractionation is observed at two other stages, suggesting the nodes might work during Cd translocation between tissues. These findings demonstrate alternating flooding-drainage impacts the mobilization of carbonate-bound Cd and, consequently, isotope fractionation in soil-rice systems.

Lithologic controls on the mobility of Cd in mining-impacted watersheds revealed by stable Cd isotopes.

Cd-rich wastes from open-pit mining can be transported into rivers, which are often followed by deposition in river sediments and/or further transfer into agricultural soils. The lithology of bedrock exerts a huge effect on physicochemical properties (e.g., buffering capacities, metal species, mineral phases, etc.) of the river system, thereby potentially impacting the Cd mobility in watersheds. However, to date, little is known about the microscopic processes (e.g., dissolution, adsorption, and precipitation) controlling the migration of Cd from mines to varied watersheds. This study, therefore, aims to determine the controlling factors on Cd mobilization in two mining-impacted watersheds with contrasting bedrock lithology using both Cd and Pb isotopes. The Pb isotope ratios of sediments and soils in both watersheds fall into a binary mixing model with two isotopically distinct sources, i.e., mining wastes and bedrock. These results indicate that mining activities are the main sources of Cd in sediments and soils. However, the Cd isotope ratios reveal different Cd migration processes between the two watersheds. In the siliceous watershed, the δ114/110Cd values of sediments decrease from -0.116‰ in the upper reach to -0.712‰ in the lower reach, with a concomitant increase in Cd concentration, which may result from Cd adsorption by goethite due to the increased pH. In contrast, in the calcareous watershed, the Cd isotope compositions of sediments (-0.345 to -0.276‰) and the pH of river water are nearly invariable, suggesting that the adsorption and release of Cd in sediments are limited. This may result from the strong pH buffering effect due to the presence of carbonate rocks. This study highlights the different fates of Cd in siliceous and calcareous watersheds and suggests that the development of Cd pollution control policies must consider regional lithology.

Cinnamomi Ramulus inhibits the growth of colon cancer cells via Akt/ERK signaling pathways.

BACKGROUND: Colon cancer (CC) ranks the second highest mortality rate among malignant tumors worldwide, and the current mainstream treatment regimens are not very effective. The unique efficacy of Chinese herb medicine (CHM) for cancer has recently attracted increasing attention. Cinnamomi Ramulus (CR), as a classic CHM, has been widely used in the treatment of a variety of diseases for hundreds of years in China, but its specific pharmacological mechanism against CC needs to be fully evaluated. METHODS: TCMSP and China National Knowledge Infrastructure database were utilized to predict the candidate ingredients of CR, and TCMSP and SwissTargetPrediction database were also employed to predict the drug targets of the candidate ingredients from CR. We subsequently evaluated the therapeutic effect of CR by orally administrating it on CC-bearing mice. Next, we further identified the potential CC-related targets by using Gene Expression Omnibus (GEO) database. Based on these obtained targets, the drug/disease-target PPI networks were constructed using Bisogenet plugin of Cytoscape. The potential core therapeutic targets were then identified through topological analysis using CytoNCA plugin. GO and KEGG enrichment analyses were performed to predict the underlying mechanism of CR against CC. Furthermore, these in silico analysis results were validated by a series of cellular functional and molecular biological assays. UPLC-MS/MS method and molecular docking analysis were employed to identify the potential key components from CR. RESULTS: In this study, we firstly found that CR has potential therapeutic effect on cancer. Then, oral administration of CR could inhibit the growth of CC cells in C57BL/6 mice, while inhibiting the viability and motility of CC cells in vitro. We obtained 111 putative core therapeutic targets of CR. Subsequent enrichment analysis on these targets showed that CR could induce apoptosis and cell cycle arrest in CC cells by blocking Akt/ERK signaling pathways, which was further experimentally verified. We identified 5 key components from the crude extract of CR, among which taxifolin was found most likely to be the key active component against CC. CONCLUSIONS: Our results show that CR as well as its active component taxifolin holds great potential in treatment of CC.

Zinc regulation of iron uptake and translocation in rice (Oryza sativa L.): Implication from stable iron isotopes and transporter genes.

Iron (Fe) is an essential nutrient for living organisms and Fe deficiency is a worldwide problem for the health of both rice and humans. Zinc (Zn) contamination in agricultural soils is frequently observed. Here, we studied Fe isotope compositions and transcript levels of Fe transporter genes in rice growing in nutrient solutions having a range of Zn concentrations. Our results show Zn stress reduces Fe uptake by rice and drives its δ56Fe value to that of the nutrient solution. These observations can be explained by the weakened Fe(II) uptake through Strategy I but enhanced Fe(III) uptake through Strategy II due to the competition between Zn and Fe(II) combining with OsIRT1 (Fe(II) transporter) in root, which is supported by the downregulated expression of OsIRT1 and upregulated expression of OsYSL15 (Fe(III) transporter). Using a mass balance box model, we also show excess Zn reduces Fe(II) translocation in phloem and its remobilization from senescent leaf, indicating a competition of binding sites on nicotianamine between Zn and Fe(II). This study provides direct evidence that how Zn regulates Fe uptake and translocation in rice and is of practical significance to design strategies to treat Fe deficiency in rice grown in Zn-contaminated soils.

Microaerophilic Oxidation of Fe(II) Coupled with Simultaneous Carbon Fixation and As(III) Oxidation and Sequestration in Karstic Paddy Soil.

Microaerophilic Fe(II)-oxidizing bacteria are often chemolithoautotrophs, and the Fe(III) (oxyhydr)oxides they form could immobilize arsenic (As). If such microbes are active in karstic paddy soils, their activity would help increase soil organic carbon and mitigate As contamination. We therefore used gel-stabilized gradient systems to cultivate microaerophilic Fe(II)-oxidizing bacteria from karstic paddy soil to investigate their capacity for Fe(II) oxidation, carbon fixation, and As sequestration. Stable isotope probing demonstrated the assimilation of inorganic carbon at a maximum rate of 8.02 mmol C m-2 d-1. Sequencing revealed that Bradyrhizobium, Cupriavidus, Hyphomicrobium, Kaistobacter, Mesorhizobium, Rhizobium, unclassified Phycisphaerales, and unclassified Opitutaceas were fixing carbon. Fe(II) oxidation produced Fe(III) (oxyhydr)oxides, which can absorb and/or coprecipitate As. Adding As(III) decreased the diversity of functional bacteria involved in carbon fixation, the relative abundance of predicted carbon fixation genes, and the amount of carbon fixed. Although the rate of Fe(II) oxidation was also lower in the presence of As(III), over 90% of the As(III) was sequestered after oxidation. The potential for microbially mediated As(III) oxidation was revealed by the presence of arsenite oxidase gene (aioA), denoting the potential of the Fe(II)-oxidizing and autotrophic microbial community to also oxidize As(III). Thisstudy demonstrates that carbon fixation coupled to Fe(II) oxidation can increase the carbon content in soils by microaerophilic Fe(II)-oxidizing bacteria, as well as accelerate As(III) oxidation and sequester it in association with Fe(III) (oxyhydr)oxides.

Changes in the microbial community during microbial microaerophilic Fe(II) oxidation at circumneutral pH enriched from paddy soil.

Fe(II)-oxidizing bacteria (FeOB) are important catalysts for iron cycling in iron-rich marine, groundwater, and freshwater environments. However, few studies have reported the distribution and diversity of these bacteria in flooded paddy soils. This study investigates the microbial structure and diversity of microaerophilic Fe(II)-oxidizing bacteria (mFeOB) and their possible role in Fe(II) oxidation in iron-rich paddy soils. Using enrichment experiments that employed serial transfers, the changes in microaerophilic microbial community were examined via 16S rRNA gene high-throughput sequencing. During enrichments, the Fe(II) oxidation rate decreased as transfers increased, and the maximum rate of Fe(II) oxidation was observed in the first transfer (0.197 mM day-1). Results from X-ray diffraction of minerals and scanning electron microscopy of the cell-mineral aggregates revealed that cell surfaces in all transfers were partly covered with amorphous iron oxide formed by FeOB. After four transfers, the phyla of Proteobacteria had a dominant presence that reached up to 95%. Compared with the original soil, the relative abundances of Cupriavidus, Massilia, Pseudomonas, Ralstonia, Sphingomonas, and Variovorax increased in FeS gradient tubes and became dominant genera after transfers. Cupriavidus, Pseudomonas, and Ralstonia have been identified as FeOB previously. Furthermore, the structure of the microbial community tended to be stable as transfers increased, indicating that other bacterial species might perform important roles in Fe(II) oxidation. These results suggest the potential involvement of mFeOB and these other microorganisms in the Fe(II)-oxidizing process of soils. It will be helpful for future studies to consider their role in related biogeochemical processes, such as transformation of organic matters and heavy metals.

Using Zn isotopes to trace Zn sources and migration pathways in paddy soils around mining area.

Paddy soils around mining areas suffer from the great threat of heavy metal pollution. The traditional source-tracing methods based on metal concentrations limit our ability to quantify the sources of heavy metals and trace their transport processes to paddy soils. In this study, Zn isotope compositions of paddy soils in Dabaoshan mine area, a typical sulfide deposit in southern China, have been systematically studied. According to a plot between 1/Zn (i.e. inverse concentration) and δ66Zn value, all the polluted paddy soils fall on the mixing line between acid mine drainage precipitate (AMD-precipitate) and fertilizer while the unpolluted paddy soil falls on the mixing line between fertilizer and bedrock. This indicates the mixing of Zn sources at least three end-members: the mining end-member (i.e. AMD-precipitate), the agricultural end-member (i.e. fertilizer), and bedrock whose geochemical signature is often overprinted by the former two sources around the mining area. The quantitative calculations to apportion the end-member's contributions show that the mining activity contributes most Zn in the paddy soils with an average of ∼66.2%. The contribution of mining activities has significant spatial variations. Specifically, the mining activities have relatively low impacts on the lower reach and the deep soil. Additionally, the apparent Zn isotope fractionation between AMD and AMD-precipitate (Δ66ZnAMD-precipitate - AMD of -0.35 to -0.08‰) in the tailings dam suggests that Zn cations in AMD coprecipitated with the secondary Fe-bearing minerals (e.g. jarosite and goethite). After being discharged from the tailings dam, Zn is mainly carried by the Fe-oxide minerals and migrated during surface runoff. Our study highlights the contribution of human activities to the Zn pollution in the paddy soils and the key role of Fe-bearing minerals in the migration of Zn. These findings provide a scientific base for the development of policy for pollution control in mining-affected region.

Zinc isotope revealing zinc's sources and transport processes in karst region.

The heavy metal pollution, mainly caused by mining-related activities over extended period of time, is imposing a severe threat to environments and human health. Environmental systems, including rivers and paddy soils, have been widely established as one of the key sinks of potentially harmful metals. Aiming to understand contamination sources and pathways of Zn in karst area, we studied the Zn concentration and isotope composition of river waters, sediments, mine tailings, paddy soils, dust and three soil profiles with different levels of Zn-pollution around a Zn-mine, southwestern China. The distinct Zn isotope compositions among tailing (-0.42 ± 0.02‰), dust (-0.24 ± 0.02‰), and geogenic soil (-0.16 ± 0.03‰) allowed for separation of anthropogenic-Zn from native Zn. In the plot of δ66Zn value and 1/Zn, all samples can be explained by the mixing of three components: mining-input, agricultural input, and background. Evolution of these three components helps produce direct sources: dust and geogenic soil. Under this framework, the Zn pollution in paddy soil and sediment can be explained by mixing of mine-tailing, dust, and geogenic soil. Our study shows that the contamination of mine drainage is limited in the area due to the relatively high pH buffered by carbonate in karst area. While the dust contributes most of the anthropogenic Zn with an average value of 19.5%. The dominant pathway of anthropogenic Zn from dust to paddy soil or sediment is through the long-term wind dispersion of fine-grained material from the tailing and the physical transmission. Under the special hydrogeological conditions of karst, mining activities will increase the migration of heavy metals. The Fe-Al oxides control the migration of Zn in soil profile, but probably do not lead to significantly Zn isotopes fractionation. This further enhances the reliability of Zn isotopes as a "fingerprint" in karst area.

Optimizing the Method of Cell Separation from Bile of Patients with Cholangiocarcinoma for Flow Cytometry.

Analysis of the change of the cells in bile is an evolving research field in biliary pathophysiology and has potential value in diagnosis and therapy. However, laboratory studies of cell in bile across the world are scarce. Bile was collected from the clinical patients with cholangiocarcinoma (CC). To optimize the cell separation method in bile of patients with CC, we studied the factors that may affect cell vitality in bile including the dilution buffer, centrifugal force, centrifugal time, and store time and temperature. Then these factors were modified and performance was evaluated by flow cytometry with respect to the percentage and total yield of viable cells. The separated cells from bile were stained with CD3, CD4, CD8, CD56, TCRγ/δ, CD16, CD14, HLA-DR, CD33, CD15, CD11b, lineage cocktail (CD3, CD14, CD19, CD20, and CD56), CD66b, and CD45 antibodies. The different buffer solutions were joined in bile of patients with CC; experiment results show that the different dilutions have nearly no effect on the ratio of cells in bile by flow cytometry. The best centrifugal procedure was 300 g, 10 min. Bile should be stored at 4°C rather than at normal temperature. Our study further showed that the shorter time of the bile storage, the higher viability of the cell, and immune cells existed in cells isolated from bile. Evaluating bile cell viability is necessary to evaluate method performance.

Rhizoma Paridis Saponins Suppresses Tumor Growth in a Rat Model of N-Nitrosomethylbenzylamine-Induced Esophageal Cancer by Inhibiting Cyclooxygenases-2 Pathway.

Rhizoma Paridis Saponins (RPS), a natural compound purified from Rhizoma Paridis, has been found to inhibit cancer growth in vitro and in animal models of cancer. However, its effects on esophageal cancer remain unexplored. The purpose of this study was to investigate the effects of RPS on tumor growth in a rat model of esophageal cancer and the molecular mechanism underlying the effects. A rat model of esophageal cancer was established by subcutaneous injection of N-nitrosomethylbenzylamine (NMBA, 1 mg/kg) for 10 weeks. RPS (350 mg/kg or 100 mg/kg) was administered by oral gavage once daily for 24 weeks starting at the first NMBA injection. RPS significantly reduced the size and number of tumors in the esophagus of rats exposed to NMBA and inhibited the viability, migration, and invasion of esophageal cancer cells EC9706 and KYSE150 in a dose dependent manner (all P < 0.01). Flow cytometry revealed that RPS induced apoptosis and cell cycle G2/M arrest in the esophageal cancer cells. The expression of cyclooxygenases-2 (COX-2) and Cyclin D1 in rat esophageal tissues and the esophageal cancer cells were also significantly reduced by RPS (all P < 0.01). Consistently, RPS also significantly decreased the release of prostaglandin E2, a downstream molecule of COX-2, in a dose-dependent manner (P < 0.01). Our study suggests that RPS inhibit esophageal cancer development by promoting apoptosis and cell cycle arrest and inhibiting the COX-2 pathway. RPS might be a promising therapeutic agent for esophageal cancer.