A meta-analysis of the risk factors for lateral epicondylitis.

BACKGROUND: Very few meta-analyses discussed risk factors for lateral epicondylitis (LE), and previous meta-analyses reached conflicting conclusions with each other on some specific risk factors. PURPOSE: To investigate the risk factors for LE through meta-analysis. STUDY DESIGN: Meta-analysis. METHODS: PubMed, Embase, and Web of Science databases were searched for relevant studies in January 2022. Raw data were extracted into a predefined worksheet, and quality analysis was conducted by the Quality in Prognosis Studies (QUIPS) tool. Pooled effect sizes and 95% confidence intervals were calculated. R package "meta" was used for statistical analysis. RESULTS: 22 studies were included in the meta-analysis. Female sex (odds ratio [OR]=1.33 and p-value<0.05), smoking history (OR=1.46 and p-value<0.001), manual labor (OR=2.39 and p-value<0.001), and hypercholesterolemia (OR=1.67 and p-value<0.05) were significant risk factors for LE. CONCLUSIONS: Female gender, smoking history, manual labor, and hypercholesterolemia could increase the risk of LE. According to an additional literature review, statin treatment for hypercholesterolemia is described as potentially related to the development of LE.

The effect of extracellular polymeric substances on MICP solidifying rare earth slags and stabilizing Th and U.

Microbially induced carbonate precipitation (MICP) has been used to cure rare earth slags (RES) containing radionuclides (e.g. Th and U) and heavy metals with favorable results. However, the role of microbial extracellular polymeric substances (EPS) in MICP curing RES remains unclear. In this study, the EPS of Lysinibacillus sphaericus K-1 was extracted for the experiments of adsorption, inducing calcium carbonate (CaCO3) precipitation and curing of RES. The role of EPS in in MICP curing RES and stabilizing radionuclides and heavy metals was analyzed by evaluating the concentration and morphological distribution of radionuclides and heavy metals, and the compressive strength of the cured body. The results indicate that the adsorption efficiencies of EPS for Th (IV), U (VI), Cu2+, Pb2+, Zn2+, and Cd2+ were 44.83%, 45.83%, 53.7%, 61.3%, 42.1%, and 77.85%, respectively. The addition of EPS solution resulted in the formation of nanoscale spherical particles on the microorganism surface, which could act as an accumulating skeleton to facilitate the formation of CaCO3. After adding 20 mL of EPS solution during the curing process (Treat group), the maximum unconfined compressive strength (UCS) of the cured body reached 1.922 MPa, which was 12.13% higher than the CK group. The contents of exchangeable Th (IV) and U (VI) in the cured bodies of the Treat group decreased by 3.35% and 4.93%, respectively, compared with the CK group. Therefore, EPS enhances the effect of MICP curing RES and reduces the potential environmental problems that may be caused by radionuclides and heavy metals during the long-term sequestration of RES.

Systems pharmacology: a combination strategy for improving efficacy of PD-1/PD-L1 blockade.

Targeting tumor microenvironment (TME), such as immune checkpoint blockade (ICB), has achieved increased overall response rates in many advanced cancers, such as non-small cell lung cancer (NSCLC), however, only in a fraction of patients. To improve the overall and durable response rates, combining other therapeutics, such as natural products, with ICB therapy is under investigation. Unfortunately, due to the lack of systematic methods to characterize the relationship between TME and ICB, development of rational immune-combination therapy is a critical challenge. Here, we proposed a systems pharmacology strategy to identify resistance regulators of PD-1/PD-L1 blockade and develop its combinatorial drug by integrating multidimensional omics and pharmacological methods. First, a high-resolution TME cell atlas was inferred from bulk sequencing data by referring to a high-resolution single-cell data and was used to predict potential resistance regulators of PD-1/PD-L1 blockade through TME stratification analysis. Second, to explore the drug targeting the resistance regulator, we carried out the large-scale target fishing and the network analysis between multi-target drug and the resistance regulator. Finally, we predicted and verified that oxymatrine significantly enhances the infiltration of CD8+ T cells into TME and is a powerful combination agent to enhance the therapeutic effect of anti-PD-L1 in a mouse model of lung adenocarcinoma. Overall, the systems pharmacology strategy offers a paradigm to identify combinatorial drugs for ICB therapy with a systems biology perspective of drug-target-pathway-TME phenotype-ICB combination.

Physicochemical Effects of Sulfur Precursors on Sulfidated Amorphous Zero-Valent Iron and Its Enhanced Mechanisms for Cr(VI) Removal.

Amorphous zerovalent iron (AZVI) has gained considerable attention due to its remarkable reactivity, but there is limited research on sulfidated amorphous zerovalent iron (SAZVI) and the influence of different sulfur precursors on its reactivity remains unclear. In this study, SAZVI materials with an amorphous structure were synthesized using various sulfur precursors, resulting in significantly increased specific surface area and hydrophobicity compared to AZVI. The Cr(VI) removal efficiency of SAZVI-Na2S, which exhibited the most negative free corrosion potential (-0.82 V) and strongest electron transfer ability, was up to 8.5 times higher than that of AZVI. Correlation analysis revealed that the water contact angle (r = 0.87), free corrosion potential (r = -0.92), and surface Fe(II) proportion (r = 0.98) of the SAZVI samples played crucial roles in Cr(VI) removal. Furthermore, the enhanced elimination ability of SAZVI-Na2S was analyzed, primarily attributed to the adsorption of Cr(VI) by the FeSx shell, followed by the rapid release of internal electrons to reduce Cr(VI) to Cr(III). This process ultimately led to the precipitation of FeCr2O4 and Cr2S3 on the surface of SAZVI-Na2S, resulting in their removal from the water. This study provides insights into the influence of sulfur precursors on the reactivity of SAZVI and offers a new strategy for designing highly active AZVI for efficient Cr(VI) removal.

Fabricating Amorphous Zero-Valent Iron for Cr(VI) Efficient Reduction: Unveiling the Effect of Ethylenediamine on Physicochemical Properties.

Amorphous zero-valent iron (AZVI) has attracted wide attention due to its high-efficiency reduction ability. However, the effect of different EDA/Fe(II) molar ratios on the physicochemical properties of the synthesized AZVI requires further investigation. Herein, series of AZVI samples were prepared by changing the molar ratio of EDA/Fe(II) to 1/1 (AZVI@1), 2/1 (AZVI@2), 3/1 (AZVI@3), and 4/1 (AZVI@4). When the EDA/Fe(II) ratio increased from 0/1 to 3/1, the Fe0 proportion on the AZVI surface increased from 26.0 to 35.2% and the reducing ability was enhanced. As for AZVI@4, the surface was severely oxidized to form a large amount of Fe3O4, and the Fe0 content was only 74.0%. Moreover, the removal ability of Cr(VI) was in the order AZVI@3 > AZVI@2 > AZVI@1 > AZVI@4. The isothermal titration calorimetry results revealed that the increase of the molar ratio of EDA/Fe(II) would lead to the stronger complexation of EDA with Fe(II), which resulted in the gradual decrease of the yield of AZVI@1 to AZVI@4 and the gradual deterioration of water pollution after the synthesis. Therefore, based on the evaluation of all indicators, AZVI@2 was the optimal material, not only because its yield was as high as 88.7% and the secondary water pollution level was low, but most importantly, the removal efficiency of Cr(VI) by AZVI@2 was excellent. Furthermore, the actual Cr(VI) wastewater with the concentration of 14.80 mg/L was treated with AZVI@2, and the removal rate of 97.0% was achieved after only a 30 min reaction. This work clarified the effect of different ratios of EDA/Fe(II) on the physicochemical properties of AZVI, which provided insights for guiding the reasonable synthesis of AZVI and is also conducive to investigating the reaction mechanism of AZVI in Cr(VI) remediation.

Efficient Removal of Antimony(V) from Antimony Mine Wastewater by Micrometer Zero-Valent Iron.

This paper investigates the effectiveness of two commercial micron zero-valent irons (mZVIs) in removing Sb(V) from antimony mine wastewater. The wastewater contains a range of complex components and heavy metal ions, including As(V), which can impact the removal efficiency of mZVI. The study aims to provide insights into actual working conditions and focuses on influencing factors and standard conditions. The results demonstrate that mZVI can reduce Sb(V) concentration in the mine wastewater from 3875.7 µg/L to below the drinking water standard of 5 µg/L within 2 h. Adding a small amount of mZVI every 30 min helps to maintain a high removal rate. The study confirms the existence of a reduction reaction by changing the atmospheric conditions of the reaction, and the addition of 1,10-phenanthroline highlights the important role of active Fe(II) in the adsorption and removal of Sb(V) by mZVI. Additionally, the paper presents an innovative experimental method of acid treatment followed by alkali treatment, which proves the interfacial reaction between mZVI and Sb(V). Overall, the study demonstrates that the removal of Sb(V) by mZVI entails a dual function of reduction and adsorption, highlighting the potential of mZVI in repairing Sb(V) in antimony mine wastewater.

Sodium citrate increases the aggregation capacity of calcium ions during microbial mineralization to accelerate the formation of calcium carbonate.

The microbially induced carbonate precipitation (MICP) technique is widely used in soil heavy metal pollution control. Microbial mineralization involves extended mineralization times and slow crystallization rates. Thus, it is important to discover a method to accelerate mineralization. In this study, we selected six nucleating agents to screen and investigated the mineralization mechanism using polarized light microscopy, scanning electron microscopy, X-ray diffraction and Fourier-transform infrared spectroscopy. The results showed that sodium citrate removed 90.1% Pb better than traditional MICP and generated the highest amount of precipitation. Interestingly, due to the addition of sodium citrate (NaCit), the rate of crystallization increased and vaterite was stabilized. Moreover, we constructed a possible model to explain that NaCit increases the aggregation capacity of calcium ions during microbial mineralization to accelerate the formation of calcium carbonate (CaCO3). Thus, sodium citrate can increase the rate of MICP bioremediation, which is important for improving MICP efficiency.

Circ_0062582 promotes osteogenic differentiation of human bone marrow mesenchymal stem cells in vitro by elevating SMAD5 expression through sponging miR-197-3p.

Circular RNAs (circRNAs) play crucial roles in many human diseases. However, the functions of circRNAs in osteoporosis (OP) are barely reported. In this study, we aimed to explore the function of circ_0062582 in osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs) in vitro. Circ_0062582 and SMAD5 were downregulated and miR-197-3p was upregulated in OP patients and increased in osteoblast medium (OM)-induced hBMSCs in vitro. Circ_0062582 knockdown inhibited the viability and osteogenic differentiation of hBMSCs. Circ_0062582 directly targeted miR-197-3p and miR-197-3p inhibition reversed the effects of circ_0062582 on hBMSC viability and osteogenic differentiation. SMAD5 was the target gene of miR-197-3p. SMAD5 overexpression promoted the viability and osteogenic differentiation of hBMSCs and attenuated miR-197-3p-mediated suppressive roles in hBMSC viability and osteogenic differentiation. In conclusion, circ_0062582 sponged miR-197-3p to elevate SMAD5 expression, thereby inducing hBMSC proliferation and osteogenic differentiation in vitro.

Rationally Engineering a CuO/Pd@SiO2 Core-Shell Catalyst with Isolated Bifunctional Pd and Cu Active Sites for n-Butylamine Controllable Decomposition.

Volatile organic amines are a category of typical volatile organic compounds (VOCs) extensively presented in industrial exhausts causing serious harm to the atmospheric environment and human health. Monometallic Pd and Cu-based catalysts are commonly adopted for catalytic destruction of hazardous organic amines, but their applications are greatly limited by the inevitable production of toxic amide and NOx byproducts and inferior low-temperature activity. Here, a CuO/Pd@SiO2 core-shell-structured catalyst with diverse functionalized active sites was creatively developed, which realized the total decomposition of n-butylamine at 260 °C with a CO2 yield and N2 selectivity reaching up to 100% and 98.3%, respectively (obviously better than those of Pd@SiO2 and CuO/SiO2), owing to the synergy of isolated Pd and Cu sites in independent mineralization of n-butylamine and generation of N2, respectively. The formation of amide and short-chain aliphatic hydrocarbon intermediates via C-C bond cleavage tended to occur over Pd sites, while the C-N bond was prone to breakage over Cu sites, generating NH2· species and long free-N chain intermediates at low temperatures, avoiding the production of hazardous amide and NOx. The SiO2 channel collapse and H+ site production resulted in the formation of N2O via suppressing NH2· diffusion. This work provides critical guidance for a rational fabrication of catalysts with high activity and N2 selectivity for environmentally friendly destruction of nitrogen-containing VOCs.

Co-driving factors of tidal effect on the abundance and distribution of antibiotic resistance genes in the Yongjiang Estuary, China.

The unreasonable use of antibiotics and the transmission of antibiotic resistance genes (ARGs) induced by antibiotics have led to a large number of ARGs entered the water environment, which seriously threatened human health and environmental safety. The estuarine aquatic environment connects with inland rivers and sea and is frequently influenced by human activities. This study aims to reveal the occurrences and abundances of ARGs and bacterial community composition by high-throughput quantitative PCR including 296 primers and high-throughput sequencing in the tide rising and ebbing of surface water in the Yongjiang Estuary, China. The results showed that there were a large number of ARGs and mobile genetic elements (MGEs) detected in the rising tide and ebb tide water bodies. The numbers of detected ARGs in each sample at rising and ebb tide ranged from 16 to 77 and 61 to 88, respectively, and the absolute abundance ranges were 1.69 × 104-1.69 × 109 copies/L and 3.18 × 103-2.57 × 109 copies/L, respectively. Obvious tidal distribution characteristics of ARGs were showed. Most of ARGs conferred resistance to multidrug, aminoglycosides and sulfanilamides. Proteobacteria, Actinobacteria and Bacteroidetes were the dominantly bacterial phylum in the Yongjiang Estuary. Network analysis results indicated that multi-genera were identified as possible ARGs hosts, and they carried more than two types of ARGs genes. Partial least squares path modeling further revealed that MGEs and bacterial community composition were the most important driving factors. The results of the study can provide the corresponding scientific basis for the diffusion and control of ARGs in estuaries.

Selection of optimal models for predicting growth stress in Artemisia desertorum by comparison of linear regression and multiple neural networks: Take the construction of a green mine in the Bayan Obo mine as an example.

In recent years, more and more countries are focusing on the control of mining sites and the surrounding ecological environment, and the new environmental concept of green mines has been proposed. By investigating the ecological background of a mine site, pollution and ecological imbalances in the mine can be predicted, managed or transformed. This study investigated the effects of rare earth elements on plant growth in the Baotou Bayan Obo Rare Earth Mine and evaluated soil contamination and subsequent remediation through the measured plant height. Using linear regression, BP(Back Propagation) neural networks, GA-BP(Genetic Algorithm- Back Propagation) neural networks, ELM(Extreme Learning Machine) and GA-ELM(Genetic Algorithm- Extreme Learning Machine) model prediction instruments, the different rare earth solution concentrations were set as input values and the heights of Artemisia desertorum, which as the model plant, were set as output values in the prediction. The results showed that the linear regression predicted the standard error of single La(III), Ce(III) solution and compound La(III) + Ce(III) solution for Artemisia desertorum growth stress was on the high side, 7.02%- 8.92%; the efficiency range of each group of models under BP neural network, GA-BP neural network and ELM neural network were 1.15%- 2.53%, 0.85%- 1.28%, 1.76%- 3.53%; while the efficiency range under GA-ELM neural network was 0.59%- 0.68%, with average error values and predicted values close to the true values. Among them, the MAPE of GA-ELM neural network are significantly lower than other models, and the error decreases with increasing concentration of the compound solution. So GA-ELM neural network can be used as an efficient, fast and reasonable optimal model for predicting the growth stress of Artemisia desertorum in Bayan Obo mining area. The experimental results can provide a theoretical basis for assessing the risk of soil rare earth contamination in the area, evaluating the expectation of later remediation, and provide a degree of new ideas for the construction of green mines.

An Improved Bibliometric Analysis on Antibiotics in Soil Research.

Antibiotic compounds can enter the environment and eventually into drinking water, when manure containing non-metabolized antibiotic residues is applied to agricultural land. In this study, the publication data was analyzed from the aspects of countries, subject categories and keywords during the period of 1946-2016 from Web of Science. The results indicated that, during the period of 2004-2016, the United States, followed by China, dominated the publication of antibiotics in soil. Three most representative subject categories were "Microbiology", "Environmental science and ecology" and "Chemistry". The most studied antibiotic was tetracycline. Antibiotic resistance bacteria (ARB) and antibiotic resistance genes (ARGs) with the fate and transport mechanisms such as degradation, adsorption and desorption were the hot research topics in this field. This study suggests that research on ARB, ARGs and antibiotics in soil should be paid more attention in the future research.

Licorice extract inhibits growth of non-small cell lung cancer by down-regulating CDK4-Cyclin D1 complex and increasing CD8+ T cell infiltration.

BACKGROUND: Targeting tumor microenvironment (TME) may provide therapeutic activity and selectivity in treating cancers. Therefore, an improved understanding of the mechanism by which drug targeting TME would enable more informed and effective treatment measures. Glycyrrhiza uralensis Fisch (GUF, licorice), a widely used herb medicine, has shown promising immunomodulatory activity and anti-tumor activity. However, the molecular mechanism of this biological activity has not been fully elaborated. METHODS: Here, potential active compounds and specific targets of licorice that trigger the antitumor immunity were predicted with a systems pharmacology strategy. Flow cytometry technique was used to detect cell cycle profile and CD8+ T cell infiltration of licorice treatment. And anti-tumor activity of licorice was evaluated in the C57BL/6 mice. RESULTS: We reported the G0/G1 growth phase cycle arrest of tumor cells induced by licorice is related to the down-regulation of CDK4-Cyclin D1 complex, which subsequently led to an increased protein abundance of PD-L1. Further, in vivo studies demonstrated that mitigating the outgrowth of NSCLC tumor induced by licorice was reliant on increased antigen presentation and improved CD8+ T cell infiltration. CONCLUSIONS: Briefly, our findings improved the understanding of the anti-tumor effects of licorice with the systems pharmacology strategy, thereby promoting the development of natural products in prevention or treatment of cancers.

A Soluplus/Poloxamer 407-based self-nanoemulsifying drug delivery system for the weakly basic drug carvedilol to improve its bioavailability.

Carvedilol (CAR), a ß-adrenoceptor and α1-receptor blocker, has pH-dependent solubility, which greatly limits its oral bioavailability. In this work, a precipitation inhibitor-based self-nanoemulsifying drug delivery system (PI-SNEDDS) was developed by employing Soluplus and Poloxamer 407 to improve drug dissolution and to inhibit drug precipitation in the gastrointestinal tract. In vitro phase distribution and in vivo dissolution studies indicated that PI-SNEDDS significantly increased drug content in the oil phase of the nanoemulsions in the stomach and greatly inhibited the subsequent precipitation of CAR in the intestine compared with the carvedilol self-nanoemulsifying drug delivery system (CAR SNEDDS) and the carvedilol tablets. Moreover, a 1.56-fold increase in the relative bioavailability of CAR was observed for the CAR PI-SNEDDS (397.41%) compared to a CAR SNEDDS (254.09%) with commercial capsules as a reference. Therefore, our developed PI-SNEDDS is a promising vehicle for improving the dissolution and bioavailability of poorly soluble drugs with pH-dependent solubility.

Effect of pH on the adsorption of arsenic(V) and antimony(V) by the black soil in three systems: Performance and mechanism.

Arsenic (As) and antimony (Sb) are listed as the priority pollutants by the U.S. Environmental Protection Agency (EPA) and the European Union (EU) due to their toxicity and potential carcinogenicity. It is necessary to investigate their adsorption over soil as such a behavior affects their mobility and bioavailability. In this study, the effect of pH on the adsorption of As(V) and Sb(V) by the black soil was investigated with three systems: the Single system, Binary system, and Sequence system. The operating pH was set at 4.0, 7.0 and 10.0. Based on the Langmuir isothermal and the pseudo-second-order kinetic models, the adsorption for As(V) was always better than Sb(V) in the whole pH range; the best adsorption performance for the two sorbates was achieved at pH of 4.0, followed by 7.0 and 10.0 in the three systems. The reasons could be that the atomic radius of arsenic is smaller than that of antimony, and the positively charged functional groups carried by the inorganic colloids in the soil contributed to binding with the negatively charged As(V)/Sb(V). A lower pH promoted the inorganic colloids to carry more positive charges. Compared to Single system, the maximum adsorption capacity (qm) and the initial adsorption rates (k2qe,cal2) of As(V) and Sb(V) in Binary system decreased obviously, suggesting competitive adsorption occurred when As(V) and Sb(V) coexisted. The findings of this workimprove the understanding of As(V)/Sb(V) adsorption behavior in soil under different situations and would facilitate a comprehensive evaluation on the risk assessment of arsenic and antimony.

Weak-binding molecules are not drugs?-toward a systematic strategy for finding effective weak-binding drugs.

Designing maximally selective ligands that act on individual drug targets with high binding affinity has been the central dogma of drug discovery and development for the past two decades. However, many low-affinity drugs that aim for several targets at the same time are found more effective than the high-affinity binders when faced with complex disease conditions, such as cancers, Alzheimer's disease and cardiovascular diseases. The aim of this study was to appreciate the importance and reveal the features of weak-binding drugs and propose an integrated strategy for discovering them. Weak-binding drugs can be characterized by their high dissociation rates and transient interactions with their targets. In addition, network topologies and dynamics parameters involved in the targets of weak-binding drugs also influence the effects of the drugs. Here, we first performed a dynamics analysis for 33 elementary subgraphs to determine the desirable topology and dynamics parameters among targets. Then, by applying the elementary subgraphs to the mitogen-activated protein kinase (MAPK) pathway, several optimal target combinations were obtained. Combining drug-target interaction prediction with molecular dynamics simulation, we got two potential weak-binding drug candidates, luteolin and tanshinone IIA, acting on these targets. Further, the binding affinity of these two compounds to their targets and the anti-inflammatory effects of them were validated through in vitro experiments. In conclusion, weak-binding drugs have real opportunities for maximum efficiency and may show reduced adverse reactions, which can offer a bright and promising future for new drug discovery.

Investigating the binding properties between antimony(V) and dissolved organic matter (DOM) under different pH conditions during the soil sorption process using fluorescence and FTIR spectroscopy.

Antimony (Sb) is listed as a priority pollutant by European Union and U.S. Environmental Protection Agency. However, reports on its environmental behavior, particularly the sorption process in soil are still limited. In this paper, Sb(V) was selected as the sorbate and the black soil as the sorbent. The initial sorption rate (k2qe,cal2) was calculated to be 0.1254 mg g-1∙min-1 and the maximum sorption amount (qm) 57.33 mg g-1. Once the dissolved organic matter (DOM) was removed from the soil, the values of k2qe,cal2 and qm went down to 0.1066 mg g-1∙min-1 and 19.01 mg g-1, respectively. These results suggested that the existence of DOM significantly influenced the mass transfer rate and sorption amount of Sb(V) in soil. In order to find out the reason why DOM exerted such an influence, the binding interaction mechanism between Sb(V) and DOM was investigated under different pH values. The protein-like and humic-like substances as well as the functional groups of CO, phenol hydroxyl, C-O, C-H, C-X and sulfur/phosphorus contributed to the formation of DOM-Sb(V)-complexes under pH of 7.0, in which the humic-like substance and the functional groups containing oxygen showed higher binding affinity for Sb(V) than protein-like substance and other functional groups, respectively. The protein-like substance and some functional groups disappeared under pH of 4.0 and 10.0. Alkaline condition resulted in a bigger impact on reducing the number of functional groups than acid condition. It can be concluded that the strongest binding interaction occurred at pH of 7.0 then followed by 4.0 and 10.0. This paper might be helpful to further studying the environmental behavior of Sb(V) in soil.

Effects of cadmium exposure on expression of glutathione synthetase system genes in Acidithiobacillus ferrooxidans.

The glutathione synthetase system (GSS) is an important pathway of glutathione synthesis and plays a key role in heavy metal resistance. In this work, the response of Acidithiobacillus ferrooxidans to extracellular Cd2+ was investigated, and the interplay between Cd2+ resistance and the expression of GSS related-genes was analyzed by reverse-transcription quantitative PCR (RT-PCR). During growth in the presence of 5, 15 and 30 mM Cd2+, the transcript levels of eight GSS pathway genes were affected between 0.81- and 7.12-fold. Increased transcription was also reflected in increased enzyme activities: with those of glutathione reductase (GR) increased by 1.10-, 2.26- and 1.54-fold in the presence of 5, 15 and 30 mM Cd2+, respectively. In contrast, the activities of catalase (CAT) and superoxide dismutase (SOD) were decreased in the presence of Cd2+. At the metabolite level, intracellular methane dicarboxylic aldehyde (MDA) content was increased 1.97-, 3.31- and 1.92-fold in the presence of 5, 15 and 30 mM Cd2+, respectively. These results suggest that Cd2+ directly inhibits the activities of CAT and SOD, breaks the redox balance of the cells, which leads to the activation of the other antioxidant pathway of GSS. Resistance of A. ferrooxidans to Cd2+ may involve modulation of expression levels of glutathione S-transferase (GST), GR, and glutathione synthetase, which may protect against oxidative damage.

A dabigatran etexilate phospholipid complex nanoemulsion system for further oral bioavailability by reducing drug-leakage in the gastrointestinal tract.

Dabigatran etexilate (DE) is insoluble at neutral pH values but soluble at low pH values due to protonation, which is the major cause for the poor bioavailability of commercial DE products. Here, we first developed a DE nanoemulsion system and improved dissolution in simulated intestinal fluids by encapsulating DE into an oil phase, but 35.8% of the drug still leaked out. Further, we prepared a DE-phospholipid complex (DE-PC) to enhance lipophilicity and solubility of DE. The resulting DE-PC nanoemulsions significantly (P<0.05) reduced drug leakage and subsequent precipitation. As a result, the relative bioavailability of DE-PC nanoemulsions increased to 147.3% and 606.6% compared to DE nanoemulsions and commercial DE products, respectively. Thus, the presently developed drug-phospholipid complex nanoemulsion system is a promising drug delivery system for improving the oral bioavailability of pH-dependent soluble drugs.