Electron repulsion tuned electronic structure of TiO2 by fluorination for efficient and selective photocatalytic ammonia generation.

The photocatalytic conversion of nitrogen into high-value ammonia products holds tremendous potential in the global nitrogen cycle. However, the activation of N2 and competition of hydrogen evolution limit the improvement of nitrogen fixation performance. In this study, we developed a fluorinated TiO2 (F-TiO2) using a hydrothermal-annealing method. The incorporation of F dopants not only enhances the adsorption and activation of N2 through electronic structure regulation, but also facilitates an in situ increase in active sites via the electron repulsion effect between F and Ti atoms. In addition, the presence of F on the surface effectively improved the nitrogen supply problem and optimized the nitrogen fixation selectivity for its hydrophobic modulation. The NH3 yield of the F-TiO2 photocatalyst reached 63.8 µmol h-1 g-1, which was 8.5 times higher than that of pure TiO2. And the selectivity experiment showed that the electronic ratio of NH3 to H2 production reached 0.890. This research offers valuable insights for the design of highly efficient and selective nitrogen-fixing photocatalysts.

The Efficacy and Safety of Polyethylene Glycol Cholesterol- and Tocopherol Polyethylene Glycol 1000 Succinate-Modified Transforming Growth Factor ß1 Small Interfering RNA Lipid Nanoparticles in the Treatment of Paclitaxel-Resistant Non-Small-Cell Lung Cancer.

The aim of this study was to explore the efficacy and safety of TGFß1 siRNA lipid nanoparticles (LNPs) modified with different PEG derivatives (PEG5000 cholesterol, abbreviated as CE; tocopherol polyethylene glycol 1000 succinate, abbreviated as TPGS) in the treatment of paclitaxel-resistant non-small-cell lung cancer. Three kinds of TGFß1 siRNA LNPs were prepared via microfluidics technology, using different PEG derivatives and dosages (CE1.5, CE2.5, TPGS2.5) as variables. Their particle size, zeta potential, contents, and encapsulation efficiencies were determined. The inhibition of TGFß1 mRNA and protein expression and the effects of the three kinds of LNPs on the proliferation of paclitaxel-resistant non-small-cell lung cancer cells (A549/T cell) were characterized. The distributions of the three siRNA LNPs in nude mice bearing A549/T tumors, especially at the tumor site, were observed using in vivo mouse imaging technology, and their corresponding efficacies were evaluated. The average particle size of the three kinds of TGFß1 siRNA LNPs was about 70-80 nm, and they were capable of charge flipping. All three siRNA LNPs could effectively inhibit the expression of TGFß1 mRNA and protein in A549/T cells and inhibit the proliferation of A549/T cells in vitro. The results of in vivo mice imaging showed that the three kinds of siRNA LNPs, when labeled with cypate, retain strong fluorescence in the tumor at 24 h. The pharmacodynamic results, such as for relative tumor volumes and tumor inhibition rates, reveal that TGFß1 siRNA LNPs modified with CE1.5, CE2.5, or TPGS2.5 can be used to effectively treat paclitaxel-resistant lung adenocarcinoma. The histopathological results showed that the three kinds of LNPs have a certain toxicity but are relatively safe compared to common forms of chemotherapy such as cabazitaxel. TGFß1 siRNA LNPs modified with CE1.5, CE2.5, and TPGS2.5 can inhibit TGFß1 mRNA and protein expression in A549/T cells in vitro and can accumulate and play a role in the tumor tissue of nude mice, features that can be exploited for treating paclitaxel-resistant lung adenocarcinoma.

[Research progress in chemical constituents, pharmacological effects, and clinical application of Curcuma wenyujin and prediction of its quality markers].

Curcuma wenyujin, as one of the eight Daodi-herbs in Zhejiang province, is widely used. It has the effects of eliminating stasis and dissipating mass, moving Qi and activating blood, and clearing heart and relieving depression. Modern studies have shown that it has anti-tumor, anti-inflammatory, anti-oxidation, anti-thrombus and liver-protecting effects and mainly contains sesquiterpenoids, monoterpenoids, diterpenoids, and curcumins. This paper reviews the research progress in the chemical constituents and pharmacological effects of C. wenyujin in the last decade, discusses the modern clinical applications combined with the traditional efficacy, and predicts its quality markers(Q-markers) from plant consanguinity, medicinal properties, efficacy, processing and measurability of chemical components based on the theory of Q-markers, so as to provide a reference for the establishment of a scientific quality evaluation system and the research and application of this herb in the future.

Promising Graphene-Based Nanomaterials and Their Biomedical Applications and Potential Risks: A Comprehensive Review.

Graphene-based nanomaterials (GBNs) have been the subject of research focus in the scientific community because of their excellent physical, chemical, electrical, mechanical, thermal, and optical properties. Several studies have been conducted on GBNs, and they have provided a detailed review and summary of various applications. However, comprehensive comments on biomedical applications and potential risks and strategies to reduce toxicity are limited. In this review, we systematically summarized the following aspects of GBNs in order to fill the gaps: (1) the history, synthesis methods, structural characteristics, and surface modification; (2) the latest advances in biomedical applications (including drug/gene delivery, biosensors, bioimaging, tissue engineering, phototherapy, and antibacterial activity); and (3) biocompatibility, potential risks (toxicity in vivo/vitro and effects on human health and the environment), and strategies to reduce toxicity. Moreover, we have analyzed the challenges to be overcome in order to enhance application of GBNs in the biomedical field.

Recent Advances in Understanding the Mechanisms of Elemene in Reversing Drug Resistance in Tumor Cells: A Review.

Malignant tumors are life-threatening, and chemotherapy is one of the common treatment methods. However, there are often many factors that contribute to the failure of chemotherapy. The multidrug resistance of cancer cells during chemotherapy has been reported, since tumor cells' sensitivity decreases over time. To overcome these problems, extensive studies have been conducted to reverse drug resistance in tumor cells. Elemene, an extract of the natural drug Curcuma wenyujin, has been found to reverse drug resistance and sensitize cancer cells to chemotherapy. Mechanisms by which elemene reverses tumor resistance include inhibiting the efflux of ATP binding cassette subfamily B member 1(ABCB1) transporter, reducing the transmission of exosomes, inducing apoptosis and autophagy, regulating the expression of key genes and proteins in various signaling pathways, blocking the cell cycle, inhibiting stemness, epithelial-mesenchymal transition, and so on. In this paper, the mechanisms of elemene's reversal of drug resistance are comprehensively reviewed.

Active targeting of orthotopic glioma using biomimetic liposomes co-loaded elemene and cabazitaxel modified by transferritin.

BACKGROUND: Effective treatment of glioma requires a nanocarrier that can cross the blood-brain barrier (BBB) to target the tumor lesion. In the current study, elemene (ELE) and cabazitaxel (CTX) liposomes were prepared by conjugating liposomes with transferrin (Tf) and embedding the cell membrane proteins of RG2 glioma cells into liposomes (active-targeting biomimetic liposomes, Tf-ELE/CTX@BLIP), which exhibited effective BBB infiltration to target glioma. RESULTS: The findings showed that Tf-ELE/CTX@BLIP was highly stable. The liposomes exhibited highly significant homologous targeting and immune evasion in vitro and a 5.83-fold intake rate compared with classical liposome (ELE/CTX@LIP). Bioluminescence imaging showed increased drug accumulation in the brain and increased tumor penetration of Tf-ELE/CTX@BLIP in orthotopic glioma model nude mice. Findings from in vivo studies indicated that the antitumor effect of the Tf-ELE/CTX@BLIP led to increased survival time and decreased tumor volume in mice. The average tumor fluorescence intensity after intravenous administration of Tf-ELE/CTX@BLIP was 65.2, 12.5, 22.1, 6.6, 2.6, 1.5 times less compared with that of the control, CTX solution, ELE solution, ELE/CTX@LIP, ELE/CTX@BLIP, Tf-ELE/CTX@LIP groups, respectively. Histopathological analysis showed that Tf-ELE/CTX@BLIP were less toxic compared with administration of the CTX solution. CONCLUSION: These findings indicate that the active-targeting biomimetic liposome, Tf-ELE/CTX@BLIP, is a promising nanoplatform for delivery of drugs to gliomas.

Nanoparticle Drug Delivery System for Glioma and Its Efficacy Improvement Strategies: A Comprehensive Review.

Gliomas are the most common tumor of the central nervous system. However, the presence of the brain barrier blocks the effective delivery of drugs and leads to the treatment failure of various drugs. The development of a nanoparticle drug delivery system (NDDS) can solve this problem. In this review, we summarized the brain barrier (including blood-brain barrier (BBB), blood-brain tumor barriers (BBTB), brain-cerebrospinal fluid barrier (BCB), and nose-to-brain barrier), NDDS of glioma (such as passive targeting systems, active targeting systems, and environmental responsive targeting systems), and NDDS efficacy improvement strategies and deficiencies. The research prospect of drug-targeted delivery systems for glioma is also discussed.

Recent Advancements in Liposome-Targeting Strategies for the Treatment of Gliomas: A Systematic Review.

Malignant tumors represent some of the most intractable diseases that endanger human health. A glioma is a tumor of the central nervous system that is characterized by severe invasiveness, blurred boundaries between the tumor and surrounding normal tissue, difficult surgical removal, and high recurrence. Moreover, the blood-brain barrier (BBB) and multidrug resistance (MDR) are important factors that contribute to the lack of efficacy of chemotherapy in treating gliomas. A liposome is a biofilm-like drug delivery system with a unique phospholipid bilayer that exhibits high affinities with human tissues/organs (e.g., BBB). After more than five decades of development, classical and engineered liposomes consist of four distinct generations, each with different characteristics: (i) traditional liposomes, (ii) stealth liposomes, (iii) targeting liposomes, and (iv) biomimetic liposomes, which offer a promising approach to promote drugs across the BBB and to reverse MDR. Here, we review the history, preparatory methods, and physicochemical properties of liposomes. Furthermore, we discuss the mechanisms by which liposomes have assisted in the diagnosis and treatment of gliomas, including drug transport across the BBB, inhibition of efflux transporters, reversal of MDR, and induction of immune responses. Finally, we highlight ongoing and future clinical trials and applications toward further developing and testing the efficacies of liposomes in treating gliomas.

The Preparation, Determination of a Flexible Complex Liposome Co-Loaded with Cabazitaxel and ß-Elemene, and Animal Pharmacodynamics on Paclitaxel-Resistant Lung Adenocarcinoma.

Paclitaxel is highly effective at killing many malignant tumors; however, the development of drug resistance is common in clinical applications. The issue of overcoming paclitaxel resistance is a difficult challenge at present. In this study, we developed nano drugs to treat paclitaxel-resistant lung adenocarcinoma. We selected cabazitaxel and ß-elemene, which have fewer issues with drug resistance, and successfully prepared cabazitaxel liposome, ß-elemene liposome and cabazitaxel-ß-elemene complex liposome with good flexibility. The encapsulation efficiencies of cabazitaxel and ß-elemene in these liposomes were detected by precipitation microfiltration and microfiltration centrifugation methods, respectively. Their encapsulation efficiencies were all above 95%. The release rates were detected by a dialysis method. The release profiles of cabazitaxel and ß-elemene in these liposomes conformed to the Weibull equation. The release of cabazitaxel and ß-elemene in the complex liposome were almost synchronous. The pharmacodynamics study showed that cabazitaxel flexible liposome and ß-elemene flexible liposome were relatively good at overcoming paclitaxel resistance on paclitaxel-resistant lung adenocarcinoma. As the flexible complex liposome, the dosage of cabazitaxel could be reduced to 25% that of the cabazitaxel injection while retaining a similar therapeutic effect. It showed that ß-elemene can replace some of the cabazitaxel, allowing the dosage of cabazitaxel to be reduced, thereby reducing the drug toxicity.

Drug delivery systems for elemene, its main active ingredient ß-elemene, and its derivatives in cancer therapy.

ß-elemene is a noncytotoxic Class II antitumor drug extracted from the traditional Chinese medicine Curcuma wenyujin Y. H. Chen et C. Ling. ß-elemene exerts its effects by inhibiting cell proliferation, arresting the cell cycle, inducing cell apoptosis, exerting antiangiogenesis and antimetastasis effects, reversing multiple-drug resistance (MDR), and enhancing the immune system. Elemene injection and oral emulsion have been used to treat various tumors, including cancer of the lung, liver, brain, breast, ovary, gastric, prostate, and other tissues, for >20 years. The safety of both elemene injection and oral emulsion in the clinic has been discussed. Recently, the secondary development of ß-elemene has attracted the attention of researchers and made great progress. On the one hand, studies have been carried out on liposome-based systems (including solid lipid nanoparticles [SLNs], nanostructured lipid carriers [NLCs], long-circulating liposomes, active targeting liposomes, and multidrug-loaded liposomes) and emulsion systems (including microemulsions, self-emulsion drug delivery systems [SEDDSs], and active targeting microemulsion) to solve the issues of poor solubility in water, low bioavailability, and severe phlebitis, as well as to improve antitumor efficacy. The pharmacokinetics of different drug delivery systems of ß-elemene are also summarized. On the other hand, a number of highly active anticancer ß-elemene derivatives have been obtained through modification of the structure of ß-elemene. This review focuses on the two drug delivery systems and derivatives of ß-elemene for cancer therapy.

Review of Anemone raddeana Rhizome and its pharmacological effects.

The chemical compositions of Anemone raddeana Rhizome, a kind of traditional Chinese medicine, were reviewed, along with its bioactivity and pharmacological properties and method improvements of extracting and detecting triterpenoid saponins. A. raddeana Rhizome is used to treat neuralgia and rheumatism, and is rich in triterpenoid saponins, most of which are pentacyclic, with oleanane as the nucleus. So far, 37 triterpenoid saponins have been determined from the herb. Its reported bioactivity and pharmacological properties have been described as anticancerous, antimicrobial, anti-inflammatory, analgesic, antipyretic, anticonvulsive, antihistaminic, and sedative. It has also been used for the induction of the humoral immune response and treatment of liver fibrosis in chronic hepatitis. However, the herb also has hemolytic effects and can be toxic, which limits its clinical application. Further studies are needed on the pharmaceutical functions, mechanisms, and immunological responses to contribute to the herb's clinical applications.

[Study on the Fingerprint of Kingkong Zedoary Turmeric Oil].

OBJECTIVE: To study the fingerprint of Zedoary Turmeric Oil (ZTO) as the bulk drug of Kingkong Elemene for making it safe, effective, stable, and controllable. METHODS: Fingerprints were detected by gas chromatography. ß-elemene peak was regarded as reference peak (S). The relative peak area of each common peak and the relative retention time were calculated. With a total of modes for reference, the fingerprints of 10 batches of Kingkong ZTO were detected, and their similarity was calculated by traditional Chinese medicine (TCM) fingerprint similarity calculation software. RESULTS: The determination method was stable and reliable. Totally 19 common characteristic peaks of Kingkong ZTO was found. The fingerprint similarity of these batches of Kingkong ZTO were not lower than 0.96. CONCLUSIONS: Gas chromatography for detecting the fingerprint of Kingkong ZTO was reliable and repeatable. The established fingerprint of Kingkong ZTO could guarantee the quality stability and safety of different product batches.

Application of poly(ethylene glycol)-distearoylphosphatidylethanolamine (PEG-DSPE) block copolymers and their derivatives as nanomaterials in drug delivery.

Poly(ethylene glycol)-distearoylphosphatidylethanolamine (PEG-DSPE) block copolymers are biocompatible and amphiphilic polymers that can be widely utilized in the preparation of liposomes, polymeric nanoparticles, polymer hybrid nanoparticles, solid lipid nanoparticles, lipid-polymer hybrid nanoparticles, and microemulsions. Particularly, the terminal groups of PEG can be activated and linked to various targeting ligands, which can prolong the circulation time, improve the drug bioavailability, reduce undesirable side effects, and especially target specific cells, tissues, and even the intracellular localization in organelles. This review herein aims to describe recent developments in drug carriers exploiting PEG-DSPE block copolymers and their derivatives, and the incorporation of different ligands to the end groups of PEG-DSPE to target delivery, focusing on their modification approaches, advantages, applications, and the probable associated drawbacks.

Pharmacokinetics of ligustrazine ethosome patch in rats and anti-myocardial ischemia and anti-ischemic reperfusion injury effect.

The objective of this study was to investigate the pharmacokinetics of the ligustrazine ethosome patch and antimyocardial ischemia and anti-ischemic reperfusion injury effect. Male Sprague Dawley rats were divided randomly into 3 groups: Group A (intragastric ligustrazine), Group B (transdermal ligustrazine ethosome patch), and Group C (conventional transdermal ligustrazine patch). After treatment, samples of blood and of various tissues such as heart, liver, spleen, lung, kidney, brain, and muscle samples were taken at different time points. Drug concentration was measured with HPLC, and the drug concentration-time curve was plotted. Pharmacokinetic software 3p97 was applied to calculate pharmacokinetic parameters and the area under the drug concentration-time curve (AUC) in various tissues. The rat model of acute myocardial ischemia was constructed with intravenous injection of pituitrin and the model of myocardial ischemia-perfusion injury was constructed by tying off the left anterior descending coronary artery of rats to observe the effect of ligustrazine ethosome patches on ischemic myocardium and ischemia-reperfusion injury. Results showed that AUC was highest in the transdermal drug delivery group of ligustrazine ethosome patch. There were significant differences in whole blood viscosity, plasma viscosity, hematocrit, red blood cell aggregation index, and deformation index between ligustrazine the ethosome patch group and ischemic control group (P < 0.01). Moreover, ligustrazine ethosome patches could reduce the scope of myocardial infarction induced by long-term ischemia. Ligustrazine ethosome patches have a sustained-release property. They can maintain stable and sustained blood drug concentration, increase bioavailability, and reduce administration times. The drug patch can decrease hemorheological indices of myocardial ischemia in rats, as well as protect acute ischemic myocardium and ischemia-reperfusion injured myocardium.

Efficient production of a thermophilic 2-deoxyribose-5-phosphate aldolase in glucose-limited fed-batch cultivations of Escherichia coli by continuous lactose induction strategy.

The production of a thermophilic 2-deoxyribose-5-phosphate aldolases (DERA) in Escherichia coli BL21 under continuous lactose induction strategy was investigated. The process was combined with the exponential feeding method, controlling the feeding rate to maintain the specific growth rate at 0.15 h(-1). The results indicate that the lactose concentration in the feed medium affected directly the expression of the target protein. The use of 50 g/L in the feed medium resulted in the biomass concentration of 39.3 g DCW/L, and an expression level of above 30%, and the maximum final DERA concentration of 16,200 U/L. Furthermore, the acetate concentration remained at a low level in the fed-batch phase, less than 0.5 g/L. In conclusion, combining glucose feeding with lactose induction is a more powerful way to achieve high cell density cultures and to efficiently produce the thermophilic DERA. The results also indicate the potential industrial utility in the scale production of other recombinant proteins.

Stable and efficient immobilization technique of aldolase under consecutive microwave irradiation at low temperature.

To establish a stable and efficient immobilization technique under microwave irradiation, a focused microwave reaction system was used, where the temperature was set appropriately in the microwave system and cooling module to produce consecutive microwave irradiation. 2-Deoxy-D-ribose-5-phosphate aldolase (DERA) was rapidly and efficiently immobilized in mesocellular siliceous foams (MCFs) under microwave irradiation. When the output power in the microwave system was set to 30 W, after 3 min, 88.4% of the enzyme protein was coupled to the wall of the support pores and the specific activity of the immobilized enzyme was 2.24 U mg(-1), 149.2% higher than that of the free enzyme and 157.0% higher than that of the non-microwave-assisted immobilized enzyme. In catalysis, microwave-assisted immobilized DERA tolerated a wider range of both pH and temperature than other DERA preparations. The thermal and storage stabilities were also significantly improved. This focused; microwave-assisted immobilization technique has proven to be simple, stable and highly efficient. This technique could also be applied to other enzyme immobilizations.

Preparation, characterization and relative bioavailability of oral elemene o/w microemulsion.

The objective was to develop an elemene oil/water (o/w) microemulsion and evaluate its characteristics and oral relative bioavailability in rats. Elemene was used as the oil phase and drug, polysorbate 80 as a surfactant along with ethanol, propylene glycol, and glycerol as the cosurfactants. The microemulsion was prepared by mixing method, or ultrasonication method in an ultrasonic bath. Its three-dimensional response surface diagram was drawn by Mathcad software. The microemulsion was characterized by visual observation, cross-polarized microscopy, size, zeta potential, acidity, viscosity, and surface tension measurement. The drug content and entrapment efficiency were determined by ultra fast liquid chromatography (UFLC) and liquid surface method. Blood was drawn from rats at different time points after oral administration of an elemene microemulsion or a commercial elemene emulsion for measurement of the drug in plasma by UFLC to establish the pharmacokinetic parameters and relative bioavailability. The elemene microemulsion as a clarified and isotropic system containing 1% elemene (w/v), 5% ethanol (v/v), 15% propylene glycol (v/v), 15% glycerol (v/v), and 5% polysorbate 80 (w/v), was characterized as (57.7 ± 2.8) nm in size, 0.485 ± 0.032 in polydispersity index, (3.2 ± 0.4) mv in zeta potential, (5.19 ± 0.08) in pH, 6 mpa·s in viscosity, (31.8 ± 0.3) mN·m(-1) in surface tension, (8.273 ± 0.018) mg·mL(-1) in content of ß-elemene, and (99.81 ± 0.24)% in average entrapment efficiency. The area under the concentration-time curves from 0 h to 24 h (AUC(0→24h)) of the elemene microemulsion and commercial elemene emulsion were integrated to be 3.092 mg·h·L(-1) and 1.896 mg·h·L(-1) respectively, yielding a relative bioavailability of 163.1%. The present study demonstrates the elemene microemulsion as a new formulation with ease of preparation, high entrapment efficiency, excellent clarity, good stability, and improved bioavailability.

Preparation and characterization of tegafur magnetic thermosensitive liposomes.

The purpose was to study the preparation and properties of tegafur magnetic thermosensitive liposomes. The method was to employ an improved chemical coprecipitation method for preparing nano-magnetic particles and a reverse-phase evaporation and ultrasonic method for preparing tegafur magnetic thermosensitive liposomes. The results showed that tegafur magnetic thermosensitive liposomes were prepared successfully. They had comparatively strong magnetism and superparamagnetism, and their temperature showed a linear positive correlation with dosages and the field strength under a current value. The conclusion was that tegafur magnetic thermosensitive liposomes with comparatively small particle size, superparamagnetism and comparatively strong magnetism were prepared successfully.

[Preparation of tegafur magnetic long-circulating thermosensitive liposomes and its pharmacokinetics in rats].

OBJECTIVE: To prepare tegafur magnetic long-circulating thermosensitive liposomes and study its pharmacokinetics and targeting properties in rats. METHODS: Tegafur magnetic long-circulating thermosensitive liposomes were prepared by reversed phase-ultrasound method and its concentration in various organs of rats were detected with high-performance liquid chromatography. RESULTS: The average size of tegafur magnetic long-circulating thermosensitive liposomes was about 126 nm, which showed strong ferromagnetism and superparamagnetism. Eight hours after administration in rats, the AUC value of tegafur magnetic long-circulating thermosensitive liposome in the liver was 17.4 times of that of the free drug, and 3.9 times of that of tegafur long-circulating liposome. The concentrations of the thermosensitive liposome in the serum and kidney were lower than those of the free drug, with a liver-targeting ratio reaching 73.9% and obviously prolonged half-life than the free drug. CONCLUSION: Tegafur complex liposome can obviously increase the drug concentration in the liver and decrease the nephrotoxicity of the drug in rats.

[Preparation and characterization of a polyvinylpyrrolidone water-based magnetic fluid].

OBJECTIVE: To prepare a stable water-based magnetic fluid. METHODS: A water-based magnetic fluid was prepared by addition of polyvinylpyrrolidone (PVP) as the coating agent for the magnetic particles. After preparation of Fe3O4 by co-precipitation method, PVP was added for its coating, followed by ultrasonic agitation and purification. RESULTS: The magnetic nanoparticles of homogeneously small size and water-based magnetic fluid were obtained, which had good dispersion in water with strong magnetism. CONCLUSION: PVP can be used as a surfactant to stabilize the magnetic fluid.