Berberine and folic acid co-modified pH-sensitive cascade-targeted PTX-liposomes coated with Tween 80 for treating glioma.

Chemotherapy is a conventional treatment for glioma, but its efficacy is greatly limited due to low blood-brain barrier (BBB) permeability and lack of specificity. Herein, intelligent and tumor microenvironment (TME)-responsive folic acid (FA) derivatives and mitochondria-targeting berberine (BBR) derivatives co-modified liposome coated with Tween 80 loading paclitaxel (PTX-Tween 80-BBR + FA-Lip) was constructed. Specifically speaking, liposomes modified by FA can be effectively target ed to glioma cells. BBR, due to its delocalized positive electricity and lipophilicity, can be attracted by mitochondrial membrane potential and concentrate on mitochondria to achieve mitochondrial targeting and induce cell apoptosis. By simultaneously modifying the liposome with FA and BBR to deliver drugs, leads to a good therapeutic effect of glioma through FA-based glioma targeting and BBR-based mitochondrial targeting. In addition, the surface of the liposome was coated with Tween 80 to further improve BBB penetration. All results exhibited that PTX-Tween 80-BBR + FA-Lip can observably improve the chemotherapy therapeutic efficacy through the highly specific tumor targeting and mitochondrial targeting, which can provide new ideas and methods for the targeted therapy of glioma.

Biotin and glucose co-modified multi-targeting liposomes for efficient delivery of chemotherapeutics for the treatment of glioma.

Glioma is one of the most common primary intracranial tumor, but the current treatments of glioma are far from satisfying. As the major treatment option for malignant glioma, chemotherapy has its own disadvantages, including low chemotherapeutic agents delivery across blood-brain barrier (BBB) and lack of specificity. Therefore, new approach permitting glioma targeting ability that can allow an efficient therapeutic delivery into the glioma regions is urgently required. Ligand-mediated liposomes have shown great potential for improving the efficiency of glioma treatment. In our study, the multi-targeting liposomes based on glucose and biotin were constructed for the first time. We synthesized two ligands (Glu3-Chol, Bio2-Chol), prepared three types of modified liposomes (Glu3-Lip, Bio2-Lip and Bio2 + Glu3-Lip) and evaluated the glioma-targeting ability of these liposomes which were using paclitaxel (PTX) as the model drug in vitro. Besides, the uptake mechanism of Bio2 + Glu3-Lip was investigated. PTX-loaded Bio2 + Glu3-Lip (PTX-Bio2 + Glu3-Lip) exhibited satisfactory targeting effect in Bend.3 and C6 cells in vitro, in which the cellular uptake of Bio2 + Glu3-Lip were 4.04- and 3.49-fold more than that of the uncoated liposomes (Lip). The results suggested the multi-targeting liposomes (Bio2 + Glu3-Lip) is a promising formulation for glioma, which was almost consistent with the results of in vivo imaging. In summary, we have designed and fabricated an effective delivery system to treat glioma.

Electroenzymatic glutamate sensing at near the theoretical performance limit.

The sensitivity and response time of glutamate sensors based on glutamate oxidase immobilized on planar platinum microelectrodes have been improved to near the theoretical performance limits predicted by a detailed mathematical model. Microprobes with an array of electroenzymatic sensing sites have emerged as useful tools for the monitoring of glutamate and other neurotransmitters in vivo; and implemented as such, they can be used to study many complex neurological diseases and disorders including Parkinson's disease and drug addiction. However, less than optimal sensitivity and response time has limited the spatiotemporal resolution of these promising research tools. A mathematical model has guided systematic improvement of an electroenzymatic glutamate microsensor constructed with a 1-2 µm-thick crosslinked glutamate oxidase layer and underlying permselective coating of polyphenylenediamine and Nafion reduced to less than 200 nm thick. These design modifications led to a nearly 6-fold improvement in sensitivity to 320 ± 20 nA µM-1 cm-2 at 37 °C and a ∼10-fold reduction in response time to 80 ± 10 ms. Importantly, the sensitivity and response times were attained while maintaining a low detection limit and excellent selectivity. Direct measurement of the transport properties of the enzyme and polymer layers used to create the biosensors enabled improvement of the mathematical model as well. Subsequent model simulations indicated that the performance characteristics achieved with the optimized biosensors approach the theoretical limits predicted for devices of this construction. Such high-performance glutamate biosensors will be more effective in vivo at a size closer to cellular dimension and will enable better correlation of glutamate signaling events with electrical recordings.

Rumen fluid fermentation for enhancement of hydrolysis and acidification of grass clipping.

Rumen fluid, formed in rumen of ruminants, includes a complex microbial population of bacteria, protozoa, fungi and archaea, and has high ability to degrade lignocellulosic biomass. In this study, rumen fluid was used to ferment grass clipping for enhancing the hydrolysis and acidification of organic matters. Results showed that strict anaerobic condition, higher grass clipping content and smaller particle size of grass clipping were beneficial to the hydrolysis and acidification of organics. The increase of SCOD and total VFA concentration respectively reached 24.9 and 10.2 g/L with a suitable grass clipping content of 5%, a particle size <0.150 mm, and a fermentation time of 48 h. The VFA production was mainly attributed to the degradation of cellulose and hemicellulose with a total solid reduction of 55.7%. Firmicutes and Fibrobacteres were the major contributors to the degradation of cellulose and hemicellulose. The activity of carboxymethyl cellulose enzyme (CMCase), cellobiase and xylanase reached 0.027, 0.176 and 0.180 U/ml, respectively. The rumen fluid microorganisms successfully enhanced the hydrolysis and acidification of grass clipping.

Construction and application of H1R ligand screening materials based on SMA stabilization and his-tag covalent immobilization of membrane proteins.

The histamine H1 receptor (H1R) plays a pivotal role in allergy initiation and undergoes the necessity of devising a high-throughput screening approach centered on H1R to screen novel ligands effectively. This study suggests a method employing styrene maleic acid (SMA) extraction and His-tag covalent bonding to immobilize H1R membrane proteins, minimizing the interference of nonspecific proteins interference while preserving native protein structure and maximizing target exposure. This approach was utilized to develop a novel material for high-throughput ligand screening and implemented in cell membrane chromatography (CMC). An H1R-His-SMALPs/CMC model was established and its chromatographic performance (selectivity, specificity and lifespan) validated, demonstrating a significant enhancement in lifespan compared to previous CMC models. Subsequently, this model facilitated high-throughput screening of H1R ligands in the compound library and preliminary activity verification of potential H1R antagonists. Identification of a novel H1R antagonist laid the foundation for further development in this area.

Leaching kinetics and bioaccumulation potential of additive-derived organophosphate esters in microplastics.

Considerable research has been conducted to evaluate microplastics (MPs) as vehicles for the transfer of hazardous pollutants in organisms. However, little effort has been devoted to the chemical release of hazardous additive-derived pollutants from MPs in gut simulations. This study looked at the leaching kinetics of organophosphate esters (OPFRs) from polypropylene (PP) and polystyrene (PS) MPs in the presence of gut surfactants, specifically sodium taurocholate, at two biologically relevant temperatures for marine organisms. Diffusion coefficients of OPFRs ranged from 1.71 × 10-20 to 4.04 × 10-18 m2 s-1 in PP and 2.91 × 10-18 to 1.51 × 10-15 m2 s-1 in PS. The accumulation factors for OPFRs in biota-plastic and biota-sediment interactions ranged from 1.52 × 10-3-69.1 and 0.02-0.7, respectively. Based on B3LYP/6-31G (d,p) calculations, the biodynamic model analysis revealed a slight increase in the bioaccumulation of OPFRs at a minor dose of 0.05% MPs. However, at higher concentrations (0.5% and 5% MPs), there was a decrease in bioaccumulation compared to the lower concentration for most OPFR compounds. In general, the ingestion of PE MPs notably contributed to the bioaccumulation of OPFRs in lugworms, whereas the contribution of PP and PS MPs was minimal. This could vary among sites exhibiting varying levels of MP concentrations or MPs displaying stronger affinities towards chemicals.

Investigation of functionalised nanoplatforms using branched-ligands with different chain lengths for glioblastoma targeting.

Glioblastoma, a common malignancy of the central nervous system, is the most destructive type of brain cancer. Clinical treatment remains a major challenge due to high infiltrative growth and the presence of the blood brain barrier (BBB). Therefore, advanced nanoplatforms that can efficiently cross the BBB and target brain tumours are highly desired. Compared with the targeting efficiency of single ligand nanoplatforms, dual targeting nanoplatforms may lead to better and controllable malignant cell selectivity. In this study, based on our previous research of branched ligands, we finally determined to use tri-branched glucose and two-branched biotin as targeting molecules, and in order to explore the synergetic-targeting capabilities and the mutual influence between the length of the two ligands, we designed three kinds of two-branched biotin ligands with a different linker and co-modified with the tri-branched glucose ligands on the surface of liposomes. The results of in vivo and in vitro experiments showed the (Glu3+Bio2)-2-Lip can exert the greatest synergistic targeting ability. The application of branched ligands, the dual-targeting design concept, and the exploration of the interaction between the chain lengths of the two ligands have brought new ideas and new methods for the targeted therapy of glioma.

Poly-l-lysine derivative-coated black phosphorus as a nanoplatform for photothermal chemotherapy to enhance anti-tumor efficiency.

Severe systemic toxicity and side effects are major obstacles to the success of chemotherapy for tumors. Regardless of the choice of chemotherapy drugs, the safety of drug delivery materials is crucial, and therefore, there have been various efforts to improve the therapeutic effect and the biological safety of drug delivery systems (DDSs). In this study, a dual stimulus-response DDS (PLL-SS@DOX-BP) was constructed based on the biomaterials of black phosphorus (BP) nanosheets and poly-l-lysine (PLL) to enhance the treatment of doxorubicin hydrochloride (DOX) for breast cancer. The PLL derivative was nano-coated on the surface of drug-loaded BP nanosheets, and it prevented premature leakage of the drug and maintained the stability of the DDS. The introduced disulfide bonds and photothermal agent BP enabled the redox and near-infrared responsive drug release of the DDS, and the coated PLL derivative on the nanocarrier decreased premature leakage of the drug before the DDS reached the tumor tissues. The in vitro and in vivo experiments showed that the combination of biomaterial (PLL) and photothermal material (BP nanosheets) exhibited excellent biological safety and remarkable drug delivery capacity. Moreover, the pharmacodynamic studies indicated that PLL-SS@DOX-BP is a powerful vehicle for photothermal therapy in combination with chemotherapy. Compared with chemotherapy alone, the developed DDS displayed enhanced anti-tumor efficiency with decreased systemic toxicity, and thus, it has the potential to be a promising anti-tumor treatment strategy.

Polyethylenimine-grafted nitrogen-doping magnetic biochar for efficient Cr(VI) decontamination: Insights into synthesis and adsorption mechanisms.

Herein, polyethylenimine (PEI)-grafted nitrogen (N)-doping magnetic biochar (PEIMW@MNBCBM) was synthesized, and characterization results showed that the microwave-assisted PEI grafting and ball milling-assisted N doping introduced abundant amino, pyridine N and pyrrole N structures onto biochar, which possessed high affinity to Cr(VI) in the anion form. The as-prepared PEIMW@MNBCBM displayed pH-dependence adsorption performance and high tolerance to co-existing ions with maximum uptake capacity of Cr(VI) identified as 183.02 mg/g. Furthermore, PEIMW@MNBCBM could bind Cr(VI) through electrostatic attraction, complexion, precipitation, reduction and pore filling. Especially, effective reduction of Cr(VI) was ascribed to cooperative electron transfer of partial oxygen-containing functional groups, intramolecular pyridine/pyrrole N, protonated amino and Fe2+ on the adsorbent, while oxygen-containing and amino functional groups from N-doping biochar and PEI synergistically complexed Cr(III) via providing lone pair electrons to form coordinate bonds. Furthermore, the stable precipitation was formed between Fe3+ and Cr(III). Additionally, the Cr(VI) elimination efficiency could maintain 95.83% even after four adsorption-desorption cycles, suggesting PEIMW@MNBCBM as a high-performance adsorbent for Cr(VI) contaminated water remediation.

Development of a Novel MR Colonography via Iron-Based Solid Lipid Nanoparticles.

PURPOSE: To develop an iron-based solid lipid nanoparticle (SLN) absorbable by the intestinal wall and assess the differential diagnostic value of intestinal lesions in magnetic resonance imaging (MRI). METHODS: SLNs were prepared with the simultaneous loading of trivalent Fe ions (Fe3+), levodopa methyl ester (DM), and fluorescein isothiocyanate (FITC). We evaluated the particle size, loading rate, encapsulation efficiency, and cytotoxicity of SLNs. The T1 contrast effects of the FeDM-FITC-SLNs and gadolinium-based contrast agent (GBCA) were compared in different mouse models: acute ulcerative colitis (AUC), chronic ulcerative colitis (CUC), colon adenocarcinoma (COAD), and normal control. MRI was performed in the same mouse with intravenous injection of GBCA on day 1 and enema of FeDM-FITC-SLNs on day 2. The signal-to-noise ratios (SNRs) were compared using one-way analysis of variance. Tissues were then collected for histology. RESULTS: The average particle size of FeDM-FITC-SLN was 220 nm. The mean FeDM loading rate was 94.3%, and the encapsulation efficiency was 60.3%. The relaxivity was 4.02 mM-1·s-1. After enema with FeDM-FITC-SLNs, MRI showed the following contrast enhancement duration: AUC = COAD > normal > CUC. Confocal fluorescence microscopy confirmed that FeDM-FITC-SLNs were mainly distributed in the intestinal mucosa and tumor capsule. CONCLUSION: Iron-based SLNs are promising alternatives for contrast enhancement at T1-weighted MRI and will help in the differential diagnosis of intestinal bowel diseases (IBDs).

Vertical microplastic distribution in sediments of Fuhe River estuary to Baiyangdian Wetland in Northern China.

Microplastics exist widely in water environment. The microplastic distribution in sediments can better reflect the long-term microplastic pollution, especially the vertical distribution. However, the vertical microplastic distribution in sediments is diverse and unclear. This paper is the first study on vertical microplastic distribution in estuary sediment of Fuhe River, the main upstream river flowing to Baiyangdian Wetland in the northern China. The typical feature of Fuhe River is that the effluent of municipal wastewater treatment plants is its main water source. Microplastics in 15 sampling sites and different depths (0-50 cm) were examined. Results showed that the microplastic content decreased with the increase of sediment depth, and the highest content was 1049 ± 462 items/kg in the topmost sediment layer (0-5 cm). The particle size of microplastics was smaller in deeper sediment layers. The proportion of colored microplastics in deeper sediment layers was larger than that in shallower layers. Polyethylene (PE) and polypropylene (PP) were the main plastic polymer types in all sediment samples. The spatial distribution characteristics of microplastics in sediments were closely related to human activities, and the microplastic content was higher in the areas with more intense human activities. This study is helpful to understand the detailed distribution characteristics of microplastics in typical rivers in the northern China, and can provide guidance for reducing microplastic pollution.

Fabrication, evaluation and applications of dissolving microneedles.

In recent years, transdermal preparations have emerged as one of the most promising modes of administration. In particular, dissolving microneedles have attracted extensive attention because of their painlessness, safety, high delivery efficiency and easily operation for patients. This article mainly reviews the preparation methods, the types of matrix polymer materials, the content of dissolving microneedles performance testing, and the applications of dissolving microneedles. It is expected to lay a solid knowledge foundation for the in-depth study of the dissolving microneedles.

Real-World Dosing Patterns and Outcomes of Patients With Metastatic Pancreatic Cancer Treated With a Liposomal Irinotecan Regimen in the United States.

OBJECTIVES: Liposomal irinotecan (nal-IRI) is a topoisomerase inhibitor proven to improve survival in metastatic pancreatic cancer (mPC). This study describes real-world characteristics of patients treated with nal-IRI for mPC. METHODS: Patients 18 years or older diagnosed with stage IV mPC and treated with nal-IRI were selected retrospectively from a deidentified electronic health record database of more than 2 million US cancer patients. Demographics, clinical and dosing characteristics, and treatment outcomes were collected. RESULTS: Of 257 total patients, 145 (57%) received nal-IRI as first- or second-line therapy. Median nal-IRI treatment duration was 51 days, longer when nal-IRI was used as first/second versus as third-line therapy or later (62 vs 44.5 days). Seventy patients (27.2%) experienced dose modification. Median time to treatment discontinuation was 2.3 versus 1.6 months for first-/second- versus third-line therapy or later, respectively. Median overall survival from nal-IRI initiation was 5.6 versus 4.1 months for first-/second- versus third-line therapy or later, respectively. Prior irinotecan treatment, baseline serum albumin less than 40 g/L, and baseline neutrophil-to-lymphocyte ratio greater than 5 were associated with reduced overall survival. CONCLUSIONS: This is the first large US study of real-world US mPC patients treated with nal-IRI. These results, comparable to the NAPOLI-1 trial, can help inform future studies and the efficacy of nal-IRI in mPC therapy.

Bio-inspired Edible Superhydrophobic Interface for Reducing Residual Liquid Food.

Significant wastage of residual liquid food, such as milk, yogurt, and honey, in food containers has attracted great attention. In this work, a bio-inspired edible superhydrophobic interface was fabricated using U.S. Food and Drug Administration-approved and edible honeycomb wax, arabic gum, and gelatin by a simple and low-cost method. The bio-inspired edible superhydrophobic interface showed multiscale structures, which were similar to that of a lotus leaf surface. This bio-inspired edible superhydrophobic interface displayed high contact angles for a variety of liquid foods, and the residue of liquid foods could be effectively reduced using the bio-inspired interface. To improve the adhesive force of the superhydrophobic interface, a flexible edible elastic film was fabricated between the interface and substrate material. After repeated folding and flushing for a long time, the interface still maintained excellent superhydrophobic property. The bio-inspired edible superhydrophobic interface showed good biocompatibility, which may have potential applications as a functional packaging interface material.

Highly Efficient Erythritol Recovery from Waste Erythritol Mother Liquor by a Yeast-Mediated Biorefinery Process.

Erythritol, a natural sugar alcohol, is produced industrially by fermentation and crystallization, but this process leaves a large amount of waste erythritol mother liquor (WEML) which contains more than 200 g/L erythritol as well as other polyol byproducts. These impurities make it very difficult to crystallize more erythritol. In our study, an efficient process for the recovery of erythritol from the WEML is described. The polyol impurities were first identified by high-performance liquid chromatography and gas chromatography-mass spectrometry, and a yeast strain Candida maltosa CGMCC 7323 was then isolated to metabolize those impurities to purify erythritol. Our results demonstrated that the process could remarkably improve the purity of erythritol and thus make the subsequent crystallization easier. This newly developed strategy is expected to have advantages in WEML treatment and provide helpful information with regard to green cell factories and zero-waste processing.

Microwave assisted alkaline pretreatment to enhance enzymatic saccharification of catalpa sawdust.

Catalpa sawdust, a promising biofuel production biomass, was pretreated by microwave-water, -NaOH, and -Ca(OH)2 to enhance enzymatic digestibility. After 48h enzymatic hydrolysis, microwave-Ca(OH)2 pretreated sample showed the highest reducing sugar yield. The content of hemicellulose and lignin in catalpa sawdust decreased after microwave-alkali pretreatment. SEM observation showed that the catalpa sawdust surface with microwave-Ca(OH)2 pretreatment suffered the most serious erosion. Crystallinity index of catalpa sawdust increased after all three kinds of pretreatment. The optimum conditions of microwave-Ca(OH)2 pretreatment were particle size of 40mesh, Ca(OH)2 dosage of 2.25% (w/v), microwave power of 400W, pretreatment time of 6min, enzyme loading of 175FPU/g, and hydrolysis time of 96h, and the reducing sugar yield of microwave-Ca(OH)2 pretreated catalpa sawdust reached 402.73mg/g, which increased by 682.15% compared with that of raw catalpa sawdust. The catalpa sawdust with microwave-Ca(OH)2 pretreatment is promising for biofuel production with great potential.

In vitro degradation and electrochemical corrosion evaluations of microarc oxidized pure Mg, Mg-Ca and Mg-Ca-Zn alloys for biomedical applications.

Calcium phosphate (CaP) ceramic coatings were fabricated on pure magnesium (Mg) and self-designed Mg-0.6Ca, Mg-0.55Ca-1.74Zn alloys by microarc oxidation (MAO). The coating formation, growth and biomineralization mechanisms were discussed. The coating degradability and bioactivity were evaluated by immersion tests in trishydroxymethyl-aminomethane hydrochloric acid (Tris-HCl) buffer and simulated body fluid (SBF) solutions, respectively. The coatings and corrosion products were characterized by scanning electron microscope (SEM), X-ray diffractometer (XRD), X-ray photoelectron spectrometer (XPS) and fourier transform infrared spectrometer (FT-IR). The electrochemical workstation was used to investigate the electrochemical corrosion behaviors of substrates and coatings. Results showed that Mg-0.55Ca-1.74Zn alloy exhibits the highest mechanical strength and electrochemical corrosion resistance among the three alloys. The MAO-coated Mg-0.55Ca-1.74Zn alloy has the potential to be served as a biodegradable implant.