Major difference in particle size, minor difference in release profile: a case study of solid lipid nanoparticles.

Solid lipid nanoparticles (SLN) have been widely used in a variety of drug delivery routes, which have the outstanding advantage of controlled drug release. The release of SLN is dominated by many factors, among which the particle size of SLN is a critical one. The aim of this project was to explore the relationship between drug release profile and particle size of SLN. SLN were synthesized via the hot high-pressure homogenization (HPH) method, budesonide (BUD) was used as the model drug, and BUD-SLN1-BUD-SLN4 with increasing particle size was obtained, i.e. 120, 240, 360, and 480 nm. The prepared SLN has good encapsulation efficiency, drug loading capacity, and stability. In vitro release behavior studies showed that the cumulative release of BUD-SLN in Tris-Maleate (Tris-M) media was negligible, while that in Tris-M plus pancreatin media or Tris-M-ethanol media obeyed Ritger-Peppas model or first-order kinetic model, respectively. Noticeably, the release behavior of SLN was to some extent related to the average particle size of SLN, but the correlation was insignificant when the intersection degree of particle size distribution was great. This study provides a new idea for the understanding of in vitro release of SLN and has a certain referencing value for the research and development of novel nanomedicines.

Inhalable Biomineralized Liposomes for Cyclic Ca2+-Burst-Centered Endoplasmic Reticulum Stress Enhanced Lung Cancer Ferroptosis Therapy.

Lung cancer with the highest mortality poses a great threat to human health. Ferroptosis therapy has recently been raised as a promising strategy for lung cancer treatment by boosting the reactive species (ROS) production and lipid peroxidation (LPO) accumulation intracellularly. However, the insufficient intracellular ROS level and the unsatisfactory drug accumulation in lung cancer lesions hamper the efficacy of ferroptosis therapy. Here, an inhalable biomineralized liposome LDM co-loaded with dihydroartemisinin (DHA) and pH-responsive calcium phosphate (CaP) was constructed as a ferroptosis nanoinducer for achieving Ca2+-burst-centered endoplasmic reticulum (ER) stress enhanced lung cancer ferroptosis therapy. Equipped with excellent nebulization properties, about 6.80-fold higher lung lesions drug accumulation than intravenous injection made the proposed inhalable LDM an ideal nanoplatform for lung cancer treatment. The Fenton-like reaction mediated by DHA with peroxide bridge structure could contribute to intracellular ROS production and induce ferroptosis. Assisted by DHA-mediated sarco-/endoplasmic reticulum calcium ATPase (SERCA) inhibition, the initial Ca2+ burst caused by CaP shell degradation triggered the Ca2+-mediated intense ER stress and subsequently induced mitochondria dysfunction to further boost ROS accumulation, which strengthens ferroptosis. The second Ca2+ burst occurred as a result of Ca2+ influx through ferroptotic pores on cell membranes, thus sequentially constructing the lethal "Ca2+ burst-ER stress-ferroptosis" cycle. Consequently, the Ca2+-burst-centered ER stress enhanced ferroptosis process was confirmed as a cell swelling and cell membrane disruption process driven by notable intracellular ROS and LPO accumulation. The proposed LDM showed an encouraging lung retention property and extraordinary antitumor ability in an orthotropic lung tumor murine model. In conclusion, the constructed ferroptosis nanoinducer could be a potential tailored nanoplatform for nebulization-based pulmonary delivery and underscore the application of Ca2+-burst-centered ER stress enhanced lung cancer ferroptosis therapy.

Study on Wear Mechanism of Helical Gear by Three-Body Abrasive Based on Impact Load.

This study aimed to explore the wear characteristics and evolution mechanisms of large-scale wind power gears under the impact load of particles of the three-body abrasive Al2O3 (0.2 mg/mL) from four aspects: oil analysis, vibration analysis, amount of gear wear, and tooth-surface-wear profile analysis. A magnetic powder brake was used to simulate the actual working conditions. Combined with the abrasive particle monitoring and the morphology analysis of the tooth-surface-wear scar, by setting quantitative hard particles in the lubricating oil, the gears are mainly operated in the abrasive wear state, and wear monitoring and wear degree analysis are carried out for the whole life cycle of the gears. Oil samples were observed and qualitatively analyzed using a particle counter, a single ferrograph, a metallographic microscope, and a scanning electron microscope. The experiments demonstrate that the initial hard particles have a greater impact in the early wear stage of the gears (<20 h), and abrasive particle concentration increases by 30%. This means that Al2O3 particles accelerate the gear wear during the running-in period. The loading method of the impact load on the oblique gear exacerbates the abrasion particle wear and expands the stress concentration, which reduces the surface of large milling particles on the surface, and reduces the width of the tooth (the part above the pitch line is severely worn), which causes the gear to break into failure. The research provides help for analyzing the mechanism of abrasive wear of gears and predicting wear life.

Hydrophilic Covalent Organic Frameworks Coated Steel Sheet As a Mass Spectrometric Ionization Source for the Direct Determination of Zearalenone and Its Derivatives.

Zearalenone has attracted worldwide attention due to its toxic properties and threat to public health. A rapid determination method for zearalenone and its derivatives by hydrophilic covalent organic frameworks coated steel sheet (HCOFCS) combined with ambient mass spectrometry (AMS) was developed. The HCOFCS behaved as both a tip for solid-phase microextraction and a solid substrate for electrospray ionization mass spectrometry (ESI-MS). To evaluate the HCOFCS-ESI-MS method, five zearalenone and its derivatives in milk samples were determined, including zearalenone (ZEA), α-zearalenol (α-ZEL), ß-zearalenol (ß-ZEL), α-zearalanol (α-ZAL), and ß-zearalanol (ß-ZAL). After the extraction procedure, the HCOFCS was directly added with a high voltage for ESI-MS, and the analysis could be completed within 1 min. The developed method showed good linearity in the range 0.1-100 µg/L with a coefficient of determination (R2) > 0.9991. The limits of detection (LODs) and limits of quantitation (LOQs) ranged from 0.05 to 0.1 and 0.2 to 0.3 µg/L, respectively. The results demonstrated that the HCOFCS combined with ESI-MS can be used for the rapid and sensitive determination of trace ZEA and its derivatives in milk samples with satisfactory recoveries from 80.58% to 109.98% and reproducibility with relative standard deviations (RSDs) no more than 11.18%. Furthermore, HCOFCS showed good reusability, which could reuse at least 10 extraction cycles with satisfactory adsorption performance.

Two different protein corona formation modes on Soluplus® nanomicelles.

Soluplus® nanomicelles have been widely reported in biomedical field for their excellent drug loading capacity and solubility enhancement ability. However, when administrated in vivo, the protein corona will be formed on Soluplus® nanomicelles, significantly affecting their drug delivery performance. Up to now, few studies examined the protein corona formation process and its impact factors of Soluplus® nanomicelles. The multiple proteins in biofluids may form protein corona in different modes due to their diversified properties. In this study, Bovine serum albumin (BSA), Lysozyme (Lyso) and Bovine hemoglobin (BHb) were chosen as model proteins to investigate the protein corona formation process of Soluplus® nanomicelles. By analyzing the polarity of the protein amino acid residues distributing microenvironments, the results showed that there were two different protein corona formation modes, i.e., surface adsorption and insertion, which were determined by the hydrophilicity of proteins. The hydrophobic BHb followed the insertion mode while hydrophilic BSA and Lyso followed the surface adsorption mode. Ultimately, upon protein corona formation, the size and surface chemistry of nanomicelles was significantly affected. We believe this study will provide a new research paradigm to the design and application of Soluplus® nanomicelles.

Inhalable solid lipid nanoparticles for intracellular tuberculosis infection therapy: macrophage-targeting and pH-sensitive properties.

Mycobacterium tuberculosis (MTB) is one of the most threatening pathogens for its latent infection in macrophages. The intracellular MTB isolated itself from drugs and could spread via macrophages. Therefore, a mannose-modified macrophage-targeting solid lipid nanoparticle, MAN-IC-SLN, loading the pH-sensitive prodrug of isoniazid (INH), was designed to treat the latent tuberculosis infection. The surface of SLNs was modified by a synthesized 6-octadecylimino-hexane-1,2,3,4,5-pentanol (MAN-SA) to target macrophages, and the modified SLNs showed a higher cell uptake in macrophages (97.2%) than unmodified SLNs (42.4%). The prodrug, isonicotinic acid octylidene-hydrazide (INH-CHO), was synthesized to achieve the pH-sensitive release of INH in macrophages. The INH-CHO-loaded SLNs exhibited a pH-sensitive release profile and accomplished a higher accumulated release in pH 5.5 media (82.63 ± 2.12%) compared with the release in pH 7.4 media (58.83 ± 3.84%). Mycobacterium smegmatis was used as a substitute for MTB, and the MAN-IC-SLNs showed a fourfold increase of intracellular antibiotic efficacy and enhanced macrophage uptake because of the pH-sensitive degradation of INH-CHO and MAN-SA in SLNs, respectively. For the in vivo antibiotic efficacy test, the SLNs group displayed an 83% decrease of the colony-forming unit while the free INH group only showed a 60% decrease. The study demonstrates that macrophage targeting and pH-sensitive SLNs can be used as a promising platform for the latent tuberculosis infection. Graphical Abstract Table of contents: Macrophage-targeting and pH-sensitive solid lipid nanoparticles (SLN) were administrated to the lung via nebulization. Macrophage targeting was achieved by appropriate particle size and surface mannose modification with synthesized MAN-SA. After being swallowed by macrophages, the prodrug, Isonicotinic acid octylidene-hydrazide (INH-CHO), quickly released isoniazid, which was triggered by the intracellular acid environment. The SLNs exhibited higher intracellular antibiotic efficacy due to their macrophage-targeting and pH-sensitive properties.

Occurrence of cyclic and linear siloxanes in indoor dust from China, and implications for human exposures.

Siloxanes are used in a wide variety of personal-care and other consumer products. Although there is clearly a potential for contamination of indoor dust with siloxanes, reports of occurrence of siloxanes in indoor dust were not available, prior to the present study. Here, we have determined the concentrations and profiles of four cyclic siloxanes, octamethylcyclotetrasiloxane (D(4)), decamethylcyclopentasiloxane (D(5)), dodecamethylcyclohexasiloxane (D(6)), and tetradecamethylcycloheptasiloxane (D(7)), as well as 11 linear siloxanes, from L(4)-L(14), in 100 dust samples collected in China. Cyclic and linear siloxanes were found in all dust samples, with the linear siloxanes L(9)-L(14) being the predominant compounds. Concentrations of total siloxanes in dust ranged from 21.5 to 21,000 (mean: 1540 +/- 2850) ng g(-1). The highest concentration of the individual linear siloxanes, L(9)-L(14), ranged between 2680 and 6170 ng g(-1). Concentrations of total linear siloxanes (TLS) were 1-2 orders of magnitude higher than concentrations of total cyclic siloxanes (TCS), in all indoor dust samples. Siloxane concentrations in dust were associated with the number of electrical/electronic appliances, number of occupants, and smokers living in the house. Based on the measured siloxane concentrations and on estimated daily ingestion rates of dust by toddlers and adults, we calculated the daily intake of siloxanes. For adults, daily exposure to total siloxanes, based on an average dust intake rate and median exposure concentration, was calculated to be 15.9 ng day(-1); the corresponding value for toddlers was 32.8 ng d(-1).

Investigate the impact of local iron-steel industrial emission on atmospheric mercury concentration in Yangtze River Delta, China.

Mercury is a global neurotoxic pollutant, which can be globally transported and bioaccumulated in the food chain. Iron-steel production is one of the most significant sources of anthropogenic atmospheric mercury emission, while information on this source is scarce. Hourly gaseous elemental mercury (GEM) and particle bound mercury (PBM) were studied inside (IP) and at the boundary (BP) of a typical iron-steel plant in the Yangtze River Delta (YRD), China from September 2016 to August 2017. The GEM concentrations were 0.97-503.1 and 0.05-112.6 ng/m3 at the IP and BP sites, respectively, while PBM concentrations were one to four orders of magnitude higher than urban and suburban ambient levels. Several lines of evidences indicated that PBM was mainly originated from the iron-steel manufacturing process, especially from sintering and coke-making processes in this iron-steel plant. However, a combined emission effect contributed to GEM variation. The receptor model of positive matrix factorization (PMF) showed that local direct emissions (coal combustion, industrial activity, vehicle exhaust, and secondary evaporation from polluted soil) contributed 51.3% of the total GEM concentration variation. Potential source contribution function (PSCF) and concentration weighted trajectory (CWT) models clearly showed that air masses moving from areas surrounding YRD had the highest concentrations of atmospheric mercury. These results provided evidence that iron-steel manufacturing emissions have a considerable effect on regional atmospheric mercury concentrations, especially PBM.

Adsorption of p-chlorophenol by biofilm components.

Through batch equilibrium experiments under the conditions of temperature 25 degrees C, pH values of 2.7, 5.3 and 6.1, the p-chlorophenol (4-cp) adsorption to biofilm components was investigated in this study. The contributions of biofilm components to 4-cp adsorption were discussed by comparing four adsorption systems, i.e. 4-cp adsorbed by model suspended particulate matter (kaolin) with biofilm coating, bacteria, bacterial exopolysaccharide (EPS) and kaolin, respectively. Langmuir and Freundlich isotherm equations were used to evaluate the experiment data. All the four adsorptions fitted for the two equations. Equilibrium isotherms were obtained for 4-cp adsorption on different adsorbents. The kinetic characteristics of 4-cp adsorption by biofilm components and the effect of pH on the kinetic process were investigated. The time to reach the highest adsorption amount and near equilibrium state in the four systems was different. The 4-cp adsorption by kaolin with biofilm coating reached near equilibrium at 60 min at pH 6.1. The 4-cp adsorption by EPS and kaolin reached near equilibrium at 150 and 180 min, respectively. But the 4-cp adsorption by bacteria showed no evident near equilibrium during 3 h in the experiment. The impact of pH value on the adsorption was also examined. The adsorption amount slightly increased with increasing pH from 2.7 to 6.1 for the adsorption systems of bacterial EPS and kaolin, but it slightly decreased in the systems of kaolin with biofilm coating and bacteria.

Penetration of three transmembrane segments of Slc11a1 in lipid bilayers.

Slc11a1 is a divalent metal cation transporter with 12 putative transmembrane domains (TM) and plays a role in host defense. In present work, we investigated the secondary structure and topology of the peptides associated to Slc11a1-TM2, TM3 and TM4 (wildtype peptides and function-relating mutants) in the phospholipid vesicles (DMPC, DMPG and their mixtures) using circular dichroism, fluorescence spectroscopy and differential scanning calorimetry. We found that TM3 is obviously different in secondary structure and topology from TM2 to TM4 in the lipid membranes. The peptide TM3 is less structured and embedded in the lipid membranes less deeply than TM2 and TM4 at pH 5.5 and 7. The insertion position of TM3 in the lipid membranes is adjusted by pH, more deeply at more acidic pH environment, whereas the locations of TM2 and TM4 in the lipid membranes are less changed with pH. The E139A substitution of TM3 significantly impairs the pH dependence of the buried depth of TM3 and causes a pronounced increase in helicity in all DMPG-containing lipid vesicles at pH 5.5 and 7 and in DMPC at pH 4. In contrast, TM2 and TM4 are similar in topology. The G169D mutation has little effect on the topological arrangement of TM4 in membranes. The property of headgroups of the phospholipids has an effect on the secondary structure and topology of the peptides. All peptides could be structured with more helicity and embedded more deeply in DMPG-containing lipid vesicles than in DMPC membrane at pH 5.5 and 7.

Development of a trickle bed reactor of electro-Fenton process for wastewater treatment.

To avoid electrolyte leakage and gas bubbles in the electro-Fenton (E-Fenton) reactors using a gas diffusion cathode, we developed a trickle bed cathode by coating a layer composed of carbon black and polytetrafluoroethylene (C-PTFE) onto graphite chips instead of carbon cloth. The trickle bed cathode was optimized by single-factor and orthogonal experiments, in which carbon black, PTFE, and a surfactant were considered as the determinant of the performance of graphite chips. In the reactor assembled by the trickle bed cathode, H2O2 was generated with a current of 0.3A and a current efficiency of 60%. This performance was attributed to the fine distribution of electrolyte and air, as well as the effective oxygen transfer from the gas phase to the electrolyte-cathode interface. In terms of H2O2 generation and current efficiency, the developed trickle bed reactor had a performance comparable to that of the conventional E-Fenton reactor using a gas diffusion cathode. Further, 123 mg L(-1) of reactive brilliant red X-3B in aqueous solution was decomposed in the optimized trickle bed reactor as E-Fenton reactor. The decolorization ratio reached 97% within 20 min, and the mineralization reached 87% within 3h.

Concentrations and assessment of exposure to siloxanes and synthetic musks in personal care products from China.

We investigated the concentrations and profiles of 15 siloxanes (four cyclic siloxanes, D(4)-D(7); 11 linear siloxanes, L(4)-L(14)), four synthetic musks (two polycyclic musks, HHCB and AHTN; two nitro musks, MX and MK), and HHCB-lactone, in 158 personal care products marketed in China. Siloxanes were detected in 88% of the samples analyzed, at concentrations as high as 52.6 mg g(-1); Linear siloxanes were the predominant compounds. Among synthetic musks, more than 80% of the samples contained at least one of these compounds, and their total concentrations were as high as 1.02 mg g(-1). HHCB was the predominant musk in all of the samples analyzed, on average, accounting for 52% of the total musk concentrations. Based on the median concentrations of siloxanes and musks and the average daily usage amounts of consumer products, dermal exposure rates in adults were calculated to be 3.69 and 3.38 mg d(-1) for siloxanes and musks, respectively.

[Distribution and species of mercury in water and sediments from Huangpu River].

Levels of total mercury, soluble mercury and particle mercury in water of Huangpu River change greatly, their average values are (0.4 +/- 0.44) ng/mL, (0.27 +/- 0.42)ng/mL, (0.13 +/- 0.10) ng/mL respectively. Mercury in water is mainly in the form of soluble mercury. Average mercury content in sediment of Huangpu River is relative high and up to (204.03 +/- 97.41) ng/g, with a range of 70.52 ng/g - 387.30 ng/g. Mercury content is high in the middle reach of Huangpu River, especially in section of Xidu-Nanpu Bridge, and low in upstream and downstream. Distribution of mercury is hightly related with distribution of industry plants and farming. Locations with high mercury content in sediment are in the downstream of locations with high mercury content in water. Mercury (in sediments) is mainly in the form of residue, exchangeable ions, and humics-bound, seldom is in the form of carbonate-bound. Contrary to residue-bound mercury, exchangeable mercury is low in the middle reach, and high in upstream and downstream. There mainly are residue-bound mercury and little humics-bound mercury, exchangeable mercury, and carbonate-bound mercury in sediment in profile, and the residue-bound mercury increases irregularly with depth. Nearing the Mouth of Yangtze River, mercury in sediment becomes more active.