Chitosan-sodium alginate-polyethylene glycol-Ally isothiocyante nanocomposites ameliorates isoproterenol-induced myocardial infarction in rats.

Myocardial infarction (MI) is a common type of ischemic heart disease that affects millions of people worldwide. In recent times, nanotechnology has become a very promising field with immense applications. The current exploration was conducted to synthesize the chitosan-sodium alginate-polyethylene glycol-Ally isothiocyanate nanocomposites (CSP-AIso-NCs) and evaluate their beneficial roles against the isoproterenol (ISO)-induced MI in rats. The CSP-AIso-NCs were prepared and characterized by several characterization techniques. The MI was initiated in the rats by the administration of 85 mg/kg of ISO for 2 days and treated with 10 and 20 mg/kg of CSP-AIso-NCs for 1 month. The changes in heart weight and bodyweight were measured. The cardiac function markers were assessed with echocardiography. The lipid profiles, Na+, K+, and Ca2+ ions, cardiac biomarkers, antioxidant parameters, and inflammatory cytokines were assessed using corresponding assay kits. The histopathological study was done on the heart tissues. The UV spectral analysis revealed the maximum peak at 208 nm, which confirms the formation of CSP-AIso-NCs. The FT-IR analysis revealed the occurrence of different functional groups, and the crystallinity of the CSP-AIso-NCs was proved by the XRD analysis. DLS analysis indicated the size of the CSP-AIso-NCs at 146.50 nm. The CSP-AIso-NCs treatment increased the bodyweight and decreased the HW/BW ratio in the MI rats. The status of lipids was reduced, and HDL was elevated in the CSP-AIso-NCs administered to MI rats. CSP-AIso-NCs decreased the LVEDs, LVEDd, and NT-proBNP and increased the LVEF level. The oxidative stress markers were decreased, and the antioxidants were increased by the CSP-AIso-NCs treatment in the MI rats. The Na+ and Ca+ ions were reduced, and the K+ ions were increased by the CSP-AIso-NCs. The interleukin-1ß and tumor necrosis factor-α were also depleted, and Nrf-2 was improved in the CSP-AIso-NCs administered to MI rats. The histological study revealed the ameliorative effects of CSP-AIso-NCs. Overall, our outcomes revealed that the CSP-AIso-NCs are effective against the ISO-induced MI rats. Hence, it could be a hopeful therapeutic nanomedicine for MI treatment.

Linear Regulating of Polymer Acceptor Aggregation with Short Alkyl Chain Units Enhances All-Polymer Solar Cells' Efficiency.

The power conversion efficiency (PCE) of all-polymer solar cells (all-PSCs) has ascended rapidly arising from the development of polymerized small-molecule acceptor materials. However, numerous insulating long alkyl chains, which ensure the solubility of the polymer, result in inferior aggregation and charge mobility. Herein, this study proposes a facile random copolymerization strategy of two small molecule acceptor units with different lengths of alkyl side chains and synthesizes a series of polymer acceptors PYT-EHx, where x is the percentage of the short alkyl chain units. The aggregation strength and charge mobility of the acceptors rise linearly with increasing the proportion of short alkyl chain units. Thus, the PYT-EH20 reaches balanced aggregation with the star polymer donor PBDB-T, resulting in optimal morphology, fastest carrier transport, and reduced recombination and energy loss. Consequently, the PYT-EH20-based device yields a 14.8% PCE, a 16% improvement over the control PYT-EH0-based device, accompanied by an increase in open-circuit voltage (Voc ), short-circuit current density (Jsc ), and fill factor (FF). This work demonstrates that the random copolymerization strategy with short alkyl chain insertion is an effective avenue for developing high-performance polymer acceptors, which facilitates further advances in the efficiency of all-PSCs.

Tailoring bacterial cellulose structure through CRISPR interference-mediated downregulation of galU in Komagataeibacter xylinus CGMCC 2955.

Diverse applications of bacterial cellulose (BC) have different requirements in terms of its structural characteristics. culturing Komagataeibacter xylinus CGMCC 2955, BC structure changes with alterations in oxygen tension. Here, the K. xylinus CGMCC 2955 transcriptome was analyzed under different oxygen tensions. Transcriptome and genome analysis indicated that BC structure is related to the rate of BC synthesis and cell growth, and galU is an essential gene that controls the carbon metabolic flux between the BC synthesis pathway and the pentose phosphate (PP) pathway. The CRISPR interference (CRISPRi) system was utilized in K. xylinus CGMCC 2955 to control the expression levels of galU. By overexpressing galU and interfering with different sites of galU sequences using CRISPRi, we obtained strains with varying expression levels of galU (3.20-3014.84%). By testing the characteristics of BC, we found that the porosity of BC (range: 62.99-90.66%) was negative with galU expression levels. However, the crystallinity of BC (range: 56.25-85.99%) was positive with galU expression levels; galU expression levels in engineered strains were lower than those in the control strains. Herein, we propose a new method for regulating the structure of BC to provide a theoretical basis for its application in different fields.

Charge Reversible and Mitochondria/Nucleus Dual Target Lipid Hybrid Nanoparticles To Enhance Antitumor Activity of Doxorubicin.

The experiment aims to increase antitumor activity while decreasing the systemic toxicity of doxorubicin (DOX). Charge reversible and mitochondria/nucleus dual target lipid hybrid nanoparticles (LNPs) was prepared. The in vitro experimental results indicated that LNPs released more amount of DOX in acidic environment and delivered more amount of DOX to the mitochondria and nucleus of tumor cells than did free DOX, which resulted in the reduction of mitochondrial membrane potential and the enhancement of cytotoxicity of LNPs on tumor cells. Furthermore, the in vivo experimental results indicated that LNPs delivered more DOX to tumor tissue and significantly prolonged the retention time of DOX in tumor tissue as compared with free DOX, which consequently resulted in the high antitumor activity and low systemic toxicity of LNPs on tumor-bearing nude mice. The above results indicated that charge reversible mitochondria/nucleus dual targeted lipid hybrid nanoparticles greatly enhanced therapeutic efficacy of DOX for treating lung cancer.

Enhanced bacterial cellulose production by Gluconacetobacter xylinus via expression of Vitreoscilla hemoglobin and oxygen tension regulation.

Oxygen plays a key role during bacterial cellulose (BC) biosynthesis by Gluconacetobacter xylinus. In this study, the Vitreoscilla hemoglobin (VHb)-encoding gene vgb, which has been widely applied to improve cell survival during hypoxia, was heterologously expressed in G. xylinus via the pBla-VHb-122 plasmid. G. xylinus and G. xylinus-vgb + were statically cultured under hypoxic (10 and 15% oxygen tension in the gaseous phase), atmospheric (21%), and oxygen-enriched conditions (40 and 80%) to investigate the effect of oxygen on cell growth and BC production. Irrespective of vgb expression, we found that cell density increased with oxygen tension (10-80%) during the exponential growth phase but plateaued to the same value in the stationary phase. In contrast, BC production was found to significantly increase at lower oxygen tensions. In addition, we found that BC production at oxygen tensions of 10 and 15% was 26.5 and 58.6% higher, respectively, in G. xylinus-vgb + than that in G. xylinus. The maximum BC yield and glucose conversion rate, of 4.3 g/L and 184.7 mg/g, respectively, were observed in G. xylinus-vgb + at an oxygen tension of 15%. Finally, BC characterization suggested that hypoxic conditions enhance BC's mass density, Young's modulus, and thermostability, with G. xylinus-vgb + synthesizing softer BC than G. xylinus under hypoxia as a result of a decreased Young's modulus. These results will facilitate the use of static culture for the production of BC.

pH-Triggered Surface Charge Reversed Nanoparticle with Active Targeting To Enhance the Antitumor Activity of Doxorubicin.

PLGA nanoparticles are widely used in tumor targeting drug delivery systems. However, the naked PLGA nanoparticles (NNPs) not only have low drug loading but also can be rapidly removed from blood circulation by the immune system. The aim of this study was to prepare pH-triggered surface charge reversed lipid hybrid PLGA nanoparticles (LNPs) to enhance drug loading and drug delivery efficiency. CHO-Arg-His-OMe and FA-PEG-DSPE were synthesized to modify PLGA nanoparticles to prepare LNPs. The drug loading and encapsulation rate of LNPs were greatly improved as compared with NNPs. In pH 7.4 medium, doxorubicin (DOX)-loaded LNPs showed negative charge and released DOX slowly. In pH 5.0 medium, DOX-loaded LNPs exhibited positive charge and released DOX quickly. DOX-loaded LNPs delivered more DOX to the nucleus of KB cells and MBA-MD-231/ADR cells than did free DOX. In addition, DOX-loaded LNPs significantly inhibited the proliferation of KB cells and MBA-MD-231/ADR cells. Compared with free DOX, the same dose of the DOX-loaded LNPs delivered more DOX to tumor tissue. Thus, DOX-loaded LNPs significantly inhibited the growth of tumor in tumor-bearing nude mice and obviously reduced the systemic toxicity of DOX. In conclusion, pH-triggered surface charge reversed DOX-loaded LNPs significantly enhanced the antitumor activity of DOX in vitro and in vivo. DOX-loaded LNPs had great potential in tumor targeted chemotherapy.

Development, Optimization, and Characterization of PEGylated Nanoemulsion of Prostaglandin E1 for Long Circulation.

Lipo-PGE1 is the most widely used formulation of PGE1 in clinic. However, PGE1 is easier to leak out from lipo-PGE1 and this will lead to the phlebophlogosis when intravenous injection. The stability of lipo-PGE1 in storage and in vivo is also discounted. The aim of this study is to develop a long-circulating prostaglandin E1-loaded nanoemulsion modified with 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE-PEG) to improve the stability and pharmacokinetics profiles of lipo-PGE1. PEGylated PGE1 nanoemulsion was prepared using a dispersing-homogenized method. The stability of nanoemulsion in 1 month was investigated. Pharmacokinetic studies were employed to evaluate the in vivo profile of the optimized nanoemulsion. The optimized nanoemulsion PGE1-PEG2000(1%)-NE showed an oil droplet size <100 nm with a surface charge of -14 mV. Approximately, 97% of the PGE1 was encapsulated in the nanoemulsion. The particle size, zeta potential, and drug loading of PGE1-PEG2000(1%)-NE were stable in 1 month. After PGE1-PEG2000(1%)-NE was intravenously administered to rats, the area under curve (AUC) and half-life of PGE1 were, respectively, 1.47-fold and 5.98-fold higher than those of lipo-PGE1 (commercial formulation). PGE1-PEG2000(1%)-NE was an ideal formulation for prolonging the elimination time of PGE1. This novel parenteral colloidal delivery system of PGE1 has a promising potential in clinic use.

PEG-detachable lipid-polymer hybrid nanoparticle for delivery of chemotherapy drugs to cancer cells.

The experiment aimed to increase the drug-delivery efficiency of poly-lactic-co-glycolic acid (PLGA) nanoparticles. Lipid-polymer hybrid nanoparticles (LPNs-1) were prepared using PLGA as a hydrophobic core and FA-PEG-hyd-DSPE as an amphiphilic shell. Uniform and spherical nanoparticles with an average size of 185 nm were obtained using the emulsification solvent evaporation method. The results indicated that LPNs-1 showed higher drug loading compared with naked PLGA nanoparticles (NNPs). Drug release from LPNs-1 was faster in an acidic environment than in a neutral environment. LPNs-1 showed higher cytotoxicity on KB cells, A549 cells, MDA-MB-231 cells, and MDA-MB-231/ADR cells compared with free doxorubicin (DOX) and NNPs. The results also showed that, compared with free DOX and NNPs, LPNs-1 delivered more DOX to the nuclear of KB cells and MDA-MB-231/ADR cells. LPNs-1 induced apoptosis in KB cells and MDA-MB-231/ADR cells in a dose-dependent manner. The above data indicated that DOX-loaded LPNs-1 could kill not only normal tumor cells but also drug-resistant tumor cells. These results indicated that modification of PLGA nanoparticles with FA-PEG-hyd-DSPE could considerably increase the drug-delivery efficiency and LPNs-1 had potential in the delivery of chemotherapeutic agents in the treatment of cancer.

A ratiometric molecular imprinted electrochemiluminescence sensor based on enhanced luminescence of CdSe@ZnS quantum dots by MXene@NaAsc for detecting uric acid.

An unlabeled ratiometric molecular imprinted electrochemiluminescence sensor was developed for the determination of trace uric acid, based on MXene@NaAsc nanocomposites, CdSe@ZnS quantum dots and molecularly imprinted polymer composites modified glass carbon electrode. MXene@NaAsc stably enhanced the electron transfer and improved electrochemiluminescence intensity by acting as a base platform and signal amplifier for CdSe@ZnS quantum dots. Specific molecular imprinting cavities based on electropolymerization with o-phenylenediamine were formed to specifically identify uric acid. Combining the good sensitivity of electrochemiluminescence and the excellent selectivity of molecularly imprinted polymer, the ratio of optical signal and electrical signal was used as a comprehensive signal to achieve the detection of uric acid. Based on this, uric acid was detected in the range from 1 × 10-10 to 1 × 10-4 mol/L with the LOD of 18.13 pmol/L (S/N = 3). The developed sensor with easy preparation, great selectivity and excellent sensitivity could successfully detect uric acid in human serum.

Dual biomass-derived porous carbon heterogeneous functionalized mesoporous CuCo2O4 nanocomposite combined with molecularly imprinted polymers as an electrochemical sensing platform for hypersensitive and selective determination of dimetridazole contaminants.

In this study, an original molecularly imprinted electrochemical sensor (MIECS) is prepared using layer-by-layer modification of sensitization nanomaterials (CuCo2O4/BPC-E) coupled with molecularly imprinted polymers (MIPs) for the ultrasensitive and rapid determination of dimetridazole (DMZ) contaminants. The biomass waste of eggshell (ES) powders subtly introduced in situ in the carbonization process of psyllium husk (PSH) substantially promotes the physicochemical properties of the resulting biomass-derived porous carbon (BPC-E). The large specific surface area and abundant pores provide a favourable surface for loading mesoporous CuCo2O4 with a spinel structure. The assembly of CuCo2O4/BPC-E on the gold electrode (GE) surface enhances the electrochemical sensing signal. The MIPs constructed using DMZ and o-phenylenediamine (oPD) as templates and functional monomers boost the targeted recognition performance of the analyte. The combined DMZ targets then undergo an electrochemical reduction reaction in situ with the transfer of four electrons and four protons. Under optimum conditions, the current response of differential pulse voltammetry (DPV) exhibits two linear ranges for DMZ detection, 0.01-10 µM and 10-200 µM. The limit of detection (LOD) is 1.8 nM (S/N = 3) with a sensitivity of 5.724 µA µM-1 cm-2. The obtained MIECS exhibits excellent selectivity, reproducibility, repeatability and stability. This electrochemical sensing system is applied to the detection of real samples (tap water, coarse fodder and swine urine), yielding satisfactory recoveries (90.6%-98.1 %), which are consistent with those obtained via HPLC. This finding verifies that the utility of MIECS for monitoring pharmaceutical and environmental contaminants and ensuring food safety.

Physicochemical properties and pork preservation effects of lotus seed drill core powder starch-based active packaging films.

Lotus seed drill core powder starch (LCPS)-based active packaging films incorporated with cellulose nanocrystals (CNC) and grapefruit essential oil-corn nanostarch Pickering emulsion (ECPE) were characterized, and their pork preservation effects were investigated in this study. In contrast with corn, potato and rice starches, LCPS showed higher amylose content, elliptical and circular shape with more uniform size distribution. Furthermore, LCPS film exhibited lower light transmittance, stronger tensile strength, and smaller elongation at break compared to the other starch films. Then, the LCPS film containing 4 % CNC and 9 % ECPE was fabricated which had stronger mechanical properties, lower water vapor permeability and oxygen transmission rate, and denser network structure. FTIR and XRD analyses also confirmed that CNC and ECPE were successfully implanted into the LCPS matrix without damaging the crystalline structure of LCPS. Herein, the LCPS/CNC/ECPE film exerted potential antibacterial activity against Escherichia coli and Staphylococcus aureus. Besides, packaging with this composite film significantly preserved the pork during cold storage via decreasing its juice loss rate, pH value, total number of colonies, total volatile base nitrogen and thiobarbituric acid reactive substance values. The present study will provide a theoretical basis for the application of LCPS as new biodegradable active films.

New generation of orthodontic devices and materials with bioactive capacities to improve enamel demineralization.

OBJECTIVE: The article reviewed novel orthodontic devices and materials with bioactive capacities in recent years and elaborated on their properties, aiming to provide guidance and reference for future scientific research and clinical applications. DATA, SOURCES AND STUDY SELECTION: Researches on remineralization, protein repellent, antimicrobial activity and multifunctional novel bioactive orthodontic devices and materials were included. The search of articles was carried out in Web of Science, PubMed, Medline and Scopus. CONCLUSIONS: The new generation of orthodontic devices and materials with bioactive capacities has broad application prospects. However, most of the current studies are limited to in vitro studies and cannot explore the true effects of various bioactive devices and materials applied in oral environments. More research, especially in vivo researches, is needed to assist in clinical application. CLINICAL SIGNIFICANCE: Enamel demineralization (ED) is a common complication in orthodontic treatments. Prolonged ED can lead to dental caries, impacting both the aesthetics and health of teeth. It is of great significance to develop antibacterial orthodontic devices and materials that can inhibit bacterial accumulation and prevent ED. However, materials with only preventive effect may fall short of addressing actual needs. Hence, the development of novel bioactive orthodontic materials with remineralizing abilities is imperative. The article reviewed the recent advancements in bioactive orthodontic devices and materials, offering guidance and serving as a reference for future scientific research and clinical applications.

Metabolic flux analysis of Gluconacetobacter xylinus for bacterial cellulose production.

Metabolic flux analysis was used to reveal the metabolic distributions in Gluconacetobacter xylinus (CGMCC no. 2955) cultured on different carbon sources. Compared with other sources, glucose, fructose, and glycerol could achieve much higher bacterial cellulose (BC) yields from G. xylinus (CGMCC no. 2955). The glycerol led to the highest BC production with a metabolic yield of 14.7 g/mol C, which was approximately 1.69-fold and 2.38-fold greater than that produced using fructose and glucose medium, respectively. The highest BC productivity from G. xylinus CGMCC 2955 was 5.97 g BC/L (dry weight) when using glycerol as the sole carbon source. Metabolic flux analysis for the central carbon metabolism revealed that about 47.96 % of glycerol was transformed into BC, while only 19.05 % of glucose and 24.78 % of fructose were transformed into BC. Instead, when glucose was used as the sole carbon source, 40.03 % of glucose was turned into the by-product gluconic acid. Compared with BC from glucose and fructose, BC from the glycerol medium showed the highest tensile strength at 83.5 MPa, with thinner fibers and lower porosity. As a main byproduct of biodiesel production, glycerol holds great potential to produce BC with superior mechanical and microstructural characteristics.

Potential thyroid hormone disorder risks of tire antioxidants to aquatic food chain organisms after absorbing free radicals in marine and freshwater environments.

Tire antioxidants are essential functional chemical additives in tire rubber production. Because of the characteristic easy precipitation in the water environment, the environmental pollution problem caused by tire antioxidants is concerning. To reveal the mechanism by which tire antioxidants reduce common oxidative factors (free radicals) in the environment and to control the potential biological thyroid hormone disorder risk of tire antioxidant derivatives, eight commonly used antioxidants in tire production were selected for analysis. Firstly, the ability of tire antioxidants to reduce three different free radicals was quantitatively characterized based on Gaussian calculation method and inferring the radical reduction mechanism of tire antioxidants. Moreover, using the PaDEL-Descriptor software and random forest algorithm found that the N-octanol/water partition coefficient, a structure descriptor of tire antioxidant molecules, significantly correlated with their reducing ability. Second, molecular docking and molecular dynamics methods were used to assess the thyroid hormone disorder risk to aquatic organisms of eight antioxidants after reducing three free radicals. And this is the first study to construct an assessment score list of potential thyroid hormone disorder risk of the derivatives of tire antioxidants after reducing free radicals to marine and freshwater aquatic organisms based on the risk entropy method. Through the screening of this list, it was found that the derivative of the antioxidant 2,2,4-trimethyl-1,2-dihydroquinoline oxidized by free radicals had the highest risk of thyroid hormone disorder. In addition, the top organism in the aquatic food chain was the most affected. This study also revealed that van der Waals interactions and hydrogen bonding were the main influencing factors of thyroid hormone disorder risk to aquatic organisms of the derivatives of tire antioxidants that reduce free radicals based on amino acid residue analysis. Overall, the results provide theoretical support for the selection of antioxidants and the avoidance and control of environmental risks in the tire rubber production process.

Effect of build orientation and layer thickness on manufacturing accuracy, printing time, and material consumption of 3D printed complete denture bases.

OBJECTIVES: To evaluate the influence of build orientation and layer thickness on manufacturing accuracy, material consumption, and printing time of complete denture (CD) bases fabricated using digital light processing (DLP). METHODS: The CD base was designed on the basis of a standard maxillary edentulous model. Seventy CD bases were fabricated using a DLP 3D printer (Pro95, SprintRay, USA) and printable CD base material (DENTCA Denture Base II, Dentca, USA) at seven build orientations (0°, labial 45°, labial 90°, posterior 45°, posterior 90°, buccal 45°, and buccal 90°) and two types of layer thicknesses (50- and 100 µm) (n = 5). All test CD bases were digitalized and superimposed on the reference cast by section-based best-fit alignment. For evaluating manufacturing accuracy, deviation analysis was performed to compare the test data with the reference cast using the "3D Compare" in the 3D metrology software. The printing time and material consumption were calculated using slicing software and recorded, respectively. The two-way ANOVA test was used for accuracy evaluation, and the non-parametric test was used to evaluate printing time and material consumption (α = 0.05). RESULTS: Statistically significant differences were found in the manufacturing accuracy (p < 0.001), printing time (p < 0.001), and material consumption (p < 0.001) among the build orientation groups. The labial 45° and labial 90° groups showed the best accuracy. The 90° build orientations required the least material consumption and longest printing time; the labial 45° group consumed the most printing materials; the 0° group required the shortest printing time to fabricate a CD base. Moreover, the layer thickness influenced the printing time (p < 0.001) rather than the accuracy (p = 0.560) and material consumption (p = 1.000). CONCLUSIONS: When DLP was used to fabricate the CD bases, the build orientation influenced the manufacturing accuracy, material consumption, and printing time. However, the layer thickness only affected the printing time. CLINICAL SIGNIFICANCE: This study suggests that optimizing the build orientation can improve the manufacturing accuracy and reduce the material consumption and printing time of a DLP-printed CD base. The fast-printing setting (100 µm layer thickness) can reduce the printing time without compromising the manufacturing accuracy of the CD base.

Enhancing the biopharmaceutical attributes of atorvastatin calcium using polymeric and lipid-polymer hybrid nanoparticles: An approach for atherosclerosis treatment.

Atherosclerosis is associated with inflammation in the arteries, a significant cause of heart attacks and strokes. Although statin therapy can reduce the chances of atherosclerotic plaque formation, they need to be administered in high doses due to low systemic bioavailability and encountered with side effects. To overcome these challenges, we developed nanoparticles using biocompatible and biodegradable lipids and polymers for improving systemic drug absorption and therapeutic response. The polymeric nanoparticles were prepared using PLGA and PVA, while hybrid nanoparticles were prepared using PLGA and Phospholipon 90 G. Both nanoparticles were systematically optimized by I-optimal response surface design. The optimum formulation composition exhibited particle size of less than 250 nm, polydispersity index of less than 0.3, entrapment efficiency of more than 70%, and sustained drug release up to 6 h. In vivo pharmacokinetic evaluation in rats indicated multi-fold improvement in the extent of drug absorption (Cmax and AUCtotal) for atorvastatin from the nanoparticles vis-à-vis the pure drug suspension. In vivo pharmacodynamic studies also indicated the excellent ability of nanoparticles to lower the elevated levels of lipids (total cholesterol, triglycerides, and low-density lipoproteins) and increase the level of high-density lipoproteins as compared to that of the pure drug suspension.

Aquatic toxicity of tire microplastics on marine and freshwater organisms: An in silico approach.

Tire wear particles are a notable source of tire microplastics (TMPs) in the environment. However, only a few reports have focused on the aquatic toxicity effects of composite TMPs and their additives and the mechanistic analysis at the microscopic level. Therefore, this paper study the toxic effects of tire microplastics and their additives on zebrafish based on theoretical chemical calculation method (Taguchi orthogonal experiment method, full factorial experimental design, molecular docking, and molecular dynamics computational technique). We designed five kinds of proportioning schemes of tire rubber polymers and additive components (64 groups in each). The compound toxicity effects of the tire rubber polymers and their additives on zebrafish were simulated and calculated. The simulation results indicated styrene butadiene rubber had the most significant toxic effect on zebrafish. Subsequently, taking the composition ratio scheme of styrene butadiene rubber with the lowest biotoxicity effect as an example, we analyzed the main effects, second-order interactions, and third-order interactions of styrene butadiene rubber polymer and its additive combination in terms of biotoxicity using the fixed effects model. The toxic effects (developmental toxicity, neurotoxicity, and reproductive toxicity) of styrene butadiene rubber on marine and freshwater organisms could be drastically alleviated by adjusting the ratio of rubber additives. The analysis of the interaction between amino acid residues and non-bonds during the docking process of styrene butadiene rubber and toxic receptors revealed the interaction mechanisms between the styrene butadiene rubber polymer and its additives and between the additive molecules. Hydrophobic interaction was found to be the key factor for the binding of styrene butadiene rubber additives to nonpolar amino acids in the receptor proteins. Our findings are expected to provide theoretical support for identifying and regulating the toxicity characteristics of rubber TMPs and to aid in proposing a strategy to alleviate the toxic effects on aquatic organisms.

Analysis of Pepsin Concentration and Influencing Factors in Saliva of Elderly Nasal Feeding Patients.

BACKGROUND: Elderly patients receiving nasal feeding have weaker physiological function, and placement of a nasogastric tube weakens the natural barrier of the cardia-esophageal sphincter; therefore, the risk of gastroesophageal reflux (GER) is higher. Many studies have shown that pepsin is extremely sensitive in predicting GERD, so this study intends to investigate the level of pepsin in saliva of elderly patients with nasal feeding and analyze its influencing factors. METHODS: This was a cross-sectional study. Patients admitted to the Chinese PLA General Hospital from April 2018 to October 2018 who received nasal feeding were included. One ml of saliva was collected from each patient in while sitting during fasting in the morning and 1 hour after lunch for 3 consecutive days. Pepsin was quantified by enzyme-linked immunosorbent assay (ELISA). The patients were predivided into two groups (≥7.75µg/ml or <7.75µg/ml) based on the median pepsin. Baseline and clinical factors were compared. RESULTS: The mean age of the patients was 91.09 ± 4.91 years. There were statistical differences in diabetes and feeding methods between the two groups. There was a positive correlation between the morning and postprandial pepsin levels (r = 0.442, P < 0.001), and has no statistical difference (P = 0.175). Multivariate analysis showed that the risk factors for higher pepsin levels were diabetes (odds ratio (OR): 2.67; 95% CI: 1.225-5.819, P = 0.013) and nasal feeding methods (OR: 2.475; 95% CI: 1.183-5.180, P=0.016). CONCLUSIONS: For patients undergoing nasal feeding who are older than 80 years, the fasting and 1-hour postprandial pepsin concentration were consistent. Diabetes and feeding methods are risk factors for high pepsin levels. For the elderly over 80 years old, age has no influence on pepsin concentration.

Bone-Targeted Calcium Phosphate-Polymer Hybrid Nanoparticle Co-Deliver Zoledronate and Docetaxel to Treat Bone Metastasis of Prostate Cancer.

Prostate cancer is the most common malignant tumor with bone metastasis, and there is still no ideal treatment for bone metastasis of prostate cancer. In this study, a pH and GSH dual sensitive calcium phosphate-polymer hybrid nanoparticle (DTX@Cap/HP) was prepared to co-deliver zoledronate (ZOL) and docetaxel (DTX) to treat bone metastasis of prostate cancer. DTX@Cap/HP exhibited high bone binding affinity and released more DTX and ZOL in acidic and high GSH concentration environment. A large amount of DTX@Cap/HP was uptaken by PC-3 cell in acidic medium than that in neutral medium. DTX@Cap/HP obviously reduced PC-3 cell proliferation and bone lesion in in-vitro 3D model of bone metastases of prostate cancer. Besides, DTX@Cap/HP also exhibited stronger anti bone metastases of prostate cancer activity in vivo as compared with the same dose of DTX + ZOL, which resulted from the co-delivery of DTX and ZOL to bone metastases of prostate cancer by DTX@Cap/HP and the synergistic effects of DTX and ZOL. DTX@Cap/HP has great potential in the treatment of bone metastases of prostate cancer.

[Drug delivery of CPC/amifostine/cisplatin complex in vitro and its ability in repairing bone defect and eliminating tumor in vivo].

OBJECTIVE: To investigate the feasibility of using calcium phosphate cement/amifostine/cisplatin complex to fill and repair bone defect, caused by tumor resection. METHODS: Drug concentration in the CPC/ amifostine/cisplatin complex was determined. Rabbits with bone defect and rats with osteosarcoma were implanted with CPC and CPC/amifostine/cisplatin complex. RESULTS: Similar bone growth was observed in the femurs of rabbits implanted with CPC/amifostine/cisplatin complex and those implanted with CPC. CPC/amifostine/cisplatin complex delivered amifostine and cisplatin consistently and eliminated osteosarcoma cells implanted in the rats. CONCLUSION: CPC/amifostine/cisplatin complex repairs bone defect caused by tumors as a filling material.