Helper Lipid-Enhanced mRNA Delivery for Treating Metabolic Dysfunction-Associated Fatty Liver Disease.

Lipid nanoparticles (LNPs) represent the forefront of mRNA delivery platforms, yet achieving precise delivery to specific cells remains a challenge. The current targeting strategies complicate the formulation and impede the regulatory approval process. Here, through a straightforward regulation of helper lipids within LNPs, we introduce an engineered LNP designed for targeted delivery of mRNA into hepatocytes for metabolic dysfunction-associated fatty liver disease (MAFLD) treatment. The optimized LNP, supplied with POPC as the helper lipid, exhibits a 2.49-fold increase in mRNA transfection efficiency in hepatocytes compared to that of FDA-approved LNPs. CTP:phosphocholine cytidylyltransferase α mRNA is selected for delivery to hepatocytes through the optimized LNP system for self-calibration of phosphatidylcholine levels to prevent lipid droplet expansion in MAFLD. This strategy effectively regulates lipid homeostasis, while demonstrating proven biosafety. Our results present a mRNA therapy for MAFLD and open a new avenue for discovering potent lipids enabling mRNA delivery to specific cells.

Small-Intensity Rainfall Triggers Greater Contamination of Rubber-Derived Chemicals in Road Stormwater Runoff from Various Functional Areas in Megalopolis Cities.

Rubber-derived chemicals (RDCs) originating from tire and road wear particles are transported into road stormwater runoff, potentially threatening organisms in receiving watersheds. However, there is a lack of knowledge on time variation of novel RDCs in runoff, limiting initial rainwater treatment and subsequent rainwater resource utilization. In this study, we investigated the levels and time-concentration profiles of 35 target RDCs in road stormwater runoff from eight functional areas in the Greater Bay Area, South China. The results showed that the total concentrations of RDCs were the highest on the expressway compared with other seven functional areas. N-(1,3-Dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD), 6PPD-quinone, benzothiazole, and 1,3-diphenylguanidine were the top four highlighted RDCs (ND-228840 ng/L). Seasonal and spatial differences revealed higher RDC concentrations in the dry season as well as in less-developed regions. A lag effect of reaching RDC peak concentrations in road stormwater runoff was revealed, with a lag time of 10-90 min on expressways. Small-intensity rainfall triggers greater contamination of rubber-derived chemicals in road stormwater runoff. Environmental risk assessment indicated that 35% of the RDCs posed a high risk, especially PPD-quinones (risk quotient up to 2663). Our findings contribute to a better understanding of managing road stormwater runoff for RDC pollution.

Enhanced hepatotoxicity in zebrafish due to co-exposure of microplastics and sulfamethoxazole: Insights into ROS-mediated MAPK signaling pathway regulation.

The combined pollution of microplastics (MPs) and sulfamethoxazole (SMZ) often occurs in aquatic ecosystems, posing a serious threat to animal and human health. However, little is known about the liver damage caused by the single or co-exposure of MPs and SMZ, and its specific mechanisms are still poorly understood. In this study, we investigated the effects of co-exposure to 20 µm or 80 nm MPs and SMZ in both larval and adult zebrafish models. Firstly, we observed a significant decrease in the number of hepatocytes and the liver damage in larval zebrafish worsened following co-exposure to SMZ and MPs. Additionally, the number of macrophages and neutrophils decreased, while the expression of inflammatory cytokines and antioxidant enzyme activities increased after co-exposure in larval zebrafish. Transcriptome analysis revealed significant changes in gene expression in the co-exposed groups, particularly in processes related to oxidation-reduction, inflammatory response, and the MAPK signaling pathway in the liver of adult zebrafish. Co-exposure of SMZ and MPs also promoted hepatocyte apoptosis and inhibited proliferation levels, which was associated with the translocation of Nrf2 from the cytoplasm to the nucleus and an increase in protein levels of Nrf2 and NF-kB p65 in the adult zebrafish. Furthermore, our pharmacological experiments demonstrated that inhibiting ROS and blocking the MAPK signaling pathway partially rescued the liver injury induced by co-exposure both in larval and adult zebrafish. In conclusion, our findings suggest that co-exposure to SMZ and MPs induces hepatic dysfunction through the ROS-mediated MAPK signaling pathway in zebrafish. This information provides novel insights into the potential environmental risk of MPs and hazardous pollutants co-existence in aquatic ecosystems.

The incidence and risk factors for extensive epidural cement leakage in cement-augmented pedicle screw fixation: a multicenter retrospective study.

INTRODUCTION: In cement-augmented pedicle screw fixation (CAPSF), epidural cement leakage (CL) is a frequently reported complication with the potential for neural injury, especially when it is extensive. To date, there has been no reports discussing basivertebral foramen morphology and pedicle screw placement, which is critical in the analysis of the risk of extensive epidural CL. Thus, this study aimed to identify the incidence and risk factors for extensive epidural CL in osteoporotic patients with CAPSF. MATERIALS AND METHODS: 371 osteoporotic patients using 1898 cement-augmented screws were included. Preoperative computed tomography (CT) was utilized to characterize basivertebral foramen morphology. Following CAPSF, the severity of epidural CL, the implantation position of pedicle screw and cement extension within the vertebral body were determined by postoperative CT. In this study, significant risk factors for extensive epidural CL were identified through logistic regression analysis. RESULTS: There were 19 patients (5.1%) and 32 screws (1.7%) with extensive epidural CL. Nine patients (involving 19 screws) had neurological symptoms. The independent risk factors for patients with extensive epidural CL were decreased BMD and increased number of augmented screws. Significant predictors for extensive epidural CL were a magistral type of basivertebral foramen, more volume of cement injected, solid screw, a shallower screw implantation, and the smaller distance between the tip of the screw and the midline of vertebral body. CONCLUSION: Extensive epidural CL risk was significant in CAPSF when a magistral basivertebral foramen was present; solid screws and more volume of cement were used; and screw tip was implanted shallower or closer to the midline.

Prediction of subsequent vertebral compression fractures after thoracolumbar kyphoplasty: a multicenter retrospective analysis.

OBJECTIVE: Second fractures at the cemented vertebrae (SFCV) are often seen after percutaneous kyphoplasty, especially at the thoracolumbar junction. Our study aimed to develop and validate a preoperative clinical prediction model for predicting SFCV. METHODS: A cohort of 224 patients with single-level thoracolumbar osteoporotic vertebral fractures (T11-L2) from 3 medical centers was analyzed between January 2017 and June 2020 to derive a preoperative clinical prediction model for SFCV. Backward-stepwise selection was used to select preoperative predictors. We assigned a score to each selected variable and developed the SFCV scoring system. Internal validation and calibration were conducted for the SFCV score. RESULTS: Among the 224 patients included, 58 had postoperative SFCV (25.9%). The following preoperative measures on multivariable analysis were summarized in the 5-point SFCV score: bone mineral density (≤-3.05), serum 25-hydroxy vitamin D3 (≤17.55 ng/mL), standardized signal intensity of fractured vertebra on T1-weighted images (≤59.52%), C7-S1 sagittal vertical axis (≥3.25 cm), and intravertebral cleft. Internal validation showed a corrected area under the curve of 0.794. A cutoff of ≤1 point was chosen to classify a low risk of SFCV, for which only 6 of 100 patients (6%) had SFCV. A cutoff of ≥4 points was chosen to classify a high risk of SFCV, for which 28 of 41 (68.3%) had SFCV. CONCLUSION: The SFCV score was found to be a simple preoperative method for identification of patients at low and high risk of postoperative SFCV. This model could be applied to individual patients and aid in the decision-making before percutaneous kyphoplasty.

Lower ratio of adjacent to injured vertebral bone quality scores can predict augmented vertebrae recompression following percutaneous kyphoplasty for osteoporotic vertebral fractures with intravertebral clefts.

BACKGROUND: Despite the favorable clinical outcome of percutaneous kyphoplasty (PKP) in symptomatic osteoporotic vertebral fractures (OVFs) patients with intravertebral clefts (IVCs), previous studies have demonstrated a high incidence of augmented vertebrae recompression (AVR). We aim to evaluate the usefulness of the adjacent and injured vertebral bone quality scores (VBQS) based on T1-weighted MRI images in AVR after PKP for OVFs with IVCs. METHODS: Patients who underwent PKP for single OVFs with IVCs between January 2014 and September 2020 were reviewed and met the inclusion criteria. The follow-up period was at least 2 years. Relevant data affecting AVR were collected. Pearson and Spearman correlation coefficients were used to calculate the correlation between the injured and adjacent VBQS and BMD T-score. We determined independent risk factors and critical values using binary logistic regression analysis and receiver operating characteristic curves (ROC). RESULTS: A total of 165 patients were included. Recompression group was found in 42 (25.5%) patients. The independent risk factors for AVR were lumbar BMD T-score (OR = 2.53, p = 0.003), the adjacent VBQS (OR = 0.79, p = 0.016), the injured VBQS (OR = 1.27, p = 0.048), the ratio of adjacent to injured VBQS (OR = 0.32, p < 0.001), and cement distribution pattern. Among these independent significant risk factors, the prediction accuracy of the ratio of adjacent to injured VBQS was the highest (Cutoff = 1.41, AUC = 0.753). Additionally, adjacent and injured VBQS were negatively correlated with lumbar BMD T-scores. CONCLUSION: For the patients after PKP treatment for OVFs with IVCs, the ratio of adjacent to injured VBQS had the best prediction accuracy in predicting recompression and when the ratio of adjacent to injured VBQS was <1.41, the augmented vertebrae were more likely to have recompression in the future.

Three new sesquiterpene polyol esters from Celastrus angulatus.

Three new sesquiterpene polyol ester compounds angulatins S-U, together with three known compounds were isolated from Celastrus angulatus Maxim. According to mainly 1D NMR and 2D NMR analysis, the structures of the new compounds were completely determined as angulatin S (1ß-furoyloxy-2ß,8α-diisobutanoyloxy-9ß-benzoyloxy-15-acetoxy-4α,6α-dihydroxy-ß-dihydroagarofuran), angulatin T (1ß,2ß,6α-triacetoxy-8ß,15-diisobutanoyloxy-9α-benzoyloxy-ß-dihydroagrofuran), and angulatin U (1ß,6α,15-triacetoxy-8ß-isobutanoyloxy-9α-benzoyloxy-ß-dihydroagarofuran).

An AIE-Active Conjugated Polymer with High ROS-Generation Ability and Biocompatibility for Efficient Photodynamic Therapy of Bacterial Infections.

New, biocompatible materials with favorable antibacterial activity are highly desirable. In this work, we develop a unique conjugated polymer featuring aggregation-induced emission (AIE) for reliable bacterial eradication. Thanks to the AIE and donor-π-acceptor structure, this polymer shows a high reactive oxygen species (ROS)-generation ability compared to a low-mass model compound and the common photosensitizer Chlorin E6. Moreover, the selective binding of pathogenic microorganisms over mammalian cells was found, demonstrating its biocompatibility. The effective growth inhibition of bacteria upon polymer treatment under light irradiation was validated in vitro and in vivo. Notably, the recovery from infection after treatment with our polymer is faster than that with cefalotin. Thus, this polymer holds great promise in fighting against bacteria-related infections in practical applications.

Establishment and Validation of Nomograms and Web Calculators for Different Cement Leakage Risk Types in Pedicle Screw Augmentation for Degenerative Lumbar Stenosis in Osteoporotic Vertebrae.

BACKGROUND: The use of cement in pedicle screw augmentation (PSA) enhances the pullout force of pedicle screws in vertebrae affected by osteoporosis. Risks involved in the use of cement for PSA include nerve injury and vascular damage caused by cement leakage. METHODS: This study included all patients who received PSA for degenerative lumbar stenosis in osteoporotic vertebrae from January 2014 to May 2022. Postoperative computed tomography was used to assess cement leakage. Correlation analysis and logistic regression analyses were used to establish the associated clinical or radiological factors, which were then used to construct nomograms and web calculators. RESULTS: The study comprised 181 patients including 886 screws inserted into 443 vertebrae. Perivertebral cement leakage was significantly associated with female sex, decreased bone mineral density, solid screws, and scattered cement distribution. Cement leakage through segmental veins (type S, 72.1%), leakage through basivertebral veins (type B, 23.9%), and instrument-related leakage (type I, 13.9%) accounted for most cement leakage. Patients with lower bone mineral density and scattered cement distribution were more likely to experience type S or type B leakage. Our analysis data showed that cement augmentation with cannulated and fenestrated screws tended toward concentrated cement distribution. Creation and verification of each nomogram additionally showcased the prognostic capability and medical significance of the corresponding model. CONCLUSIONS: Nomograms and web-based calculators can accurately forecast the probability of cement leakage. PSA should be routinely performed using cannulated and fenestrated screws, along with a moderate amount of high-viscosity cement, with continuous monitoring using fluoroscopy.

Anatomic distribution of basivertebral foramen with a magistral form in vertebral bodies of T10~L5 and its clinical significance for extensive epidural cement leakage in cement-augmented pedicle screw fixation: a multicenter case-control study.

BACKGROUND: There are no reports discussing anatomic distribution of basivertebral foramen (BVF) in the osteoporotic vertebral body, which is critical in the analysis of the risk of epidural cement leakage (ECL) after cement-augmented pedicle screw fixation (CAPSF). METHODS: 371 osteoporotic patients using 1898 cement-augmented screws were included. Preoperative computed tomography (CT) was used to determine the frequency, width, height, and depth of magistral BVF in T10~L5. Additionally, we measured the distance between BVF and the left/right borders of vertebral body as well as the distance between BVF and upper/lower endplates. Following CAPSF, the severity of ECL and the position of pedicle screws were determined by postoperative CT. Finally, significant risk factors for extensive ECL were identified through binary logistic regression analysis. RESULTS: Of 2968 vertebral bodies ranging from T10 to L5, 801 (42.2%) had a magistral BVF. From T10 to L5, the frequency of magistral BVF appeared to gradually increase. The magistral BVF was much closer to the upper endplate and the depth accounted for about a quarter of anteroposterior diameter of vertebral body. Overall, there were 19 patients (5.1%) and 32 screws (1.7%) with extensive ECL, nine of whom had neurological symptoms. The independent risk factors for extensive ECL were the magistral BVF (OR = 8.62, P < 0.001), more volume of cement injected (OR = 1.57, P = 0.031), reduced distance from screw tip to vertebral midline (OR = 0.76, P = 0.003) and vertebral posterior wall (OR = 0.77, P < 0.001) respectively. CONCLUSION: When planning a CAPSF procedure, it is important to consider anatomical distribution of BVF and improve screw implantation methods.

Subchronic co-exposure of polystyrene nanoplastics and 3-BHA significantly aggravated the reproductive toxicity of ovaries and uterus in female mice.

Both nanoplastics (NPs) and 3-tert-butyl-4-hydroxyanisole (3-BHA) are environmental contaminants that can bio-accumulate through the food chain. However, the combined effects of which on mammalian female reproductive system remain unclear. Here, the female ICR-CD1 mice were used to evaluate the damage effects of ovaries and uterus after NPs and 3-BHA co-treatment for 35 days. Firstly, co-exposure significantly reduced the body weight and organ index of ovaries and uterus in mice. Secondly, combined effects of NPs and 3-BHA exacerbated the histopathological abnormalities to the ovaries and uterus and decreased female sex hormones such as FSH and LH while increased antioxidant activities including CAT and GSH-Px. Moreover, the apoptotic genes, inflammatory cytokines and the key reproductive development genes such as FSTL1 were significantly up-regulated under co-exposure conditions. Thirdly, through transcriptional and bioinformatics analysis, immunofluorescence and western blotting assays, together with molecular docking simulation, we determined that co-exposure up-regulated the FSTL1, TGF-ß and p-Smad1/5/9 but down-regulated the expression of BMP4. Finally, the pharmacological rescue experiments further demonstrated that co-exposure of NPs and 3-BHA mainly exacerbated the female reproductive toxicity through FSTL1-mediated BMP4/TGF-ß/SMAD signaling pathway. Taken together, our studies provided the theoretical basis of new environmental pollutants on the reproductive health in female mammals.

The Potential Impact of Basivertebral Foramen Morphology and Pedicle Screw Placement on Epidural Cement Leakage With Cement-Augmented Fenestrated Pedicle Screw Fixation: A Multicenter Retrospective Study of 282 Patients and 1404 Augmented Screws.

BACKGROUND: Epidural cement leakage (CL) is a common complication in cement-augmented fenestrated pedicle screw fixation (CAFPSF) with the potential for neural injury. However, there are no reports discussing basivertebral vein morphology and pedicle screw placement, which are critical in the analysis of the risk of epidural CL after CAFPSF. OBJECTIVE: To identify the incidence and risk factors of epidural CL in osteoporotic patients during CAFPSF. METHODS: Two hundred and eighty-two osteoporotic patients using 1404 cement-augmented fenestrated screws were included. Preoperative computed tomography (CT) was used to characterize the morphology of posterior cortical basivertebral foramen. After CAFPSF, the severity of epidural CL, the implantation position of the screw tip, and cement extension within the vertebral body were determined by postoperative CT scans. In this study, significant risk factors for epidural CL were identified through logistic regression analysis. RESULTS: In total, 28 patients (18.8%) and 108 screws (7.7%) had epidural CL and 7 patients (13 screws) experienced neurological symptoms. Although local epidural CL was generally not clinically significant, extensive epidural leakage posed a higher risk of neurological symptoms. Significant predictors for extensive epidural CL were a magistral type of basivertebral foramen and the smaller distance between the tip of the screw and the posterior wall of the vertebral body. CONCLUSION: In osteoporotic patients receiving CAFPSF, epidural CL is relatively common. The morphology of basivertebral foramen should be taken into account when planning a CAFPSF procedure. It is important to try and achieve a deeper screw implantation, especially when a magistral type of basivertebral foramen is present.

Establishment of a novel risk prediction model for recompression of augmented vertebrae at the thoracolumbar junction and modified puncture technique for prevention: a multicenter retrospective study.

OBJECTIVE: Recompression of augmented vertebrae (RCAV) is often seen after percutaneous kyphoplasty (PKP), especially at the thoracolumbar junction. The authors aimed to develop and validate a risk prediction model (nomogram) for RCAV and to evaluate the efficacy of a modified puncture technique for RCAV prevention after PKP for thoracolumbar osteoporotic vertebral fractures (OVFs). METHODS: Patients who underwent PKP for single thoracolumbar OVFs (T10-L2) between January 2016 and October 2020 were reviewed and followed up for at least 2 years. All patients were randomly divided into a training group (70%) and a validation group (30%). Relevant potential data affecting recompression were collected. Predictors were screened by using binary logistic regression analysis to construct the nomogram. Calibration and receiver operating characteristic curves were used to evaluate the consistency of the prediction models. Finally, the efficacy of the modified puncture technique for prevention of RCAV in OVF patients with a preoperative intravertebral cleft (IVC) was further demonstrated through binary logistic regression analysis. RESULTS: Overall, 394 patients were included and 116 of them (29.4%) sustained RCAV. The independent risk factors included decreased bone mineral density, lower level of serum 25-hydroxy vitamin D3, larger C7-S1 sagittal vertical axis (SVA), preoperative IVC, and solid-lump cement distribution. The area under the curve (AUC) of the prediction model was 0.824 in the training group and 0.875 in the validation group patients. The calibration curve indicated the predictive power of this nomogram, with the preoperative IVC having the highest prediction accuracy (AUC 0.705). The modified puncture technique significantly reduced the incidence of RCAV by enhancing bone cement distribution into a sufficiently diffused distribution in OVF patients with preoperative IVC. CONCLUSIONS: The nomogram prediction model had satisfactory accuracy and clinical utility for identification of patients at low and high risk of postoperative RCAV. Patients at high risk of postoperative RCAV might benefit from the target puncture technique and vitamin D supplementation as well as effective antiosteoporotic therapies.

Occurrence and risks of 23 tire additives and their transformation products in an urban water system.

Tire wear particles (TWPs) enter road surface with the friction between tires and road surfaces. Under the volatilization, leaching, and transformation action on TWPs by sunlight and rain, tire additives are released into urban water systems, such as surface rainfall runoff, wastewater treatment plants (WWTPs), receiving surface waters, and drinking water treatment plant (DWTP). In this study, we investigated the occurrence of 23 tire additives and their transformation products in the urban water system of the Pearl River Delta region, South China. Nineteen target compounds were detected in the surface runoff, with 1,3-Diphenylguanidine (DPG) showing highest maximum concentration of 58780 ng/L. Benzothiazole and its transformation products are detected at the frequency of 100 % with the total concentrations of 480-42160 ng/L. The antioxidant derivative N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine-quinone (6PPD-Q) was also detected up to 1562 ng/L, which was considerably higher than that of the parent compound 6PPD (the maximum concentration of 7.52 ng/L). Eleven and 8 compounds were detected in WWTPs influents and effluents, respectively, with removal rates of - 62-100 %. Seventeen compounds were detected in the receiving Zhujiang and Dongjiang rivers, while 9 compounds were detected in drinking water sources and DWTP samples. Road runoff, with total concentrations of target compounds up to 79200 ng/L, is suggested as the main non-point source for receiving rivers, while WWTPs effluents are the point sources due to incomplete removal of target compounds after accepting the initial runoff. 6PPD-Q and other 10 compounds displayed median to high ecological risks in surface waters, and the human daily intake of tire additives was estimated to be 2.63 × 10-8-3.16 × 10-5 mg/(kg d) via drinking water. This is the first report of the 6PPD-Q and 1,3-Diphenylurea levels in surface waters in China.

Controlled-release alginate-bentonite polymer gel granules of emamectin benzoate and control efficacy against Spodoptera frugiperda.

BACKGROUND: The fall armyworm (FAW), Spodoptera frugiperda (J. E. Smith), is known to cause large agricultural production losses. Emamectin benzoate is one of the most effective insecticides to control this pest; however, its effective time is not sufficiently long to control FAW. Therefore, it is important that new controlled insecticide formulations with new application methods are developed. RESULTS: A series of emamectin benzoate polymer gel granules were prepared with sizes ranging from 0.95 to 1.5 mm. As the bentonite content increased, the release rate decreased. The cumulative release process of emamectin benzoate mainly depends on the cracks in the surface of the granules, and the release rate can be described by non-Fickian and Fickian diffusion, which are closely related to the water content. By spreading the developed polymer gel granules into maize leaf whorls, the control effect reached 83% after 21 days in field trials. CONCLUSION: A novel polymer gel granule was developed that can effectively regulate emamectin benzoate release. By broadcasting polymer gel granules into maize leaf whorls, significant control efficacy against FAW can be obtained, and this could potentially be used for the effective control of FAW. © 2022 Society of Chemical Industry.

Preparation of bi-layer-polymer coated silica using atom transfer radical polymerization and its application as restricted access phase for HPLC separation of hydrophobic molecules in biological fluids.

A novel restricted access material was prepared by surface initiated atom transfer radical polymerization. The bi-layer-polymer structures were created on the surface of silica layer-by-layer. The inner layer was composed of poly(styrene-co-divinylbenzene), which was grafted first for binding small molecules based on hydrophobic and π-π interactions. The poly(styrene-co-divinylbenzene) bonded silica has good selectivity for aromatic hydrocarbons. It also has hydrophobicity and column efficiency similar to a C(18) bonded silica. The material has shown good ability of protein exclusion after grafting hydrophilic polymer on the external surface while its hydrophobicity and selectivity do not have obvious change. It demonstrated that the material is still qualified for hydrophobic extraction. In the study, the relations between the polymer structures and chromatographic properties of the materials were investigated. The synthetic conditions were optimized. The results have shown that the material prepared in the study has application potential in the HPLC analysis of hydrophobic molecules from biological samples by direct injection. It demonstrated that atom transfer radical polymerization can be used as a method in the preparation of restricted access material.

Influence of biofilms on the adsorption behavior of nine organic emerging contaminants on microplastics in field-laboratory exposure experiments.

Microplastics (MPs) are ubiquitous in aquatic environments, which are important carriers of emerging contaminants (ECs). Biofilms can be attached to the surface of MPs in a natural aquatic environment, which may influence chemical adsorption; however, knowledge of its impact is still limited. This study investigated the effect of biofilms on MPs on the adsorption of ECs through field-laboratory exposure experiments. Three types of MPs were naturally colonized with biofilms in lake. Then, biofilm-absent/biofilm-attached MPs were exposed to nine EC solutions at a concentration of 8 µg/L of each compound in laboratory. Most compounds exhibited 3.8 times lower concentrations on biofilm-attached MPs than on biofilm-absent MPs; only a few compounds showed enhanced adsorption. Pseudo-equilibrium was achieved within 72 h based on adsorption kinetics, implying fast adsorption of ECs on biofilm-attached MPs. The partition coefficients (Kd) for biofilm-attached MPs were 0.14 (diclofenac) to 535 (miconazole) L/kg and were positively correlated with octanol/water partition coefficients (Kow). This indicated that chemical properties (such as Kow) of the compounds determined their final adsorption amounts on MPs, although these were influenced by the presence of the biofilm. Hence, multiple influencing factors should be considered when evaluating the carrier potential of MPs for ECs in aquatic environments.

Development of Saikosaponin D Liposome Nanocarrier with Increased Hepatoprotective Effect Against Alcoholic Hepatitis Mice.

The mortality rate of ethanol induced liver disease has substantially raised to alert level with an increasing use of alcohol, but development of definite hepatoprotective drug is still challenging. The efficacy of Saikosaponin D, one of the natural herbal medicine has been studied in different diseases. Nonetheless, its clinical application is restricted by poor bioavailability, stability and solubility. This study sought to develop a Saikosaponin D loaded liposome via thin film hydration method. The surface morphology, encapsulation efficiency and drug loading capacity were detected with transmission electron microscopy and HPLC, in vitro dissolution was via dialysis method, but efficacy and safety evaluation was through pharmacokinetics, while the assessment of hepatoprotective activity on alcohol induced acute hepatitis mice models was conducted. The optimized liposomes showed significant greater therapeutic effect on liver, through decreased serum levels of alanine transaminase (ALT) and aspartate transaminase (AST), malondialdehyde (MDA), tumor necrosis factor alpha (TNF-α), total cholesterol (TC) and triglyceride (TG) in liver homogenate. In contrast, levels of glutathione peroxidase (GSH-Px) and total superoxide dismutase (T-SOD) were increased significantly. Pathological study exhibited remarkable alteration of hepatitis liver architecture to almost normal state after administration of Saikosaponin D liposome. The increased hepatoprotective effect of Saikosaponin D liposome was observed during the attenuation of alcoholic hepatitis in mice, which might be ascribable to the anti-oxidative and anti-inflammatory properties of the drug. This study provides a theoretical basis for developing advanced system of Saikosaponin D delivery for the promotion of the therapeutic effects of the liposome against various kinds of diseases.

Study on the cellular internalization mechanisms and in vivo anti-bone metastasis prostate cancer efficiency of the peptide T7-modified polypeptide nanoparticles.

Bone-metastasis prostate cancer (BMPCa)-targeting gene therapy is gaining increasing concern in recent years. The peptide T7-modified polypeptide nanoparticles for delivery DNA (CRD-PEG-T7/pPMEPA1) was prepared as our previous study. However, the feasibility of CRD-PEG-T7/pPMEPA1 for BMPCa treatment, the mechanisms underlying cellular uptake, anti-BMPCa effect, and administration safety requires further research. LNCaP cells treated with endocytosis inhibitors and excessive T7 under different culture condition were carried out to investigate the mechanisms of cellular uptake of the CRD-PEG-T7-pPMEPA1. A transwell assay was applied to evaluate the cell migration ability. Besides, the tumor volume and survival rates of the PCa xenograft mice model were recorded to estimate the anti-tumor effect. In addition, the weight profiles of the PCa tumor-bearing mice, the blood chemistry, and the HE analysis of visceral organs and tumor was conducted to investigate the administration safety of CRD-PEG-T7/pPMEPA1. The results showed that PCa cellular uptake was decreased after treating with excessive free T7, endocytosis inhibitors and lower incubation temperature. Besides, CRD-PEG-T7/pPMEPA1 could inhibit the LNCaP cells chemotaxis and tumor growth. In addition, the survival duration of the PCa tumor-bearing mice treating with CRD-PEG-T7/pPMEPA1 was significantly prolonged with any systemic toxicity or damage to the organs. In conclusion, this research proposes a promising stratagem for treatment BMPCa by providing the biocompatible and effective carrier for delivery DNA therapeutic agents.

Comparison and intrinsic correlation analysis based on composition, microstructure and enzymatic hydrolysis of corn stover after different types of pretreatments.

Pretreatment is a key step in the energy utilization of lignocellulosic biomass. Different types of pretreatments (ultrafine grinding pretreatment, alkaline hydroxide peroxide pretreatment, dilute acid pretreatment, and ammonia fiber expansion pretreatment) were conducted on corn stover. The lignocellulosic composition, microstructural parameters, and glucose yield of differently pretreated corn stover were characterized and compared. Then qualitative and quantitative correlation analyses of the parameters were carried out to explore the correlations among the composition, microstructure properties, and enzymatic hydrolysis efficacy of corn stover after different types of pretreatments and identify the main properties affecting enzymatic hydrolysis. Qualitative correlation analysis found that cellulose content, specific surface area, pore volume, enzyme-accessible pore volume, and surface area of cellulose had significant positive correlations with glucose yield. The results of quantitative correlation analysis were GY = 15.01 × cellulose content-339.05, GY = 13.06 × SSA + 172.35, GY = 7226.27 × PV + 129.14, GY = 8628.61 × EAPV + 125.61, and GY = 1.18 × SAC-287.21.