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An increasing number of studies have shown that exposure to particulate matter with a diameter ≤ 2.5 μm (PM2.5) could affect the onset and development of cardiovascular diseases. To explore the underlying mechanisms, the studies conducted in vitro investigations using different cell lines. In this review, we examined recently published reports cited by PubMed or Web of Science on the topic of cardiovascular toxicity induced by PM2.5 that carried the term in vitro. Here, we summarized the suggested mechanisms of PM2.5 leading to adverse effects and cardiovascular toxicity including oxidative stress; the increase of vascular endothelial permeability; the injury of vasomotor function and vascular reparative capacity in vascular endothelial cell lines; macrophage polarization and apoptosis in macrophage cell lines; and hypermethylation and apoptosis in the AC16 cell line and the related signaling pathways, which provided a new research direction of cardiovascular toxicity of PM2.5.

Poly(3,4-ethylenedioxythiophene) mixed with poly (styrenesulfonate) (PEDOT:PSS) is considered as one of the most valuable conductive polymers due to its high conductivity, transparency and mechanical flexibility. Many experiments have proved that H2SO4 post-treatment is an effective way to enhance the electrical conductivity of PEDOT:PSS films. Here we reported a method for the fabrication of PEDOT:PSS films with conductivity as high as 6323.9 ± 364.5 S/cm, based on a two-step H2SO4 post-treatment. This very high conductivity is, as far as we know, the highest reported value for PEDOT:PSS films by solution preparation. The removal of PSS and redox reaction are the keys to enhance the conductivity of PEDOT:PSS films.

BACKGROUND: Coronary computed tomography angiography (CCTA) is a noninvasive imaging modality to detect and diagnose coronary artery disease. Due to the limitations of equipment and the patient’s physiological condition, some CCTA images collected by 64-slice spiral computed tomography (CT) have motion artifacts in the right coronary artery, left circumflex coronary artery and other positions. OBJECTIVE: To perform coronary artery motion artifact correction on clinical CCTA images collected by Siemens 64-slice spiral CT and evaluate the artifact correction method. METHODS: We propose a novel method based on the generative adversarial network (GAN) to correct artifacts of CCTA clinical images. We use CCTA clinical images collected by 64-slice spiral CT as the original dataset. Pairs of regions of interest (ROIs) cropped from original dataset or images with and without motion artifacts are used to train the dual-zone GAN. When predicting the CCTA images, the network inputs only the clinical images with motion artifacts. RESULTS: Experiments show that this network effectively corrects CCTA motion artifacts. Regardless of ROIs or images, the peak signal to noise ratio (PSNR), structural similarity (SSIM), mean square error (MSE) and mean absolute error (MAE) of the generated images are greatly improved compared to those of the input data. In addition, based on scores from physicians, the average score for the coronary artery artifact correction of the output images is higher. CONCLUSIONS: This study demonstrates that the dual-zone GAN has the excellent ability to correct motion artifacts in the coronary arteries and maintain the overall characteristics of CCTA clinical images.

Wounds affect various functions of the skin, and treating them has always been a challenge for humans. Skin grafts have been traditionally used to treat wounds; however, they have certain shortcomi...

Recently conducted biomedical studies have shown that the drug diffusivity of hyaluronic acid hydrogel plays an important role in the treatment of joint diseases. The drug diffusivity is closely related to the water content of hydrogel. In addition, different water content will not only affect its mechanical and tribological properties, but also change the effect of drug release.In this work, a Molecular dynamics simulation was used to investigate the effect of water content on spatial distribution, tribological and mechanical properties of a hyaluronic acid hydrogel network. This paper focuses on the analysis and calculation of the radial distribution function of 20, 40, 60, and 80% water content model and the friction force and mechanical parameters under the influence of different load and friction speed.The results show that at 20 and 40% water content, the spatial distribution is loose and the intermolecular force is not strong, resulting in a major lack in tribological and mechanical properties; whereas at 60 and 80% water content, the spatial distribution becomes gradually compact and the intermolecular force is gradually increased. The tribological and mechanical properties manifest a marked improvement.The calculations reveal that the hydrogel model has the best wear resistance, pressure resistance, and plastic deformation resistance at 80% water content. In the range of 20-80% water content, the mechanical properties and friction properties of hydrogels become better and better with the increase of water content.

An increasing number of scaffold materials are available for repairing alveolar bone defects. As each material has its own advantages and disadvantages, these characteristics should be carefully considered. This paper presents a review of the currently available materials for repairing alveolar bone defects, including artificial ceramics, polymers, and metals. The combination of seed cells or growth factors with these materials is the future trend for the treatment of alveolar bone defects. In this study, a comprehensive analysis of the advantages, disadvantages, and development status of various materials is carried out, providing a basis for future material selection.

Molybdenum disulfide (MoS2) coatings are known for their ultralow friction coefficient (0.005) due to the appearance of tribofilms with a lamellar structure. Nevertheless, the dynamics of MoS2 shee...

Objective. To explore the pharmacological mechanism of a Chinese patent drug (Kunling Pill (KLP)) on improving diminished ovarian reserve based on proteomic analysis. Methods. A total of 18 patients divided into three groups (the normal ovary reserve (NOR), diminished ovary reserve (DOR), and KLP groups) undergoing assisted reproductive technology by standard ovarian stimulation protocols were recruited to collect follicular fluid. Data-independent acquisition mass spectrometry was used to identify differentially expressed proteins by nano-LC-MS/MS. Bioinformatic analysis was conducted to predict the functions and pathways of the identified proteins. Clinical, hormonal, and biochemical parameters were also analyzed in the three groups. Results. A total of 144 differentially expressed proteins were screened out, including 56 proteins that were downregulated and 88 proteins that were upregulated in the DOR group compared with the NOR group, while 27 proteins were shared in the KLP-treated group. Among them, 10 proteins were upregulated and 17 proteins were downregulated in the KLP-treated group compared with the DOR group. The most enriched biological processes accounted for 28 GO terms, including cellular process, biological regulation, metabolic process, and regulation of biological process. Significant pathways were associated with fatty acid elongation, fatty acid degradation, fatty acid metabolism, nicotinate and nicotinamide metabolism, and valine, leucine, and isoleucine degradation. Conclusion. Our study provides the proteome profiles of human follicular fluid from DOR patients treated by KLP. Functional analyses of proteome datasets revealed that core proteins (SAA1, MIF, and PRDX5) and related pathways (fatty acid metabolism, nicotinate and nicotinamide metabolism, and tyrosine and purine metabolism) are possible pharmacological mechanisms through which KLP improves DOR. Therefore, these findings may help better understand the complex mechanisms through which DOR is treated by the Chinese patent drug KLP.

Therapeutic efficacy against cancer relies heavily on the ability of the therapeutic agents to reach their final targets. The optimal targets of most cancer therapeutic agents are usually biological macromolecules at the subcellular level, which play a key role in carcinogenesis. Therefore, to improve the therapeutic efficiency of drugs, researchers need to focus on delivering not only the therapeutic agents to the target tissues and cells but also the drugs to the relevant subcellular structures. In this review, we discuss the most recent construction strategies and release patterns of various cancer cell subcellular-targeting nanoformulations, aiming at providing guidance in the overall design of precise nanomedicine. Additionally, future challenges and potential perspectives are illustrated in the hope of enhancing anticancer efficacy and accelerating the translational progress of precise nanomedicine.

Appropriate scaffolds for tissue-engineered bone not only require mechanical strength, but also conditions that promote new bone growth. Bone tissue engineering scaffolds should establish the internal pore structure of the scaffolds and promote new bone growth. Additive manufacturing technology is widely used in the field of bone tissue engineering because it can directly and accurately construct the pore structure in 3D space, ensure internal connectivity of the scaffolds, and directly use biological materials. This paper reviews the development of additive manufacturing technology for bone tissue engineering. The differences between various additive manufacturing technologies are reviewed, with emphasis on the application of new technologies and materials. This paper also reviews the modeling processes used in bone tissue engineering, with emphasis on the optimization of the architectural design to achieve gradient structure and improved porosity and mechanical properties. Finally, this paper summarizes the 3D bioprinting technology that has fluid containing nutrients, matrix, and cells as constituent materials. Current problems and directions for the future development of additive manufacturing technology in the field of bone tissue engineering are also discussed.

Although superlubricity is highly desirable for many engineering applications, its implementation has so far been seriously restricted due to limitations in contact size, environmental adaptability and life time. By designing superlattice films with alternating molybdenum disulfide (MoS2) and tungsten carbide (WC) layers, we show that long-term macroscale superlubricity (friction coefficient of 0.006) in low vacuum (~10-3 Pa) after a short running-in period in air. Such unusual behavior is enabled when the fine structure of the bilayer unit is rationally controlled to yield incommensurate contacts between MoS2 and metal oxides nanoparticles produced spontaneously during tribological sliding. Our analysis indicates that the WC phase is critical for superlubricity by helping stiffen the film, facilitate preferential growth of crystalline MoS2 along (002) plane parallel to substrate, and produce lubricous nanoparticles. We further demonstrate the superlattice design is generally applicable for MoS2/ceramics materials to achieve long life-time macroscale superlubricity with easy self-rejuvenation capability.

Bone defects are the second most common tissue grafts after blood. However, bone grafts face several problems, such as bone scaffolds, which have low bioactivity and are prone to corrosion. Much of the current research on bone scaffolds is focused on the mechanical aspects such as structure and strength. Surface modification of the bone scaffold is carried out in terms of the mechanical structure or structural design of the bone scaffold with reference to a bionic structure. However, with the development of mechanical designs, materials science, and medicine, many studies have reported that promoting bone growth by modifying the structure of the scaffold or coating is not possible. Therefore, the application of a bioactive coating to the surface of the bone scaffold is particularly important to generate a synergistic effect between the structure and active coating. In this article, we present several perspectives to improve the bioactivity of bone scaffolds, including corrosion resistance, loading of bioactive coatings or drugs on bone scaffolds, improved adhesion to the surface of the bone scaffolds, immune response modulation, and drawing on bionic structures during manufacturing.

Three-dimensional 3D printing binders are important in the modern industry. Several types of binders and printing materials are used. Thus, printing binder requirements differ considerably depending on the printing methods utilized. In this study, the characteristics and research status of biomimetic materials and polymer binders used in Selective Laser Sintering-based printing (SLS), Spray molding technology (such as, solid inkjet printing [3DP] and Metal binder jet printing (MBJ), and extruded bio-printing technology (EBP) are reviewed.

Some chemotherapy can damage tumor cells, releasing damage-related molecular patterns including ATP to improve immunological recognition against the tumor by immunogenic cell death (ICD). However, the immune-stimulating ATP may be rapidly degraded into immunosuppressive adenosine by highly expressed CD39 and CD73 in the tumor microenvironment, which leads to immune escape. Based on the above paradox, a liposome nanoplatform combined with ICD inducer (oxaliplatin) and CD39 inhibitor (POM-1) is designed for immunochemotherapy. The liposomes efficiently load the phospholipid-like oxaliplatin prodrug, and the cationic charged surface could adsorb POM-1. Rationally designed DSPE-PEG

Fine particulate matter (PM

Stage I non-small cell lung cancer (NSCLC) presents diverse outcomes. To identify molecular features leading to tumor recurrence in early-stage NSCLC, we perform multiregional whole-exome sequencing (WES), RNA sequencing, and plasma-targeted circulating tumor DNA (ctDNA) detection analysis between recurrent and recurrent-free stage I NSCLC patients (CHN-P cohort) who had undergone R0 resection with a median 5-year follow-up time. Integrated analysis indicates that the multidimensional clinical and genomic model can stratify the prognosis of stage I NSCLC in both CHN-P and EUR-T cohorts and correlates with positive pre-surgical deep next generation sequencing (NGS) ctDNA detection. Increased genomic instability related to DNA interstrand crosslinks and double-strand break repair processes is significantly associated with early tumor relapse. This study reveals important molecular insights into stage I NSCLC and may inform clinical postoperative treatment and follow-up strategies.

Pulmonary fibrosis (PF) is a chronic progressive disease with an extremely high mortality rate and is a complication of COVID-19. Inhalable microspheres have been increasingly used in the treatment of lung diseases such as PF in recent years. Compared to the direct inhalation of drugs, a larger particle size is required to ensure the sustained release of microspheres. However, the clinical symptoms of PF may lead to the easier deposition of microspheres in the upper respiratory tract. Therefore, it is necessary to understand the effects of PF on the deposition of microspheres in the respiratory tract.In this study, airway models with different degrees of PF in humans and mice were established, and the transport and deposition of microspheres in the airway were simulated using computational fluid dynamics.The simulation results showed that PF increases microsphere deposition in the upper respiratory tract and decreases bronchial deposition in both humans and mice. Porous microspheres with low density can ensure deposition in the lower respiratory tract and larger particle size. In healthy and PF humans, porous microspheres of 10 µm with densities of 700 and 400 kg/m³ were deposited most in the bronchi. Unlike in humans, microspheres larger than 4 µm are completely deposited in the upper respiratory tract of mice owing to their high inhalation velocity. For healthy and PF mice, microspheres of 6 µm with densities of and 100 kg/m³ are recommended.The results showed that with the exacerbation of PF, it is more difficult for microsphere particles to deposit in the subsequent airway. In addition, there were significant differences in the deposition patterns among the different species. Therefore, it is necessary to process specific microspheres from different individuals. Our study can guide the processing of microspheres and achieve differentiated drug delivery in different subjects to maximize therapeutic effects.

Abnormal lipid accumulation in macrophages may lead to macrophages foaming, which is the most important pathological process of atherosclerosis. Atmospheric PMMacrophages derived from THP-1 cells were exposed to PMThe survival rate of macrophages was reduced by PMPM

This study was undertaken to determine if coronary computed tomographic angiography (CCTA) can help to assess patent foramen ovale (PFO) with high accuracy and reproducibility when compared to Transesophageal Echocardiography (TEE). In total, 75 patients (31 men, 44 women; mean age, 45 ± 9 years) with suspected PFO were evaluated using coronary CCTA and TEE. PFO tunnel length (TL) and the opening diameter of the left atrial entrance (ODLAE) and right atrial entrance (ODRAE), as well as contrast shunt (if present due to PFO), were measured by both modalities. PFO was detected in 67 patients with TEE. The sensitivity for the detection of PFO with CCTA was 85.3%; specificity, 71.4%; positive predictive value, 96.7%; and negative predictive value, 33.3%. Both modalities demonstrated good agreement in measuring TL and ODLAE of PFO. However, the ODRAE of TEE was different from that of CCTA (1.14 ± 0.4 mm and 1.45 ± 0.5 mm, respectively, p = 0.04). The intraobserver and interobserver variability and agreement for TL, ODRAE, and ODLAE of PFO were excellent between the two measurements. CCTA provided a method for detection of PFO with high accuracy and reproducibility compared with TEE. Therefore, CCTA is a practical and efficient alternative to TEE for PFO diagnosis.

Ethnopharmacological relevance Danggui Buxue Decoction (DBT) is classical prescriptions, which contains two Traditional Chinese Medicines of Angelicae sinensis radix and Astragali radix. According to the preliminary work of our laboratory and numerous studies, it has been found that DBT has a therapeutic effect on diabetic nephropathy (DN). However, the mechanisms underlying its action remain unclear. Aim of the study The aim of this study was to evaluate the impact of DBT on kidney disease in diabetic mice and further explore its protective mechanism. Methods DN mice model was induced by high-fat fodder and streptozotocin (STZ). Qualitative and quantitative analysis of 6 compounds in DBT was carried out by HPLC, including calycosin-7-glucoside, ferulic acid, ononin, calycosin, formononetin, and levostilide A. Hematoxylin-Eosin (HE) staining was used to determine the degree of kidney pathological damage. The UPLC-Q Exactive MS technique was used to analyze the lipids metabolism profile of kidneys samples and multiple statistical analysis methods were used to screen and identify biomarkers. Transcriptomics analyses were carried out using RNAseq. The possible molecular mechanism was unraveled by network pharmacology. Results Thirty-one significantly altered lipid metabolites were identified in the model group comparing with the control group. DBT improved aberrant expression of several pathways related to lipidomics, including glycerophospholipid metabolism and sphingolipid metabolism. Comprehensive analysis indicated that DBT intervention reduced the content of Cers, phosphatidylethanolamines and phosphatidylcholines in mouse kidneys by downregulating the transcription level of Degs2 and Cers, reducing lipid accumulation and promoting Akt phosphorylation by upregulating the expression of Acers and Pdk1. Network pharmacology analysis showed that components in DBT, such as kaempferol, ferulic acid and astragaloside IV, could be responsible for the pharmacological activity of DN by regulating the AGE-RAGE, PI3K/Akt, MAPK and NF-κB signaling pathways in diabetic complications. Conclusions These results showed that DBT may improve DN by affecting insulin resistance, chronic inflammation and lipid accumulation.

The many types of material currently used to treat bone injuries (caused by various reasons) have undergone changes over time. From the initial metal implants of stainless steel or titanium to thos...

Purpose Thymosin β-4(Tβ-4) is a macromolecular protein drug with potential for drug development in wound repair but is limited by the shortcomings of macromolecular protein, such as large volumes, poor membrane permeability, and unstable physicochemical characteristics. Ethosomes could enhance cell membrane fluidity and reduce epidermal membrane density to make macromolecular drugs through the stratum corneum into the deeper layers of the skin easily. Herein, we developed and characterized a novel transdermal delivery vehicle to load macromolecular protein peptides and use Tβ-4 as a model drug wrapped into ethosomes. Methods We used the orthogonal method to optimize the formulation of the ethosome preparation prepared by the ethonal infusion method. Ethosomal gels were characterized by using different analytical methods. Transdermal release rate in vitro have been demonstrated in Franz diffusion cells and the efficacy of drug-loaded nanocarriers in vivo was investigated in a mouse model. Results Optimized Tβ-4 ethosomal gels have good physicochemical properties. The drug amounts of the cumulative release in the ethosomal gel within 5 hours were 1.67 times that of the T-β4 gel in vitro release study, and the wound healing time of ethosomal gel group was only half of the T-β4 gel group in vivo pharmacokinetic study. Compared with the free drug group, the ethosome preparation not only promotes the percutaneous absorption process of the macromolecular protein drugs but also shortened wound recovery time. Conclusion Hence, we provide a possible good design for ethosomal gel system that can load macromolecular protein peptide drugs to achieve transdermal drug administration, promoting the percutaneous absorption of the drug and improving the effect.

Background Shunxinzufang decoction is tutors, empirical formula and has been used in Chinese patients of HFpEF for several years. The aim of this study was to make into sustained release granules and select the best formula for the preparation of Shunxin sustained release granules and to evaluate its in vivo and in vitro drug release behavior. Methods Response surface methodology and Center composite design were applied to screen the optimal formula of Shunxin sustained release granules. HPLC was used to detect indicative ingredients—paeoniflorin, calycosin-7-glucoside and ferulic acid in Shunxin sustained release granules. The in vitro sustained release character of indicative ingredients was investigated in simulated digestive fluids. In-vivo process of active components was studied through pharmacokinetics. Results The optimal formula of Shunxin sustained release granules consisted of 35% shunxinzufang extract and 65% HPMC/starch (HPMC/starch ratio = 2:1). Three indicative components can be separated well under selected HPLC conditions. Compared with Shunxinzufang extract, the active components of Shunxin sustained release granules have obvious sustained-release character and improved bioavailability. Conclusion Shunxin sustained release granules has obvious sustained-release character and improved bioavailability.

Background Epidemiological studies have confirmed atmospheric PM2.5 could affect asthma, and dyslipidemia may be related to pathogenesis of asthma. Recent studies show Notch ligands had lipid combination domains which are responsible for regulating lipid levels. However, the effect of PM2.5 on asthmatic rats’ lipid levels and the role of Notch signaling pathway is unclear. Methods Rats were treat with ovalbumin (OVA) to establish asthma models. Notch signaling pathway inhibitor (DAPT) was injected intraperitoneally. Asthmatic and healthy rats were exposed to different concentrations of PM2.5. Lung tissues were collected and the expression of Hes1 protein was detected by Western Blot. Blood samples were collected to detect the serum lipid levels. Results Hes1 expression levels in healthy and asthma pathway inhibition groups were lower than those in control groups. Compared with control group, rats exposed to PM2.5 in middle and high dose, the levels of TG and TC were decreased. Similar results were observed after exposure to the same concentration of PM2.5 in asthmatic rats. Rats, which were exposed to PM2.5 after being established the asthma model successfully, could exhibit more significant dyslipidemia than those with direct exposure. After Notch signaling pathway inhibited, TC and LDL in asthma pathway inhibition group were lower than those in healthy group. Conclusions PM2.5 can affect the lipid levels of asthmatic rats through the Notch signaling pathway.

To better treat gastric diseases and lower systemic side effect, it is essential to design new vectors to control drug release in stomach. Aiming to this challenge, we developed a new gastroretentive drug delivery system: nanomicelles-loaded gastroretentive beads. Firstly, the chitosan-coated emodin-loaded nanomicelles were developed and characterized. In vitro cytotoxicity of emodin-loaded nanomicelles, emodin suspensions and blank nanomicelles was evaluated with human gastric carcinoma SGC-7901 cells by MTT, indicating that the blank nanomicelles had null cytotoxicity and emodin-loaded nanomicelles had better antitumor efficacy compared with emodin suspensions. Secondly, nanomicelles-loaded floating mucoadhesive beads (NFM-Beads) were prepared, and the swelling, degradation, mucoadhesion and floating ability in vitro were separately investigated. FT-IR spectroscopy was applied to identify the formation of nanomicelles and NFM-Beads. Emodin release from NFM-Beads in vitro was fitted to anomalous transport mechanism. In vivo gastroretention behavior of NFM-Beads was evaluated by BaSO4-based X-ray imaging exams, showing that NFM-Beads can be retained in rabbit stomach for at least 8 h. Overall, the new NFM-Beads system could be an effective approach to improve the therapeutic potency of drug against gastric cancer.

In recent years, immunotherapy has produced many unexpected breakthroughs in oncological therapy; however, it still has many deficiencies. For example, the number of patients who are unresponsive to anti-programmed death-ligand 1 (PD-L1), anti-cytotoxic T-like antigen-4 (CTLA4), and anti-programmed death-1 (PD1) therapies cannot be ignored, and the search for an undiscovered immunosuppressive pathway is imminent. Five decades ago, researchers found that activation of the adenosinergic pathway was negatively correlated with prognosis in many cancers. This review describes the entire process of the adenosinergic pathway in the tumor microenvironment and the mechanism of immunosuppression, which promotes tumor metastasis and drug resistance. Additionally, the review explores factors that regulate this pathway, including signaling factors secreted by the tumor microenvironment and certain anti-tumor drugs. Additionally, the combination of adenosinergic pathway inhibitors with chemotherapy, checkpoint blockade therapy, and immune cell-based therapy is summarized. Finally, certain issues regarding treatment via inhibition of this pathway and the use of targeted nanoparticles to reduce adverse reactions in patients are put forward in this review. Graphical Abstract The inhibitors of adenosinergic pathway loaded nanoparticles enter tumor tissue through EPR effect, and inhibit adenosinergic pathway to enhance or restore the effect of immune checkpoint blockade therapy, chemotherapies and immune cell-based therapy. Note: EPR means enhanced penetration and retention, × means blockade.

Skeletal biomechanics focuses on both transient and long-term effects of bone stress, using the basic theory and method of material mechanics, elasto-plasticity theory, and fracture mechanics,is considered to be one of the most important branches in biomechanics. In order to achieve complete and comprehensive evaluation of skeletal biomechanics, researchers developed a variety of levels of skeletal biomechanical evaluation methods, including mechanical testing, theoretical research, microstructure research and finite element analyses. At present, most of the mechanical evaluation methods were performed by a combination of mechanical tests and finite element (FE) simulation studies for the evaluation of mechanical properties. This study summerized the research in multi-level mechanical test methods, different research methods of microstructure, and the reconstruction of various FE skeletal models to study bone mechanics. The mentioned methods and techniques can be served as the basis for systematic studies of the biomechanical properties of bones.

Two-dimensional layered molybdenum disulfide (MoS2) has been recognized as a promising material for an atomic thin solid lubricant. In this study, we investigated the microscopic friction behavior of MoS2 using a reactive force-field (ReaxFF) molecular dynamics simulation. The effects of the interlayer distance and temperature on the frictional force during the sliding process were studied. The results showed that the friction was mainly affected by the interaction between S atoms at the interface. As the distance between layers decreased, the gradually increasing interlayer repulsive interaction deformed the Mo-S bond of the MoS2 and changed the positions of S atoms at the interface. The migration of S atoms at the interface contributed to the low friction behavior of the MoS2.

Two CFD models A and B were developed based on APV high-pressure homogenizer and it was determined that the mathematical model and analysis method of B were more consistent with the actual homogenization process. The internal flow field of the high-pressure micro-jet homogenizer was simulated using Fluent software. The homogenization pressure, ratio of oil to water, and temperature were investigated. The optimal parameter combination obtained from numerical simulation of orthogonal experiment was 20 °C, 70 MPa, and 1:12. APV high-pressure homogenizer orthogonal experiment was conducted and the optimal experimental parameter combination obtained was 50 °C, 70 MPa, and 1:15. The two groups of optimal parameters were used in the homogeneous experiments. TEM images were used for comparative analysis of the particle size，and the particle size obtained by numerical simulation was slightly larger. A comparison of experimental and numerical simulation results indicate that the single factor experiment and the orthogonal experiment were not entirely chime. The reason for the discrepancy is because the emulsifier was added in the homogeneous experiment such that there were more flow field variation factors in the homogenization process and the numerical process did not define all relevant conditions. However, the highly similar development trend verifies the effectiveness of the B model, which can provide an important reference in the development and use of homogenizers.

Rhei Radix et Rhizoma is widely used in Traditional Chinese Medicine to attack stagnation, clear damp heat, relieve fire, cool blood, remove blood stasis and detoxify recorded in Chinese Pharmacopoeia. Modern pharmacological research has showed the extract of Rhei Radix et Rhizoma has the effect of lowering blood lipids, but the main active components and their mechanisms are still not clear.To reveal the lipid regulating components from Rhei Radix et Rhizoma and preliminarily explore their related action mechanisms.A rat model of dyslipidemia was established by administration of a high-fat emulsion via gavage, and the intervention effect of different polar fractions of Rhei Radix et Rhizoma on rat blood lipids as well as their related action mechanisms were preliminarily investigated. The effective components were inferred based on the above tests and identified by high performance liquid chromatography in comparison with reference substances, their UV absorption and high resolution mass spectra characteristics.The extract with dichloromethane fraction (DF) containing rhubarb free anthraquinones (aloe-emodin, rhein, emodin, chrysophanol and physcion) significantly regulated the disordered blood lipids, lowered TC and LDLC, reversed TG and increased HDLC level in dyslipidemic rats and also showed lipid-lowering effect on lipid abnormalities in HepG2 cells. DF could alter the signaling pathways such as PPARα and AMPK implicated in lipid metabolism, and it down-regulated the mRNA expression of liver APOA2, SCD-1, HMGCR, SREBP-2 and PCSK9, but up-regulated the expressions of liver APOE, LPL and intestinal ABCG8. Besides, it could change the composition of Firmicutes, Bacteroidetes and Proteobacteria in dyslipidemic rat feces samples.Rhubarb free anthraquinones have a significant regulating effect on the levels of serum TC, LDLC and HDLC, and probably possess a bidirectional regulatory effect on TG level in dyslipidemic rats. These effects may be achieved by regulating the expressions of the liver PPARα and SREBP target genes, PCSK9 and the intestinal ABCG8 genes, which are involved in blood cholesterol transport, liver lipid metabolism and intestinal cholesterol excretion. Rhubarb free anthraquinones may also affect energy metabolism by changing the composition of gut microflora related to lipid metabolism in dyslipidemic rats.

Hybrid heterojunction solar cells (HHSCs) using crystalline Si nanowires (SiNWs) as the absorber and conducting polymer poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) as the hole-selective transport layer (HTL) show great potential in both low-cost and high-power conversion efficiency (PCE). However, due to the poor wettability of the PEDOT:PSS solution on SiNWs, conformal coverage of PEDOT:PSS on SiNWs is not easy to achieve. Here, an effective method was developed to decrease the surface tension of the PEDOT:PSS and increase the wettability between PEDOT:PSS and SiNWs by incorporating organosilane into the PEDOT:PSS solution. Two kinds of organosilanes including tetramethoxysilane (TMOS) and vinyltrimethoxysilane (VTMO) were selected as the additives. The surface passivation quality of the SiNWs was dramatically enhanced. The HHSCs utilizing VTMO as the additive show a higher open circuit voltage and higher PCE compared with the TMOS adding ones. By spin-coating Ag nanowires onto the PEDOT:PSS HTL layer and using spin-coated phenyl-C61-butyric acid methyl ester as the electron-selective transport layer, a champion PCE up to 18.12% and a fill factor of 80.1% have been achieved on the full solution processed PEDOT:PSS/n-type SiNWs HHSCs. The findings provide a simple and promising method to achieve high-performance PEDOT:PSS/SiNWs HHSCs.

Background: Mono-2-ethylhexyl phthalate (MEHP) is a major metabolite of di (2-ethylhexyl) phthalate (DEHP). Our previous researches have shown that MEHP can induce lipid accumulation in preadipocytes, while, the underlying mechanism is unclear. The present study was undertaken to clarify the effect of Notch pathway on lipid accumulation induced by MEHP. Methods: 3T3-L1 preadipocytes were exposed to MEHP (0, 10, 50, 250 µM and 0.1%DMSO) for the whole differentiation phase. Then the level of TG and cell cycle were detected. RT-PCR was used to detect the mRNA expression and Western blot was used to detect the expression of protein by Notch pathway genes and lipid metabolic related genes. Results: In this study, the level of TG in the 250 µM and 250 µM MEHP groups was significantly higher than that in the control, DMSO and 10 µM MEHP groups (P

In a previously described chimeric peptide, we reported that the multifunctional opioid/neuropeptide FF (NPFF) receptor agonist 0 (BN-9) produced antinociception for 1.5 h after supraspinal administration. Herein, four cyclic disulfide analogs containing l- and/or d-type cysteine at positions 2 and 5 were synthesized. The cyclized analogs and their linear counterparts behaved as multifunctional agonists at both opioid and NPFF receptors in vitro and produced potent analgesia without tolerance development. In comparison to 0, cyclized peptide 6 exhibited sevenfold more potent μ-opioid receptor agonistic activity in vitro. Interestingly, the cyclized analog 6 possessed an improved stability in the brain and an increased blood-brain barrier permeability compared to the parent peptide 0 and produced more potent analgesia after supraspinal or subcutaneous administration with improved duration of action of 4 h. In addition, antinociceptive tolerance of analog 6 was greatly reduced after subcutaneous injection compared to fentanyl, as was the rewarding effect, withdrawal reaction, and gastrointestinal inhibition.

Autologous or allogeneic bone grafts are common methods to treat bone defects. Bone tissue engineering combining carrier material with the active factor can induce a generation of new bone at the bone defect site. However, its clinical application is restricted by the limited donors, the high morbidity at the donor site, the low activity in vivo, and dose-independent adverse effect. To overcome the limitations of traditional therapies, it is urgent to find and develop a repair material that can replace natural bones. Hence, we designed and prepared suitable MPEG-PCL microspheres loaded bone morphogenetic protein-2 (BMP-2/MPEG-PCL-MS) to effectively solve the problem mentioned above, prolong its reaction time at the targeted site, and avoid the pain of patients caused by frequent administration. The physicochemical properties and in vitro release behaviors were good. The microspheres showed high biocompatibility and strongly induced osteogenesis in vivo. BMP-2/MPEG-PCL-MS has been proven to exert sustained-release in vivo and maintain the inherent BMP-2 activity. They can be directly injected into the bone defect site, or implanted to a large bone defect site together with stent material to exert therapeutic effects. Hence, this smart drug delivery system has promising potential for clinical applications and provides a well-controlled design for combination of tissue engineering and pharmaceutics for further exploration.

Bone defects are a major threat to human health, and heterotopic bone provides advantages that other materials do not provide in the treatment of bone defects. MPEG-PCL microspheres loaded with bone morphogenetic protein-2 (BMP-2/MPEG-PCL-MS) are an emerging means of culturing heterotopic bone. However, the effect of such microspheres on the quality of heterotopic bone osteogenesis has rarely been studied. The performance of heterotopic bone as a bone repair material has also rarely been reported. To explore the effect of microspheres on heterotopic bone osteogenesis and to explore the performance of heterotopic bone in bone repair, we designed compression tests, nanoindentation tests, and a finite element (FE) simulation. The effects of microspheres on the quality of heterotopic bone osteogenesis and performance of heterotopic bone as a bone repair material were evaluated from the mechanical properties, material properties, and FE simulation. The results demonstrate that eight-week heterotopic bone using microspheres has suitable mechanical and material properties, performs well in bone repair FE simulation, and can meet the material requirements of bone repair. Hence, this heterotopic bone as bone repair material has promising potential for clinical applications, and provides a good strategy for combination between tissue engineering and pharmaceutical science.