Synthesis of Taxifolin-Loaded Polydopamine for Chemo-Photothermal-Synergistic Therapy of Ovarian Cancer.

Chemotherapy is a well-established method for treating cancer, but it has limited effectiveness due to its high dosage and harmful side effects. To address this issue, researchers have explored the use of photothermal agent nanoparticles as carriers for precise drug release in vivo. In this study, three different sizes of polydopamine nanoparticles (PDA-1, PDA-2, and PDA-3) were synthesized and evaluated. PDA-2 was selected for its optimal size, encapsulation rate, and drug loading rate. The release of the drug from PDA-2@TAX was tested at different pH and NIR laser irradiation levels. The results showed that PDA-2@TAX released more readily in an acidic environment and exhibited a high photothermal conversion efficiency when exposed to an 808 nm laser. In vitro experiments on ovarian cancer cells demonstrated that PDA-2@TAX effectively inhibited cell proliferation, highlighting its potential for synergistic chemotherapy-photothermal treatment.

Wearing individualized 3D printed oral stent to protect normal tissues in patients with nasopharyngeal carcinoma during radiotherapy.

PURPOSE: To demonstrate a new individualized 3D printed oral stent in radiotherapy of nasopharyngeal carcinoma (NPC) patients and carry out a comparative analysis combining with clinical case. MATERIAL AND METHODS: Thirty NPC patients treated in our institution from September 2021 to October 2022 were prospectively enrolled. An individualized 3D printed oral stent was designed for each patient, and one set of computed tomography (CT) slices were obtained with /without wearing the oral stent, respectively. After delineation of target volumes and organs at risk (OARs) on the two CT slices, we finished two treatment plans by using the same target objectives, critical constraints and plan setup for each patient. Finally, the dose distribution and other dosimetric parameters of target volumes and OARs between the two plans were compared. RESULTS: Tongue volume and tongue length outside of mouth was 10.4 ± 2.5 cm3 and 2.8 ± 0.6 cm, respectively, distance between dorsal surface of oral tongue and plate increased from 0.3 ± 0.3 cm to 2.2 ± 0.5 cm by wearing the oral stent. For the target volume, there was no significant difference. However, Dmax of tongue, tongue tip and periglottis decreased significantly from 6352.6 ± 259.9 cGy to 5994.9 ± 478.9 cGy, 3499.8 ± 250.6 cGy to 3357.7 ± 158.0 cGy and 6345.5 ± 171.0 cGy to 6133.4 ± 263.3 cGy, respectively (p = 0.000); Dmean of tongue, tongue tip and periglottis decreased significantly from 3714.7 ± 204.2 cGy to 3169.7 ± 200.9 cGy, 3060.8 ± 216.2 cGy to 2509.6 ± 196.7 cGy and 3853.3 ± 224.9 cGy to 3079.3 ± 222.0 cGy, respectively (p = 0.000). CONCLUSION: The individualized 3D printed oral stent can reduce the dose of oral tissues and organs, so as to reduce the oral adverse reactions and improve the compliance of patients and the quality of their life. The technique can be used in radiotherapy of NPC patients.

Multistage pH-responsive codelivery liposomal platform for synergistic cancer therapy.

BACKGROUND: Small interfering RNA (siRNA) is utilized as a potent agent for cancer therapy through regulating the expression of genes associated with tumors. While the widely application of siRNAs in cancer treatment is severely limited by their insufficient biological stability and its poor ability to penetrate cell membranes. Targeted delivery systems hold great promise to selectively deliver loaded drug to tumor site and reduce toxic side effect. However, the elevated tumor interstitial fluid pressure and efficient cytoplasmic release are still two significant obstacles to siRNA delivery. Co-delivery of chemotherapeutic drugs and siRNA represents a potential strategy which may achieve synergistic anticancer effect. Herein, we designed and synthesized a dual pH-responsive peptide (DPRP), which includes three units, a cell-penetrating domain (polyarginine), a polyanionic shielding domain (ehG)n, and an imine linkage between them. Based on the DPRP surface modification, we developed a pH-responsive liposomal system for co-delivering polo-like kinase-1 (PLK-1) specific siRNA and anticancer agent docetaxel (DTX), D-Lsi/DTX, to synergistically exhibit anti-tumor effect. RESULTS: In contrast to the results at the physiological pH (7.4), D-Lsi/DTX lead to the enhanced penetration into tumor spheroid, the facilitated cellular uptake, the promoted escape from endosomes/lysosomes, the improved distribution into cytoplasm, and the increased cellular apoptosis under mildly acidic condition (pH 6.5). Moreover, both in vitro and in vivo study indicated that D-Lsi/DTX had a therapeutic advantage over other control liposomes. We provided clear evidence that liposomal system co-delivering siPLK-1 and DTX could significantly downregulate expression of PLK-1 and inhibit tumor growth without detectable toxic side effect, compared with siPLK-1-loaded liposomes, DTX-loaded liposomes, and the combinatorial administration. CONCLUSION: These results demonstrate great potential of the combined chemo/gene therapy based on the multistage pH-responsive codelivery liposomal platform for synergistic tumor treatment.

[Co-delivery of Pirarubicin and Vinorelbine by Micelles for the Treatment of Breast Cancer].

OBJECTIVE: To develop a pirarubicin (THP) and vinorelbine (VRL) codelivery nano-micellar system (T+V-CS micelles) of pirarubicin (THP) and vinorelbine (VRL) by using chondroitin sulfate-cholesterol polymers (CS-Chol) and DSPE-mPEG 2000 and to evaluate the therapeutic efficacy of the codelivery nano-micelles in breast cancer treatment. METHODS: T+V-CS micelles were prepared by ultrasonic-dialysis method, and the physicochemical characterization were evaluated using multiple technological means. The anti-tumor efficacy of T+V-CS micelles in vitro was evaluated by MTT assay and cell cycle arrest analysis. Evaluation of the therapeutic effect of T+V-CS micelles in vivo was carried out on xenograft 4T1 murine breast cancer bearing BALB/c mice model. RESULTS: T+V-CS micelles displayed a nearly spherical shape when observed through transmission electron microscope. The particle size and polydispersity indexes (PDI) of T+V-CS micelles was (155.5±4.5) nm and 0.170±0.003 respectively, while the Zeta potential was (-23.0±0.9) mV. Meanwhile, T+V-CS micelles demonstrated high encapsulation efficiency of (81.87±2.56)% for THP and (87.54±2.82)% for VRL and a high overall drug loading efficiency of (10.20±1.20)%. In vitro and in vivo studies of the therapeutic efficacy of breast cancer showed that T+V-CS micelles had synergistic anti-tumor effect and induced increased G 2/M cell cycle arrest in 4T1 cells, which could significantly inhibit tumor growth and prolong survival compared with the therapeutic efficacy of micelles loaded with a single kind of drug or free drug solutions. CONCLUSION: The study showed that T+V-CS micelles had excellent anti-tumor effect, offering a reference to the clinical treatment of breast cancer.

Aqueous synthesis of PEGylated Ag2S quantum dots and their in vivo tumor targeting behavior.

With significantly decreased light scattering and tissue autofluorescence, fluorescence imaging in the second near infrared (NIR-II, 1000-1700 nm) region has been heavily explored in biomedical field recently. Silver sulfide quantum dots (Ag2S QDs) with unique optical properties were one of the most classic NIR-II imaging probes. However, the Ag2S QDs for in vivo purpose were mainly obtain by oil phase-based high-temperature route at present. Here, we proposed a mild aqueous route to prepare NIR-II emissive Ag2S QDs for in vivo tumor imaging. Original Ag2S QDs was obtained by mixing sodium sulfide and silver nitrate in a thiol-terminated polyethylene glycol (mPEG-SH) solution. Treating the original Ag2S QDs with extra mPEG-SH ligands produced highly PEGyalted Ag2S QDs. These re-PEGylated Ag2S QDs exhibited much better blood circulation and tumor accumulation in vivo comparing with the original ones, which can serve as excellent tumor imaging probes. The whole-body blood vessel imaging of living mice was achieved with high resolution, the bio-distribution of these QDs were studied by NIR-II imaging as well. This work also highlighted the importance of ligand density for tumor targeting.

Experimental Study on the Efficacy of Site-Specific PEGylated Human Serum Albumins in Resuscitation From Hemorrhagic Shock.

OBJECTIVES: To evaluate the resuscitative efficacy and the effect on reperfusion injury of two site-specific PEGylated human serum albumins modified with linear or branched PEG20kDa, compared with saline, 8% human serum albumin and 25% human serum albumin, in a hemorrhagic shock model. SETTING: Laboratory. SUBJECTS: Male Wistar rats. DESIGN: Prospective study. INTERVENTIONS: Rats were bled to hemorrhagic hypovolemic shock and resuscitated with different resuscitation fluids. MEASUREMENTS AND MAIN RESULTS: The mean arterial pressure and blood gas variables were measured. Hemorheology analysis was performed to evaluate the influence of resuscitation on RBCs and blood viscosity. The microvascular state was indirectly characterized in terms of monocyte chemotactic protein-1 and endothelial nitric oxide synthase that related to shear stress and vasodilation, respectively. The levels of inflammation-related factors and apoptosis-related proteins were used to evaluate the reperfusion injury in lungs. The results showed that PEGylated human serum albumin could improve the level of mean arterial pressure and blood gas variables more effectively at the end of resuscitation. poly(ethylene glycol) modification was able to increase the viscosity of human serum albumin to the level of effectively enhancing the expression of monocyte chemotactic protein-1 and endothelial nitric oxide synthase, which could promote microvascular perfusion. The hyperosmotic resuscitative agents including both 25% human serum albumin and PEGylated human serum albumins could greatly attenuate lung injury. No significant therapeutic advantages but some disadvantages were found for Y shaped poly(ethylene glycol) modification over linear poly(ethylene glycol) modification, such as causing the decrease of erythrocyte deformability. CONCLUSIONS: Linear high molecular weight site-specific PEGylated human serum albumin is recommended to be used as a hyperosmotic resuscitative agent.

Employment of Molecularly Imprinted Polymers to High-Throughput Screen nNOS-PSD-95 Interruptions: Structure and Dynamics Investigations on Monomer-Template Complexation.

Molecularly imprinted polymers (MIPs) are employed to screen nNOS-PSD-95 (neuronal nitric oxide synthase post-synaptic density protein-95) interruptions. 5-(3,5-Dichloro-2-hydroxybenzylamino)-2-hydroxybenzoic acid (ZL006; a potential drug candidate for the treatment of stroke, depression, and pain) is employed as a template. Four kinds of functional monomers (2-VP: 2-vinylpyridine; 4-VP: 4-vinylpyridine; MMA: methyl methacrylate; and MAAM: methacrylamide) are designed, and their complexation with ZL006 in various solvents (methanol, acetonitrile, toluene, chloroform) is investigated by molecular dynamics simulations and quantum mechanics calculations. Both 4-VP and MAAM have stronger interactions with ZL006 than those of 2-VP and MMA. The appropriate ratio of monomer to template is 3:1. Intermolecular hydrogen bonds play a dominant role in monomer-template complexation. Ideal solvents are toluene and chloroform, and the solvation effect on monomer-template complexation is revealed. Both molecular modeling and adsorption experiments demonstrate that as-synthesized ZL006-MIP with 4-VP as a monomer has better selectivity than that employing MAAM to screen for nNOS-PSD-95 interruptions.

Thiol click modification of cyclic disulfide containing biodegradable polyurethane urea elastomers.

Although the thiol click reaction is an attractive tool for postpolymerization modification of thiolmers, thiol groups are easily oxidized, limiting the potential for covalent immobilization of bioactive molecules. In this study, a series of biodegradable polyurethane elastomers incorporating stable cyclic disulfide groups was developed and characterized. These poly(ester urethane)urea (PEUU-SS) polymers were based on polycaprolactone diol (PCL), oxidized dl-dithiothreitol (O-DTT), lysine diisocyanate (LDI), or butyl diisocyanate (BDI), with chain extension by putrescine. The ratio of O-DTT:PCL was altered to investigate different levels of potential functionalization. PEG acrylate was employed to study the mechanism and availability of both bulk and surface click modification of PEUU-SS polymers. All synthesized PEUU-SS polymers were elastic with breaking strengths of 38-45 MPa, while the PEUU-SS(LDI) polymers were more amorphous, possessing lower moduli and relatively small permanent deformations versus PEUU-SS(BDI) polymers. Variable bulk click modification of PEUU-SS(LDI) polymers was achieved by controlling the amount of reduction reagent, and rapid reaction rates occurred using a one-pot, two-step process. Likewise, surface click reaction could be carried out quickly under mild, aqueous conditions. Furthermore, a maleimide-modified affinity peptide (TPS) was successfully clicked on the surface of an electrospun PEUU-SS(BDI) fibrous sheet, which improved endothelial progenitor cell adhesion versus corresponding unmodified films. The cyclic disulfide containing biodegradable polyurethanes described provide an option for cardiovascular and other soft tissue regenerative medicine applications where a temporary, elastic scaffold with designed biofunctionality from a relatively simple click chemistry approach is desired.

Application of polysaccharide-based crosslinking agents based on schiff base linkages for biomedical scaffolds.

Chemical crosslinking is a method widely used to enhance the mechanical strength of biopolymer-based scaffolds. Polysaccharides are natural and biodegradable carbohydrate polymers that can act as crosslinking agents to promote the formation of scaffolds. Compared to synthetic crosslinking agents, Polysaccharide-based crosslinking agents have better biocompatibility for cell adhesion and growth. Traditional Chinese medicine has special therapeutic effects on various diseases and is rich in various bioactive ingredients. Among them, polysaccharides have immune regulatory, antioxidant, and anti-inflammation effects, which allow them to not only act as crosslinking agents but endow the scaffold with greater bioactivity. This article focuses on the latest developments of polysaccharide-based crosslinking agents for biomedical scaffolds, including hyaluronic acid, chondroitin sulfate, dextran, alginate, cellulose, gum polysaccharides, and traditional Chinese medicine polysaccharides. Also, we provide a summary and prospects on the research of polysaccharide-based crosslinking agents.

Sodium alginate/polyvinyl alcohol nanofibers loaded with Shikonin for diabetic wound healing: In vivo and in vitro evaluation.

Diabetic wounds are typically chronic wounds and the healing process is limited by problems such as high blood glucose levels, bacterial infections, and other issues that make wound healing difficult. Designing drug-loaded wound dressings is an effective way to promote diabetic wound healing. In this study, we developed an SA/PVA nanofiber (SPS) containing Shikonin (SK) for the treatment of diabetic wounds. The prepared nanofibers were uniform in diameter, had good hydrophilicity and high water vapor permeability, and effectively promoted gas exchange between the wound site and the outside world. The results of in vitro experiments showed that SPS was effective in antimicrobial, antioxidant, and biocompatible. In vivo tests showed that the wound healing rate of mice treated with SPS reached 85.5 %. Immunohistochemical staining results showed that SPS was involved in the diabetic wound healing process through the up-regulation of growth factors (CD31, HIF-1α) and the down-regulation of inflammatory factors (CD68). Western blotting experiments showed that SPS attenuated the inflammation through the inhibition of the IκBα/NF-κB signaling pathway. These results suggest that SPS is a promising candidate for future clinical application of chronic wound dressings.

Chitosan-modified dihydromyricetin liposomes promote the repair of liver injury in mice suffering from diabetes mellitus.

Liver injury caused by type-II diabetes mellitus (DM) is a significant public-health concern worldwide. We used chitosan (CS) to modify dihydromyricetin (DHM)-loaded liposomes (DL) through charge interaction. The effect of CS-modified DL (CDL) on liver injury in mice suffering from DM was investigated in vivo and in vitro. CDL exhibited superior antioxidant capacity and stability. Pharmacokinetic analyses revealed a 3.23- and 1.92-fold increase in the drug concentration-time curve (953.60 ± 122.55 ng/mL/h) in the CDL-treated group as opposed to the DHM-treated group (295.15 ± 25.53 ng/mL/h) and DL-treated group (495.31 ± 65.21 ng/mL/h). The maximum drug concentration in blood (Tmax) of the CDL group saw a 2.26- and 1.21-fold increase compared with that in DHM and DL groups. We observed a 1.49- and 1.31-fold increase in the maximum drug concentration in blood (Cmax) in the CDL group compared with that in DHM and DL groups. Western blotting suggested that CDL could alleviate liver injury in mice suffering from DM by modulating inflammatory factors and the transforming growth factor-ß1/Smad2/Smad3 signaling pathway. In conclusion, modification of liposomes using CS is a viable approach to address the limitations of conventional liposomes and insoluble drugs.

Human apolipoprotein E peptides inhibit hepatitis C virus entry by blocking virus binding.

UNLABELLED: Hepatitis C virus (HCV) entry is a multiple-step process involving a number of host factors and hence represents a promising target for new antiviral drug development. In search of novel inhibitors of HCV infection, we found that a human apolipoprotein E (apoE) peptide, hEP, containing both a receptor binding fragment and a lipid binding fragment of apoE specifically blocked the entry of cell culture grown HCV (HCVcc) at submicromolar concentrations. hEP caused little cytotoxicity in vitro and remained active even if left 24 hours in cell culture. Interestingly, hEP inhibited neither human immunodeficiency virus (HIV)-HCV pseudotypes (HCVpp) nor HIV and Dengue virus (DENV) infection. Further characterization mapped the anti-HCV activity to a 32-residue region that harbors the receptor binding domain of apoE, but this fragment must contain a cysteine residue at the N-terminus to mediate dimer formation. The anti-HCV activity of the peptide appears to be dependent on both its length and sequence and correlates with its ability to bind lipids. Finally, we demonstrated that the apoE-derived peptides directly blocked the binding of both HCVcc and patient serum-derived virus to hepatoma cells as well as primary human hepatocytes. CONCLUSION: apoE peptides potently inhibit HCV infection and suggest a direct role of apoE in mediating HCV entry. Our findings also highlight the potential of developing apoE mimetic peptides as novel HCV entry inhibitors by targeting HCV-host interactions.

Extraction, purification and characterisation of chondroitin sulfate in Chinese sturgeon cartilage.

BACKGROUND: Chinese sturgeon (Acipenser sinensis), a rare species, is an important fishery resource in China. To save this species from overfishing, damming and pollution, artificial propagation has been developed rapidly in recent years. However, the cartilage from Chinese sturgeon, which contains an abundance of chondroitin sulfate (CS), is currently discarded as solid waste after consumption of the fish. The aim of this study was to investigate the extraction, purification and characterisation of CS from Chinese sturgeon cartilage. RESULTS: The optimal extraction parameters were a ratio of aqueous NaOH to cartilage powder of 9.2, a concentration of aqueous NaOH of 4.4% and an extraction time of 3.9 h. Under these optimal conditions the yield of crude CS from Chinese sturgeon cartilage was 26.51%, in agreement with the model prediction (26.54%). Purification by DEAE-52 cellulose and Sephadex G-100 column chromatography yielded a single fraction, CS-11. Its characterisation indicated that CS-11 was consistent with the polysaccharide backbone structure -4GlcAß-3GalNß- and was present in the form of chondroitin-4-sulfate and chondroitin-6-sulfate. CONCLUSION: The results of this study provide a basis for promoting the utilisation of Chinese sturgeon resources and are significant for the development and utilisation of CS from Chinese sturgeon cartilage in the food industry.

Energy metabolism response induced by microplastic for marine dinoflagellate Karenia mikimotoi.

Microplastic contaminations threaten the entire marine ecosystem and cause severe ecological stress. This study explored the energy metabolism change of Karenia mikimotoi under exposure to nanoplastics (NPs) and microplastics (MPs) (65 nm, 100 nm, and 1 µm polystyrene (PS), and 100 nm polymethyl methacrylate (PMMA)) at a concentration of 10 mg L-1. Membrane potential, esterase activity, polysaccharide content, and ATPase activity were detected to assess the energy metabolism of K. mikimotoi under MPs/NPs exposure. Transcriptome and metabolomic analyses were used to investigate the intrinsic mechanisms of energy metabolism changes. Smaller PS particles caused greater damage to the cell membrane potential, increased the polysaccharide content, and resulted in a heavier weakening of the ATPase enzymatic activity in K. mikimotoi cells, suggesting that smaller-sized PS had more influence on esterase activity and energy metabolism than the bigger-sized PS. The results evidenced that energy metabolism relates to the size and type of MPs/NPs, and nano-scale plastic particles could induce greater metabolic changes.

Do microplastics affect sulfamethoxazole sorption in soil? Experiments on polymers, ionic strength and fulvic acid.

Microplastics (MPs) and sulfamethoxazole (SMX) are emerging contaminants that are ubiquitous in the soil environment. In this study, we investigated MPs polymer type and soil environmental factor effects on SMX adsorption behavior in the soil system. Our results showed that MPs dosage affected the soil particles' SMX adsorption rate and capacity (Qe). Adding 1 % polystyrene (PS) increased the SMX adsorption rate significantly. The value of K1, which represented the adsorption rate, increased from 0.569 h-1 to 1.019 h-1. However, the addition of MPs reduced the soil's SMX equilibrium adsorption capacity slightly. Moreover, increasing salinity strength enhanced SMX adsorption capacity by MPs significantly. However, increasing calcium ions concentration decreased SMX adsorption in the MPs amended soil due to multivalent cationic bridging and competitive adsorption mechanisms. In addition, we observed that fulvic acid addition inhibited SMX adsorption. This study suggests that the addition of MPs reduced the adsorption of SMX in the soil slightly due to dilution effect. Meanwhile, changes in environmental factors also affected the adsorption behavior of SMX in soil amended with MPs.

Sodium alginate/poly(vinyl alcohol)/taxifolin nanofiber mat promoting diabetic wound healing by modulating the inflammatory response, angiogenesis, and skin flora.

Diabetes-related ulcers are still a therapeutic problem because of their susceptibility to infection, ongoing inflammation, and diminished vascularization. The design and development of novel dressings are clinically urgent for the treatment of chronic wounds due to diabetic ulcers. In this study, we made taxifolin (TAX) loaded sodium alginate (SA)/poly(vinyl alcohol) (PVA) nanofibers for the treatment of chronic wounds. The SA/PVA/TAX nanofibers that have been created are smooth and bead-free, with good thermal stability, hydrophilicity, and mechanical properties. The release profile indicated a sustained drug release, with a cumulative release rate of 64.6 ± 3.7 % at 24 h. In vitro experiments have shown that SA/PVA/TAX has good antibacterial activity, antioxidant activity, and biocompatibility. In vivo experiments have shown that SA/PVA/TAX exhibits desirable biochemical properties and is involved in the diabetic wound healing process by promoting cell proliferation (Ki67), angiogenesis (CD31, VEGFA), and alleviating inflammation (CD68). Western blotting experiments suggest that SA/PVA/TAX may promote diabetic wound healing by inhibiting the TLR4/NF-κB/NLRP3 signaling pathway and upregulating the expression of VEGFA and PDGFA. The 16S rRNA sequencing results showed that SA/PVA/TAX increased the wound surface flora's diversity and reversed the skin microbiota's structural imbalance. Therefore, SA/PVA/TAX can promote diabetic wound healing by modulating the inflammatory response, angiogenesis, and skin flora and has the potential to be an excellent wound dressing.

Mechanical properties, biosafety, and shearing bonding strength of glass fiber-reinforced PEEK composites used as post-core materials.

OBJECTIVE: To investigate the mechanical properties, biosafety, and shearing bonding strength of glass fibers-reinforced polyether-ether-ketone (PEEK-GF) for post-core materials. METHODS: PEEK-GF composites with different glass fiber contents were prepared by extrusion injection and named PEEK-GF30, PEEK-GF40, and PEEK-GF50. Mechanical properties including flexural modulus, flexural strength, Vickers hardness, and compression strength were tested. The cross-sectional morphology was examined using scanning electron microscopy (SEM). Cytotoxicity was studied in vitro with Cell-counting kit-8 (CCK-8). Cell morphology was observed under a microscope. Cell growth on the composites' surfaces was analyzed with DAPI staining. The shearing bonding strength (SBS) of PEEK-GF50 was assessed after applying different pretreatments. Failure modes were evaluated by microscopy. SEM and contact-angle measurements were performed on the surfaces. Statistical analysis was conducted using one-way ANOVA (P < 0.05). RESULTS: The mechanical properties of PEEK-GF composites improved with increased GF content. The PEEK-GF50 group exhibited flexural modulus (17.4 ± 0.5 GPa) close to that of dentin (18.6 GPa) and showed the highest flexural strength (350.0 ± 2.9 MPa), Vickers hardness (47.6 ± 4.5 HV), and compressive strength (264.0 ± 18.0 MPa). The SEM analysis demonstrated that the PEEK matrix combined well with glass fibers. The CCK-8 results confirmed the biosafety of all groups. DAPI staining indicated that cells were growing well on the composites' surface. The sample that was pretreated with sandblasting and plasma showed the highest SBS (16.0 ± 1.7 MPa). SIGNIFICANCE: The PEEK-GF composites demonstrated excellent mechanical properties, biosafety, and SBS, and have great potential to serve as post-core materials.

Antimicrobial peptide temporin derivatives inhibit biofilm formation and virulence factor expression of Streptococcus mutans.

Introduction: Temporin-GHa obtained from the frog Hylarana guentheri showed bactericidal efficacy against Streptococcus mutans. To enhance its antibacterial activity, the derived peptides GHaR and GHa11R were designed, and their antibacterial performance, antibiofilm efficacy and potential in the inhibition of dental caries were evaluated. Methods: Bacterial survival assay, fluorescent staining assay and transmission electron microscopy observation were applied to explore how the peptides inhibited and killed S. mutans. The antibiofilm efficacy was assayed by examining exopolysaccharide (EPS) and lactic acid production, bacterial adhesion and cell surface hydrophobicity. The gene expression level of virulence factors of S. mutans was detected by qRT-PCR. Finally, the impact of the peptides on the caries induced ability of S. mutans was measured using a rat caries model. Results: It has been shown that the peptides inhibited biofilm rapid accumulation by weakening the initial adhesion of S. mutans and reducing the production of EPS. Meanwhile, they also decreased bacterial acidogenicity and aciduricity, and ultimately prevented caries development in vivo. Conclusion: GHaR and GHa11R might be promising candidates for controlling S. mutans infections.

Site-specific chemical modification of human serum albumin with polyethylene glycol prolongs half-life and improves intravascular retention in mice.

Human serum albumin (HSA) is used as an important plasma volume expander in clinical practice. However, the infused HSA may extravasate into the interstitial space and induce peripheral edema in treating the critical illness related to marked increase in capillary permeability. Such poor intravascular retention also demands a frequent administration of HSA. We hypothesize that increasing the molecular weight of HSA by PEGylation may be a potential approach to decrease capillary permeability of HSA. In the present study, HSA was PEGylated in a site-specific manner and the PEGylated HSA carrying one chain of polyethylene glycol (PEG) (20 kDa) per HSA molecule was obtained. The purity, PEGylated site and secondary structure of the modified protein were characterized by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), thiol group blockage method and circular dichroism (CD) measurement, respectively. In addition, the pharmacokinetics in normal mice was investigated, vascular permeability of the PEGylated HSA was evaluated in lipopolysaccharide (LPS)-induced lung injury mouse model and the pharmacodynamics was investigated in LPS-induced sepsis model with systemic capillary leakage. The results showed that the biological half-life of the modified HSA was approximately 2.3 times of that of the native HSA, PEG-HSA had a lower vascular permeability and better recovery in blood pressure and haemodilution was observed in rats treated with PEG-HSA. From the results it can be inferred that the chemically well-defined and molecularly homogeneous PEGylated HSA is superior to HSA in treating capillary permeability increase related illness because of its longer biological half-life and lower vascular permeability.

A Hierarchical Ensemble Deep Learning Activity Recognition Approach with Wearable Sensors Based on Focal Loss.

Abnormal activity in daily life is a relatively common symptom of chronic diseases, such as dementia. There will probably be a variety of repetitive activities in dementia patients' daily life, such as repeated handling of objects and repeated packing of clothes. It is particularly important to recognize the daily activities of the elderly, which can be further used to predict and monitor chronic diseases. In this paper, we propose a hierarchical ensemble deep learning activity recognition approach with wearable sensors based on focal loss. Seven basic everyday life activities including cooking, keyboarding, reading, brushing teeth, washing one's face, washing dishes and writing are considered in order to show its performance. Based on hold-out cross-validation results on a dataset collected from elderly volunteers, the average accuracy, precision, recall and F1-score of our approach are 98.69%, 98.05%, 98.01% and 97.99%, respectively, in identifying the activities of daily life for the elderly.