Solvent-Free Templated Synthesis of Core-Crosslinked Star-Shaped Polymers in Supramolecular Body-Centered Cubic Phase.

This study reports the exploration of a solvent-free supramolecular templated synthesis strategy toward highly core-cross-linked star-shaped polymers (CSPs). To achieve this, a kind of cross-linkable giant surfactant, based on a functionalized polyhedral oligomeric silsesquioxanes (POSS) head tethered with a diblock copolymer tail containing reactive benzocyclobutene groups, is designed and prepared. By varying the volume fraction of linear block copolymer tail, these giant surfactants can self-assemble into a body-centered cubic (BCC) structure in bulk, in which the supramolecular spheres are composed of a core of POSS cages, a middle shell of crosslinkable poly(4-vinylbenzocyclobutene) (PBCB) blocks, and a corona of inert polystyrene (PS) blocks. The solvent-free thermally induced cross-linking reaction of the benzocyclobutene groups can be finished in 5 min upon heating, resulting in well-defined polymeric spheres with over 90 linear chains surrounding the cross-linked cores. The outer PS blocks serve as the protection corona to ensure that cross-linking of giant surfactants occurs in each supramolecular spherical domain. Given the modular design and diversity of the POSS-based giant surfactants, it is believed that the strategy may enable access to a wide range of CSPs.

Immunomodulatory effects of platelets on the severity of hand, foot, and mouth disease infected with enterovirus 71.

BACKGROUND: Enterovirus 71 (EV71) infection contributes to hand, foot, and mouth disease (HFMD) with severe neurogenic complications, leading to higher morbidity. In addition to their typical roles in coagulation, platelets could serve as essential immune regulatory cells to play a key role in the pathogenesis of this viral infection. METHODS: Platelet parameters were measured using an automatic hematology analyzer. T-helper type 1 (Th1) and Th2 cells were analyzed by flow cytometry. The levels of cytokines and key transcription factors were determined. RESULTS: The levels of platelet count and plateletcrit were positively associated with the severity of HFMD. Th1 and Th2 cells as well as their corresponding cytokines were increased in the severe group compared to the healthy volunteers. Moreover, the levels of platelets were negatively correlated with the level of interferon-γ (IFN-γ), but positively correlated with the frequency of Th1 cells. Coculture of platelets and naive CD4+ T cells showed that platelets from mild patients promote Th1 cell differentiation and IFN-γ secretion. CONCLUSIONS: Our study has shown for the first time that the distinct roles of platelets are responsible for the regulation of pathogenic CD4+ T cell differentiation and function in the pathogenesis of HFMD caused by EV71. IMPACT: Our study has shown for the first time that the distinct roles of platelets are responsible for the regulation of pathogenic CD4+ T cell differentiation and function in the pathogenesis of HFMD caused by EV71. For the first time, we have discovered the role of platelets in children's HFMD caused by EV71 infection, which may provide a better treatment for HFMD in the future. This article describes new discoveries in platelet immunity.

Tumor-Targeted Delivery of Bufalin-Loaded Modified Albumin-Polymer Hybrid for Enhanced Antitumor Therapy and Attenuated Hemolysis Toxicity and Cardiotoxicity.

A novel albumin polymer hybrid with a core-shell structure was designed to target delivery of bufalin, which is an antineoplastic monomer with serious cardiotoxicity. The sheath layer was composed of ursodeoxycholic acid (UA)-modified bovine serum albumin (UA-BSA), while the stable core consisted of poly n-butyl cyanoacrylate (PBCA) nanoparticles. The UA-BSA was synthetized, and the substitution degree was characterized. The physical properties of bufalin-loaded UA-modified protein-PBCA nanocomplexes (BF-uPPNCs), such as morphology, particle size, and encapsulation efficiency, were evaluated. FTIR and DSC revealed the bufalin to be in an amorphous state. Furthermore, the in vitro release study indicated a sustained release profile of BF-uPPNCs. The MTT and cellular uptake study demonstrated that BF-uPPNCs significantly improved the inhibitory effect of the bufalin accompanied with an enhanced cell uptake capacity on HepG2 cells. In addition, in vivo research demonstrated that BF-uPPNCs had a better antitumor effect coupled with improved therapeutic effect, and reduced hemolysis, vascular irritation, and cardiotoxicity. This work therefore presented a novel albumin polymer hybrid with favorable stability, efficient tumor-targeted delivery potential, and side effect reduction ability, which can be a potential vehicle for an anticancer drug.

Prediction of solvent-induced morphological changes of polyelectrolyte diblock copolymer micelles.

Self-assembly processes of polyelectrolyte block copolymers are ubiquitous in industrial and biological processes; understanding their physical properties can also provide insights into the design of polyelectrolyte materials with novel and tailored properties. Here, we report systematic analysis on how the ionic strength of the solvent and the length of the polyelectrolyte block affect the self-assembly and morphology of the polyelectrolyte block copolymer materials by constructing a salt-dependent morphological phase diagram using an implicit solvent ionic strength (ISIS) method for dissipative particle dynamics (DPD) simulations. This diagram permits the determination of the conditions for the morphological transition into a specific shape, namely vesicles or lamellar aggregates, wormlike/cylindrical micelles, and spherical micelles. The scaling behavior for the size of spherical micelles is predicted, in terms of radius of gyration (R(g,m)) and thickness of corona (Hcorona), as a function of solvent ionic strength (c(s)) and polyelectrolyte length (NA), which are R(g,m) ∼ c(s)(-0.06)N(A)(0.54) and Hcorona ∼ c(s)(-0.11)N(A)(0.75). The simulation results were corroborated through AFM and static light scattering measurements on the example of the self-assembly of monodisperse, single-stranded DNA block-copolynucleotides (polyT50-b-F-dUTP). Overall, we were able to predict the salt-responsive morphology of polyelectrolyte materials in aqueous solution and show that a spherical-cylindrical-lamellar change in morphology can be obtained through an increase in solvent ionic strength or a decrease of polyelectrolyte length.

"Smart" DNA interfaces.

This review focuses on surface-grafted DNA, and its use as a molecular building block that exploits its unique properties as a directional (poly)anion that exhibits molecular recognition. The selected examples highlight innovative applications of DNA at surfaces and interfaces ranging from molecular diagnostics and sequencing to biosensing.

Differences in facial profile and dental esthetic perceptions between young adults and orthodontists.

INTRODUCTION: The principal aim of this study was to investigate differences in perception of soft-tissue facial profiles and dental esthetics between young Chinese adults and orthodontists. METHODS: Eight hundred ninety-two subjects (444 male, 448 female), ages 16 to 24 years, chose 1 image from among 5 profile silhouettes and from among 10 ranked color photographs of the aesthetic component (AC) of the index of orthodontic treatment need that most closely resembled their own profile and dental esthetic appearance, respectively. A panel of 20 orthodontists then independently repeated the same image selection process. Each subject also completed the Eysenck personality questionnaire for psychoticism. We used the Mann-Whitney U test and the Spearman rank correlation test, with statistical significance set at α = 0.05. RESULTS: Only 37.0% of subjects had straight profiles by objective orthodontic assessment, but 85.0% chose straight profiles by subjective self-perception. About 17.5%, mainly females, chose the mild convex as the ideal profile. Only 2.5% of the subjects were ranked 1 on the AC by orthodontists, but 43.6% chose 1, or ideal, by self-perception. Male subjects scored significantly higher than did female subjects for self-perceived facial profiles (more protruded chins) and for the AC (more attractive dental appearance). Subjects with high psychoticism T scores (>50) scored significantly lower for self-perceived facial profiles (more retruded chins) and on the AC (less attractive dental appearance). CONCLUSIONS: Young Chinese adults perceived their facial profiles and dental appearances to be significantly more straight and attractive, respectively, than did the orthodontists. A significant proportion of the young adults, mainly women, preferred a mild convex facial profile. High psychoticism scores might significantly affect the self-perception of orthodontic treatment needs.

High transparency, degradable and UV-protective poly(lactic acid) composites based on elongational rheology and chain extender assisted melt blending.

Conventional polylactic acid (PLA) melt plasticization and toughening processes are typically achieved at the expense of PLA strength and transparency, which is clearly detrimental to its application in areas such as smart home and food packaging. Herein, an ultraviolet (UV)-protective PLA-based composite (PP6) that simultaneously achieves high strength (63.3 MPa), high plasticity (125.3 %), and enhanced toughness (4.3 kJ/m2) by adding only 6 wt% poly(3-hydroxybutyrate-4-hydroxybutyrate) (P34HB) under the assist of 1 wt% chain extender was prepared using melt blending technique. Benefiting from the cross-linking effect of the chain extender and the elongational flow during processing, the compatibility between P34HB and PLA, as well as the thermomechanical properties, heat resistance, and biodegradable properties of the composite, have been enhanced significantly. The extremely low melt enthalpy (1.9 J/g) and the low crystallinity PLA phase contribute to an appropriate transparency (78.3 % of glass in 400-1100 nm). The prepared composites display mid- and long-wave UV-protective performance, which is superior to conventional industrial glasses. Through the superior elongational rheology technology, PP6 maintains favorable overall properties even after six thermomechanical cycles. Collectively, the composite fabricated in this work is an attractive candidate for future applications such as smart windows, food packaging, agricultural films, and biomedical applications.

Development of a hydroxypropyl methyl cellulose/polyacrylic acid interpolymer complex formulated buccal mucosa adhesive film to facilitate the delivery of insulin for diabetes treatment.

Buccal mucosa administration is a promising method for insulin (INS) delivery with good compliance. However, buccal mucosa delivery systems still face challenges of long-term mucosal adhesion, sustained drug release, and mucosal drug penetration. To address these issues, a double-layer film consisting of a hydroxypropyl methylcellulose/polyacrylic acid interpolymer complex (IPC)-formulated mucoadhesive layer and an ethylcellulose (EC)-formulated waterproof backing layer (IPC/EC film) was designed. Protamine (PTM) and INS were co-loaded in the mucoadhesive layer of the IPC/EC film (PTM-INS-IPC/EC film). In ex vivo studies with porcine buccal mucosa, this film exhibited robust adhesion, with an adhesion force of 120.2 ±â€¯20.3 N/m2 and an adhesion duration of 491 ±â€¯45 min. PTM has been shown to facilitate INS mucosal transfer. Pharmacokinetic studies indicated that the PTM-INS-IPC/EC film significantly improved the absorption of INS, exhibiting a 1.45 and 2.24-fold increase in the area under the concentration-time curve (AUC0-∞) compared to the INS-IPC/EC film and free INS, respectively. Moreover, the PTM-INS-IPC/EC film effectively stabilized the blood glucose levels of type 1 diabetes mellitus (T1DM) rats with post oral glucose administration, maintaining lower glucose levels for approximately 8 h. Hence, the PTM-INS-IPC/EC film provides a promising noninvasive INS delivery system for diabetes treatment.

Starch/polyvinyl alcohol blended materials used as solid carbon source for tertiary denitrification of secondary effluent.

Starch/polyvinyl alcohol (PVA) blended materials for using as a solid carbon source (SCS) were prepared by blending PVA and gelatinized starch in an aqueous solution system, in which PVA served as framework material and starch as carbon source. The optimization of starch content and temperature effects were investigated. It was indicated that higher denitrification efficiency could be achieved with more starch in the materials. The average specific denitrification rates were 0.93, 0.66, 0.37 and 0.36 mg/(g x day) corresponding to starch content of 70%, 60%, 40% and 30% respectively at 37 degrees C. The denitrification rates increased when operating temperature was raised from 23 degrees C to 30 degrees C and then 37 degrees C. The mechanism of carbon release was analyzed incorporating the experimental results of abiotic release in deionized water. The organic carbon was mainly hydrolyzed by microbes, and the biological release efficiencies were at the range of 89.2% to 96.0%. A long-term experiment with a continuous flow reactor with SCS material containing 70% starch was conducted to gain some experience for practical application. When the influent nitrate concentration was in the range of 35.2 to 39.1 mg/L, hydraulic retention time of 4 hr, and operating temperature of 30 degrees C, a nitrogen removal efficiency up to 94.6% and denitrification rate of 0.217 kg/(m3 x day) was achieved. The starch-based materials developed in this study can be used as a solid carbon source for tertiary nitrogen removal from secondary effluent.

[Experimental study on application recombinant human bone morphogenetic protein 2(rhBMP-2)/poly-lactide-co-glycolic acid (PLGA)/fibrin sealant(FS) on repair of rabbit radial bone defect].

This paper is aimed to investigate the repair of rabbit radial bone defect by the recombinant human bone morphogenetic protein 2/poly-lactideco-glycolic acid microsphere with fibrin sealant (rhBMP-2/PLGA/FS). The radial bone defect models were prepared using New Zealand white rabbits, which were randomly divided into 3 groups, experiment group which were injected with eMP-2/PLGA/FS at bone defect location, control group which were injected with FS at bone defect location, and blank control group without treatment. The ability of repairing bone defect was evaluated with X-ray radiograph. Bone mineral density in the defect regions was analysed using the level of ossification. The osteogenetic ability of repairing bone defect, the degradation of the material, the morphologic change and the bone formation were assessed by HE staining and Masson staining. The result showed that rhBMP-2/PLGA/FS had overwhelming superiority in the osteogenetic ability and quality of bone defect over the control group, and it could promote the repair of bone defect and could especially repair the radial bone defect of rabbit well. It may be a promising and efficient synthetic bone graft.

Regeneration and utilization of graphite from the spent lithium-ion batteries by modified low-temperature sulfuric acid roasting.

Recycling spent graphite in spent lithium-ion batteries (LIBs) is crucial for lacking high-quality graphite and environmental protection. Here, an environmentally friendly and economical modified method based on sulfate roasting was proposed to recycle spent graphite via low temperature roasting at 250 °C with sodium fluoride as an assistant additive. Recycling leads to graphite with a high purity of 99.55 % and chemical structures for energy storage. Batteries manufactured in regenerated graphite deliver a high initial charge capacity of 333.9 mAh/g with an initial columbic efficiency of 85.71% and excellent capacity retention of 91.2% after 400 cycles. In addition, the waste produced in the method could be well treated, and by-products 177 g of sodium sulfate would be collected per 1 kg spent graphite and NaF, equivalent to 78.95% of the added amount obtained through wastewater and exhaust gas, respectively. The regenerated sodium fluoride will be re-applied to the recovery spent graphite. The loop-closed method shows great promise for the industrial-scale recycling of spent graphite for energy storage applications.

Dual-modified albumin-polymer nanocomplexes with enhanced in vivo stability for hepatocellular carcinoma therapy.

Etoposide (ETO) is a semi-synthetic derivative of podophyllotoxin with a definite antitumour effect, but its use is hampered by poor solubility and numerous side-effects. In this work, we developed a hyaluronic acid and ethylenediamine dual-modified albumin-polymer nanocomplex for tumour targeted delivery of ETO. The ETO loaded dual-modified albumin-polymer nanocomplexes (E-HEAP NCs) was composed of a hyaluronic acid decorated cationic albumin shell and a stable poly (butyl cyanoacrylate) core. E-HEAP NCs exhibited a high encapsulation efficiency, great stability in vivo. Furthermore, blank HEAP NCs carrier showed excellent biocompatibility in vitro cell cytotoxicity assay. While, E-HEAP NCs represented superior inhibitory effect on HepG2 cells than free ETO. Additionally, E-HEAP NCs exhibited an excellent tumour-targeting effect, due to the enhanced targeting efficacy of hyaluronic acid and albumin-mediated transcytosis. Moreover, E-HEAP NCs displayed an enhanced antitumour effect and extended the survival period in tumour bearing mice. In summary, the developed novel protein-polymer nanocomplex can potentially serve as a drug delivery system for improved cancer therapy.

Regulation of RDN on Th1/ILC1 cell imbalance in HFMD patients caused by EV71 infection.

Enterovirus 71 (EV71) infection is more likely to cause hand, foot and mouth disease (HFMD) in children, which can lead to neurogenic complications and higher mortality. As a commonly used clinical medicine, Reduning injection (RDN) helps to shorten the symptoms of patients with HFMD and facilitate the early recovery of children. However, the regulatory mechanism of RDN on the HFMD immune system disorder caused by EV71 remains to be discussed. This study collected detailed treatment data of 56 children with HFMD who entered the affiliated Children's Hospital of Nanjing Medical University during 2019. Retrospective analysis of clinical data showed that the symptoms of the RDN treatment group were improved compared with the untreated group. To explore its mechanism, the relevant detection indicators were detected by flow cytometry, enzyme-linked immunosorbent assay and real-time quantitative PCR. It was found that the number and function of innate immune (ILCs) and adaptive immunity (Th1, Th2 and secreted cytokines) were reduced, suggesting that RDN plays a role by regulating cellular immunity. The in vitro differentiation inhibition test further confirmed that RDN affected Th1 differentiation by inhibiting the expression of transcription factors on the basis of Th1 cell differentiation in vitro.

Construction and clinical significance of normal uterine arterial vascular network models.

AIMS: To construct in vitro models of normal uterine arterial vascular network through vascular corrosion casting and explore their characteristics and clinical significances. METHODS: Three sets of uterus, vagina and bilateral adnexa were perfused and cast via uterine artery and ovarian artery, using 25, 20 and 15% chlorinated poly vinyl chloride, respectively, and constructed into models one, two and three of the uterine arterial network correspondingly, followed by observing their characteristics. RESULTS: There existed important similarities and differences among the three models in displaying uterine arterial network: in model one, the uterine arterial trunk, its branches and partial spiral arteries were sharply demonstrated except the tiny ones; model two further displayed the communicating branches between bilateral spiral arteries, the arterial vascular network of ovarian artery and the anastomoses between the arterial blood supply of uterus and ovaries; model three presented the tiny branches, especially the obvious communicating branches, the complete arterial vascular network of ovary and fallopian tube and anastomoses between them. CONCLUSIONS: A panorama of the uterine arterial vascular network is obtained under organic combination of the three models, which is surely promising for clinical teaching, selections of different approaches and interventional therapy in obstetrics and gynecology.

Artemisinin Loaded mPEG-PCL Nanoparticle Based Photosensitive Gelatin Methacrylate Hydrogels for the Treatment of Gentamicin Induced Hearing Loss.

OBJECTIVE: Artemisinin (ART) is a natural anti-malarial sesquiterpene lactone which has the ability to treat and activate the CLRN1 pathway to play a pivotal role in hearing loss and hair cell function. To investigate the therapeutic effect of ART in hearing loss induced by gentamicin (GM), an ART-loaded poly(ethylene glycol)-b-poly(ε-caprolactone) mPEG-PCL nanoparticle-based photosensitive hydrogel was developed and tested in this study. MATERIALS AND METHODS: Artemisinin-loaded mPEG-PCL nanoparticles (mPEG-PCL-ART-NPs) were prepared by a double emulsion method and the formulation was optimized by an orthogonal experimental design. The particle size, zeta potential, morphology and in vitro dissolution of the mPEG-PCL-ART-NPs were well characterized. Biocompatibility of the mPEG-PCL-ART-NPs were tested on HeLa cells with an MTT assay. The photo-crosslinkable biodegradable gelatin methacrylate (GelMA) hydrogel was prepared and its physicochemical properties (such as substitution, photocrosslinking efficiency, cell viability morphology, mechanical and swelling properties) were evaluated. Finally, mPEG-PCL-ART-FITC-NPs, loaded mPEG-PCL-ART-NPs, and loaded mPEG-PCL-ART-NPs-GelMA hydrogels were fabricated and a GM toxicity-induced guinea pig ear damage model was established to determine the effectiveness of the materials on returning auditory function and cochlea pathomorphology. RESULTS: The zeta potential of the mPEG-PCL-ART-NPs was about -38.64 ± 0.21 mV and the average size was 167.51 ± 1.87 nm with an encapsulation efficacy of 81.7 ± 1.46%. In vitro release studies showed that the mPEG-PCL-ART-NPs possessed a sustained-release effect and the MTT experiments showed good biocompatibility properties of the drug-loaded nanoparticles. The results indicated that the 5% GelMA with MA-4% hydrogel had a better crosslinking density and 3D structure for drug loading and drug delivery than controls. Skin penetration results showed that the mPEG-PCL-ART-NPs increased adhesive capacity and avoided fast diffusion in the skin. Most importantly, auditory brainstem response results indicated that the mPEG-PCL-ART-NPs-GelMA hydrogel alleviated hearing loss induced by GM. CONCLUSION: These results suggested that the presently fabricated mPEG-PCL-ART-NPs-GelMA hydrogels are promising formulations for the treatment of hearing loss induced by GM and lay the foundation for further clinical research of inner ear induction therapy.

Abnormalities of ILC1 in children with hand, foot and mouth disease during enterovirus 71 infection.

Children with HFMD due to EV71 infection are more likely to suffer from neurogenic complications, leading to higher morbidity and mortality. ILCs play crucial roles in the initiation of host immunity. However, the contribution of ILCs to the occurrence and development of HFMD due to EV71 infection remains to be explored. The results of our study showed that the levels of peripheral ILC1s and Th1 cells were increased in children with severe HFMD compared to healthy children, as were ILC1- and Th1-related cytokines and transcription factors. Furthermore, HFMD children with a higher frequency of circulating ILC1s exhibited a 2.9-fold greater risk of severity when HFMD was accompanied by VEM. Our study is the first to show that ILC1 abnormalities contribute to the pathogenesis of the severity of HFMD, in which ILC1s are aberrant increased and affect the cellular and humoral immunity. ILC1s could be used in the diagnosis of HFMD.