Facile Preparation of ß-Cyclodextrin-Modified Polysulfone Membrane for Low-Density Lipoprotein Adsorption via Dopamine Self-Assembly and Schiff Base Reaction.

A facile method for the immobilization of ß-cyclodextrin on polysulfone membranes with the aim of selectively adsorbing low-density lipoprotein (LDL) was established, which is based on the self-assembly of dopamine on the membrane followed by the Schiff base reaction with mono-(6-ethanediamine-6-deoxy)-ß-cyclodextrin. The surface modification processes were validated using X-ray photoelectron spectroscopy and attenuated total reflectance Fourier-transform infrared spectroscopy. Surface wettability and surface charge of the membranes were investigated through the water contact angle and zeta potential analysis. The cyclodextrin-modified polysulfone membrane (PSF-CD) showed good resistance to protein solutions, as shown by the measurement of BSA adsorption. The assessment of BSA adsorption revealed that the cyclodextrin-modified polysulfone membrane (PSF-CD) exhibited excellent resistance to protein solutions. To investigate the adsorption and desorption behaviors of the membranes in single-protein or binary-protein solutions, an enzyme-linked immunosorbent assay was employed. The results revealed that the PSF-CD possessed remarkable adsorption capacity and higher affinity for LDL in both single-protein and binary-protein solutions, rendering it a suitable material for LDL apheresis.

Feasibility of Exploiting Physiological and Motion Features for Camera-based Sleep Staging: A Clinical Study.

Camera-based sleep monitoring is an emergent research topic in sleep medicine. The feasibility of using both the physiological features and motion features measured by a video camera for sleep staging was not thoroughly investigated. In this paper, we built a camera-based non-contact sleep monitoring setup in the Institute of Respiratory Diseases, Shenzhen People's Hospital, and created a clinical sleep dataset (nocturnal video data of 11 adults) including the expert-corrected PSG references synchronized with the video. The camera-based measurements have shown high correlations with the PSG. It obtains an overall Mean Absolute Error (MAE) of 1.5 bpm for heart-rate (HR), 0.7 bpm for breathing-rate (BR), 13.9 ms for heart-rate variability (HRV), and an accuracy of 93.5% for leg motion detection. The statistical analysis indicates that the averaged HR and variations of BR are distinct features for annotating four sleep stages (awake, REM, light sleep, and deep sleep). HRV parameter (SDNN) can clearly differentiate rapid-eye-movement (REM) and non-REM, while the leg movement is a distinctive feature for separating awake and sleep. The clinical trial demonstrated the feasibility of using physiological and motion features measured by a camera for joint sleep staging, and provides insights for sleep-related feature selection.

Fabrication and Study of Dextran/Sulfonated Polysulfone Blend Membranes for Low-Density Lipoprotein Adsorption.

The abnormal increase in low-density lipoprotein (LDL) in human blood is a main independent risk factor for the pathogenesis of atherosclerosis, whereas a reduced LDL level effectively lowers morbidity. It is important to develop LDL adsorption materials with high efficiency and selectivity, as well as to simplify their fabrication processes. In this paper, polysulfone (PSF), sulfonated polysulfone (SPSF), and sulfonated polysulfone/dextran (SPSF/GLU) membranes were successfully fabricated for LDL adsorption using a solution casting technique. Attenuated total reflectance Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy measurements confirmed the success of the preparation. The water contact angle decreased from 89.7 ± 3.4° (PSF) to 76.4 ± 3.2° (SPSF) and to 71.2 ± 1.9° (SPSF/GLU), respectively. BSA adsorption testing showed that the SPSF/GLU with surface enrichment of sulfonate groups and glycosyl groups possessed higher resistance to protein solution. The adsorption and desorption behaviors of the studied samples in single-protein or binary-protein solutions were systematically investigated by enzyme-linked immunosorbent assay (ELISA), The results showed that SPSF/GLU, which had excellent resistance to protein adsorption, possessed a similar adsorption capacity to that of PSF. SPSF membrane exhibited excellent selective affinity for LDL in single and binary protein solutions, suggesting potential applications in LDL removal.

Binary Promoter Improving the Moderate-Temperature Adhesion of Addition-Cured Liquid Silicone Rubber for Thermally Conductive Potting.

The strong adhesion of thermally conductive silicone encapsulants on highly integrated electronic devices can avoid external damages and lead to an improved long-term reliability, which is critical for their commercial application. However, due to their low surface energy and chemical reactivity, the self-adhesive ability of silicone encapsulants to substrates need to be explored further. Here, we developed epoxy and alkoxy groups-bifunctionalized tetramethylcyclotetrasiloxane (D4H-MSEP) and boron-modified polydimethylsiloxane (PDMS-B), which were synthesized and utilized as synergistic adhesion promoters to provide two-component addition-cured liquid silicone rubber (LSR) with a good self-adhesion ability for applications in electronic packaging at moderate temperatures. The chemical structures of D4H-MSEP and PDMS-B were characterized by Fourier transform infrared spectroscopy. The mass percentage of PDMS-B to D4H-MSEP, the adhesion promoters content and the curing temperature on the adhesion strength of LSR towards substrates were systematically investigated. In detail, the LSR with 2.0 wt% D4H-MSEP and 0.6 wt% PDMS-B exhibited a lap-shear strength of 1.12 MPa towards Al plates when curing at 80 °C, and the cohesive failure was also observed. The LSR presented a thermal conductivity of 1.59 W m-1 K-1 and good fluidity, which provided a sufficient heat dissipation ability and fluidity for potting applications with 85.7 wt% loading of spherical α-Al2O3. Importantly, 85 °C and 85% relative humidity durability testing demonstrated LSR with a good encapsulation capacity in long-term processes. This strategy endows LSR with a good self-adhesive ability at moderate temperatures, making it a promising material requiring long-term reliability in the encapsulation of temperature-sensitive electronic devices.

Promoters for Improved Adhesion Strength between Addition-Cured Liquid Silicone Rubber and Low-Melting-Point Thermoplastic Polyurethanes.

A polydimethylsiloxane armed with epoxy, alkoxy and acrylate groups was synthesized from silanol terminated-PDMS and epoxy and acrylate groups functionalized silane coupling agents, and utilized as the adhesion promoter (AP) to prepare addition-cured liquid silicone rubber that exhibited self-adhesion ability (SA-LSR) with biocompatible thermoplastic polyurethanes (TPU) sheets. The structural characteristics of AP were characterized by Fourier transform infrared (FTIR) spectroscopy, which demonstrated the strong adhesion to polyester-based TPU sheets due to a sufficient amount of acrylate groups, epoxy groups and silanol groups obtained by the hydrolysis of alkoxy groups. In detail, the peel-off strength of SA-LSR and TPU joints reached up to 7.63 N mm-1 after the optimization of adhesion promoter including type and content, and curing condition including time and temperature. The cohesive failure was achieved during the sample breakage process. Moreover, the SA-LSR showed a good storage stability under proper storage conditions. This design strategy provided the feasibility to combine the advantages of addition-cured liquid silicone rubber and plastics with low melting points, promoting the potential application range of those silicone-based materials.

Regulation of host and virus genes by neuronal miR-138 favours herpes simplex virus 1 latency.

MicroRNA miR-138, which is highly expressed in neurons, represses herpes simplex virus 1 (HSV-1) lytic cycle genes by targeting viral ICP0 messenger RNA, thereby promoting viral latency in mice. We found that overexpressed miR-138 also represses lytic processes independently of ICP0 in murine and human neuronal cells; therefore, we investigated whether miR-138 has targets besides ICP0. Using genome-wide RNA sequencing/photoactivatable ribonucleoside-enhanced crosslinking and immunoprecipitation followed by short interfering RNA knockdown of candidate targets, we identified the host Oct-1 and Foxc1 messenger mRNAs as miR-138's targets, whose gene products are transcription factors important for HSV-1 replication in neuronal cells. OCT-1 has a known role in the initiation of HSV transcription. Overexpression of FOXC1, which was not known to affect HSV-1, promoted HSV-1 replication in murine neurons and ganglia. CRISPR-Cas9 knockout of FOXC1 reduced viral replication, lytic gene expression and miR-138 repression in murine neuronal cells. FOXC1 also collaborated with ICP0 to decrease heterochromatin on viral genes and compensated for the defect of an ICP0-null virus. In summary, miR-138 targets ICP0, Oct-1 and Foxc1 to repress HSV-1 lytic cycle genes and promote epigenetic gene silencing, which together enable favourable conditions for latent infection.

Glucose-Responsive Microspheres as a Smart Drug Delivery System for Controlled Release of Insulin.

BACKGROUND AND OBJECTIVES: Diabetes mellitus, a disease of glucose regulation, has become one of the most common medical problems in the world. At present, alternative therapy for diabetes has, to a large extent, been widely concerned with the improvement of treatment efficacy. The aims of this study were to characterize and evaluate the surface morphology of the novel glucose-responsive injectable microspheres containing insulin, along with their in vitro release and in vivo efficacy. METHODS: In this study, glucose-responsive microspheres as an emerging smart drug delivery system for controlled release of insulin were developed by an improved water-in-oil-in-water (W/O/W) double emulsion preparation method. Here, methoxypolyethylene glycol-hydrazone-4-methoxypolyethylene glycol benzoate (mPEG-Hz-mPEG4AB) was synthesized as a pH-responsive carrier. RESULTS: The microspheres had a good spherical structure with a particle size of 5 ~ 10 µm. Approximately 61% of insulin was released in 15 h under a high glucose environment but was barely released within the normal glucose range in in vitro studies. After a subcutaneous injection of insulin microspheres in rats, blood glucose levels rapidly decreased within 2 h and could be maintained for 2 days in the normal range. Histopathological evaluation indicated that the microspheres were almost non-irritating. CONCLUSIONS: The pH-responsive mPEG-Hz-mPEG4AB could be used as an efficient insulin microsphere carrier, and the optimized microspheres had good morphology and sustained hypoglycemic effect.

[Mechanisms of herpes simplex virus latency and reactivation].

Herpes simplex virus (HSV), including HSV-1 and HSV-2, is an important pathogen that can cause many diseases. Usually these diseases are recurrent and incurable. After lytic infection on the surface of peripheral mucosa, HSV can enter sensory neurons and establish latent infection during which viral replication ceases. Moreover, latent virus can re-enter the replication cycle by reactivation and return to peripheral tissues to start recurrent infection. This ability to escape host immune surveillance during latent infection and to spread during reactivation is a viral survival strategy and the fundamental reason why no drug can completely eradicate the virus at present. Although there are many studies on latency and reactivation of HSV, and much progress has been made, many specific mechanisms of the process remain obscure or even controversial due to the complexity of this process and the limitations of research models. This paper reviews the major results of research on HSV latency and reactivation, and discusses future research directions in this field.

Novel Fluorinated Polymers Containing Short Perfluorobutyl Side Chains and Their Super Wetting Performance on Diverse Substrates.

Because the emission of perfluorooctanoic acid (PFOA) was completely prohibited in 2015, the widely used poly- and perfluoroalkyl substances with long perfluoroalkyl groups must be substituted by environmentally friendly alternatives. In this study, one kind of potential alternative (i.e., fluorinated polymers with short perfluorobutyl side chains) has been synthesized from the prepared monomers {i.e., (perfluorobutyl)ethyl acrylate (C4A), (perfluorobutyl)ethyl methacrylate (C4MA), 2-[[[[2-(perfluorobutyl)]sulfonyl]methyl]amino]ethyl acrylate (C4SA), and methacrylate (C4SMA)}, and the microstructure, super wetting performance, and applications of the synthesized fluorinated polymers were systematically investigated. The thermal and crystallization behaviors of the fluoropolymer films were characterized by differential scanning calorimetry and wide-angle X-ray diffraction analysis, respectively. Dynamic water-repellent models were constructed. The stable low surface energy and dynamic water- and oil-repellent properties of these synthesized fluorinated polymers with short perfluorobutyl side chains were attributed to the synergetic effect of amorphous fluorinated side chains in perfluoroalkyl acrylate and crystalline hydrocarbon pendant groups in stearyl acrylate. Outstanding water- and oil-repellent properties of fabrics and any other substrates could be achieved by a facile dip-coating treatment using a fluorinated copolymer dispersion. As a result, we believe that our prepared fluorinated copolymers are potential candidates to replace the fluoroalkylated polymers with long perfluorinated chains in nonstick and self-cleaning applications in our daily life.

Microphase Structure, Crystallization Behavior, and Wettability Properties of Novel Fluorinated Copolymers Poly(perfluoroalkyl acrylate-co-stearyl acrylate) Containing Short Perfluorohexyl Chains.

Novel fluorinated copolymers of stearyl acrylate (SA) and (perfluorohexyl)ethyl acrylate (C6A), (perfluorohexyl)ethyl methacrylate (C6MA), 2-[[[[2-(perfluorohexyl)]-sulfonyl]methyl] amino]ethyl acrylate (C6SA), and methacrylate (C6SMA) were synthesized via miniemulsion copolymerization. The extremely hydrophobic monomers perfluoroalkyl acrylate (FA) and SA acted as the reactive costabilizer in the miniemulsion system. The microstructure and surface wetting properties of the copolymers were characterized by (1)H NMR, FT-IR, and dynamic contact angle test. The crystallization behaviors and fine surface structures of the copolymer films were determined by differential scanning calorimetry (DSC) and wide-angle X-ray diffraction (WAXD) analysis. The self-assembled aggregation and roughness of the copolymer films were investigated by atomic force microscopy (AFM). The results showed that the fluorinated side chains interrupted and impeded the crystallizable side chains of SA from forming complete crystals. And the Tm and ΔHf of the copolymers were decreased as a consequence of this effect. The fluorinated side chains in P(C6A/SA) and P(C6MA/SA) arranged between the crystallizable hydrocarbon side chains of SA, while the crystallization structure of fluorinated and nonfluorinated pendant groups existed all at once in copolymers P(C6SA/SA) and P(C6SMA/SA). The four copolymers exhibited very low surface free energy and excellent dynamic water repellency attributed to the restriction of perfluoroalkyl groups combined with crystallization of stearyl pendant groups.

[Analysis of adverse reactions induced by subcutaneous immunotherapy against dust mite allergy in 234 cases with allergic rhinitis and asthma].

OBJECTIVE: To investigate the incidence of local reactions (LRs) and systemic reactions (SRs) of subcutaneous immunotherapy (SCIT) and to analyze the potential risk factors of such reactions in Chinese population. METHOD: This is a retrospective study on 234 dust mite sensitized patients with allergic rhinitis and asthma who received allergen immunotherapy in our hospital from 2003 to 2010. Chart review was conducted to capture clinical data of reactions to immunotherapy. Parameters included signs and symptoms, the onset of reaction, and interventions in treating such reactions, particularly, the administration of epinephrine (EPI) and adjustment of vaccine dosage due to LRs and SRs. RESULT: The 234 patients received a total of 7679 injections. Among them, 4973 LRs (64.8%) and 235 SRs (3.1%) were observed in 67 patients (28.6% of all patients). SRs included respiratory symptoms (205 events, 88.4%) and cutaneous symptoms (31.5%). Of the total of 235 SR events, 212 (90.2%) were presented as mild SRs and 23 (9.8%) were in severe SR category (grade III and grade IV, EAACI grading system). Overall, severe SRs accounted for 0.3% of total injections. Seventeen of the 23 SR events required epinephrine treatment (0.2% of total injections). Of the 67 patients, 61 completed the course of treatment after dose adjustment; 36 patients had their doses decreased prior to further advancing to target dose. Nineteen subjects tolerated splitting two injections at 30 minutes interval. Six patients advanced the dose based on protocol and another 6 had to stop immunotherapy. Most of the SRs (77.4%) occurred during the maintenance phase of immunotherapy. The levels of TIgE, SIgE D1 and SIgE D2 were found to be significantly higher in patients with SRs comparing to patients without SRs (P < 0.05). SRs more commonly occurred in patients with age less than 14 years than their older counterparts (95.5% vs. 85.6%, OR = 3.58, 95%CI = 1.040 - 12.322, P < 0.01). The incidence of SRs were significantly higher in asthma patients who received SCIT than non-asthma patients (OR = 2, 95%CI = 1.136 - 4.624). CONCLUSION: Our study suggests that risk factors of SRs include maintenance phase (higher allergen vaccine doses), patients with asthma, age of less than 14 years, higher levels of TIgE, and SIgE D1 and SIgE D2. Effective management includes proper dose adjustment, splitting doses into 2 injections at 30 min apart, and strictly following immunotherapy indications.