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We propose a strategy of combining covalent and noncovalent cross-links into carboxyl nitrile rubber (XNBR) networks to fabricate multifunctional elastomers with self-healing and shape memory ability. Specially, commercially available XNBR was cross-linked by diethylenetriamine (DETA) and trimethylolpropane tris(3-mercaptopropionate) (TMPT) through hydrogen bond interaction and thiol-ene “click” reaction, generating reversible hydrogen bonds and robust covalent bonds cross-links, respectively. The modulus of the resulted polymers is consistently enhanced with the increase of TMPT loading, indicating the cross-linking networks are gradually constrained. In addition, the samples demonstrate self-healing and shape memory functions due to the reversible hydrogen bonds and robust covalent cross-links. When the content of TMPT is 0, the sample shows the high elongation at break and appropriate tensile strength. It can achieve almost complete healing due to the material contains noncovalent bonds only. When the content of TMPT is 2 phr, the sample exhibits both pretty self-healing and moderate shape memory ability. This strategy might provide an alternative way to construct intelligent multifunctional polymers with versatile functions.

Sulfobutyl ether-beta-cyclodextrin sodium salt contained in the marketed intravenous voriconazole injection as a solubilizer may cause harmful accumulations. This study aimed to evaluate the safety, tolerability, and pharmacokinetics (PKs) of two intravenous voriconazole formulations containing excipients from different manufacturers using increasing dose administrations in healthy Chinese volunteers. A randomized, double-blind, placebo-controlled trial was conducted in three cohorts with 42 healthy Chinese volunteers. Each cohort of 14 volunteers was allocated in proportion (8:4:2) to test the formulation, reference voriconazole, or placebo successively by single-dose then multiple-dose administrations of 3, 4, and 6 mg/kg. Forty-one volunteers completed all drug administrations. The pharmacokinetics of test formulations are characterized by high interindividual variability (coefficient of variance of C

To improve the damping properties of rubbers, organic tackifiers such as hydrocarbon resins, rosin esters, and polyterpenes are often incorporated to increase the intermolecular friction of the rubber, thus increasing the energy dissipation (damping) during dynamic loading. However, this is often at the expense of the cross-linking density and mechanical properties of the rubbers. Ionic cross-links introduce unique properties to rubbers, such as a combination of mechanical reinforcement and high extensibility, as well as self-healing and damping, thanks to the reversible ionic association. Hence creating an ionic network would be an interesting alternative to adding small molecular tackifiers to rubbers. The reversible ionic association inevitably causes structural instability over time (i.e., creep) or at elevated temperatures (ionic transition generally happens at 60–80 °C). To balance the dynamic damping, viscoelasticity, and mechanical stability of these materials, we prepared 1-vinyl imidazole modified brominated poly(isobutylene-co-isoprene) (BIIR) elastomers by solid-state rubber compounding and curing processes, and we investigated the effects of ionic networks and an aliphatic petroleum resin (C5) on the viscoelastic and electromechanical properties of the ionic-cross-linked elastomers. We found that the mechanical reinforcement can be achieved simultaneously with a broad effective damping temperature range through optimizing the ionic network and C5 concentrations. The polar ionic clusters also increased the dielectric permittivity while maintaining a low dielectric loss of the elastomers. The ionic modified BIIR exhibited actuation and energy harvesting properties similar to those of the commercial VHB-4910 elastomer under similar configurations, which provides alternative dielectric elastomers with reprocessability for vibration and energy harvesting applications.\ud \ud

Preparation of covalently crosslinked elastomers with an integration of high mechanical performance, enhanced creep resistance and retained malleability by incorporating quadruple hydrogen bonds into dynamic boronic ester bonds crosslinked SBR.

Background Previous studies on the burden of cardiovascular diseases (CVDs) were mainly based on limited data of the study period or area, or did not include detailed risk factor analysis. Objective To investigate up-to-date temporal and regional trends and risk factors of mortality and disability-adjusted life years (DALYs) attributed to CVDs by age, sex, and disease throughout the world. Methods Data for the disease burden of CVDs in 195 countries and territories from 1990 to 2017, including mortality, DALYs, age-standardized mortality rates, and age-standardized DALY rates, were estimated from the Global Burden of Disease Study 2017. Risk factors attributable to deaths and DALYs for CVDs were also estimated using the comparative risk assessment framework. Results The number of deaths from CVDs increased by 48.62%, from 11.94 (95% UI 11.78–12.18) million in 1990 to 17.79 (17.53–18.04) million in 2017. However, the age-standardized mortality rate decreased by an average of − 1.45% (− 1.72% to − 1.18%) annually. After fluctuation in the expected age-standardized mortality rate of CVDs in most of the socio-demographic index (SDI) scale, these rates decrease rapidly for SDI values of 0.7 and higher. In 2017, metabolic risks accounted for 73.48% of deaths and 73.25% of DALYs due to CVDs, behavioral factors accounted for 63.23% of deaths and 66.71% of attributable DALYs. Conclusion CVDs remain a major global health burden due to the increment in death numbers and DALYs. Aging and the main risk factors are the main drivers of mortality and health loss. More attention to main risk factors should be paid with supportive health policies.

The effect of deep eutectic solvent (DES) modified silica on the properties of nature rubber (NR) composites were investigated. The DES is an environment-friendly and low-cost solvent, which was prepared by mixing choline chloride and urea in a 1:2 molar ratio. The NR composites filled with DES modified silica were prepared and the properties were tested. The interaction between the DES and silica were characterized by Fourier transform infrared spectroscopy (FTIR), the interaction between silica and silica were tested by differential scanning calorimetry (DSC). The dynamic properties, such as rolling resistance and wet skid resistance, and were tested by dynamic mechanical analysis (DMA). Morphologies of the composites were characterized by scanning electron microscopy (SEM). The results indicate that the DES can interact with silica by hydrogen bond to improve the compatibility between the rubber and silica. When the content of DES was 3 phr, the tensile strength, modulus at 300%, tear strength, and the crosslinking density of the composites was increased. At the same time, the proper content of DES can reduce the rolling resistance of the vulcanized rubber while maintaining good wet skid resistance.

With the rapid development of nanomanufacturing, scaling up of nanomaterials requires advanced manufacturing technology to composite nanomaterials with disparate materials (ceramics, metals, and polymers) to achieve hybrid properties and coupling performances for practical applications. Attempts to assemble nanomaterials onto macroscopic materials are often accompanied by the loss of exceptional nanoscale properties during the fabrication process, which is mainly due to the poor contacts between carbon nanomaterials and macroscopic bulk materials. In this work, we proposed a novel cross-scale manufacturing concept to process disparate materials in different length scales and successfully demonstrated an electrothermal shock approach to process the nanoscale material (e.g., carbon nanotubes) and macroscale (e.g., glass fiber) with good bonding and excellent mechanical property for emerging applications. The excellent performance and potentially lower cost of the electrothermal shock technology offers a continuous, ultrafast, energy-efficient, and roll-to-roll process as a promising heating solution for cross-scale manufacturing.

The aim of this study was to explore the impact of tension fatigue on the structure and properties of filled SBR and SBR/TPI blends. The effect of tension fatigue on the dynamic properties of carbon black-filled styrene-butadiene rubber (SBR) and SBR/trans-1,4-polyisoprene (SBR/TPI) blend vulcanizates were investigated by dynamic mechanical analysis (DMA). The Mooney-Rivlin analysis of tensile stress-strain data is used for the determination of a rubber network crosslink density. The fatigue fracture surface of SBR/TPI vulcanizates was observed with a scanning electron microscopy (SEM). The crystallinity of TPI in carbon black-filled SBR/TPI (80/20) was characterized by X-ray diffraction (XRD). The results showed that the incorporation of TPI into SBR vulcanizates influences the fatigue properties of the blend vulcanizates. The blend vulcanizates showed optimum fatigue properties with 20 phr TPI. With increasing fatigue cycles, the tensile properties and crosslink density of SBR vulcanizates were decreased substantially. Compared with that of SBR vulcanizates, the tensile properties and crosslink density of SBR/TPI (80/20) blend vulcanizates changed little with the increase in fatigue cycles, and tan δ and E′ decreased gradually with the fatigue cycles. There was a sharp decrease in the E′ and tan δ curve in the temperature range of 40 ~ 60°C. The XRD diffraction peak corresponding to 3.9 Å broadened when the fatigue cycles were increased to 1 million times, and a new peak with inter-planar spacing at 7.6 and 4.7 Å appeared.

Objective: Our objective is to explore the effect of applying cloud video conferencing methods to the informed consent process in an early-phase clinical trial during the COVID-19 pandemic.Methods: All participants who intended to participate in the trial were informed via a cloud video conference before signing the informed consent forms (ICF). Then, the attitudes of the participants with the cloud video conference and their understanding of the trial were evaluated using a questionnaire when they visited to sign the ICF onsite.Results: A total of 165 subjects participated in the cloud video conference process, and 142 visited the site to sign and date the ICFs at the center during the appointment time. The survey showed that nearly 100% of the subjects evaluated the video-based informed consent process as very good or good and gave correct answers to questions about the trial. Furthermore, 136 (95.8%) subjects believed that the knowledge about the trial derived via the video-based informed consent process was consistent with the onsite reality, and 139 (97.9%) subjects expressed their willingness to participate in an informed consent procedure undertaken through an online video conference.Conclusions: The video-based informed consent process achieved the same effects as an onsite informed consent process. The former saves time and cost of transportation for the subject and exhibits good public acceptance; especially in light of the COVID-19 pandemic, this process is conducive for reducing the risk of subject infection due to travel and would also help avoid crowding on site.

Background: The aim of this study was to examine how body image, Disease Activity Score in 28 joints, the feeling of being anxious, depression, fatigue, quality of sleep, and pain influence the quality of life (QoL) in patients with rheumatoid arthritis (RA).Methods: A multicenter cross-sectional survey with convenience sampling was conducted from March 2019 and December 2019, 603 patients with RA from five hospitals were evaluated using the Body Image Disturbance Questionnaire, Disease Activity Score in 28 joints, Hospital Anxiety and Depression Scale, Fatigue Severity Scale, Pittsburgh Sleep Quality Index, Short Form 36 Health Survey, and Global Pain Scale. The relationship between quality of life and other variables was evaluated by using the structural equation model (SEM).Results: A total of 580 patients were recruited. SEM fitted the data very well with a root mean square error of approximation (RMSEA) of 0.072. Comparative fit index of 0.966, and Tucker-Lewis index of 0.936. The symptoms and the normalized factor load of six variables showed that the normalized factor load of pain was 0.99.Conclusions: The QoL model was used to fit an SEM to systematically verify and analyze the population disease data, biological factors, and the direct and indirect effects of the symptom group on the QoL, and the interactions between the symptoms. Therefore, the diagnosis, treatment and rehabilitation of RA is a long-term, dynamic, and complex practical process. Patients' personal symptoms, needs, and experiences also vary greatly. Comprehensive assessment of patients' symptoms, needs, and experiences, as well as the role of social support cannot be ignored, which can help to meet patients' nursing needs, improve their mood and pain-based symptom management, and ultimately improve patients' QoL.

With silica firstly modified by 3-aminopropyl-triethoxysilane (APES), graphene oxide (GO) was prepared by modified Hummer’s method. APES-silica/GO (AsGO) hybrids were fabricated through hydrogen bond to reduce the polarity of silica and GO and increase the compatibility between natural rubber (NR) and AsGO. Subsequently, AsGO was incorporated into NR latex. The interaction between GO and silica in AsGO was characterized by X-ray diffraction, Raman, and Zeta potential. It was confirmed by transmission electron microscopy that the silica was uniformly dispersed on the surface of the GO. The filler–rubber interfacial interaction was thoroughly investigated. The amount of constrained region was quantified through differential scanning calorimetry results, and it showed that the high volume fraction of constrained region is responsible for the strong interfacial interaction. Besides, the mechanical performance, dynamic property, and electrical and thermal conductivity of NR-AsG x were studied. The results showed that the overall performance of NR-AsG x has an optimum value when the GO loading is 1.5 phr, which is due to the good filler dispersion and strong interface interaction.

An investigation of the effect of an ionic liquid, 1-butyl-3-methylimidazolium tetrafluoroborate (BMI), on the properties of silica reinforced styrene-butadiene rubber (SBR), aimed to correlate the...

Background Since the outbreak of 2019 novel coronavirus (SARS‐CoV‐2) pneumonia, many patients with underlying disease, such as interstitial lung disease (ILD), were admitted to Tongji hospital in Wuhan, China. To date, no data have ever been reported to reflect the clinical features of Corona Virus Disease 2019 (COVID‐19) among these patients with pre‐existing ILD. Methods We analyzed the incidence and severity of COVID‐19 patients with ILD among 3201 COVID‐19 inpatients, and compared two independent cohorts of COVID‐19 patients with pre‐existing ILD (n=28) and non‐ILD COVID‐19 patients (n=130). Results Among those 3201 COVID‐19 inpatients, 28 of whom were COVID‐19 with ILD (0.88%). Fever was the predominant symptom both in COVID‐19 with ILD (81.54%) and non‐ILD COVID‐19 patients (72.22%). However, COVID‐19 patients with ILD were more likely to have cough, sputum, fatigue, dyspnea, and diarrhea. Very significantly higher number of neutrophils, monocytes, IL‐8, IL‐10, IL‐1β and D‐Dimer was characterized in COVID‐19 with ILD as compared to those of non‐ILD COVID‐19 patients. Furthermore, logistic regression models showed neutrophils counts, pro‐inflammatory cytokines (TNF‐α, IL6, IL1β, IL2R), and coagulation dysfunction biomarkers (D‐Dimer, PT, Fbg) were significantly associated with the poor clinical outcomes of COVID‐19. Conclusion ILD patients could be less vulnerable to SARS‐CoV‐2. However, ILD patients tend to severity condition after being infected with SARS‐CoV‐2. The prognosis of COVID‐19 patients with per‐existing ILD is significantly worse than that of non‐ILD patients. And more, aggravated inflammatory responses and coagulation dysfunction appear to be the critical mechanisms in the COVID‐19 patients with ILD. This article is protected by copyright. All rights reserved.

The effect of network structure on dynamic compressive fatigue behavior and static compressive mechanical properties of styrene-butadiene rubber (SBR) were investigated. A series of SBR compounds with different amounts of sulfur and dicumyl peroxide (DCP) were prepared, and their crosslinking densities were calculated using the Flory–Rehner equation. Compressive fatigue resistance and creep behavior of the vulcanizates were performed on a mechanical testing and simulation (MTS) machine. The fatigue damage surface of SBR vulcanizates before and after a dynamic compressive fatigue test was observed with a scanning electron microscopy (SEM). The results suggested that the surface of the samples was badly damaged as the number of compressive cycles increased. By comparison, compressive fatigue caused less surface damage to sulfur-cured SBR than to peroxide-cured SBR. The peroxide-cured SBR samples showed higher energy dissipation than sulfur-cured SBR during cyclic compression. The peroxide-cured SBR showed lower creep strain and compression set than the sulfur-cured SBR. The -Sx- linkages provided by the sulfur curing system allow dynamic compressive deformation but suffer from poor static compressive resistance. However, the carbon-carbon linkages from DCP are irreversible and provide higher resistance to static compressive stress, but they do not show obvious dynamic compressive fatigue resistance.

Herein, dopamine is grafted onto multi-walled carbon nanotubes (MWCNTs), and then grafted dopamine is used as a chemical activation point to initiate the in-situ synthesis of silver nanoparticles (Ag-NPs). The foam technology with supercritical N2 (Sc-N2) gas was used to prepare a lightweight and flexible silicone rubber foam material with efficient electromagnetic shielding performance. The prepared material has uniform cells and a density of only 0.3 g/cm3. The electrical conductivity can be achieved as high as 5.69 S/m. At the same time, the optimal modified conductive filler MWCNTs conditions are determined: DOPA concentration is 2 g/L, deposition time is 18 h, formaldehyde concentration is 5 g/L and AgNO3 concentration is 16 g/L. From the perspective of electromagnetic interference shielding performance (EMI SE), the value of prepared silicone rubber foam with 15 parts of MWCNT-PDA-Ag (VMPA15) can reach 36 dB, far exceeding the commercial requirement (20 dB). The EMI shielding performance is also improved with the increased thickness of the sample. When the sample thickness is 10 mm, the EMI SE value can be as high as 52 dB; more importantly, this type of VMPA foam has a shielding mechanism based on absorption, which is the most effective for solving the problem of secondary magnetic pollution caused by electromagnetic wave reflection.

The influence of ambient temperature on the tensile stress-strain curve of polyaspartic ester polyurea (PAE-PU) was investigated to discuss the yield and breakage mechanism of tensile deformation. Temperature has a significant effect on the tensile stress-strain curve of PAE-PU. At low temperature (27, 40 °C), it shows obvious yield and forced high elasticity. After the temperature exceeds 80 °C, the yield phenomenon disappears and shows high elasticity of rubber: the strain energy and breakage energy are significantly reduced. The yield activation energy of PAE-PU was calculated by yield strain time at different temperatures. It was found that the yield activation energy decreased with the increase of tensile rate. When the tensile rate is 500mm/min, among the activation energies calculated by breakage strength, yield strength and Young’s modulus at different temperatures, the ordinary elastic deformation activation energy is higher, while the yield and breakage activation energy are close and lower. The latter two are close to the hydrogen bond energy and one order of magnitude lower than the chemical bond energy of molecular chain.

A novel series of shape memory blends of trans-1,4-polyisoprene (TPI) and low-density polyethylene (LDPE) were prepared using a simple physical blending method. The mechanical, thermal and shape memory properties of the blends were studied and schemes proposed to explain their dual and triple shape memory behaviors. It was found that the microstructures played an important role in the shape memory process. In TPI/LDPE blends, both the TPI crosslinking network and LDPE crystalline regions could work as fixed domains, while crystalline regions of LDPE or TPI could act as reversible domains. The shape memory behaviors were determined by the components of the fixed and reversible domains. When the blend ratio of TPI/LDPE was 50/50, the blends showed excellent dual and triple shape memory properties with both high shape fixity ratio and shape recovery ratio. © 2017 Society of Chemical Industry

The crystallization of trans-1,4-polyisoprene (TPI) was influenced by many factors, such as the processing temperature, pressure and stress. The crystallization of TPI prepared under different conditions (temperature, pressure and tension) was characterized by Fourier transform infrared spectroscopy (FTIR), polarizing light microscopy(POM)and X-ray diffraction(XRD). The experimental results showed that the absorption frequency and the intensity of the FTIR spectra were not influenced by Mooney viscosity of TPI, however, it deeply affected by the sample preparation methods. The spectrum of hot pressed films showed a combination of α-form and β-form crystals, while that of solution cast films showed the characteristic absorption bands of α-form crystals and less β-form crystals. Spherulites of TPI could be obtained at several different crystallization temperatures (45 °C, 18 °C and 9 °C), but the size of the spherulites decreased from ~180 μm to ~70 μm with the decrease of temperature from 45 °C and 9 °C. When the temperature of the specimen decreased at a uniform rate (1.5 °C/min), large size spherulites were obtained. With the increase of pressure, the spherulites were not perfect. XRD patterns of TPI revealed that both α-form and β-form crystals existed in stretched specimens. Part of the α-form crystals transformed into β-form crystals during the extension.

The influence of carbon black on physical mechanical properties, compressive fatigue life, and the temperature changes during compression fatigue process of styrene-butadiene rubber (SBR) vulcanizates were explored. A series of unfilled and filled SBR compounds were prepared, and the compressive fatigue behaviors of the vulcanizates were performed on a mechanical testing and simulation (MTS) machine. The top surfaces of the filled SBR were imaged using scanning electron microscopy (SEM) after 105 cycles of compressive fatigue. The filled SBR shows greater compressive fatigue resistance than the unfilled SBR. The incorporation of carbon black into SBR improves the creep resistance. The best compressive fatigue resistance for the filled SBR was achieved by the addition of 30 phr carbon black. With the increase of carbon black content, the energy dissipation and the heat build-up increase simultaneously. Furthermore, SEM images of the vulcanizates suggest that the crack propagation mechanism of the unfilled and the filled SBR was different. For the unfilled SBR, due to periodical compressive stress, the polymer chains can be destroyed, and the cracks can be easily initiated and propagated, showing serious damage on the top surfaces of the specimen. However, for the filled SBR, the carbon black agglomeration around the cracks can greatly delay the generation of the cracks, decrease the fatigue damage, and ultimately improve the fatigue resistance.

In this article, we primarily introduced a method to prepare epoxidized Eucommia ulmoides gum (EEUG) and studied its application as interfacial additive in styrene-butadiene rubber (SBR)/silica composites. We prepared the EEUG from the Eucommia gum extract solution using E. ulmoides leaves pretreated with enzymatic solutions as the raw material, petroleum ether as the solvent, and peracetic acid (CH3COOOH) as the oxidant under a certain temperature. Accordingly, we focused on studying the effects of a series of factors, such as the mole ratio (γ) of peracetic acid to double bonds of Eucommia gum and reaction time on the epoxidation degree and crystallization degree of Eucommia gum in the epoxidation process, in order to control the properties of the EEUG. Regarding the study of the application of EEUG in SBR/silica composites, we found that the addition of EEUG greatly promoted the properties of SBR/silica composites by improving the dispersion of silica in SBR composites, which possessed excellent mechanical properties, including higher tensile strength, tear strength, 100 and 300% modulus, wear resistance, and low heat buildup. Copyright © 2016 John Wiley & Sons, Ltd.

In many polymer applications such as inner tire liners and fuel hoses, imparting excellent gas barrier properties and light-weight properties are of prime importance. Research into this direction have been completed based on a judicious choice of polymer type or a blend thereof and the compounding ingredients. Although butyl rubber has been the polymer of choice because of its excellent gas barrier property, yet investigations were targeted to improve these properties with further modification in the polymer type and variation in compounding ingredients. In this study, a (90:10) blend of Chlorobutyl Rubber and Epoxidized Natural Rubber by weight was used as the base. Hollow glass microsphere (HGM) at fixed concentrations were used to optimize the gas barrier and light-weight properties. It was observed that the physical properties decrease, especially the tensile strength with increasing HGM. In this blend, HGMs were effective in imparting the best overall combination of properties. J. VINYL ADDIT. TECHNOL., 2016. © 2016 Society of Plastics Engineers

In this paper, we consider an unknown source problem for the modified Helmholtz equation. The Tikhonov regularization method in Hilbert scales is extended to deal with ill-posedness of the problem. An a priori strategy and an a posteriori choice rule have been present to obtain the regularization parameter and corresponding error estimates have been obtained. The smoothness parameter and the a priori bound of exact solution are not needed for the a posteriori choice rule. Numerical results are presented to show the stability and effectiveness of the method.

Mechanical properties of glass fiber reinforced polymer (GFRP) composites degrade under the combined effects of mechanical load and alkaline solution, affecting the service ability and safety of GFRP reinforced structures. In this study, GFRP bars were loaded with cyclic tension at different stress levels and immersed in alkaline solution for days to investigate the tensile properties and degradation law of GFRP bars. The degradation mechanisms were studied at micro-, meso- and macro-scales with scanning electron microscopy (SEM) and three-dimensional X-ray microscopy, respectively. The results show that tensile strength and degradation rate of GFRP bars are mainly dependent on the different stress levels and alkaline solution. When stress level is higher, the tensile strength degrades more quickly, especially in the early stages of soaking. With the loading and immersion time, the elastic modulus and Poisson&rsquo, s ratio increase at first and then decrease. The ultimate tensile strain is relatively stable, whereas the ultimate elongation is significantly reduced. A strength-degradation model was proposed and fit well with experimental data, demonstrating that the model can be applied to predict tensile strength degradation under combined effects of the load and alkaline solution.

Pharmacokinetics of exogenous strontium (Sr) and bioequivalence of a new oral formulation of strontium ranelate compared with the brand-name drug in healthy Chinese subjects was evaluated. A balanced, randomized, single-dose, two-treatment parallel study was conducted in 36 healthy Chinese subjects. Subjects were randomly allocated into two groups of 18 to receive a single oral dose of test formulation and reference formulation under a fasting state, respectively. Blood samples were collected at 19 designated time points up to 240-h post-dose. Serum concentrations of Sr were quantified by ICP-MS. A total of 36 subjects were enrolled and completed the study. Nine mild adverse events in 6 subjects were reported. The C

A rapid and sensitive liquid chromatography–tandem mass spectrometric method was developed for the first time and validated for the determination of cefprozil diastereomers in human plasma. The plasma samples were prepared by protein precipitation using acetonitrile. Detection was performed using an electronic spray ion source in the negative ion mode, operating in the multiple reaction monitoring of the transitions m/z 388.0 to m/z 205.0 for cefprozil diastereomers and m/z 346.1 to m/z 268.1 for cephalexin (the internal standard). The calibration curves of cis-cefprozil and trans-cefprozil were linear in the ranges 0.125–16.0 µg/mL and 0.0403–1.72 µg/mL, respectively. The lower limits of quantification of cis- and trans-cefprozil were 0.125 and 0.0403 µg/mL in human plasma, respectively. The intra- and inter-day precisions of cis- and trans-cefprozil were all

8013 Background: Previous studies indicate patients with relapsed/refractory multiple myeloma (RRMM) who receive high-dose BCMA-targeting CAR-T cells may achieve better remission but have worse adverse events. Moreover, once the disease progresses again, the re-infusion of CAR-T cells is not effective. To solve this dilemma, we have developed a novel BCMA-targeting CAR-T (CT103A) with a lentiviral vector containing a CAR structure with a fully human scFv, CD8a hinger and transmembrane, 4-1BB co-stimulatory and CD3z activation domains. Methods: ChiCTR1800018137 is a single-center and single-arm trial of CT103A in patients with RRMM. The primary objectives are to characterize the safety and tolerability in patients with R/R MM. The secondary objectives include evaluation of anti-myeloma activity, cytokines, CAR-T cell persistence, and pharmacokinetics. Between September 21, 2018, and January 21, 2019, nine patients (including 3 patients having relapsed after being given a murine BCMA CAR-T) received CT103A in 3+3 dose-escalation trial (three doses at 1, 3, 6 ×106/kg) after a conditioning chemotherapy regimen of cyclophosphamide and fludarabine. All Patients had received a median of 4 prior lines (range 3 - 5) of MM therapy. Results: At the time of the February 4, 2019 data analysis, the overall response rate was 100% (Table), and all patients had a rapid response within 14 days, with 67% (2/3) reaching CR/sCR at the lowest dose. The pharmacokinetics of CT103A were assessed by a digital polymerase chain reaction. Robust expansions were seen even at the lowest dosage level. In addition, Cmax and AUC0-28 reached levels comparable to reported CD19 CAR-T. In the first two dose groups, the grade of cytokine release syndrome (CRS) was 0 - 2. In the 6 ×106 /kg dose group, DLT had been observed in one patient. Conclusions: Data from this early-stage clinical study showed the unparalleled safety and efficacy of CT103A. Major AEs were transient, manageable, and reversible. three patients who relapsed the murine BCMA CAR-T were treated with CT103A, two patients achieved CR, and one patient achieved VGPR. 100% ORR and a rapid response within 2 weeks, suggests CT103A could be developed as a competitive therapeutic to treat patients with RRMM. Treatment Response (Case 1,5 and 7 are patients who relapsed the murine BCMA CAR-T). Clinical trial information: ChiCTR1800018137. [Table: see text]

A sensitive and selective LC-MS/MS method for the determination of agomelatine in human plasma was developed and validated. After simple liquid-liquid extraction, the analytes were separated on a Zorbax SB-C18 column (150 × 2.1 mm i.d., 5 µm) with an isocratic mobile phase consisting of 5 mm ammonium acetate solution (containing 0.1% formic acid) and methanol (30:70, v/v) at a flow-rate of 0.3 mL/min. The MS acquisition was performed in multiple reaction monitoring mode with a positive electrospray ionization source. The mass transitions monitored were m/z 244.1 → 185.3 and m/z 285.2 → 193.2 for agomelatine and internal standard, respectively. The methods were validated for selectivity, carry-over, matrix effects, calibration curves, accuracy and precision, extraction recoveries, dilution integrity and stability. The validated method was successfully applied to a pharmacokinetic study of agomelatine in Chinese volunteers following a single oral dose of 25 mg agomelatine tablet.

Chlorinated trans-1,4-polyisoprene (CTPI) was synthesized by a water phase suspension method. The crystalline morphology of nascent CTPI was characterized by polarizing optical microscopy (POM). The effect of CTPI on the curing characteristics, mechanical properties, and fracture surface of neoprene/trans-1,4-polyisoprene (CR/TPI) blend vulcanizates were investigated. The experimental results showed that the scorch time and the optimum time of CR/TPI/CTPI compounds were shortened with the incorporation of CTPI into the compounds. At the same time, the dispersibility of carbon black in the compounds was improved. With the incorporation of CTPI into the CR/TPI compounds, the fatigue failure surface of CR/TPI/CTPI vulcanizate was quiet different from that of CR compounds. The flexing resistance of CR/TPI/CTPI vulcanizates obviously improved, and the fatigue failure surface showed zigzag morphology. Dynamic mechanical analysis (DMA) revealed that the compatibility between CR and TPI was improved with the inco...

Trans‐1,4‐polyisoprene (TPI) with a Mooney viscosity of 120 was filled with 37.5 phr aromatic oil to prepare oil‐extended trans‐1,4‐polyisoprene (OETPI) by a dry oil‐extending process. The curing characteristics of TPI gum, OETPI gum, and TPI/SBR compounds were studied and the mechanical properties of vulcanizates were also investigated. The experimental results showed that the Shore A hardness, Mooney viscosity, and mechanical properties of OETPI gum decreased, compared with that of TPI gum. The modulus at 100% elongation, Shore A hardness, and tensile strength of OETPI vulcanizates also decreased, while the abrasion loss, compression heat build‐up, and compression set increased. Compared with TPI/SBR, the dispersibility of carbon black in OETPI/SBR compounds was improved. The mechanical properties of OETPI/SBR vulcanizates changed little, while the wet skid resistance and fatigue resistance was greatly improved.

The pyrolytic carbon black (PCB) made from used tires was used in styrene‐butadiene rubber (SBR). The basic properties of PCB were characterized. The effects of PCB on the processing properties of SBR compounds and the mechanical properties of vulcanizates were investigated and compared with other traditional fillers. The results showed that the chemical composition of PCB was mainly C, O, S, Zn and Si. The content of ash wa as much as 13.3%. The SEM photos showed that the primary particle size of PCB was smaller than that of N774, but the aggregate size was larger than that of N774. The effect of PCB on the processing properties of SBR compounds was similar to that of other fillers. The reinforcing effect of PCB was similar to that of N774, but inferior to that of N330.

A low‐molecular‐weight trans‐1,4‐polyisoprene (LMTPI) was synthesized with hydrogen as a molecular weight regulator. The effect of hydrogen pressure on the molecular weight of TPI was investigated. Increasing the H2 pressure effectively reduced the molecular weight of TPI. When LMTPI was used as plasticizer in styrene‐butadiene rubber (SBR), the scorch time and optimum‐curing time of the SBR compounds increased compared with that of SBR compounds containing aromatic oil. The rebound resilience and anti‐fatigue of SBR vulcanizates were improved. The effect of pelletized sulfur (LMTPI as carrier) on the mechanical properties of natural rubber (NR) vulcanizates was studied and compared with that of powder sulfur and a commercial pelletized sulfur (Rhenogran S‐80). The pelletized sulfur could improve the processing properties of the NR compound. It also could effectively improve the flexing resistance and retain good mechanical properties of NR vulcanizates.

A new organic-solvent-free water-phase suspension method was used to synthesize partially epoxidized high trans-1,4-polyisoprene (TPI) to improve its properties, including oil resistance and wet-skid resistance. The epoxidation was conducted in an aqueous peracetic acid solution and on the TPI granules prepared by a bulk precipitation method with supported titanium catalyst. The effects of the synthesis conditions, including reaction temperature, reaction time, and pH value, on the epoxy content were investigated. Epoxidized trans-1,4-polyisoprene (ETPI) with epoxy contents between 10 and 80% were obtained within 4 h. Both the amorphous and crystalline regions of TPI were epoxidized. The crystallization properties decreased with increasing epoxy content. ETPIs possessed lower mechanical properties than TPI but could be enhanced by vulcanization. The oil resistance and wet-skid resistance were significantly improved after epoxidation. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2008

A rapid and sensitive liquid chromatography-tandem mass spectrometric method was developed for the first time and validated for the determination of cefprozil diastereomers in human plasma. The plasma samples were prepared by protein precipitation using acetonitrile. Detection was performed using an electronic spray ion source in the negative ion mode, operating in the multiple reaction monitoring of the transitions m/z 388.0 to m/z 205.0 for cefprozil diastereomers and m/z 346.1 to m/z 268.1 for cephalexin (the internal standard). The calibration curves of cis-cefprozil and trans-cefprozil were linear in the ranges 0.125-16.0 µg/mL and 0.0403-1.72 µg/mL, respectively. The lower limits of quantification of cis- and trans-cefprozil were 0.125 and 0.0403 µg/mL in human plasma, respectively. The intra- and inter-day precisions of cis- and trans-cefprozil were all9.7%, and the accuracy ranged from 99.2 to 104.7% and from 100.6 to 102.2%, respectively. The validated method was successfully applied to a bioequivalence study of two cefprozil formulations in 24 healthy Chinese volunteers. The two cefprozil tablets were bioequivalent by measurement of cis-, trans- and total cefprozil. We suggest that the bioequivalence of cefprozil formulations can be evaluated only using cis-cefprozil as the analyte in future studies.

Ethylene/vinyl acetate rubber (EVM) was reinforced by sodium methacrylate (NaMAA) that was in situ prepared through the neutralization of sodium hydroxide and methacrylic acid in EVM during mixing. The mechanical properties of EVM vulcanizates with different NaMAA loadings and at different crosslink densities were studied and compared with those of high abrasion furnace carbon black (HAF) filled EVM vulcanizates. The fracture surfaces of gum and filled EVM vulcanizates were observed with scanning electron microscopy. The results showed that NaMAA-reinforced EVM vulcanizates had better mechanical properties than HAF/EVM vulcanizates. When the NaMAA loading was 50 phr, the tensile strength of the NaMAA/EVM vulcanizate was 30 MPa, the tear strength was 102 kN/m, and the elongation at break was over 400%. Fourier transform infrared analysis confirmed that NaMAA formed in the compounding process and underwent polymerization during vulcanization. Scanning probe microscopy analysis revealed that nanoscale particles dispersed in the NaMAA/EVM vulcanizates. The mechanical properties were correlated with the fracture morphology of all the vulcanizates. The tensile rupture of NaMAA-filled EVM vulcanizates occurred through tearing from a crack in the bulk of the samples. Tear deviation occurred with the addition of NaMAA and resulted in a rough surface, leading to an improvement in the tear strength of NaMAA-filled EVM vulcanizates. The micrographs of the tear surfaces of the vulcanizates indicated that the different fracture modes depended on the NaMAA loading and the crosslink density. © 2004 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 42: 1715–1724, 2004

Ethylene–vinyl acetate rubber (EVM) filled with magnesium methacrylate (MDMA) was cured with dicumyl peroxide (DCP). The experimental results showed that the mechanical properties of MDMA/EVM vulcanizates were superior to those of high-abrasion furnace carbon black/EVM vulcanizates. The tensile strength of the MDMA/EVM vulcanizate could reach 22.5 MPa and the tear strength was 83.5 kN/m, whereas its elongation at break remained over 300%, even when the MDMA content was 50 phr. FTIR analysis confirmed that polymerization of MDMA occurred under the initiation of DCP, and the polymerization conversion of MDMA decreased with the increase of MDMA content. When the MDMA content increased from 10 to 50 phr, the conversion of MDMA in EVM decreased from 68 to 20%. SEM and TEM observations indicated that 20 μm particles of MDMA powder changed into about 20 nm particles during the curing process, and the finer particles dispersed evenly in the EVM vulcanizates. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 93: 2379–2384, 2004

Ethylene–vinyl acetate copolymer (EVM) vulcanizates with good mechanical properties and high transparency were obtained using sodium methacrylate (NaMAA) as a reinforcing agent. Sodium methacrylate was in situ prepared through the neutralization of sodium hydroxide (NaOH) and methacrylic acid (MAA) in an EVM and used to reinforce the EVM cured by dicumyl peroxide (DCP). Different factors such as the DCP content, NaMAA content, and the mol ratio of NaOH/MAA were included to study their effects on the mechanical properties, optical properties, stress-relaxation behavior, and crosslink structure of the EVM vulcanizates. The rheological behavior of the EVM compounds was also investigated and compared with that of the high abrasion furnace carbon black (HAF)/EVM compounds. The experimental results show that with an increase of the NaMAA content the curing rate index (CR) of the EVM compounds is greatly speeded up, while the Mooney viscosities of the compounds remain nearly unchanged. The mechanical properties and optical properties of the NaMAA-reinforced EVM vulcanizates depend on the NaMAA content and the mol ratio of NaOH/MAA. The formulation of DCP of 3 phr and a NaOH/MAA mol ratio of 1.0 is recommended for the EVM vulcanizate with high mechanical properties. At a given NaOH/MAA mol ratio of 1.0, all the EVM vulcanizates are transparent and the light transmission is over 76% in the NaMAA content range of 10–50 phr. The NaMAA/EVM vulcanizates show faster stress relaxation and more obvious stress-softening effects than those of the HAF/EVM vulcanizates. Crosslink density analysis indicated that the EVM vulcanizates contain both covalent and ionic bonds. The ionic crosslink densities greatly increase with an increasing NaMAA content. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 89: 2192–2200, 2003

High performance ethylene-vinyl acetate copolymer (EVM) vulcanizate was obtained by directly blending EVM with magnesium methacrylate (MDMA) at a high level. The mechanical properties and crosslink density of the peroxide-cured EVM vulcanizates were investigated. Dynamic mechanical thermal analysis (DMTA) was used to study dynamic properties of EVM reinforced by MDMA. The results showed that the commercial MDMA can greatly improve the modulus at 100% and tensile strength of the EVM vulcanizates, while retaining their high elongation at break. DMTA results revealed that the glass transition temperature ( T g ) of the vulcanizate shifted to lower temperature with the increase of MDMA loading. Fourier transform infrared (FTIR) spectrum indicated that the double bonds in MDMA reacted after peroxide curing. Crosslink density analysis showed that EVM vulcanizate contained both ionic bonds and covalent bonds. Ionic crosslinks greatly increased with increasing amount of MDMA and dicumyl peroxide (DCP).

1. The aim of the study was to evaluate the pharmacokinetics of peramivir after single intravenous (i.v.) doses in healthy Chinese subjects.2. In a cross-over study, 12 subjects were given 300 and 600 mg peramivir by i.v. infusion. Blood and urine samples were collected at 17 designated time points and 7 designated intervals up to 36 h post-dose. Plasma and urine concentrations of peramivir were quantified by LC-MS/MS.3. After single i.v. doses of 300 and 600 mg peramivir, Cmax and AUC0–t of peramivir were 21.4 ± 3.7, 41.1 ± 5.3 mgċL−1 and 55.90 ± 10.62, 112.1 ± 13.2 mgċh L−1, respectively. Cmax and AUC increased in proportion to the dose. Within 12 h, accumulative urinary recoveries of peramivir after single i.v. doses of 300 and 600 mg peramivir were 84.31 ± 11.75% and 88.10 ± 7.39%, respectively.4. In healthy Chinese subjects, peramivir displayed linear pharmacokinetics in the range of 300–600 mg, and was primarily excreted via urine as unchanged drug.

Advances in the understanding of cardiovascular pathogenesis have highlighted that inflammation plays a central role in atherosclerotic coronary heart disease. Therefore, exploring pharmacologically based anti-inflammatory treatments to be used in cardiovascular therapeutics is worthwhile to promote the discovery of novel ways of treating cardiovascular disorders.The myocardial cell line H9c2(2-1) was exposed to lipopolysaccharide (LPS) in culture and resulted in a cellular pro-inflammation status. miR-21 microRNA levels were detected using quantitative real-time polymerase chain reaction (Q-RT-PCR). The influence of lovastatin on miR-21 under normal and pro-inflammatory conditions was tested after being added to the cell culture mixture for 24 hours. Conditional gene function of two predicted cardiovascular system relevant downstream targets of miR-21, protein phosphatase 1 regulatory subunit 3A (PPP1R3A) and signal transducer and activator of transcription 3 (STAT3), were analyzed with immunoblotting.Forty-eight hours of LPS treatment significantly increased the miR-21 to 170.71%± 34.32% of control levels (P = 0.002). Co-treatment with lovastatin for 24 hours before harvesting attenuated the up-regulation of miR-21 (P = 0.013). Twenty-four hours of lovastatin exposure up-regulated PPP1R3A to 143.85%± 21.89% of control levels in cardiomyocytes (P = 0.023). Lovastatin up-regulated the phosphorylation level of STAT3 compared to the background LPS pretreatment (P = 0.0077), this effect was significantly (P = 0.018) blunted when miR-21 was functionally inhibited.miR-21 plays a major role in the regulation of the cellular anti-inflammation effects of lovastatin.

A sensitive and selective LC-MS/MS method for the determination of agomelatine in human plasma was developed and validated. After simple liquid-liquid extraction, the analytes were separated on a Zorbax SB-C18 column (150 × 2.1 mm i.d., 5 µm) with an isocratic mobile phase consisting of 5 mm ammonium acetate solution (containing 0.1% formic acid) and methanol (30:70, v/v) at a flow-rate of 0.3 mL/min. The MS acquisition was performed in multiple reaction monitoring mode with a positive electrospray ionization source. The mass transitions monitored were m/z 244.1 → 185.3 and m/z 285.2 → 193.2 for agomelatine and internal standard, respectively. The methods were validated for selectivity, carry-over, matrix effects, calibration curves, accuracy and precision, extraction recoveries, dilution integrity and stability. The validated method was successfully applied to a pharmacokinetic study of agomelatine in Chinese volunteers following a single oral dose of 25 mg agomelatine tablet.