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Photofunctional materials based on donor-acceptor molecules have drawn intense attention due to their unique optical properties. Importantly, Systematic investigation of substitution effects on excited-state charge transfer dynamics of donor-acceptor molecules is a powerful approach for identifying application-relevant design principles. Here, by coupling phenothiazine (PTZ) at the ortho-, meta-, and para-positions of the benzene ring of benzophenone (BP), three regioisomeric BP-PTZ dyads were designed to understand the relationship between substituted positions and excited-state evolution channels. Ultrafast transient absorption is used to detect and trace the transient species and related evolution channels of BP-PTZ dyads at excited state. In a non-polar solvent, BP-o-PTZ undergoes the through-space charge transfer process to produce a singlet charge-transfer (1CT) state, which subsequently proceeds the intersystem crossing process and transforms into a triplet charge-transfer (3CT) state; BP-m-PTZ experiences intramolecular charge transfer (ICT) process to generate the 1CT state, which subsequently transforms into the 3CT state by the intersystem crossing (ISC) and finally converts into the local-excited triplet (3LE) state; as for BP-p-PTZ, only 3LE states can be detected after the ISC process from the 1CT state. On the other hand, the twisted ICT states are generated via twisted motion between the donor and acceptor for all BP-PTZ dyads or planarization of the PTZ unit in high polar solvents. The excited-state theoretical calculations unveil that the features of ICT and intramolecular interaction between the three dyads play a decisive role in determining the through-bond charge transfer and through-space charge transfer processes. Also, these results demonstrate that the excited-state evolution channels of PTZ derivatives could be modified by tuning the substituted positions of the donor-acceptor dyads. This study provides a deep perspective for the substitute-position effect on donor-acceptor-type PTZ derivatives. [ABSTRACT FROM AUTHOR]

The densification behaviors of MgO‐doped‐Al2O3 ceramics in the flashing stage and the steady stage were investigated using the classic kinetic model. The results show that the most densification of MgO‐doped Al2O3 was completed during the flashing stage. The densification mechanism transferred from particle rearrangement resulted from Columbic force among particles under the effect of electrical field in the flashing stage to the lattice diffusion in the steady stage. Therefore, the densification rate in the steady stage dramatically decreased. Additionally, the estimated densification activation energy in the steady stage of flash sintering is 396 kJ/mol, much lower than the activation densification of lattice diffusion measured from conventional sintering, likely due to the effect of electric field/current‐induced point defects on the diffusion. [ABSTRACT FROM AUTHOR]

Herein, the effects of electrical field on the microstructure and mechanical properties of flash sintered (FS-ed) MgO-doped-Al 2 O 3 ceramics were investigated. The results showed that compared with pressureless sintered sample without electrical field, the relative density of FS-ed alumina ceramics were remarkably enhanced, and increased from 91.92% to 99.36%, then decreased to 94.73% since the applied electric field increased from 2500 V/cm to 5000 V/cm. In addition, the FS-ed MgO-doped-Al 2 O 3 ceramics exhibited ultra-fine grain (mean grain size ≤0.32 μm) and homogeneous microstructures. The mechanical properties including hardness and fracture toughness of the FS-ed specimens mainly depended on their relative densities and microstructures. Consequently, they possessed excellent hardness and fracture toughness, reaching 20.89 GPa and 4.44 MPa m1/2, respectively. [ABSTRACT FROM AUTHOR]

MgO-doped-Al 2 O 3 ceramic discs were fabricated by flash sintering (FS) and pressureless sintering (PS). The results showed that MgO-doped Al 2 O 3 exhibited typical characteristics of flash sintering under an electric field in excess 2500 V/cm. Compared with the PS- fabricated specimen, the flash sintered specimens exhibited sub-micron grains (≤760 nm) and homogeneous microstructures. The relative density of the flash sintered MgO-doped Al 2 O 3 ceramics increased with current density, reaching 99.91 % when the current density increased to 7 mA/mm2. The FS-fabricated sample exhibited higher hardness (21.02 GPa) and fracture toughness (3.46 MPa m1/2) than PS-fabricated sample. [ABSTRACT FROM AUTHOR]

The multi-scale flow mechanism is crucial for the force and heat loaded on near-space vehicles, the control of spacecraft, and the propelling and cooling of microelectromechanical systems. Since the continuum and rarefied flows often coexist, the prediction of multi-scale flow is complicated. One efficient way is constructing numerical methods by adopting the multi-scale temporal integral solutions (or characteristic line solutions) for model equations in the gas-kinetic theory. The model equations can be classified into the Fokker–Planck type and Bhatnagar–Gross–Krook type (BGK-type). Since these numerical methods are strictly based on model equations, they are also restricted by the model equations. The difficulty in constructing a model equation that has complete asymptotic preserving property for gas mixture with non-equilibrium internal energy will prevent the further extension of these methods. Therefore, this paper addresses the question whether a multi-scale numerical method can be established by directly adopting the relaxation rates of macroscopic variables, such as stress and heat flux, because these relaxation rates are the aggregate effect of particle collisions and are the essential constrains when constructing model equations. Since the particle-BGK method is concise, its collision term is replaced by the direct relaxation process, where the macroscopic variables first evolve according to their relaxation rates, and then, the after-collision molecules get their velocities from the after-evolution macroscopic variables. Therefore, the modified particle-BGK method does not depend on model equations. Finally, the validity and accuracy of the present method are examined with homogenous relaxation case, shock tube, shock structure, cavity flow, and hypersonic cylinder flow in transitional regime. [ABSTRACT FROM AUTHOR]

To prolong the service life and structural stability of CoCrNiAlY–yttria stabilized zirconia–LaMgAl11O19 (LaMA) dual ceramic coating during high temperature exposure, an AlY plating layer was deposited on top LaMA. Results revealed that this coating without AlY plating layer showed a rapid mass increase from 6.62 mg/cm2 at 20 h to 10.63 mg/cm2 at 80 h, but also suffered from a fast TGO growth and severe elemental diffusion, resulting in an exacerbating interface fracture of the coating. However, AlY plating layer was first oxidized, and Y2O3 induced the formation of a dense α‐Al2O3 reaction layer on the top LaMA layer, which greatly prevented the internal penetration of O2. This coating with AlY plating layer showed a relatively stable structure, a very slow TGO growth, and a slight mass increase trend from 8.19 mg/cm2 at 20 h to 8.73 mg/cm2 at 80 h. Potential oxidation damage mechanisms of the coatings with or without AlY plating layer were comprehensively clarified. [ABSTRACT FROM AUTHOR]

By utilizing the bipolarity of 1,2‐diphenylphenanthroimidazole (PPI), two types of asymmetrical tripartite triads (PPI‐TPA and PPI‐PCz) were designed with triphenylamine (TPA) and 9‐phenylcarbazole (PCz). These triads are deep‐blue luminescent materials with a high fluorescence quantum yield of nearly 100 %. To trace the photophysical behaviors of these triads, their excited‐state evolution channels and interchromophoric interactions were investigated by ultrafast time‐resolved transient absorption and excited‐state theoretical calculations. The results suggest that the electronic nature, asymmetrical tripartite structure, and electron–hole distance of these triads, as well as solvent polarity, determine the lifetime of intramolecular charge transfer (ICT). Interestingly, PPI‐PCz triads show anti‐Kasha ICT, and the charge‐transfer direction among the triads is adjustable. For the PPI‐TPA triad, the electron is transferred from TPA to PPI, whereas for the PPI‐PCz triad the electron is pushed from PPI to PCz. Exploration of the excited‐state ICT in these triads may pave the way to design better luminescent materials in the future. [ABSTRACT FROM AUTHOR]

Background: There is a growing body of evidences indicating iNOS has involved in the pathogenesis of SLE. However, the role of iNOS in SLE is inconsistency. This systematic review was designed to evaluate the association between iNOS and SLE. Results: Six studies were included, reporting on a total of 277 patients with SLE. The meta-analysis showed that SLE patients had higher expression of iNOS at mRNA level than control subjects (SMD = 2.671, 95%CI = 0.446–4.897, z = 2.35, p = 0.019), and a similar trend was noted at the protein level (SMD = 3.602, 95%CI = 1.144–6.059, z = 2.87, p = 0.004) and positive rate of iNOS (OR = 9.515, 95%CI = 1.915–47.281, z = 2.76, p = 0.006) were significantly higher in SLE group compared with control group. No significant difference was observed on serum nitrite level between SLE patients and control subjects (SMD = 2.203, 95%CI = -0.386–4.793, z = 1.64, p = 0.095). The results did not modify from different sensitivity analysis, representing the robustness of this study. No significant publication bias was detected from Egger's test. Conclusions: There was a positive correlation between increasing iNOS and SLE. However, the source of iNOS is unknown. Besides NO pathway, other pathways also should be considered. More prospective random studies are needed in order to certify our results. [ABSTRACT FROM AUTHOR]

• The small molecule II-6s shows fungicidal effects against Candida albicans (C. albicans) and sensitizes C. albicans resistant strain to fluconazole. • II-6s synergises with fluconazole by inhibiting the membrane efflux pump of C. albicans. • II-6s induces mitochondrial damage of C. albicans and affects energy metabolism. • II-6s inhibits MAPK signalling pathway, especially Hog1 of C. albicans. Candida albicans (C. albicans) is the most common opportunistic fungal species in the oral cavity. The emergence of drug resistance of C. albicans has necessitated the development of novel antifungal agents. This study evaluated the antifungal activity of a previously developed antimicrobial small molecule, namely II-6s, and explored its potential synergism with fluconazole against C. albicans and the underlying mechanisms. The antifungal effects of II-6s against C. albicans were evaluated with microdilution and time-killing assays. Synergism of II-6s with fluconazole was determined by calculating the fractional inhibitory concentration index (FICI). The effects of II-6s on efflux pump, mitochondrial function and energy metabolism were examined to investigate the underlying mechanism of synergism. The antifungal mechanism of II-6s against C. albicans was further explored with RNA-seq and validated with specific mutant strains. II-6s exhibited a fungicidal effect against C. albicans with a minimum fungicidal concentration of 31.25 µg/mL. II-6s also inhibited C. albicans biofilm with a sessile minimum inhibitory concentration at 500 µg/mL. More importantly, II-6s showed a synergistic effect with fluconazole against a fluconazole-resistant strain of C. albicans , which expressed elevated levels of CDR1 (FICI < 0.5). II-6s inhibited the efflux pump activity of C. albicans. Consistently, II-6s inhibited energy metabolism of C. albicans by reducing the mitochondrial membrane potential and ATP generation, and inhibited utilisation of the non-fermentable carbon source. II-6s also inhibited the mitogen-activated protein kinase signal pathway, particularly HOG1 , which may explain its antifungal activity against C. albicans. The small molecule II-6s inhibits the growth of C. albicans by targeting HOG1. II-6s also synergises with fluconazole by inhibiting the drug efflux pump, representing a promising antifungal agent for the control of candidiasis. [ABSTRACT FROM AUTHOR]

A novel Al plating layer was deposited on the CoCrNiAlY–YSZ–RSZ dual - ceramic thermal barrier coating. The hot corrosion behaviors of these coatings in molten sulfate mixture were studied by the detail characterizations. This coating without Al plating possessed a fast mass gain trend, severe elemental diffusion and rapid TGO growth during the hot sulfate exposure, resulting in a significant increase in mass gain from 6.12 mg/cm2 at 20 h to 13.67 mg/cm2 at 100 h and aggravated coating fracture. In comparison, a continuously dense Al 2 O 3 barrier layer formed on the coating's surface, preventing or delaying the infiltration of the molten sulfate and oxygen, and eventually led to an enhanced corrosion resistance. This coating with Al plating showed a slight mass gain from 8.20 mg/cm2 at 20 h to 9.31 mg/cm2 at 100 h, but also exhibited very slow TGO growth and stable structure. The potential molten sulfate corrosion mechanisms of these coatings with and without Al plating were systematically discussed. [ABSTRACT FROM AUTHOR]

Multi-scale phenomena are prevalent and significant across various disciplines. For multi-scale flow physics in the gas-kinetic theory based on Boltzmann equation or its simplified mathematical models (called Boltzmann model equations), the multi-scale mechanism can be modeled by the philosophy of unified modeling, where the free transport behaviors of gas particles and their collision behaviors are coupled by the temporal integral solutions (or characteristic line solutions) of Boltzmann model equations, which leads to a unified/multi-scale property in all scales. Also, the stochastic particle methods are based on these Boltzmann model equations. The corresponding numerical methods are, thus, limited by these model equations. This paper aims to overcome this restriction by replacing these modeled collision operators with a simple direct relaxation (DR) process. Since the collision term of Boltzmann model equation should fulfill the correct relaxation rates of non-equilibrium macro-variables, such as stress tensor and heat flux vector, along with other basic properties, such as conservation and H theorem, the DR process is designed to be directly based on these crucial relaxation rates. Therefore, with the DR strategy for calculating particle collisions, the numerical method can be established without constructing collision operator. Furthermore, the DR has the flexibility and simplicity to recover various models. In this work, Xu's and Yuan's new models are recovered in to illustrate the validation and performance of DR. Moreover, since at the inlet/outlet boundaries, subsonic, supersonic, and hypersonic flows can simultaneously exist, a generalized numerical boundary condition is also considered in the particle methods developed in this paper. Finally, the validation and accuracy of the present method are examined with a series of test cases. [ABSTRACT FROM AUTHOR]

The nearly fully dense ultra‐high pure (>99.99%) α‐Al2O3 ceramics were prepared by flash sintering at the furnace temperature of 1300°C. Compared with the samples sintered at 1300 and 1650°C without electrical field, the flash‐sintered samples exhibited remarkably improved density and finer grains. The flash‐sintered samples also exhibited high hardness, which is even higher than that of the hot‐pressed sample. Therefore, it is believed that flash sintering could be an effective technique for the preparation of ultra‐high pure alumina ceramics. [ABSTRACT FROM AUTHOR]

• Monoamine oxidase A was immobilized on carboxyl terminated magnetic beads (MBs@COOH@MAOA) for the first time. • MBs@COOH@MAOA showed much better performance in ligand fishing than MBs@NH 2 @MAOA. • H. zeylanica was explored for screening MAOA inhibitors for the first time. • Six potential monoterpene indoles were fished out and identified as MAOA inhibitors. In this study, a novel magnetic bead-based ligand fishing method was developed for rapid discovery of monoterpene indoles as monoamine oxidase A inhibitors from natural products. In order to improve the screening efficiency, two different magnetic beads, i.e. amine and carboxyl terminated magnetic beads, were comprehensively compared in terms of their ability to immobilize monoamine oxidase A (MAOA), biocatalytic activity and specific adsorption rates for affinity ligands. Carboxyl terminated magnetic beads performed better for MAOA immobilization and demonstrated superior performance in ligand fishing. The MAOA immobilized magnetic beads were applied to screen novel monoamine oxidase inhibitors in an alkaloid-rich plant, Hunteria zeylanica. Twelve MAOA affinity ligands were screened out, and ten of them were identified as monoterpene indole alkaloids by HPLC-Obitrap-MS/MS. Among them, six ligands, namely geissoschizol, vobasinol, yohimbol, dihydrocorynanthenol, eburnamine and (+)-isoeburnamine which exhibited inhibitory activity against MAOA with low IC 50 values. To further explore their inhibitory mechanism, enzyme kinetic analysis and molecular docking studies were conducted. [ABSTRACT FROM AUTHOR]

Hyperspectral and light detection and ranging (LiDAR) data fusion and classification has been an active research topic, and intensive studies have been made based on mathematical morphology. However, matrix-based concatenation of morphological features may not be so distinctive, compact, and optimal for classification. In this work, we propose a novel Coupled Higher-Order Tensor Factorization (CHOTF) model for hyperspectral and LiDAR data classification. The innovative contributions of our work are that we model different features as multiple third-order tensors, and we formulate a CHOTF model to jointly factorize those tensors. Firstly, third-order tensors are built based on spectral-spatial features extracted via attribute profiles (APs). Secondly, the CHOTF model is defined to jointly factorize the multiple higher-order tensors. Then, the latent features are generated by mode-n tensor-matrix product based on the shared and unshared factors. Lastly, classification is conducted by using sparse multinomial logistic regression (SMLR). Experimental results, conducted with two popular hyperspectral and LiDAR data sets collected over the University of Houston and the city of Trento, respectively, indicate that the proposed framework outperforms the other methods, i.e., different dimensionality-reduction-based methods, independent third-order tensor factorization based methods, and some recently proposed hyperspectral and LiDAR data fusion and classification methods. [ABSTRACT FROM AUTHOR]

• A novel modeling approach for failure analysis is proposed. • Harmonic response analysis was performed to verify the FEM modeling approach. • The vibration response and fatigue life were calculated by transient dynamic analysis method. The installing angle of the static blades of the compressor in gas turbines affects the aerodynamic forces which leads to the vibration variation of the dynamic blades, and may causes the High Cyclic Fatigue failure of the blades. In order to study the influence mechanism of the installing angle on the fatigue life of the blades, the finite element model of the cyclic symmetrical impeller structure is established, and the aerodynamic loads under the various configurations are exerted to the surface of the blade. The modal analyses under the airflow prestress and the centrifugal force are carried out and the main natural frequencies are obtained. In order to verify correctness of the finite element modeling method, the harmonic response analysis is also conducted. The transient dynamic method is adopted to solve the vibrational responses of the blade under consideration of the Rayleigh damping. The displacement responses of the key points on the blade are calculated and are compared with the experimental results to select the reasonable damping for the life analysis. Applying Goodman and S-N curves, the fatigue life of the blade is analyzed to assess the safety of the structures. By comparison of the vibrational displacement of the experiment and the numerical calculation, the reasonable damping value is determined for the vibration response and fatigue life calculation. The fatigue life calculations of the two configurations are carried out under the premise of the approximate same mean values of the dynamic stress, the influence of the amplitude of the dynamic forces on the fatigue life is very significant. The amplitude and mean value of the dynamic stress at the danger points of the blade root should be paid more attention. [ABSTRACT FROM AUTHOR]

The article presents a case study of 58-year old man whose echocardiography revealed a tumor in the left atrium and mild mitral regurgitation of heart after he reported shortness of breath on exertion.

Background Heterozygous loss-of-function mutations in the tumour necrosis factor alpha induced protein 3 (TNFAIP3) gene cause an early-onset auto-inflammatory disease named haploinsufficiency of A20 (HA20). Here we describe three unrelated patients with autoimmune lupus nephritis (LN) phenotypes carrying three novel mutations in the TNFAIP3 gene. Methods Whole-exome sequencing (WES) was used to identify the causative mutations in three biopsy-proven LN patients. Sanger sequencing and quantitative polymerase chain reaction (qPCR) were used to validate the mutations identified by WES. RNA sequencing, qPCR and cytometric bead array was used to detect inflammatory signatures in the patients. Results The patients predominantly presented with an autoimmune phenotype, including autoimmune haemolytic anaemia, multipositive autoantibodies and LN. Additionally, novel phenotypes of allergy and pericardial effusion were first reported. WES identified three novel heterozygous mutations in the TNFAIP3 gene, including a novel splicing mutation located in the canonical splicing site (c.634+2T>C) resulting in an intron 4 insertion containing a premature stop codon, a de novo novel copy number variation (exon 7–8 deletion) and a novel nonsense mutation c.1300_1301delinsTA causing a premature stop codon. We further identified hyperactivation signatures of nuclear factor- kappa B and type I IFN signalling and overproduction of pro-inflammatory cytokines in the blood. This report expanded the phenotype to a later age, as two girls were diagnosed at age 3 years and one man at age 29 years. Conclusions Kidney involvement may be the main feature of the clinical spectrum of HA20, even in adults. Genetic screening should be considered for early-onset LN patients. [ABSTRACT FROM AUTHOR]

Objectives: Given the limited tocilizumab (TCZ) treatment data for systemic juvenile idiopathic arthritis (sJIA) in China, we evaluated the long-term efficacy and safety of TCZ in Chinese patients with sJIA.In this multicentre, interventional Phase IV study, patients with sJIA and inadequate clinical response to non-steroidal anti-inflammatory drugs/corticosteroids received TCZ infusions every 2 weeks based on body weight (< 30 kg, 12 mg/kg; ≥ 30 kg, 8 mg/kg), over a 52-week open-label period and an 8-week safety follow-up period. The primary endpoint was the proportion of patients with a JIA American College of Rheumatology (ACR) 30 response and absence of fever at Week 12.Sixty-two patients were enrolled and treated (12-mg/kg group, 34; 8-mg/kg group, 28). At Week 12, 87.1% (95% confidence interval 78.8%–95.4%) of patients had JIA ACR 30 response and absence of fever; Week 52 results were similar. The proportion of JIA ACR 30/50/70/90 responders rapidly increased at Week 12, up to Week 52. High-sensitivity C-reactive protein (hsCRP) levels decreased within 4 weeks; 44/58 patients (75.9%) with elevated baseline hsCRP recovered at Week 52. Childhood Health Assessment Questionnaire pain scores, disability index scores, and mean corticosteroid dose decreased over time. Height standard deviation score changes at Week 52 indicated catch-up growth. Most adverse events (AEs) were mild (serious AE incidence, 17.7%). No deaths or macrophage activation syndrome occurred.This is the first multicentre trial to report the efficacy and safety of TCZ in Chinese patients with sJIA at 52 weeks. No new safety concerns were found.Key points• This is the first multicentre trial providing strong evidence for tocilizumab (TCZ) treatment for systemic juvenile idiopathic arthritis (sJIA) in China.• The study reported TCZ had good efficacy and favourable safety profiles in Chinese sJIA patients in the long term (52 weeks).• TCZ treatment showed rapid disease control, which was maintained over time, catch-up growth benefits in patients, tapering and discontinuation of corticosteroids, and improved quality of life.Method: Given the limited tocilizumab (TCZ) treatment data for systemic juvenile idiopathic arthritis (sJIA) in China, we evaluated the long-term efficacy and safety of TCZ in Chinese patients with sJIA.In this multicentre, interventional Phase IV study, patients with sJIA and inadequate clinical response to non-steroidal anti-inflammatory drugs/corticosteroids received TCZ infusions every 2 weeks based on body weight (< 30 kg, 12 mg/kg; ≥ 30 kg, 8 mg/kg), over a 52-week open-label period and an 8-week safety follow-up period. The primary endpoint was the proportion of patients with a JIA American College of Rheumatology (ACR) 30 response and absence of fever at Week 12.Sixty-two patients were enrolled and treated (12-mg/kg group, 34; 8-mg/kg group, 28). At Week 12, 87.1% (95% confidence interval 78.8%–95.4%) of patients had JIA ACR 30 response and absence of fever; Week 52 results were similar. The proportion of JIA ACR 30/50/70/90 responders rapidly increased at Week 12, up to Week 52. High-sensitivity C-reactive protein (hsCRP) levels decreased within 4 weeks; 44/58 patients (75.9%) with elevated baseline hsCRP recovered at Week 52. Childhood Health Assessment Questionnaire pain scores, disability index scores, and mean corticosteroid dose decreased over time. Height standard deviation score changes at Week 52 indicated catch-up growth. Most adverse events (AEs) were mild (serious AE incidence, 17.7%). No deaths or macrophage activation syndrome occurred.This is the first multicentre trial to report the efficacy and safety of TCZ in Chinese patients with sJIA at 52 weeks. No new safety concerns were found.Key points• This is the first multicentre trial providing strong evidence for tocilizumab (TCZ) treatment for systemic juvenile idiopathic arthritis (sJIA) in China.• The study reported TCZ had good efficacy and favourable safety profiles in Chinese sJIA patients in the long term (52 weeks).• TCZ treatment showed rapid disease control, which was maintained over time, catch-up growth benefits in patients, tapering and discontinuation of corticosteroids, and improved quality of life.Results: Given the limited tocilizumab (TCZ) treatment data for systemic juvenile idiopathic arthritis (sJIA) in China, we evaluated the long-term efficacy and safety of TCZ in Chinese patients with sJIA.In this multicentre, interventional Phase IV study, patients with sJIA and inadequate clinical response to non-steroidal anti-inflammatory drugs/corticosteroids received TCZ infusions every 2 weeks based on body weight (< 30 kg, 12 mg/kg; ≥ 30 kg, 8 mg/kg), over a 52-week open-label period and an 8-week safety follow-up period. The primary endpoint was the proportion of patients with a JIA American College of Rheumatology (ACR) 30 response and absence of fever at Week 12.Sixty-two patients were enrolled and treated (12-mg/kg group, 34; 8-mg/kg group, 28). At Week 12, 87.1% (95% confidence interval 78.8%–95.4%) of patients had JIA ACR 30 response and absence of fever; Week 52 results were similar. The proportion of JIA ACR 30/50/70/90 responders rapidly increased at Week 12, up to Week 52. High-sensitivity C-reactive protein (hsCRP) levels decreased within 4 weeks; 44/58 patients (75.9%) with elevated baseline hsCRP recovered at Week 52. Childhood Health Assessment Questionnaire pain scores, disability index scores, and mean corticosteroid dose decreased over time. Height standard deviation score changes at Week 52 indicated catch-up growth. Most adverse events (AEs) were mild (serious AE incidence, 17.7%). No deaths or macrophage activation syndrome occurred.This is the first multicentre trial to report the efficacy and safety of TCZ in Chinese patients with sJIA at 52 weeks. No new safety concerns were found.Key points• This is the first multicentre trial providing strong evidence for tocilizumab (TCZ) treatment for systemic juvenile idiopathic arthritis (sJIA) in China.• The study reported TCZ had good efficacy and favourable safety profiles in Chinese sJIA patients in the long term (52 weeks).• TCZ treatment showed rapid disease control, which was maintained over time, catch-up growth benefits in patients, tapering and discontinuation of corticosteroids, and improved quality of life.Conclusion: Given the limited tocilizumab (TCZ) treatment data for systemic juvenile idiopathic arthritis (sJIA) in China, we evaluated the long-term efficacy and safety of TCZ in Chinese patients with sJIA.In this multicentre, interventional Phase IV study, patients with sJIA and inadequate clinical response to non-steroidal anti-inflammatory drugs/corticosteroids received TCZ infusions every 2 weeks based on body weight (< 30 kg, 12 mg/kg; ≥ 30 kg, 8 mg/kg), over a 52-week open-label period and an 8-week safety follow-up period. The primary endpoint was the proportion of patients with a JIA American College of Rheumatology (ACR) 30 response and absence of fever at Week 12.Sixty-two patients were enrolled and treated (12-mg/kg group, 34; 8-mg/kg group, 28). At Week 12, 87.1% (95% confidence interval 78.8%–95.4%) of patients had JIA ACR 30 response and absence of fever; Week 52 results were similar. The proportion of JIA ACR 30/50/70/90 responders rapidly increased at Week 12, up to Week 52. High-sensitivity C-reactive protein (hsCRP) levels decreased within 4 weeks; 44/58 patients (75.9%) with elevated baseline hsCRP recovered at Week 52. Childhood Health Assessment Questionnaire pain scores, disability index scores, and mean corticosteroid dose decreased over time. Height standard deviation score changes at Week 52 indicated catch-up growth. Most adverse events (AEs) were mild (serious AE incidence, 17.7%). No deaths or macrophage activation syndrome occurred.This is the first multicentre trial to report the efficacy and safety of TCZ in Chinese patients with sJIA at 52 weeks. No new safety concerns were found.Key points• This is the first multicentre trial providing strong evidence for tocilizumab (TCZ) treatment for systemic juvenile idiopathic arthritis (sJIA) in China.• The study reported TCZ had good efficacy and favourable safety profiles in Chinese sJIA patients in the long term (52 weeks).• TCZ treatment showed rapid disease control, which was maintained over time, catch-up growth benefits in patients, tapering and discontinuation of corticosteroids, and improved quality of life.Given the limited tocilizumab (TCZ) treatment data for systemic juvenile idiopathic arthritis (sJIA) in China, we evaluated the long-term efficacy and safety of TCZ in Chinese patients with sJIA.In this multicentre, interventional Phase IV study, patients with sJIA and inadequate clinical response to non-steroidal anti-inflammatory drugs/corticosteroids received TCZ infusions every 2 weeks based on body weight (< 30 kg, 12 mg/kg; ≥ 30 kg, 8 mg/kg), over a 52-week open-label period and an 8-week safety follow-up period. The primary endpoint was the proportion of patients with a JIA American College of Rheumatology (ACR) 30 response and absence of fever at Week 12.Sixty-two patients were enrolled and treated (12-mg/kg group, 34; 8-mg/kg group, 28). At Week 12, 87.1% (95% confidence interval 78.8%–95.4%) of patients had JIA ACR 30 response and absence of fever; Week 52 results were similar. The proportion of JIA ACR 30/50/70/90 responders rapidly increased at Week 12, up to Week 52. High-sensitivity C-reactive protein (hsCRP) levels decreased within 4 weeks; 44/58 patients (75.9%) with elevated baseline hsCRP recovered at Week 52. Childhood Health Assessment Questionnaire pain scores, disability index scores, and mean corticosteroid dose decreased over time. Height standard deviation score changes at Week 52 indicated catch-up growth. Most adverse events (AEs) were mild (serious AE incidence, 17.7%). No deaths or macrophage activation syndrome occurred.This is the first multicentre trial to report the efficacy and safety of TCZ in Chinese patients with sJIA at 52 weeks. No new safety concerns were found.Key points• This is the first multicentre trial providing strong evidence for tocilizumab (TCZ) treatment for systemic juvenile idiopathic arthritis (sJIA) in China.• The study reported TCZ had good efficacy and favourable safety profiles in Chinese sJIA patients in the long term (52 weeks).• TCZ treatment showed rapid disease control, which was maintained over time, catch-up growth benefits in patients, tapering and discontinuation of corticosteroids, and improved quality of life. [ABSTRACT FROM AUTHOR]

Glucocorticoids (GCs) are potent anti-inflammatory and immunosuppressant medications and remain the cornerstone of systemic lupus erythematosus (SLE) therapy. However, ongoing exposure to GCs has the potential to elicit multiple adverse effects. Considering the irreplaceability of GCs in SLE therapy, it is important to explore the optimal regimen of GCs. Here, we compared the long-term efficacy and safety of pulsed and oral GC therapy in a lupus-prone mouse model. Mice were grouped using a randomized block design. We monitored survival rates, proteinuria, serum autoantibodies, and complement 3 (C3) levels up to 28 weeks of age, and assessed renal damage, bone quality, lipid deposition in the liver and marrow, glucose metabolic parameters, and levels of hormones of the hypothalamic-pituitary-adrenal (HPA) axis. Finally, we explored the mechanisms underlying the superior efficacy of the pulse regimen over oral prednisone regimen. We found that both GC regimens alleviated the poor survival rate, proteinuria, and glomerulonephritis, while also reducing serum autoantibodies and increasing the level of C3. The pulsed GC regimen showed less resistance to insulin, less suppression of the HPA axis, less bone loss, and less bone marrow fat deposition than the oral GC regimen. Additionally, GC-induced leucine zipper (GILZ) was significantly overexpressed in the GC pulse group. These results suggest that the GC pulse regimen ameliorated symptoms in lupus-prone mice, with fewer side effects, which may be related to GILZ overexpression. Our findings offer a potentially promising GC treatment option for SLE. [Display omitted] • Methylprednisolone (MP) pulse regimen has fewer side effects than oral prednisone regimen. • MP pulse regimen and oral prednisone regimen have similar efficacy. • GILZ overexpression may be a potential mechanism for MP pulse regimen's fewer side effects. • MP pulse regimen is a potentially promising GC treatment option for SLE. [ABSTRACT FROM AUTHOR]

SiC w -Al 2 O 3 -YAG ceramic composites were prepared by hot oscillatory pressing (HOP) and traditional hot pressing (HP). The results showed that compared with static pressure, the oscillatory pressure could effectively promote densification and mechanical properties of the composites. The sample prepared by HOP exhibited higher hardness (15.72 ± 0.20 GPa) and fracture toughness (7.13 ± 0.19 MPa m1/2). The current work suggests that HOP could be an effective technique for the preparation of whisker reinforced ceramic composites. [ABSTRACT FROM AUTHOR]

Objective Type 1 regulatory T (Tr1) cells are involved in the pathogenesis of numerous immune-mediated diseases. However, little is known about whether and how Tr1 cells affect the development of IgA vasculitis (IgAV). We aimed to investigate this question in IgAV patients. Methods. Tr1 cells in peripheral blood and kidney tissue of IgAV patients were analysed by multi-parametric flow cytometry and immunofluorescence techniques. An in vitro assay of suppression of T cell proliferation and cytokine release was performed to evaluate the function of Tr1 cells. Real-time PCR and cell stimulation in vitro were used to explore the roles of IL-27 and early growth response gene 2 (EGR2). Results The frequency of Tr1 cells was decreased in peripheral blood but increased in kidney tissue from IgAV patients. A defective suppressive function of Tr1 cells in IgAV was observed. The frequency of Tr1 cells and the cytokines secreted by them were up-regulated in the presence of recombinant IL-27 in vitro. Moreover, IL-27 also increased the expression of EGR2. Furthermore, lower frequency of Tr1 cells during remission had a higher recurrence rate. Conclusion Tr1 cells are involved in the pathogenesis of IgAV. The low IL-27 in IgAV is responsible for impaired frequency and function of Tr1 cells, and EGR2 may be the specific transcription factor involved in the progression. Tr1 may be a risk factor for IgAV recurrence. [ABSTRACT FROM AUTHOR]

Environmentally friendly fabrication of engineered bamboo lumber is enabled by the application of renewable, formaldehyde-free bio-adhesives. In this study, protein-based adhesives made from pig blood (PB) were developed for this purpose. PB was modified by alkali (NaOH) and glutaraldehyde into either alkali-modified pig blood adhesive (APB), glutaraldehyde-modified pig blood adhesive (GPB), or alkali-and-glutaraldehyde-modified pig blood adhesive (AGPB), which were expected to be more water-resistant. Two-ply laminated bamboo lumber samples were assembled, and their bonding strengths were measured. The thermal properties, presence of functional groups, and cross-sectional micro-morphologies of the modified adhesives and unmodified PB were characterized by thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM). The thermal stabilities of all the modified adhesives were improved compared to that of the unmodified PB. FTIR confirmed that the NaOH treatment successfully induced the unfolding of the PB protein, exposing the hydrophobic groups in the APB and that glutaraldehyde became grafted onto primary amides in the AGPB. Compared with the PB and APB, the cross-sectional micro-morphologies of the GPB and AGPB were more homogeneous and compact. The wet shear strength of the laminated bamboo lumber (LBL) was clearly increased by the modified adhesives. The AGPB had a higher wet shear strength of 4.6 MPa. Thus, the GPB and AGPB can be considered as potential protein adhesives for use in a variety of engineered bamboo products. [ABSTRACT FROM AUTHOR]

A novel Pt doping was designed to improve the thermal stability of CrWN coating in a nitrogen atmosphere. The deposited CrWN coating possessed a multilayer structure and a coherent growth mode, resulting in considerable mechanical strength and large size grain. An uneven atomic migration also occurred during the coating deposition resulting in a coarse cluster surface. The W atom enrichment layer was rapidly oxidized during the nitrogen annealing and thus led to serious mechanical degradation. The doping of Pt atoms effectively blocks the coherent growth of the grains, which creates a significant mixing effect, leading to a smooth surface with uniform element distribution. Although local incoherent growth compromised the mechanical behavior of CrWN–Pt coating, but the prominent pinning effect of dispersed Pt oxides can reduce oxidative erosion rate and stabilize the oxide layer up to some extent during nitrogen annealing. • Structure and thermal stability of Pt doped CrWN coating were investigated. • The CrWN coating showed a rough surface and poor thermal stability. • Pt doping triggered a significant structural modification and pinning effect. • The CrWN–Pt coating showed a smooth surface and good thermal stability. [ABSTRACT FROM AUTHOR]

Background: Immunoglobulin A vasculitis (IgAV) is the most common vasculitis in children. Previously, we demonstrated that patients with IgAV show abnormal proliferation of cluster of differentiation (CD)4+C-X-C chemokine receptor type (CXCR)5+ follicular helper T (Tfh) cells. Here, we explored the status of Tfh cell subsets and plasma cytokine levels in patients with IgAV. Methods: CD4+CXCR5+CD45RA−, CD45RA-CXCR3+CCR6−, CD45RA−CXCR3−CCR6−, CD45RA−CXCR3−CCR6+, and CD45RA−CXCR3+CCR6+ Tfh cell fractions and plasma concentrations of interferon-γ, interleukin (IL)-4, and IL-17A were evaluated by flow cytometry and a flow cytometric bead array, respectively, in 30 patients with IgAV and 15 healthy controls (HCs). Results: Tfh2 and Tfh17 cell fractions were larger and the Tfh2+Tfh17/Tfh1 ratio and plasmaIL-4 and -17A levels were higher in patients with IgAV than in the HCs. Only Tfh1 cell counts were reduced in the abdominal subtype. The elevations in Tfh2 and Tfh17 cell counts and plasma IL-4 levels were abrogated by treatment. Tfh2 cell number was positively correlated with serum IgA and plasma IL-4 levels, but negatively correlated with the serum C4 concentration, while Tfh17 cell number was positively correlated with the serum IgA level and Tfh2 cell counts. Conclusions: Abnormally high numbers of Tfh2 and Tfh17 cells are linked to the occurrence and development of IgAV, but are not specific to the abdominal type. Only Tfh1 cells play a critical role in abdominal-type IgAV. [ABSTRACT FROM AUTHOR]

Previous studies have reported inconsistent results on the relationship between alcohol intake and the risk of systemic lupus erythematosus (SLE). Therefore, we conducted a systematic review and meta-analysis to illustrate the potential role of alcohol intake on the progression of SLE.An electronic search of the PubMed, EmBase, and the Cochrane library databases was conducted from their inception up to March 2020. Observational studies that investigated the role of alcohol intake on the risk of SLE were eligible for inclusion in this study. The pooled odds ratio (OR) with 95% confidence interval (CI) was calculated as an effect estimate using the random-effects model.Seven case-control studies (n = 3, 251) and three cohort studies (n = 322, 479) were selected for the final meta-analysis. Mild (OR: 0.85; 95% CI: 0.53–1.38; p = 0.515) or heavy (OR: 0.63; 95% CI: 0.37–1.09; p = 0.102) alcohol intake were not associated with the risk of SLE, while moderate alcohol intake could protect against the risk of SLE (OR: 0.71; 95% CI: 0.55–0.93; p = 0.012). Sensitivity analysis suggested that heavy alcohol intake was associated with a reduced risk of SLE (OR: 0.47; 95% CI: 0.32–0.67; p < 0.001).This study found that moderate alcohol intake could protect against the risk of SLE, while mild or heavy alcohol intake did not significantly affect the risk of SLE. [ABSTRACT FROM AUTHOR]

Background: Both antibody secreting cells (ASCs) and memory B cells are essential for the maintenance of humoral immunity. To date, limit studies have focused on the two populations in Kawasaki disease (KD). To address the status of humoral immunity during KD, our current concentration is on the variations of ASCs and memory B cells, as well as their subsets in both acute and remission stages of KD. Methods: ASCs were defined as the population with high expressions of CD27 and CD38 among CD3-CD20- lymphocytes. Based on the expression of surface marker CD138 and intracellular marker IgG, ASCs were further divided into two subsets. Memory B cells were characterized by the expressions of IgD, CD27 and IgM, upon which memory B cells were further categorized into CD27 + IgD- (switched memory, Sm), CD27-IgD- (Double negative, DN) and CD27 + IgD + IgM+ (marginal zone, MZ) B cells. Collectively, six populations were analyzed using flow cytometry. The blood samples were collected from KD patients in different stages and healthy controls. Results: In the acute stage, the percentages of ASCs, CD138+ ASCs, and IgG+ ASCs were significantly increased. In contrast, the percentages of memory B cells including Sm and MZ B cells were significantly decreased. Correlation analysis found ASCs positively correlated with the level of serum IgM, whereas MZ B cells not only positively correlated with the level of serum IgG, IgA, and IgM, but also positively correlated with the level of serum complement C3 and C4 and negatively correlated with the value of C-reactive protein (CRP). In the remission stage, the percentages of IgG+ ASCs and MZ B cells were significantly reduced, whereas other subsets presented heterogeneous variations. Conclusions: Our study provided direct evidence that ASCs contributed to the pathogenesis of KD, and it was the first time to describe the variation of memory B cells in this disease. Among the subsets, only IgG+ ASCs presented a significant increase in the acute stage and decreased after IVIG administration, indicating the involvement of IgG+ ASCs in the inflammation of KD and also suggesting that IVIG played an inhibitory role in the expression of cytoplasmic IgG. [ABSTRACT FROM AUTHOR]

Objective: Circulating follicular helper T (cTfh) cells are a specialized subset of CD4+ T cells that express the CXC-chemokine receptor 5 (CXCR5). These cells exhibit immune activities by inducing B cell differentiation and proliferation via the secretion of interleukin (IL)-21. Multiple studies have demonstrated that cTfh cells are associated with the progression and severity of numerous diseases. To investigate the role of cTfh cells in the development of Kawasaki disease (KD), we analyzed the distinct subpopulations of cTfh cells and serum IL-21 levels in different phases of KD. Methods: According to the differential expression of inducible co-stimulator (ICOS) and programmed cell death protein 1 (PD-1), cTfh cells were divided into distinct subsets. We used flow cytometry and flow cytometric bead arrays (CBA) to analyze subsets of CD4+CXCR5+ T cells and serum IL-21 levels. The samples were collected from control subjects and Kawasaki disease patients in the acute and remission phases. Results: In the acute phase (AP), the percentages of ICOShighPD-1high, ICOS+PD-1+, ICOS−PD-1+, CD45RA−IL-21+ cTfh cells and serum IL-21 levels significantly increased. Furthermore, the percentages of ICOShighPD-1high and ICOS+PD-1+ cTfh cells positively correlated with erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) values, whereas the percentage of ICOS−PD-1+ cTfh cells indicated negative correlations. The percentages of ICOS+PD-1+, ICOShighPD-1high and CD45RA−IL-21+ cTfh cells correlated positively with serum IL-21 levels. In the remission phase (RP), the percentages of ICOS−PD-1+, CD45RA−IL-21+ cTfh cells and serum IL-21 levels were significantly decreased. In contrast, the percentages of ICOS+PD-1+, ICOShighPD-1high, and ICOS+PD-1− cTfh cells were further increased. Among these subsets, only CD45RA−IL-21+ cTfh cells correlated positively with serum IL-21 levels. Conclusions: The present study is the first investigation that examined the distribution of circulating cTfh cell subsets in Kawasaki disease. Both cTfh cells and serum IL-21 are essential to the pathogenesis of KD. Our study provides further understanding of the immune response involved in KD and offers novel insights in the pathogenetic mechanism of this disease. [ABSTRACT FROM AUTHOR]

Hepatitis B virus (HBV) has been suspected to contribute to several autoimmune diseases, including Sjögren’s syndrome (SS), although the exact mechanism is unknown. The 2′-5′ oligoadenylate synthetase (OAS1) is one of the most important components of the immune system and has significant antiviral functions. We studied a polymorphism rs10774671 of OAS1 gene in Han Chinese descent. The minor allele G was significantly associated with a decreased risk for SS, anti-SSA-positive SS, and anti-SSA-positive SS complicated with HBV infection, which have not been seen in anti-SSA-negative SS and HBcAb-negative SS patients. Gene expression analysis showed that the risk-conferring A allele was correlated with lower expression of p46 and increased expression of p42, p48, and p44. A functional study of enzymatic activities revealed that the p42, p44, and p48 isoforms display a reduced capacity to inhibit HBV replication in HepG2 cells compared to the normal p46 isoform. Our data demonstrated that the functional variant, rs10774671, is associated with HBV infection and anti-SSA antibody-positive SS. The SAS variant switches the primary p46 isoform to three alternatives with decreased capacities to inhibit HBV replication. These data indicated that individuals harboring the risk allele might be susceptible to hepatitis B infection and SS development. [ABSTRACT FROM AUTHOR]