Search

The relative abundance of myeloid-derived suppressor cells (MDSCs) compared to cytotoxic T cells determines the outcomes of diseases and the efficacy of immunotherapy. Ubiquitin-specific peptidase 12 (USP12), a member of the USP family of deubiquitinases, targets multiple signalling pathways and regulates diverse biological processes, including cell proliferation and survival. It is well known that ubiquitylation is an important mechanism for regulating the immune response. However, it is unclear whether USP12 regulates tumour growth by influencing MDSCs. In the present study, we reported that USP12 deficiency decreased infiltration and impaired the suppressor function of monocytic (M)-MDSCs, resulting in increased CD8 more...

Small-signal modeling of grid-tied inverters (GTIs) is an essential work in stability analysis of GTIs-weak grid coupling system. Different from previous small-signal modeling methods of GTIs with black-box property, a reduced-order modeling method has been proposed in this paper to provide an impedance model with white-box property. Firstly, Impedance and admittance are seamlessly incorporated into the modeling method, where concepts of partial admittances, partial impedance, active power admittance and reactive power admittance are especially introduced. As a result, simplified expressions of impedance model of GTIs have been obtained with physical interpretations of dq impedances strengthened. After that, dominated relationships between terms of GTIs impedance matrix and its internal physical parts are explicitly revealed to represent white-box property of the proposed impedance model. Specifically, the influence and effect mechanism of feedforward voltage compensation (FVC), current controller (CC), phase lock loop (PLL) and power points (Id, Iq) are emphasized based on the proposed impedance model. Finally, perturbations generated independent with PLL are injected into a hardware in-loop experiment platform, and impedance measurement results are provided to verify the conclusions drawn from the improved modeling method. more...

The formation and rupture of gas film in the process of formation, rupture and coalescence of antibubbles were investigated by high-speed photography. It was found that a gas film will appear and wrap a droplet when the droplet hit a layer of liquid film or foam before impacting the gas-liquid interface. The gas film may survive the impact on the gas-liquid interface and act as the gas film of an antibubble. A multilayer droplet will be formed when the droplet hits through several layer of liquid films, and a multilayer antibubble will be formed when the multilayer droplet impact a gas-liquid interface or a single layer of foam on the liquid surface. The way to generate antibubbles by liquid films will undergo the formation and rupture of gas films. The coalescence of two antibubbles, which shows a similar merging process of soap bubbles, also undergo the rupture and formation of gas films. The rupture of gas film of antibubble caused by aging and impact is also discussed. more...

To find a cost-effective carbon source for partial denitrification (PD), brewery wastewater was utilized to test the viability of initiating PD. The S

The human immunodeficiency virus-1 (HIV-1) envelope protein gp120 is the major contributor to the pathogenesis of HIV-associated neurocognitive disorder (HAND). Neuroinflammation plays a pivotal role in gp120-induced neuropathology, but how gp120 triggers neuroinflammatory processes and subsequent neuronal death remains unknown. Here, we provide evidence that NLRP3 is required for gp120-induced neuroinflammation and neuropathy. Our results showed that gp120-induced NLRP3-dependent pyroptosis and IL-1β production in microglia. Inhibition of microglial NLRP3 inflammasome activation alleviated gp120-mediated neuroinflammatory factor release and neuronal injury. Importantly, we showed that chronic administration of MCC950, a novel selective NLRP3 inhibitor, to gp120 transgenic mice not only attenuated neuroinflammation and neuronal death but also promoted neuronal regeneration and restored the impaired neurocognitive function. In conclusion, our data revealed that the NLRP3 inflammasome is important for gp120-induced neuroinflammation and neuropathology and suggest that NLRP3 is a potential novel target for the treatment of HAND. more...

Chronic inflammation develops when the immune system is unable to clear a persistent insult. Unresolved chronic inflammation leads to immunosuppression to maintain the internal homeostatic conditions, which is mediated primarily by myeloid-derived suppressor cells (MDSCs). Toll-like receptors 2 (TLR2) has an important role in chronic inflammation and can be activated by a vast number and diversity of TLR2 ligands, for example Pam2CSK4. However, the regulatory effect of TLR2 signaling on MDSCs in chronic inflammation remains controversial. This study demonstrated that heat-killed Mycobacterium bovis BCG-induced pathology-free chronic inflammation triggered suppressive monocytic MDSCs (M-MDSCs) that expressed TLR2. Activation of TLR2 signaling by Pam2CSK4 treatment enhanced immunosuppression of M-MDSCs by upregulating inducible nitric oxide synthase (iNOS) activity and nitric oxide (NO) production partly through signal transducer and activator of transcription 3 (STAT3) activation. Thus, TLR2 has a fundamental role in promoting the MDSC-mediated immunosuppressive environment during chronic inflammation and might represent a potentially therapeutic target in chronic inflammation disease. more...

Background Diverse clinical and serological manifestations of systemic lupus erythematosus (SLE) compromise its diagnosis and treatment. A more reliable biomarker for SLE, which can play a critical role in either diagnosis, monitoring the disease progress or evaluating the response to treatment for individualized therapeutic, is necessary. DNA sensor is an important mediator of inflammation in systemic autoimmune diseases. However, the potential role for DNA sensor as disease activity biomarkers for SLE remained obscure. We detected the aberrant activation of DNA sensors and the corresponding IFN-β response in SLE patients, and to evaluate their potential role as disease biomarkers for SLE. Methods We quantified the expressions of IFN-I and DNA sensor, such as cGAS, IFI16, DDX41, DAI and their down-stream adaptor STING in PBMC derived from patients with SLE (n=100), healthy controls (HCs) (n=62) by real-time PCR. The relationships between the expression of cGAS or IFI16 and clinical features in SLE patients were investigated. ROC curve analysis was performed to examine the predictive value of cGAS and IFI16 in SLE diagnosis, disease activity monitoring, specific organ manifestation and therapeutic response. RNA interference-mediated depletion of IFI16 or cGAS was conducted to evaluate their impact on IFN-I response. Results The expressions of cGAS and IFI16 were significantly higher in PBMC from SLE patients, closely correlated with the SLEDAI scores and high anti-dsDNA antibody titers. While the AUC for cGAS (0.767) was less than that of IFI16 and IFN-β, the AUC for IFI16 (0.856) and IFN-β (0.856) were similar. Expression of cGAS and IFI16 combine with IFN-β in PBMC showed high sensitivity (89.2%) and specificity (89.1%) for discrimination between mild and moderate/severe disease activity in SLE. Higher expression of IFI16 was association with ocular disorder in SLE patients. Neither IFI16 nor cGAS was a reliable indicator of therapeutic response. RNA interference-mediated depletion of IFI16 or cGAS prevented active SLE serum-induced upregulating in both IFN-α and IFN-β. Conclusions High expression levels of cGAS and IFI16 in PBMC from SLE patients correlated strongly with disease activity. Both cGAS and IFI16 mediated signaling pathway were account for the robust production of IFN-β. Expression of cGAS and IFI16 combined with IFN-β in PBMC might serve as potential biomarkers for early diagnosis and monitoring disease activity in SLE. more...

Harmonic resonance caused by interactions between grid-tied inverters (GTIs) and weak grid are becoming increasingly prominent. Small-signal modeling of GTIs is the most fundamental work in to analyze the harmonic stability of GTI-weak grid coupling system. Different from generic small-signal modeling of GTIs in dq coordinate, a simplified impedance modeling method has been proposed in this paper after focusing interesting frequency band onto low-medium frequency range. In the simplified modeling method, a partial admittance is introduced, and coupling terms between d and q channels are identified as negligible parts and non-negligible parts, respectively. As a result, a simplified small-signal model of GTI has been obtained, and connections among terms of GTI’s impedance and its physical parts are highlighted to strengthen physical interpretations of dq impedances. In addition, concepts of active power admittance and reactive power admittance are introduced in this paper to demonstrate the influence mechanism of power-level’s variations on GTI’s impedance. Finally, the theoretical analysis in frequency domain and simulation results in time domain are provided to prove that the proposed simplified modelling method can be used to analyze the resonance mechanism and predict the stability of GTI-weak grid coupling system. more...

OBJECTIVE: To construct a HIV-1 gp120 transgenic mice (gp120 Tg) with vimentin (VIM) gene knockout. METHODS: Female HIV-1 gp120 Tg mice were mated to VIM heterozygote mice (F0). All the offspring mice were derived from these original founders so that both genotypes had the same mixed genetic background. The F1 mice were bred to generate of VIM(+/+), VIM(-/-), VIM(+/+)/gp120 Tg and VIM(-/-)/gp120 Tg mice. PCR was performed for genotyping of the mice, and the expressions of VIM and gp120 in the brain tissues were examined using immunoblotting. RESULTS: The results of PCR showed the presence of the target bands in VIM(+/+), VIM(-/-), VIM(+/+)/gp120 Tg and VIM(-/-)/gp120 Tg mice. In VIM(-/-)/gp120 Tg mice, gp120 expression was detected throughout the brain regions while no VIM expression was detected. CONCLUSION: We generated gp120 transgenic mouse models with VIM gene knockout, which facilitate the exploration of the role of VIM in gp120-induced neurotoxicity. more...

Highlights • Directional transport and random motion of particles in ALF ultrasonic cavitation structure are investigated. • Particles tend to transport along the bubble chain repeatedly and predictably. • The motion of particles is related to the cavitation bubbles attached to the particles., The motion of particles of different properties and sizes in ALF ultrasonic cavitation structure is investigated experimentally with high-speed photography. Particles tend to transport along the bubble chain and move towards the focus repeatedly and predictably in ALF cavitation structures. Particles at the focus aggregate and separate alternately over time. The separation of particles mainly occurs in the expansion process of cavitation bubbles, while the movement and aggregation of particles mostly take place during the collapse stage. The directional transport of particles along the bubble chain of ALF cavitation cloud and the random aggregation and dispersion at the focus of ALF are all related to the cavitation bubbles attached to the particles. The directional transportation (predictable, repeatable and pipeline-free) and aggregation of particles in ALF cavitation clouds may be used in special occasions, for example, drug delivery and targeted therapy. more...

To improve the linear range of measurement, a restrictor is usually added to the main flow channel of a capillary-tube-type thermal mass flowmeter. However, as the linear range of the flowmeter increases, the singularity will occur in the low mass flow velocity section of the flowmeter calibration data, which will lead to a significant decrease in the measurement accuracy in this section. To address this issue, first, this paper developed a microelectromechanical system (MEMS) thermal gas flowmeter based on the principle of capillary-tube-type thermal mass flow. Then, the effect of the bypass ratio on its performance was further investigated using quantitative analysis and was verified using Fluent numerical analysis. In addition, to explain the singularity, the bypass ratio-sensitivity relationship model was built. Based on this model, the bypass ratio can be changed by adjusting the restrictor parameters to optimize the performance of the MEMS thermal gas flowmeter. Moreover, six numerical simulation models of restrictors with different aperture diameters and aperture numbers were designed. The numerical analysis results show that within a certain range of aperture diameters and aperture numbers, the singularity is more easily weakened when the aperture diameter decreases or the aperture number increases. Finally, the restrictor with the optimum aperture number and suitable aperture diameter was selected as the test model for calibration, and the goodness of fit R2 of the calibration results is improved from 0.9937 to 0.9972, the singularity in the low mass flow velocity section is significantly weakened, and the sensitivity is improved. more...

This publisher’s note contains a correction to Opt. Lett. 47, 1673 (2022)10.1364/OL.454450.

The study of proton therapy equipment has earned more and more attention in China in recent years. A superconducting cyclotron based proton therapy facility is being developed at Huazhong University of Science and Technology (HUST). Since the proton beam is extracted out of the compact, high energy cyclotron by electrostatic deflectors followed by a series of magnetic channels, the fierce interaction between the proton beam and the deflector septum is the main cause of beam loss, leading to unwanted excess radiation and heat. Excess Radiation effect results in activation or damage to superconducting materials and high risk of quench of superconducting magnets , while thermal effect involves temperature rise and deformation of the septum, both of these phenomena put extraordinary demands on high efficiency extraction of the cyclotron. This paper introduces the design of the electrostatic deflector, including the structure optimization and the material selections. Moreover, in order to minimize the damage to the deflector destruction caused by the proton beam loss, numerical simulations of radiation effect and thermal effect have been conducted by applying Monte Carlo Geant4 code and computational fluid dynamics (CFD) on ANSYS respectively. The energy depositions of the proton beam in diverse septum materials are compared. Meanwhile, the energy and angular distributions of secondary particles are obtained. The maximum temperatures and deformations of the septum in various cases of thickness and material are investigated. The results based on these analyses will give us valuable implications for the development of a superconducting cyclotron. more...

Micro punching process is suitable for mass production of micro parts. It is a challenge to fabricate micro punching mold with complex cross-sectional shape on-machine. The micro punching system’s structure design has to meet the requirement of large punching force. In this study, a micro punching system has been developed with a micro electrical discharge machining (EDM) module. A series of machining operations, from the fabrication of micro molds to punching, have been completed with no secondary clamping error. The micro die and reversed electrode are prepared using micro EDM milling. The micro punch is fabricated using reversed electrode. The punching clearance is around 11 μm. Complex shape punched holes and blanked parts have been successfully fabricated on copper, brass, 304 stainless steel, and 3J21 alloy. After punching, there was no damage on the edges of micro die and micro punch. The key dimensional error of blanked part varies by different materials, which is less than 2.5 μm. more...

Characteristic mode (CM) theory provides a physical and intuitive guidance for discussing electromagnetic radiating or scattering issues and is a useful tool for the antenna design. The effective mode sorting is the key to the CM analysis. However, due to the mode degeneration or mode swapping in the observed frequency range, the mode tracking must be performed to obtain the correct mode sorting. Current mode tracking algorithms are mainly based on the correlation of eigenvectors, but they are computationally expensive and time-consuming. Here, the eigenvector number is limited by selecting the eigenvalues, to speed up the tracking realisation. At the same time, the factors affecting the correctness of the mode tracking are discussed, including the selected eigenvalue number and the mesh fineness. Some numerical examples are given to verify the reliability of the improved algorithm. more...

A SCC-250 MeV cyclotron, producing a 250 MeV proton beam, is under development in Huazhong University of Science and Technology (HUST) for proton therapy. The magnetic flux density, as a function of radius, decreases rapidly in the beam extraction region, which increases the radial beam size continuously along the extraction orbit. In this paper, an extraction channel inside the SCC-250 MeV is designed to control the beam size using passive magnetic channels. An equivalent lumped parameter method is used to establish the model of the extraction channel in the complex fringe magnetic field of the main magnet. Then, the extraction channel is designed using the lattice design software MADX. The beam envelopes are verified using particle tracing method. The maximum radial size of 6.8 mm and axial size of 4.3 mm meet the requirements of the extraction from the SCC-250 MeV. more...

As one of the micro-forming technologies, micro punching process produces workpieces in high efficiency and low cost. It has attracted the attention of researchers from all over the world in recent years. The current micro punching mold is prepared on-line by micro electrical discharge machining (EDM) with simple cross-sectional shape. During punching, the punching load is small due to the soft material and small circumference of workpiece. To form micro part with complex cross sectional shape using micro punching technology, three-dimensional micro-EDM milling and reversed micro EDM are used to generate micro die and punch on-line to provide a solution to alignment of die and punch on machine. In order to obtain high dimensional accuracy of micro punching mold, in this paper, dimensional errors including electrode, reversed electrode, micro die and micro punch caused during machining process are identified. The correlation between dimensional errors and the clearance of micro die and micro punch are analyzed. Based on preliminary experimental results and dimensional error control strategy, the final punching clearance of micro punch molds was machined within the required range. more...

The graphene and LiNO3 composites (GLs) were produced by a new facility method: burning the mixture of graphene and LiNO3. The electrochemical properties of GLs as supercapacitor electrode materials were evaluated roundly, and results showed that GLs possess much high specific capacitance at a high current density and scan rate (3339.7 F/g at 1 mV/s and 80.07 F/g at 20 A/g, respectively) with excellent cycling stability, which are superior to other reported graphene/metals composites thus far. The achievements of such high performance GLs composites may open up a new window for energy storage applications and wearable electronics in the future. more...

Ultrasound (US)-triggered sonodynamic therapy (SDT) that enables noninvasive treatment of large internal tumors has attracted widespread interest. For improvement in the therapeutic responses to SDT, more effective and stable sonosensitizers are still required. Herein, ultrafine titanium monoxide nanorods (TiO more...

The urban space environment has been proven to be related to the health of the elderly. However, as a high-density city, Macau’s limited urban space must cope with the growing population and the arrival of an aging society. In the existing studies, less attention has been paid to Macau, especially the relationship between Macanese elderly and urban space. This study uses Baidu Street View (BSV) on the Macau Peninsula and conducts field surveys to obtain street view data to evaluate the openness, greenness, interface coverage, and road area ratio of street space and its association with the physical and mental health of the elderly and social health. The results show that the data truly reflect the overall street space conditions on the Macau Peninsula. The street openness, greenery rate, and interface enclosure are all related to the elderly in various evaluations in areas with a higher population dependency index and aging index. Human space perception is related to health gain, and road area ratio is weaker than other indicators. The research results have certain policy implications and have practical significance for city managers and designers. more...

This review tries to cover as many research fields and literatures associated with cavitation in thin liquid layer as possible. The intent was to summarize (i) list all the research fields related to cavitation in thin liquid layer that can be collected, (ii) advances in the investigation of cavitation in thin liquid layer, and (iii) draw attention to the relatively macroscopic cavitation behavior in thin liquid layer. more...

Sonodynamic therapy (SDT) is a non-invasive and highly penetrating treatment strategy under ultrasound irradiation. However, uncertainty in the mechanism of SDT has seriously hindered its future clinical application. Here, the mechanism of SDT enhanced by the wettability of nanoparticles is investigated. Nanoparticles can adsorb and stabilize nanobubbles in liquid, thus enhancing SDT efficiency. The stability of the nanobubbles is positively correlated with the desorption energy of the nanoparticles, which is determined by the wettability of the nanoparticles. This conclusion is verified for mesoporous silica and polystyrene nanoparticles and it is found that nanoparticles with a water contact angle of about 90° possess the largest desorption energy. To further apply this conclusion, thrombus models are constructed on rats and the experimental results demonstrate that nanoparticles with the largest desorption energy have the highest thrombolytic efficiency. It is believed that these findings will help to better understand the SDT mechanism and guide new strategies for rational design of nanoparticles adopted in SDT. more...

An antibubble is the opposite of a soap bubble: a thin spherical gas shell containing liquid inside and surrounded by liquid outside. The dynamic behaviour of antibubbles when a spark-induced cavitation bubble oscillates in their vicinity is studied using a high-speed video camera. It is found that the rupture process of antibubble impacted by shock wave is different from that of antibubble due to aging or puncture. There is a stable phase relationship between the cavitation bubble deformation and the antibubble deformation. The non-uniformity of the thickness of the gas film strongly influences the rupture process of the antibubble. The antibubbles will split horizontally into two parts, and the gas in the gas film of antibubbles will move and gather to the point where the air film is thickest, and then divide into two gas bubbles. The dynamics of antibubble deformation under the impact of primary shock wave and secondary shock wave induced by the growth and collapse of cavitation bubble is analysed. more...

The objective of this study was to determine whether Lactobacillus rhamnosus GG culture supernatant (LCS) has a preventive effect against gut-derived systemic neonatal Escherichia coli (E. coli) K1 infection. The preventive effects were evaluated in human colonic carcinoma cell line Caco-2 and neonatal rat models. Our in vitro results showed that LCS could block adhesion, invasion and translocation of E. coli K1 to Caco-2 monolayer via up-regulating mucin production and maintaining intestinal integrity. In vivo experiments revealed that pre-treatment with LCS significantly decrease susceptibility of neonatal rats to oral E. coli K1 infection as reflected by reduced bacterial intestinal colonization, translocation, dissemination and systemic infections. Further, we found that LCS treated neonatal rats have higher intestinal expressions of Ki67, MUC2, ZO-1, IgA, mucin and lower barrier permeability than those in untreated rats. These results indicated that LCS could enhance neonatal resistance to systemic E. coli K1 infection via promoting maturation of neonatal intestinal defense. In conclusions, our findings suggested that LCS has a prophylactic effect against systemic E. coli K1 infection in neonates. Future studies aimed at identifying the specific active ingredients in LCS will be helpful in developing effective pharmacological strategies for preventing neonatal E. coli K1 infection. more...

Evidence indicates that there is an emerging tendency towards autoimmunity occuring in major depressive disorder (MDD). The aim of our study is to investigate the mechanism of autoimmune process in MDD from a novel insight of Th17 cells, which have been identified as the significant activators of autoimmunity. We included 40 patients with MDD and 30 healthy control subjects. An indirect immunofluorescence test was used for the detection of serum antinuclear antibodies (ANA), and revealed that the patient group was positive more frequently than the control group. By flow cytometric analysis, depressed subjects revealed a significant increase in peripheral Th17 cell number, and an obvious decrease in T-reg cell number, showing an imbalance of Th17/Treg ratio compared to healthy controls. We also found a higher level of RORγt (retinoic acid-related orphan receptor-γt, the specific transcription factor of Th17 cell) mRNA expression in peripheral blood lymphocytes by RT-PCR and serum concentration of IL-17 by ELISA in patients. In conclusion, our study showed a potential role of Th17 cells in the autoimmune process in MDD patients, thus contributing to the existing evidence of autoimmune inclination in MDD. more...

Introduction. Measurement of glomerular filtration rate (GFR) is critical for the diagnosis and stratification of chronic kidney disease (CKD). Recent studies have shown that cystatin C is superior to creatinine for the detection of impaired GFR, and several cystatin C-based equations for estimating GFR have been developed for this clinical application. We conducted the present study to assess the applicability of cystatin C as a routine clinical laboratory index and to determine the performance of cystatin Cbased equations in estimating GFR in CKD patients in China. Methods. Performance evaluation of particle-enhanced turbidimetric cystatin C assay on the Abbott Aeroset analyser was carried out according to the National Committee for Clinical Laboratory document EP10-A2. Estimated GFR, which was generated from cystatin C-based equations, was compared with measured GFR, which was detected by plasma clearance of 99mTc-DTPA. Results. Our cystatin C assay showed a very low total imprecision and linearity drift. All eight cystatin C-based GFR estimating equations underestimated or overestimated GFR as compared with GFR determined by 99mTc-DTPA clearance. Conclusion. Although the cystatin C assay is acceptable for routine clinical laboratory monitoring, none of the existing cystatin C-based equations were ideal for estimating GFR in Chinese CKD patients. more...