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Objectives and design Dendritic cells (DCs) are one of the key immune cells in bridging innate and adaptive immune response against Mycobacterium tuberculosis (Mtb) infection. Interferons (IFNs) play important roles in regulating DC activation and function. Virus-inhibitory protein, endoplasmic reticulum-associated, interferon-inducible (Viperin) is one of the important IFN-stimulated genes (ISGs), and elicits host defense against infection. Methods We investigated the effects and mechanisms of Viperin on DC activation and function using Viperin deficient bone marrow-derived dendritic cells (BMDCs) during Mtb infection. Results Viperin deficiency enhanced phagocytic activity and increased clearance of Mtb in DCs, produced higher abundance of NO, cytokine including interleukin-12 (IL-12), Tumor necrosis factor-α (TNF-α), IL-1β, IL-6 and chemokine including CXCL1, CXCL2 and CXCL10, elevated MHC I, MHC II and co-stimulatory molecules expression, and enhanced CD4+ and CD8+ T cell responses. Mechanistically, Viperin deficiency promoted DC activation and function through NF-κB p65 activation. NF-κB p65 inhibitor prevented cytokine and chemokine production, and co-stimulatory molecules expression promoted by Viperin deficiency. Conclusions These results suggest that Mtb induced Viperin expression could impair the activation of host defense function of DCs and DC-T cell cross talk during Mtb infection. This research may provide a potential target for future HDT in TB therapy.

Yulan Huang,* Shitong He,* Yitian Chen, Junli Sheng, Yuling Fu, Xialin Du, Yalong Yang, Honglin Liu, Zhenyu Han, Yingqi Huang, Qian Wen, Chaoying Zhou, Xinying Zhou, Shengfeng Hu, Li Ma Institute of Molecular Immunology, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, 510515, People’s Republic of China*These authors contributed equally to this workCorrespondence: Li Ma; Shengfeng HuInstitute of Molecular Immunology, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, 510515, People’s Republic of China, Email mali_61648322@smu.edu.cn; hushengfeng@smu.edu.cnBackground: As deubiquitinases (DUBs), ubiquitin C-terminal hydrolase (UCH)-L1 has been shown to play a crucial role in regulating diverse biological processes. However, its function in macrophage polarization remains unclear.Methods: We performed in vivo and in vitro experiments to investigate the role of ubiquitin carboxyl-terminal hydrolase L1 (UCHL1), a kind of DUBs, in macrophage differentiation by using UCHL1-deficiency mice.Results: We demonstrated that LPS stimulation induced UCHL1 expression in macrophages. The deficiency of UCHL1 expression decreased the expression of CD80 and CD86 but increased the expression of CD206. The expression of TNF-α, IL-6, iNOS, and IL-10 was downregulated, while that of Arg1, Ym1, and Fizz1 was upregulated in UCHL1 deficient macrophages. Moreover, we observed that UCHL1 promoted the degradation of p110α through autophagy, but paradoxically increased the activity of AKT, thereby promoting polarization of macrophages into pro-inflammatory states.Conclusion: In this study, we identified UCHL1 as a positive regulator of M1 macrophage polarization. Our findings may help in developing therapeutic interventions for the treatment of inflammatory diseases and pathogenic infections.Keywords: UCHL1, macrophages, AKT, p110α, autophagy

Mycobacterium tuberculosis, the pathogen that causes tuberculosis, exhibits complex host–pathogen interactions. Pattern recognition receptors and their downstream signaling pathways play crucial roles in determining the outcome of infection. In particular, the scaffold protein β-arrestin 2 mediates downstream signaling of G protein–coupled receptors. However, the role of β-arrestin 2 in conferring immunity against M. tuberculosis has not yet been explored. We found that β-arrestin 2 was upregulated in the lesioned regions of lung tissues in patients with tuberculosis. M. tuberculosis infection upregulated β-arrestin 2 expression in human macrophages, and silencing of β-arrestin 2 significantly enhanced bactericidal activity by enhancing the expression of proinflammatory cytokines such as TNF-α. β-Arrestin 2 was shown to inhibit the activation of the TLR2/ERK1/2 pathway and its transcriptional regulation activity upon M. tuberculosis infection. Furthermore, β-arrestin 2 transcriptionally regulates TNF-α by binding to CREB1. These observations revealed that the upregulation of β-arrestin 2 is critical for M. tuberculosis to escape immune surveillance through an unknown mechanism. Our research offers a novel interference modality to enhance the immune response against tuberculosis by targeting β-arrestin 2 to modulate the TLR2–β-arrestin 2–ERK1/2–CREB1–TNF-α regulatory axis.

In this study the two-dimensional flow over a square cylinder placed in between parallel plates is simulated numerically by using the lattice Boltzmann method (LBM) at low Reynolds numbers. Both the plates are obstructed by solid rectangular blocks of variable length. The fluid was allowed to flow between the parallel plates for Reynolds number (Re) from 75 to 150, and blockage ratio (g*) from 1 to 3. The numerical investigation does not simply yield the predictable primary region of recirculating flow connected to the obstructions; it also shows supplementary regions of the flow downstream of the single cylinder placed in a computational domain. These supplementary separation zones were not already described in the research. The numerical analysis shows that the flow downstream of obstructions and the single cylinder remained two-dimensional for Re varied from 75 to 150. Results available in previous research are reported and compared with both of the available experimental and numerical results for code validation with a single cylinder. Furthermore, the effects of various Re and blockage ratio on the lift forces and drag coefficient is analyzed. Under these circumstances, good agreement between experimental and numerical results are obtained. The hydrodynamic forces of the cylinder are strongly influenced by the spacing ratios.

This paper proposes a multi-reflection heliostat to improve solar power tower plant performance. It can eliminate the significant cosine loss by keeping its aperture always facing the sun. The key structural parameters are specially designed for a superior solar image property. On its basis, a case study on the three-reflection heliostat is first conducted. By the field efficiency distribution comparison between the two types of heliostats, the multi-reflection heliostat is found to have an efficiency advantage in central region. Then in reference to the original Gemasolar field, the three-reflection heliostat field is generated by the proposed layout method. Its optical efficiency is 5.56% higher and the land area is 68.31% smaller, compared to the performance of the optimized Gemasolar field. For the purpose of practical application, the heliostat with ganged multi-reflection modules is developed. The occupied land area of its field is 51.28% less than that of the latter one. The prototype of five-reflection heliostat is developed for a further performance validation. In the outdoor test, the solar concentrating performance agrees well with the simulation result.

A numerical study is performed to analyze the effect of small control cylinders on fluid force reduction and vortex shedding suppression on the flow past three inline square cylinders using the lattice Boltzmann method. The Reynolds number Re = 160 is fixed while the spacing between the cylinders is taken in the range of 1.0D ≤ g* ≤ 5.0D (where D is the size of the main cylinder) and the control cylinder size is varied from 0.1D to 0.5D. To systematically understand the effect of control cylinders on the forces, a detailed analysis of Strouhal number (St), mean drag coefficient (CDmean), and root mean square values of the drag and lift coefficients is presented in this paper. In this study, it is observed that the average mean drag coefficient (CDmeanaverage) and Strouhal number reached either maximum or minimum values at different values of separation ratio (g*) and small control cylinder size (d). It is found that at (g*, d) = (5.0, 0.0) and (1.0, 0.5), the average CDmean attains its maximum (CDmeanaverage = 0.7813) and minimum (CDmean = 0.0988) values. Furthermore, at (g*, d) = (5.0, 0.3) and (2.0, 0.0) the average St attains its maximum (St = 0.1780) and minimum (St = 0.041) values. It is found that the flow regimes completely change in the presence of control cylinders. In particular, at g* = 4.0 there is a critical flow regime when the size of the control cylinder changes from 0.1 to 0.5. The sudden jump in the mean drag coefficient and Strouhal number for the middle cylinder with their maximum and minimum values also confirms the critical flow regime. The effect of control cylinders within tandem square cylinders has not been studied before.

Vitamin B6 is necessary to maintain normal metabolism and immune response, especially the anti‐inflammatory immune response. However, the exact mechanism by which vitamin B6 plays the anti‐inflammatory role is still unclear. Here, we report a novel mechanism of preventing excessive inflammation by vitamin B6 via reduction in the accumulation of sphingosine‐1‐phosphate (S1P) in a S1P lyase (SPL)‐dependent manner in macrophages. Vitamin B6 supplementation decreased the expression of pro‐inflammatory cytokines by suppressing nuclear factor‐κB and mitogen‐activated protein kinases signalling pathways. Furthermore, vitamin B6–reduced accumulation of S1P by promoting SPL activity. The anti‐inflammatory effects of vitamin B6 were inhibited by S1P supplementation or SPL deficiency. Importantly, vitamin B6 supplementation protected mice from lethal endotoxic shock and attenuated experimental autoimmune encephalomyelitis progression. Collectively, these findings revealed a novel anti‐inflammatory mechanism of vitamin B6 and provided guidance on its clinical use.

Summary Objectives Interferons (IFNs) play multifunctional roles in host defense against infectious diseases by inducing IFN-stimulated genes (ISGs). However, little is known about how ISGs regulate host immune response to Mycobacterium tuberculosis (Mtb) infection, the major cause of tuberculosis (TB). Methods We thus profiled the potential effects and mechanisms of eight Mtb-induced ISGs on Mtb infection by RNA interference in human macrophages (Mφs) derived from peripheral blood monocytes (hMDMs) and THP-1 cell line derived Mφs (THP-1-Mφs). Results MxA silencing significantly decreased intracellular Mtb infection in Mφs. Mechanistically, MxA silencing promoted inflammatory cytokines IL-1β, IL-6 and TNF-α production, and induced NF-κB p65 activation. Pharmacological inhibition of NF-κB p65 activation or gene silencing of NF-κB p65 blocked the increased production of IL-1β, IL-6 and TNF-α and restored Mtb infection by MxA silencing. Furthermore, pharmacological inhibition of TAK1 and IKKα/β blocked NF-κB p65 activation and subsequent production of pro-inflammatory cytokines by MxA silencing. Isoniazid (INH) treatment and MxA silencing could promote TAK1-IKKα/β-NF-κB signaling pathway activation and combat Mtb infection independently. Conclusions Our results reveal a novel role of MxA in regulating TAK1-IKKα/β-NF-κB signaling activation and production of antimicrobial inflammatory cytokines upon Mtb infection, providing a potential target for clinical treatment of TB.

A numerical investigation into the effects of flapping modes on the aerodynamic performance of insect hovering flight is carried out through the solution of the two-dimensional unsteady Navier-Stokes equations. Four types of idealized flapping modes with the identical quasi-steady lift force are compared, and the influences of the Reynolds number (Re), the translational duration and the rotational duration on the aerodynamic characteristics of the hovering are systematically analyzed flight. It is found that the instantaneous aerodynamic forces of the wing differ significantly in each flapping mode. The mode with harmonic translation and harmonic rotation leading the highest lifting efficiency is suitable for long-time flight while the mode with harmonic translation and trapezoid rotation giving the largest instantaneous forces is suitable for maneuvering flight. When Re increases from 100 to 1000, the lift force and lifting efficiency of the wing are increased significantly with the increasing Re first, and then slow down with the further increase in Re. In addition, the fast-translational mode with short translational duration will reduce the time-averaged lift force and the efficiency, whereas the fastrotational mode with short rotational duration can enhance the time-averaged lift force with the sustained efficiency.

Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) infection is the deadliest infectious disease and a global health problem. Macrophages (Mφs) and neutrophils that can phagocytose Mtb represent the first line of immune response to infection. Glycogen synthase kinase-3α/β (GSK-3α/β) represents a regulatory switch in host immune responses. However, the efficacy and molecular mechanisms of how GSK-3α/β interacts with Mtb infection in Mφs remain undefined. Here, we demonstrated that Mtb infection downregulated GSK-3α/β activity and promoted matrix metalloproteinase-1 (MMP-1) and MMP-9 expressions in Mφs derived from acute monocytic human leukemia THP-1 cells (THP-1-Mφs). We confirmed the upregulation of MMP-9 expression in tissues of TB patients compared with patients of chronic inflammation (CI). In THP-1-Mφs and C57BL/6 mice, GSK-3α/β inhibitor SB216763 significantly increased MMP-1/9 production and facilitated Mtb load, while MMP inhibitors blocked MMP-1/9 expression and Mtb infection. Consistently, GSK-3α/β silencing significantly increased MMP-1/9 expression and Mtb infection, while overexpression of GSK-3α/β and constitutive activated GSK-3α/β mutants significantly reduced MMP-1/9 expression and Mtb infection in THP-1-Mφs. MMP-1/9 silencing reduced Mtb infection, while overexpression of MMP-1/9 promoted Mtb infection in THP-1-Mφs. We further found that GSK-3α/β inhibition increased Mtb infection and MMP-1/9 expression was blocked by ERK1/2 inhibitor. Additionally, we showed that protein kinase C-δ (PKC-δ) and mammalian target of rapamycin (mTOR) reduced GSK-3α/β activity and promoted MMP-1/9 production in Mtb-infected THP-1-Mφs. In conclusion, this study suggests that PKC-δ-mTOR axis suppresses GSK-3α/β activation with acceleration of MMP-1/9 expression through phospho-ERK1/2. These results reveal a novel immune escape mechanism of Mtb and a novel crosstalk between these critical signaling pathways in anti-TB immunity.

Two-dimensional unsteady wake characteristics and Strouhal number discontinuity have been investigated numerically in flow past rectangular cylinder of different aspect ratio using lattice Boltzmann method. Effect of aspect ratio (AR) has been studied for Reynolds number (Re) in the range from 75 to 150. For investigation the aspect ratio range between 0.05 and 1 has been considered. Different flow regimes, such as two-rows flow regime, modulated flow regime, fully developed flow regime and irregular flow regime have been identified based on the values of Reynolds number for different aspect ratios of the rectangular cylinder. The effects of the aspect ratios and Reynolds numbers on fluid forces, flow separation and vortex shedding frequency have been examined in detail. The results reveal that there exists an aspect ratio where the Strouhal number shows discontinuity. Especially for Re = 145 and 150, a discontinuity in Strouhal number, is observed at around 0.5 ≤ AR ≤ 0.6 where a few extra small peaks are found in the power spectra result of the lift coefficient and irregular vortex pattern behind the rectangular cylinder with no fixed shedding frequency from vorticity contour and streamline visualization. The results further show that the flow characteristics change from two-rows flow regime to fully developed flow regime by changing the values of AR.

Numerical simulations are carried out to study the effect of aspect ratio (AR) and gap spacing (g) for flow past a row of rectangular cylinders using lattice Boltzmann method (LBM). The Reynolds number (Re) is fixed at 150, gap spacing is taken in the range from 0.25 to 4 while the aspect ratio varies from 0.5 to 2. Depending on AR and g, the flow is classified in to three major classes; (i) modulated (ii) symmetric and (iii) synchronized. In each class different flow patterns are observed. In modulated class, the flow behind cylinders shows merging and distortion while the force coefficients are modulated. The observed flow patterns for this class are:nearly-bistable, deflected, flip-flopping and chaotic. The flow behind middle cylinder in symmetric class is either steady or nearly steady. In this class symmetric and nearly-symmetric flow patterns are observed. In synchronized class, the flow behind each cylinder is fully developed with alternate negative and positive vortices. The flow pattern observed for this class are: quasi-synchronized, synchronized and non-synchronized. Fluid forces acting on each cylinder, flow structure mechanism, time signal analysis of drag and lift coefficients and vortex shedding frequencies are investigated systematically for different AR and g. The results show that at small g and AR, flow is complex and is more affected by AR as compared to g. At large g and AR the flow is synchronized throughout the computational domain. The results further show that the mean drag coefficients of all cylinders increase with corresponding decrease in g for fixed AR. While at fixed values of g the mean drag coefficients show variation for all AR. At large g and fixed AR the mean drag coefficient of all cylinders approaches to single cylinder and all cylinders experience same drag. It has been observed that the smaller spacing values have more influence on Strouhal number as compared to higher spacing values.

This study systematically examines the influence of length of dual splitter plates placed at front and rear sides of two side-by-side square cylinders on flow features and fluid force reduction. The Reynolds number is kept at 150 for all computations, and the separation ratio and splitter plate length are varied from 0.5 to 5 and 1 to 5, respectively. The method of investigation is the single-relaxation-time lattice Boltzmann method. The vortex shedding suppression phenomenon occurred due to the presence of dual splitter plates. It is found that the increase in splitter plate length influences the wake structure and increases the wake length by stabilizing the shear layers before rolling up. It is also found that at small separation ratios by placing the dual splitter plates stabilize the flow. The length of splitter plates for minimal drag on the cylinders is found for each separation ratio. Significant reduction in the drag forces is found for both cylinders. At the optimum position the drag coefficient of lower cylinder and upper cylinder is reduced by 45 and 62%, respectively, at separation ratio 0.5 and splitter plate’s length 5. Systematic analysis shows that the splitter plates not only significantly reduce the drag on the cylinders, but also considerably suppress the vortex shedding.

HERC5 (homologous to mouse HERC6) is an E3 enzyme that mediates interferon-stimulated gene 15 (ISG15)-induced ISGylation of protein targets to inhibit protein function, thereby playing a vital role in various physiological functions. However, the direct role of HERC5 in macrophages after M. tuberculosis infection has not yet been studied. In the present study, we showed that HERC5 plays a vital role in promoting the inflammatory immune response. HERC5 deficiency in macrophages enhanced bacterial growth, both in vitro and in vivo. We demonstrated that HERC5 increased pro-inflammatory cytokine production in macrophages by positively regulating the PI3K-AKT signaling pathway. Finally, we found that HERC5 regulated PTEN ISGylation and degradation, thereby promoting activation of the PI3K-AKT signaling pathway. Our findings identified an essential role of HERC5 in the ISGylation of PTEN and contributed to our understanding of its protective effects against M. tuberculosis infection. Therefore, HERC5 is a potential target for therapeutic intervention against tuberculosis. Funding Information: This work was supported National Natural Science Foundation of China (81772150, 81901614, 82072242, 82070906), Guangdong Basic and Applied Basic Research Foundation (2019A1515011103). Declaration of Interests: The authors declare no competing financial interests. Ethics Approval Statement: All the mice were maintained under specific pathogen-free conditions with the approval of the Scientific Investigation Board of the Biosafety Management Committee of Southern Medical University

The aspirated hypersonic air-breathing propulsion system requires a large amount of power generation, but its special structure makes it impossible to adopt common power generation methods. The high-temperature gaseous hydrocarbon fuel thermal power generation (TPG) system was developed to solve the power generation problem for hypersonic air-breathing propulsion system. But off-design operating conditions of the hypersonic propulsion system results in a more complex process for both propulsion system and the TPG system. To better analyzing the dynamic thermos-physical characteristics of hypersonic airbreathing propulsion system considering thermal-mechanical coupling process among cooling/TPG system, a dynamic analytical model was developed, and the dynamic thermos-physical characteristics of TPG system under different off-design working conditions were conducted. It can be concluded from the analytical results that the dynamic process of thermos-physical characteristics shows a complex trend under the flight Mach number and fuel equivalence ratio off-design working conditions. Such complexity of dynamic characteristics brings difficulties in fuel supply for the propulsion system.

Flapping-wing micro air vehicles controlled by tail are poor in stability and maneuverability. A crank-slider and double-pendulum control mechanism which integrates flap and control and provides a good maneuverability by breaking the symmetry between the flapping motions of two lateral wings is proposed for the design of flapping-wing micro air vehicles. The kinematics of this mechanism is analyzed and the effects of flapping angles, flapping amplitudes, and the differences between the flapping angles of two lateral wings on the maneuverability are discussed. The results indicate that flapping angle differences between two lateral wings generated by breaking the symmetry play the most important role in providing good maneuverability. The maneuverability of turning is obtained by moving the pivots of the flapping bars in the system and a servo-gear-rack device is used to realize the movement. The proposed novel flap–control mechanism is compact and easy to control.

A numerical investigation is performed to examine the effect of side ratios (SR), separation ratio (g*), and Reynolds number (Re) on the flow around tandem rectangles using the lattice Boltzmann method. The SR is set at 0.25, 0.5, 0.75 and 1. The g* is varied from 0.5 to 10. The Reynolds number is set at 75, 100, 125 and 150. The results reveal that the upstream cylinder has higher drag forces compared to the downstream cylinder. The results further show that in case of wide-wake shear layer reattachment flow, strongly interactive vortex shedding flow and weakly interactive vortex shedding flow regimes, a small increase in mean drag coefficient of upstream cylinder for all considered cases in this study is attributed to the reduction of wake width, which confirms the weakened influenced by the upstream cylinder. The results show that as the vortex shedding mostly occurs behind the downstream cylinder only, root-mean-square value of lift coefficient is a considerably larger for the downstream cylinder than for the upstream cylinder. The results further show that as the flow regime transition occurs the lift coefficients indicates either in-phase or anti-phase flow behavior. The numerical results are presented in detail in the form of vorticity contour, streamline, time history analysis of forces and vortex shedding frequencies.

Asymmetric flight of insects and birds is often seen in nature which is a conventional way for them to obtain the flexibility of maneuver in turning, hovering, and gliding. A numerical study on the interaction between contralateral wings of a dragonfly in asymmetric forward flight is carried out using the finite volume method. Various asymmetric flights with different advance ratios are considered where the aerodynamic forces, torques of each wing, pressure distributions, vorticity, and velocity fields are analyzed. A number of symmetric flights corresponding to the asymmetric flights are also studied. The results indicate that the interaction between the contralateral wings of a dragonfly is very small even when the dragonfly is in an asymmetric flight no matter how the advance ratios vary in the range concerned. With a typical example of asymmetric forward flights the difference in the mean value of vertical force coefficient is generally less than 5% compared with that for its corresponding symmetric flight. It is found that a small lateral flow region (LFR) is formed near the body, and there is a small lateral flow across the symmetric plane of the body. But this flow is very weak and resulted interaction between contralateral wings is very small. The result has confirmed in a way that dragonflies take a quite different way from fruit flies to obtain the lift with the contralateral wings. That is, fruit flies employ clap-and-fling mechanism which needs contralateral wings to be close enough to extrude the flow and generate lift, which means the contralateral two wings are so close that strong interaction happens, while dragonflies flap their contralateral wings on two sides of the vertical central plane with a relatively far distance between the wings where the interaction of contralateral wings is negligibly weak.

Mycobacterium tuberculosis, which primarily infects mononuclear phagocytes, remains the leading bacterial cause of enormous morbidity and mortality because of bacterial infections in humans throughout the world. The IL-1 family of cytokines is critical for host resistance to M. tuberculosis. As a newly discovered subgroup of the IL-1 family, although IL-36 cytokines have been proven to play roles in protection against M. tuberculosis infection, the antibacterial mechanisms are poorly understood. In this study, we demonstrated that IL-36γ conferred to human monocyte-derived macrophages bacterial resistance through activation of autophagy as well as induction of WNT5A, a reported downstream effector of IL-1 involved in several inflammatory diseases. Further studies showed that WNT5A could enhance autophagy of monocyte-derived macrophages by inducing cyclooxygenase-2 (COX-2) expression and in turn decrease phosphorylation of AKT/mTOR via noncanonical WNT signaling. Consistently, the underlying molecular mechanisms of IL-36γ function are also mediated by the COX-2/AKT/mTOR signaling axis. Altogether, our findings reveal a novel activity for IL-36γ as an inducer of autophagy, which represents a critical inflammatory cytokine that control the outcome of M. tuberculosis infection in human macrophages.

Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) represents one of the greatest threats to human health., Interferons (IFNs) in combination with the first-line of anti-TB drugs have been used for treating TB for decades in the clinic, but how Mtb infection regulates interferon-stimulated genes (ISGs) in human macrophages (Mϕs) remains unknown. In this study, we investigated the expression-signature and associated innate signaling mechanisms of ISGs in Mtb-infected human monocyte-derived Mϕs (hMDMs) and THP-1-derived Mϕs (THP-1-Mϕs). Among 28 of the detected ISGs, 90% of them exerted a significant increase in Mtb-infected Mϕs. Additionally, we found that cytosolic cyclic (GMP-AMP) synthase (cGAS), toll-like receptor-2 (TLR-2) and TLR-4 signaling pathways participated in ISG induction. Their downstream elements of TANK-binding kinase 1 (TBK1), nuclear factor-kappa B (NF-&kappa, B), mitogen-activated protein kinase (MAPK), and Janus kinase-signal transducer and activator of transcription (JAK-STAT) were selectively involved in Mtb-mediated ISG production. Finally, the numerous types of ISG expression in hMDMs of TB patients were more susceptible to restimulation of Mtb infection or/and IFN treatment than that of healthy people. Hence, different signaling pathways define different ISG expression during Mtb infection and this helps to illustrate how ISGs are elucidated and to better understand the host immune responses to Mtb infection in Mϕs.

In order to study the flexible deformation process of the micro flapping wing during its fluttering, the dynamic three-dimensional reconstruction of the wings is carried out by the RealSense SR300 depth camera. The wing flapping parameters is measured and the deformation of different wings flapping are analyzed. The results show that the wing deformation of the large flexible wing is irregularly adaptive during the flapping process, and it has a larger amount of arch deformation, and the asymmetry of the flexible deformation of the wings on both sides is greater than that of the small flexible wing.

In this paper, a prototype of a hovering flapping wing micro air vehicle is developed. The aerodynamic force of the prototype at different flapping frequencies and pitch angles is measured, and a hovering flight control scheme for the vehicle is designed based on the measured results. Finally, a flight test of the prototype is carried out. The tail deflection of the prototype is controlled by a micro linear rudder, and the pitch attitude of the prototype is adjusted during flight. The hovering flight within a certain range is realized. The feasibility of the hovering flight control scheme of flapping wing micro air vehicle is verified.

Summary Objectives Although it has been reported that Interferon regulatory factor 1 (IRF1) inhibits Mycobacterium tuberculosis (Mtb) infection via inducible nitric oxide synthase (iNOS) in mice, how it counteracts with mycobacterial infection in human remains largely obscure. This study was conducted to investigated the effect of IRF1 on Mtb infection in human macrophages (Mϕs). Methods We thus investigated the IRF1 expression by using PBMC and monocytes of pulmonary tuberculosis (TB) patients and human monocyte-derived macrophages (hMDMs) and THP-1-derived macrophages (THP-1-Mϕ). We used gain-of-function and loss-of-function approaches to explore the role of IRF1 on Mtb infection. Results IRF1 was significantly induced in PBMC and monocytes of pulmonary TB patients in vivo and in human Mϕs in vitro. We demonstrated that IRF1 protects Mϕs from Mtb infection. Concurrently, IRF1 promotes the expression of several pro-inflammatory cytokines including IL-6, TNF-α and IL-8, indicating IRF1-mediated activation of innate immunity upon Mtb infection. Gain-of-function and loss-of-function approaches have demonstrated that IRF1 suppresses the mechanistic target of rapamycin (mTOR)/p70 S6 kinase (p70 S6K) cascade to exert its anti-Mtb effect. Conclusions The discovery of a novel function of IRF1 in facilitating anti-mycobacterial effect through suppressing mTOR/p70 S6K signaling in Mϕs may provide a promoting therapeutic target for tuberculosis.

Power generation is urgent needed by the hypersonic air-breathing propulsion system, but the on-board power generation method is heavily restricted by its special structure. The outlet high temperature hydrocarbon fuel of the cooling channel in the hypersonic propulsion system can be used to generate power. However, the hydrocarbon fuel temperature is highly related with hypersonic propulsion system dynamic working conditions. To analyze the dynamic thermos-physical characteristics of high temperature hydrocarbon fuel thermal power generation (TPG) system, a zero-dimensional dynamic analytical model was developed, dynamic characteristics of the TPG system under different working conditions were conducted. Results show that there is overshoot of outlet fuel temperature under flight Mach number increase conditions and fuel equivalence ratio decrease conditions, which can be more than 10 K. Whilst there are both negative and positive overshoot of the generated power under the above working conditions, the largest magnitude of negative and positive overshoot can be more than 1 kW. Furthermore, the dynamic time of outlet fuel temperature and generated power are about 20–30s. Such complexity of dynamic characteristics brings difficulties in fuel supply for the propulsion system.

The increasing demand for cost reduction in aerospace electric propulsion makes the application of krypton Hall thrusters a compelling choice. However, these thrusters continue to experience performance limitations. Nonetheless, their working performance and stability have been greatly improved via their operation in the rotating supply mode. The present study is based on previous research results pertaining to the rotating supply mode and subsequent studies of the specific mechanism by which the rotating supply mode influences the ionization process and performance of the krypton Hall thruster. The ionization performance of the thruster was analyzed using an image diagnosis method. The rotating supply mode reduces the width of the ionization zone, increases the ionization intensity, and moves the ionization zone upstream of the discharge channel. Considering the flow rate-ampere characteristics at a discharge voltage of 300 V, the rotating supply mode can reduce the width of the ionization zone by 10%–20%, increase the ionization intensity by approximately 14%, and move the maximum ionization intensity peak position nearly 2 mm upstream of the discharge channel, compared to the axial supply mode. The experimental data explains the mechanism by which the rotating supply mode optimizes the ionization process in the krypton Hall thruster.

In this paper, the numerical investigations for drag reduction and vortex shedding suppression behind a square cylinder are carried out in presence of small control cylinders placed both at upstream and downstream locations of main cylinder. The numerical computations are performed in the ranges of $$80 \le Re \le 200$$ and $$0.5 \le g \le 6$$ , (where Re is the Reynolds number and g is the gap spacing between the control cylinders and main square cylinder, respectively) using a single relaxation time lattice Boltzmann method (SRT-LBM). Firstly, the present code is validated for flow past a single square cylinder at different Reynolds numbers. The effects of Re and g are investigated in terms of vortex shedding frequency, time-history analysis of drag and lift coefficients, energy spectra analysis of lift coefficient, vorticity contours visualization and forces exerted on the cylinder. Three different types of flow patterns are observed at different combinations of Reynolds numbers and gap spacings. The maximum reduction in the mean drag force and root-mean-square value of lift coefficient is found. Furthermore, the applications of SRT-LBM for suppression of vortex shedding and reduction in the drag force are also discussed.

Two-dimensional numerical study has been carried out to investigate the effect of gap spacings for flow past five side-by-side rectangular cylinders using the lattice Boltzmann method at a Reynolds number of 150 and aspect ratio defined as AR=length/height=1.5. The gap spacing between the cylinders is varied systematically from g=0.5 to 4, so that the sensitivity of the flow and force statistics can be inspected. The gap spacings have strong effect on the hydrodynamic interaction of the cylinders wakes which significantly affects the flow structure. The flow behavior can be grouped into five patterns: (i) symmetric, (ii) flip-flopping, (iii) in-phase and anti-phase modulated deflected, (iv) in-phase modulated non-synchronized and (v) in-phase and anti-phase modulated synchronized. Calculations of mean drag coefficient, Strouhal number and root-mean-square value of drag and lift coefficients are carried out on each cylinder and compared with available literature. Each flow pattern will be studied in terms of wake structure, power spectra analysis of lift coefficients and time analysis of drag and lift coefficients. The average Strouhal number and average drag coefficient show significant variation against gap spacing.

Tuberculosis (TB) and human immunodeficiency virus type 1 (HIV-1) infection are closely intertwined, with one-quarter of TB/HIV coinfected deaths among people died of TB. Effector CD8(+) T cells play a crucial role in the control of Mycobacterium tuberculosis (MTB) and HIV-1 infection in coinfected patients. Adoptive transfer of a multitude of effector CD8(+) T cells is an appealing strategy to impose improved anti-MTB/HIV-1 activity onto coinfected individuals. Due to extensive existence of heterologous immunity, that is, T cells cross-reactive with peptides encoded by related or even very dissimilar pathogens, it is reasonable to find a single T cell receptor (TCR) recognizing both MTB and HIV-1 antigenic peptides. In this study, a single TCR specific for both MTB Ag85B199-207 peptide and HIV-1 Env120-128 peptide was screened out from peripheral blood mononuclear cells of a HLA-A*0201(+) healthy individual using complementarity determining region 3 spectratype analysis and transferred to primary CD8(+) T cells using a recombinant retroviral vector. The bispecificity of the TCR gene-modified CD8(+) T cells was demonstrated by elevated secretion of interferon-γ, tumour necrosis factor-α, granzyme B and specific cytolytic activity after antigen presentation of either Ag85B199-207 or Env120-128 by autologous dendritic cells. To the best of our knowledge, this study is the first report proposing to produce responses against two dissimilar antigenic peptides of MTB and HIV-1 simultaneously by transfecting CD8(+) T cells with a single TCR. Taken together, T cells transduced with the additional bispecific TCR might be a useful strategy in immunotherapy for MTB/HIV-1 coinfected individuals.

Various stroke trajectories may be observed in insect hovering flight in nature; however their influences on the flight performance of insect are not well estimated. In this study, a numerical investigation into the effects of stroke trajectories on the aerodynamic performance of insect hovering flight is carried out through the solution of the two-dimensional unsteady incompressible Navier-Stokes equations. An insect wing model with ellipse cross section in hovering flight is considered for the purpose and four types of idealized trajectories (Named linear, oval, figure-eight and double-eight) which possess different deviation characteristics from the stroke plane are examined. The influences of the deviation amplitude of trajectory, the attack angle of wing and the inclined angle of stroke plane on the aerodynamic characteristics of hovering wing are systematically analyzed. The results show that in the case of the wing in a normal hovering flight where the stroke plane is horizontal, the trajectory deviation from the stroke plane weakens the aerodynamic performance for each trajectory case considered, and this deteriorative effect becomes more serious as the amplitude of deviation increases. With regard to the influence of the angle of attack, the results show that the time-averaged drag force and power consumption increase monotonically with the angle, whereas the time-averaged lift force and the lifting efficiency increase first and then decrease as the angle increases further. In the case of a hovering flight with an inclined stroke plane, distinctly different trends from a normal hovering flight are obtained.

A numerical study on the effects of the asymmetry in flapping motions on the aerodynamic performance of a 2-D inclined hovering wing is carried out through the solution of the two-dimensional unsteady Navier-Stokes equations. Asymmetric flapping motions with different flapping durations as well as different angles of attack during downstroke and upstroke are considered, correspondingly the aerodynamic forces, the energy consumption and the flow structures of the wing are examined for the purpose. The results show that the asymmetry either in flapping duration or in angle of attack can effectively alter the aerodynamic characteristics of the wing. It is found that much larger vertical force is generated in the downstroke with smaller duration. As for the angle of attack, an increase in the angle during the downstroke gives rise to a larger vertical force and lifting efficiency while for the upstroke the increase in the angle results in a larger thrust force. Furthermore, a combined model with asymmetry in both flapping duration and angles of attack is also studied and the results show that a combined flapping motion with a faster downstroke and a higher downstroke angle of attack can produce much larger vertical force than a motion with asymmetry simply in stroke duration or angle of attack. The present results provide physical insight into a better understanding of the asymmetric stroke mechanisms in the flapping motion of insects.