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Tuberculosis (TB), caused by mycobacterium tuberculosis (M. tuberculosis) infection, is one of the leading causes of death globally and poses a threat to public health. During infection, M. tuberculosis causes redox imbalance and dysfunctions of protective immunity. Transcription factor nuclear factor erythroid 2 (NF-E2)-related factor (Nrf2) is a major modulator of cellular redox homeostasis via transcriptional induction of cytoprotective genes to protect cell against the damage from insults. Thus, we hypothesize that Nrf2 may regulate protective immunity against M. tuberculosis. RNA-seq and immunoblotting results suggested that the expression of Nrf2 protein increased after M. tuberculosis infection, and decreased upon long-term M. tuberculosis infection, while Keap1 protein maintained a low expression level during M. tuberculosis infection. Furthermore, Nrf2 activator sulforaphane (SFN) decreased proinflammatory cytokines production, phagocytosis and host cell apoptosis, while increasing ROS levels and promoting autophagy in THP1 macrophages infected with M. tuberculosis. In addition, SFN-activated Nrf2 augmented bacterial killing by macrophages, which might be due to the regulation of protective immunity via Nrf2. Combined, our results extend the understanding of the complex innate immunity regulation by Nrf2 against mycobacterial infection. Also, these findings suggested that the regulation of Nrf2 signaling cascade could be used as a therapeutic target for the treatment of TB patients and the development of better anti-TB vaccines.

Mycobacterium tuberculosis (M. tuberculosis) is an intracellular bacteria capable of evading the human immune system through various mechanisms. M. tuberculosis secretes many virulence factors when infecting host cells. The 6 kDa early secretory antigen target (ESAT-6) is one of the most virulent factors producted by the ESX-1 system, which acts alone or in conjunction with culture filtrate protein 10 (CFP-10) to involve in host-pathogen interactions. ESAT-6 has been widely investigated in M. tuberculosis pathogenicity and vaccination. Nonetheless, little is known about its contribution to M. tuberculosis immune evasion and the involved cellular mechanisms. In this study, differential genes between BCG with the region of difference-1 (RD1) gene and Bacille Calmette-Guérin (BCG) infected dendritic cells (DC) were analyzed to reveal that ESAT-6, expressed in the RD1 region, involves host denfensive function of DC in response to BCG. In vitro evidence indicated that ESAT-6 (5 μg/ml) inhibits M. tuberculosis-induced apoptosis in THP-1(A) macrophages by suppressing TLR2 and via caspase-9 and caspase-3 endogenous pathways. It also inhibits the expression of IL-10, TNF-α, IL-12, and the phagocytosis of macrophages. Additionally, ESAT-6 suppresses the bactericidal activity of macrophages, including ROS production, and the killing of M. tuberculosis. In summary, these data suggest a central role of ESAT-6 in M. tuberculosis’s evasion from macrophage recognition, phagocytosis, killing, and apoptosis. Our work may provide a theoretical basis for exploring new molecular targets of M. tuberculosis both for innovative vaccines and therapeutic inventions.

Objective To investigate the effect of protein tyrosine phosphatase receptor type O (PTPRO) on the phagocytic activity of alveolar epithelial cells in LPS-induced acute lung injury. Methods Mice were randomly divided into the normal control group and LPS stimulation group. The infiltration of inflammatory cells was detected by HE staining. The cytokine TNF-α level in lung was analyzed by ELISA. Western blotting was performed to detect the effect of LPS on PTPRO protein expression in lung. After the expression of PTPRO in MLE-12 cells was silenced by siRNA in vitro, flow cytometry was used to detect the effects of LPS and PTPRO siRNA on the phagocytic activity of MLE-12 cells, and the effects of LPS and PTPRO siRNA on the expression of PTPRO, AKT and phosphorylated AKT protein were measured by Western blotting. Results After the establishment of murine acute lung injury model by LPS injection(1 mg/kg), the infiltrated polymorphonuclear leukocytes were markedly increased. The level of TNF-α in lung tissue and the expression of PTPRO in MLE-12 cells were both significantly increased after LPS stimulation. However, the activity of MLE-12 cells to phagocytose fluorescent microbeads was evidently decreased after silencing PTPRO. Furthermore, silencing PTPRO induced a remarkable decrease in the phosphorylation of AKT in MLE-12 cells. Conclusion PTPRO can promote phagocytic activity of MLE-12 cells via activating AKT signaling pathway.

An unreported unprecedented spike of ∼μs line-width, followed by an overshoot, was discovered at the rising edge of transient electroluminescence (TEL) from guest-doped organic light-emitting diodes with strong electron-donating abilities from the host carbazole groups. By changing the device structures and TEL measurement parameters, a series of experimental results demonstrate that this TEL spike is not related to exciton interactions such as singlet-triplet and triplet-triplet annihilations but originated from the radiative recombination of pre-stored electrons with injected holes. Surprisingly, these pre-stored guest electrons do not come from the energy-level traps in the host-guest systems; instead, the guest molecules receive the electrons transferred from the host carbazole groups due to their strong electron-donating abilities. Moreover, the observed spikes show rich and extraordinary temperature dependences. Based on the detailed understanding of the spike formation mechanism, we have proposed the requirements for the occurrence of spike and realized the artificial adjustments of the spike intensity. For instance, the instantaneous luminescent intensity of this spike can reach over 80 times the magnitude of the TEL plateau. Accordingly, this work deepens the physical understanding of this novel spike in TEL and paves the way for fabricating an electro-optic sensor to detect instantaneous weak current signals.

Background: Cancer is a leading cause of death worldwide. Extensive research over decades has led to the development of therapies that inhibit oncogenic signaling pathways. The mammalian target of rapamycin (mTOR) signaling pathway plays an important role in the development of many cancers. Several mTOR inhibitors are approved for the treatment of cancers. However, the anticancer efficacies of mTOR inhibitor monotherapy are still limited. Methods: Western blot was used to detect the expression of indicated molecules. Thioredoxin reductase (TrxR) activity in cells was determined by the endpoint insulin reduction assay. Immunofluorescence staining was used to analyze precise location and expression of target proteins. Nude mice were used for xenograft tumor models. Results: We identified a synergistic lethal interaction of mTOR and TrxR inhibitors and elucidated the underlying molecular mechanisms of this synergism. We demonstrated that mTOR and TrxR inhibitors cooperated to induce cell death by triggering oxidative stress, which led to activation of autophagy, endoplasmic reticulum (ER) stress and c-Jun N-terminal Kinase (JNK) signaling pathway in cancer cells. Remarkably, we found that auranofin (AF) combined with everolimus significantly suppressed tumor growth in HCT116 and SGC-7901 xenograft models with no significant signs of toxicity. Conclusion: Our findings identify a promising therapeutic combination for cancer and has important implications for developing mTOR inhibitor-based combination treatments.

Mycobacterium tuberculosis (M. tuberculosis) is the pathogen which causes tuberculosis (TB), a significant human public health threat. Co-infection of M. tuberculosis and the human immunodeficiency...

Background. Untreated nephropathy can progress to renal failure. The traditional Mongolian remedy Narenmandula regulates the kidney “yang.” This study aimed to identify key microRNAs (miRNAs) targeted by Narenmandula in a rat model of nephropathy. Methods. Fifteen rats exhibiting normal renal function were randomized to three study arms. Nephropathy was induced in n = 10 rats using doxorubicin hydrochloride, followed by either Narenmandula treatment (treatment group) or no treatment (control group). In n = 5 rats, no doxorubicin was given and renal function remained unchanged (healthy group). Microarray analysis identified miRNAs which were differentially expressed (DE-miRNAs) between groups. Target genes of DE-miRNAs were predicted using miRWalk version 2.0, followed by enrichment analysis using DAVID, and construction of the miRNA coregulatory network using Cytoscape. Results. Nephropathy was successfully induced, with doxorubicin resulting in differential expression of 3645 miRNAs (1324 upregulated and 2321 downregulated). Narenmandula treatment induced differential expression of a total of 159 miRNAs (102 upregulated and 57 downregulated). Upregulated DE-miRNAs (e.g., miR-497-5p, miR-195-5p, miR-181a-5p, miR-181c-5p, and miR-30e-5p) and downregulated DE-miRNAs (e.g., miR-330-3p and miR-214-3p) regulated a high number of target genes. Moreover, the miRNA pairs (e.g., miR-195-5p—miR-497-5p, miR-181a-5p—miR-181c-5p, and miR-30e-5p—miR-30a-5p) coregulated a high number of genes. Enrichment analysis indicated functional synergy between miR-30e-5p—miR-30a-3p, miR-34a-5p—miR-30e-5p, miR-30e-5p—miR-195-3p, and miR-30a-3p—miR-195-3p pairs. Conclusion. Narenmandula may modulate doxorubicin-induced nephropathy via targeting miR-497-5p, miR-195-5p, miR-181a-5p, miR-181c-5p, miR-30e-5p, miR-330-3p, miR-214-3p, miR-34a-5p, miR-30a-3p, and miR-30a-5p.

Sepsis is a life-threateningorgandysfunction caused by the cytokine storm induced by the severe bacterial infection. Excessive inflammatory responses are responsible for the lethal organ damage during the early stage of sepsis. Helminth infection and helminth-derived proteins have been identified to have the ability to immunomodulate the host immune system by reducing inflammation against inflammatory diseases. Trichinella spiralis cystatin (Ts-Cys) is a cysteine protease inhibitor with strong immunomodulatory functions on host immune system. Our previous studies have shown that excretory-secretory proteins of T. spiralis reduced sepsis-induced inflammation and Ts-Cys was able to inhibit macrophages to produce inflammatory cytokines. Whether Ts-Cys has a therapeutic effect on polymicrobial sepsis and related immunological mechanism are not yet known.Sepsis was induced in BALB/c mice using cecal ligation and puncture (CLP), followed by intraperitoneal injection of 15 µg recombinant Ts-Cys (rTs-Cys). The therapeutic effect of rTs-Cys on sepsis was evaluated by observing the 72-hour survival rates of CLP-induced septic mice and the acute injury of lung and kidney through measuring the wet/dry weight ratio of lung, the levels of blood urea nitrogen (BUN) and creatinine (Cr) in sera and the tissue section pathology. The potential underlying mechanism was investigated using mouse bone marrow-derived macrophages (BMDMs) by observing the effect of rTs-Cys on LPS-stimulated macrophage polarization. The expression of genes associated with macrophage polarization in BMDMs and tissues of septic mice was measured by Western Blotting and qPCR.In this study, we demonstrated the treatment with rTs-Cys alleviated CLP-induced sepsis in mice with significantly reduced pathological injury in vital organs of lung and kidney and reduced mortality of septic mice. The further study identified that treatment with rTs-Cys promoted macrophage polarization from classically activated macrophage (M1) to alternatively activated macrophage (M2) phenotype via inhibiting TLR2/MyD88 signal pathway and increasing expression of mannose receptor (MR), inhibited pro-inflammatory cytokines (TNF-α, IL-6 and IL-1β) and increased regulatory anti-inflammatory cytokines (IL-10 and TGF-β) in sera and tissues (lung and kidney) of mice with polymicrobial sepsis.Our results demonstrated that rTs-Cys had a therapeutic effect on sepsis through activating regulatory macrophages possibly via suppressing TLR2/MyD88 signal pathway. We also identified that rTs-Cys-induced M2 macrophage differentiation was associated with increased expression of MR on the surface of macrophages. Our results underscored the importance of MR in regulating macrophages during the treatment with rTs-Cys, providing another immunological mechanism in which helminths and their derived proteins modulate the host immune system. The findings in this study suggest that rTs-Cys is a potential therapeutic agent for the prevention and treatment of sepsis and other inflammatory diseases.

This study investigates a fuzzy predictive functional control scheme of a class of non-linear systems. According to the Takagi-Sugeno fuzzy model, a fuzzy prediction model of the presented non-linear system is given. Also, the fuzzy prediction model is transformed into the transfer function model. Then, a novel fuzzy predictive functional control scheme is proposed for a class of non-linear systems by combining the multi-variable centralised control and predictive functional control. The rigorous theoretical derivation is presented to ensure the stabilisation of the non-linear systems. Two representative cases, including the three-dimensional brushless DC motor and the 4D Chen system, are implemented to confirm the validity and superiority compared with an existing pure fuzzy control method.

This study focuses on a fuzzy generalised predictive control (FGPC) method for a time-delay hydro-turbine governing system (HTGS). First, based on the time-delay Takagi-Sugeno fuzzy model, a time-delay HTGS and its fuzzy prediction model are given. Second, with the help of delay fuzzy linearisation and a fourth-order Runge-Kutta algorithm, a transformed controlled auto-regressive integrated moving average model is obtained. Then, a new FGPC scheme for the time-delay HTGS is proposed. Finally, numerical simulations are implemented to verify the validity and superiority of the proposed method. It also provides a reference for the stability control of relevant hydropower station systems.

The traditional method of fundamental solution (T-MFS) is known as an effective method for solving the scattering of elastic waves, but the T-MFS is inefficient in solving large-scale or broadband frequency problems. Therefore, in order to improve the performance in efficiency and memory requirement for treating practical complex 2-D broadband scattering problems, a new algorithm of fast multi-pole accelerated method of fundamental solution (FM-MFS) is proposed. Taking the 2-D scattering of SH waves around irregular scatterers in an elastic half-space as an example, the implementation steps are presented in detail. Based on the accuracy and efficiency verification, the FM-MFS is applied to solve the broadband frequency scattering of plane SH waves around group cavities, inclusions, a V-shaped canyon and a semi-elliptical hill. It shows that, compared with T-MFS, the FM-MFS has great advantages in reducing the consumed CPU time and memory for 2-D broadband scattering. Besides, the FM-MFS has excellent adaptability both for broad-frequency and complex-shaped scattering problems.

Objective To investigate the effect of insulin-like growth factor 1 (IGF-1) on the phagocytic activity of mouse BV-2 microglial cells. Methods Western blotting was performed to detect the protein levels of IGF-1 and IGF-1 receptor (IGF-1R) in the murine brain after the establishment of acute central nervous system inflammation models by intraperitoneal lipopolysaccharide (LPS) injection (10 mg/kg). The protein level of IGF-1R on BV-2 microglial cells that had been stimulated by 500 ng/mL LPS for 4, 12 and 24 hours was measured by Western blotting. To assess the phagocytic activity of microglial cells in response to IGF-1, BV-2 microglial cells were stimulated by IGF-1 at different concentrations for 24 hours after pretreated with or without wortmannin (PI3K/AKT signaling pathway blocker), and then incubated with fluorescent microbeads for 2 hours followed by measurement of phagocytosis of the fluorescent microbeads by flow cytometry. After treatment of IGF-1 (50 ng/mL), p-AKT and AKT signaling pathways in the BV-2 microglial cells were detected by Western blotting. Results Intraperitoneal LPS injection caused increased levels of IGF-1 and IGF-1R in the mouse brain. LPS upregulated the protein expression of IGF-1R on BV-2 microglial cells. The activity of BV-2 microglial cells to phagocytose fluorescent microbeads gradually increased with IGF-1 concentration rising and peaked in the IGF-1 treatment at 50 ng/mL, and gradually decreased thereafter. And IGF-1 induced the phosphorylation of AKT in BV-2 microglial cells. However, after the PI3K/AKT signaling pathway was blocked via wortmannin, the effect of IGF-1 on the activity of BV-2 microglial cells to phagocytose fluorescent microbeads was significantly alleviated. Conclusion IGF-1 can promote phagocytic activity of BV-2 cells via activating PI3K/AKT signaling pathway, which suggests a potential role of IGF-1 in regulating the cerebral inflammation.

Our recent study demonstrated that the QKI-5 regulated miRNA, miR-196b-5p, and it functions as an onco-microRNA in non-small cell lung cancer (NSCLC) by directly targeting GATA6 and TSPAN12. However, the role of miR-196b-5p in NSCLC progression and metastasis still remains unclear. We found that miR-196b-5p promotes lung cancer cell proliferation and colony formation by directly targeting tumor suppressor, FAS. The expression of FAS was significantly downregulated in NSCLC tissue samples and was negatively correlated with the miR-196b-5p expression. Knocking down FAS activates NFkB signaling and subsequent IL6 secretion, resulting in phosphorylation of signal transducer and activator of transcription 3 (STAT3) to promote lung cancer cell growth. Our findings indicated that miR-196b-5p might exhibit novel oncogenic function by FAS-mediated STAT3 activation in NSCLC, and suggested that targeting the miR-196b-5p/FAS/NFkB/IL6/STAT3 pathway might be a promising therapeutic strategy in treating NSCLC.

Sepsis-associated encephalopathy (SAE) is a devastating neurological complication of sepsis with intolerable high motility. SAE is accompanied with brain vascular injury, endothelial hyperpermeability, and neutrophil infiltration into the brain tissue, key inflammatory processes leading to further brain edema and neuronal cell apoptosis. Recent studies from us and others suggest that the chemokine receptor C-X-C Motif Chemokine Receptor 2 (CXCR2) is crucial for neutrophil recruitment during SAE. Here we use CXCR2 antagonist SB225002 to characterize the role of CXCR2 in brain infiltration of neutrophil in a murine model of SAE. Systemic administration of high-dose LPS (10 mg/kg) induced evident neutrophil infiltration into the cerebral cortex in wild-type mice. However, CXCR2 antagonist SB225002 markedly attenuated neutrophil infiltration into brain. The CXCR2 expression on neutrophils in the peripheral circulation was dramatically downregulated in response to this LPS dose, and endothelial CXCR2 was significantly upregulated, suggesting endothelial but not neutrophil CXCR2 plays a more important role in neutrophil infiltration into brain. Strikingly, although these CXCR2 antagonist SB225002 treated mice displayed reduced neutrophil infiltration, no change in neutrophil rolling and adhesion was observed. Furthermore, we confirmed that CXCR2 agonist CXCL1 induced a marked increase in actin stress fiber synthesis and paracellular gap formation in cultured cerebral endothelial cells, which is attenuated by SB225002. Thus, these results demonstrate a selective role for endothelial CXCR2 to regulate cerebral vascular permeability and neutrophil transmigration in high-dose LPS induced neuroinflammation, and also suggest a therapeutic potential of CXCR2 antagonist SB225002 in SAE.

Objective To investigate the role of CXCR2 in the cerebral endothelial activation and migration of neutrophils into the brain in septic encephalopathy (SE) induced by lipopolysaccharide (LPS). Methods C57BL/6J mice and CXCR2-knockout mice were randomly divided into a normal control group, a wildtype mice group with LPS treatment and CXCR2-knockout mice group with LPS treatment. Mouse SE models were induced by intraperitoneal LPS injection. Naphthol AS-D chloroacetate histochemical staining of the brain section was performed to quantitate the neutrophils infiltrating into the cerebral cortex. TNF-α and CXCL1 concentrations in the brain and plasma were determined by ELISA. After the stimulation of LPS (1 μg/mL) and TNF-α (200 ng/mL), the levels of CXCR2 protein in the primary mouse brain microvascular endothelial cells isolated from the cerebral cortex were detected by Western blotting. The levels of F-actin and vascular cell adhesion molecule 1 (VCAM-1) protein in the primary mouse brain microvascular endothelial cells stimulated by CXCL1 (100 ng/mL) were detected by Western blotting. Results After intraperitoneal LPS injection, there was a significant increase in the level of TNF-α in the brain and plasma and there was also an evident increase in the level of CXCL1 in the brain of wild type mice (C57BL/6J mice). And intraperitoneal LPS injection caused increased neutrophil infiltration into the cerebral cortex in the wild type mice (C57BL/6J mice). But CXCR2-knockout mice displayed evidently reduced neutrophil infiltration into the cerebral cortex compared with the wildtype mice. In vitro LPS and TNF-α upregulated the expression of CXCR2 in the primary brain microvascular endothelial cells. CXCL1 increased remarkably the expression of endothelial F-actin and VCAM-1. Conclusion In the SE model, CXCR2 participates in the cerebral endothelial activation and neutrophil migration into the brain.

Acetaminophen (APAP) is the leading cause of drug-induced acute liver failure. Sphingosine-1-phosphate (S1P), whose formation is catalyzed by sphingosine kinase (SPHK)-1 or -2, is a bioactive lipid implicated in human health and disease. Here, we show that APAP-treated sphK1-deficient (sphK1(−/−)) mice exhibited markedly less liver damage and reduced inflammation compared with the wild-type mice. SPHK1 deficiency alleviated APAP-induced endoplasmic reticulum (ER) stress by affecting the phosphorylation of inositol-requiring enzyme 1α (IRE1α) and protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK)-eukaryotic translation initiation factor 2α (eIF2α), levels of activating transcription factor 4 (ATF4), and activation of activating transcription factor 6 (ATF6). SPHK1 deficiency also inhibited mitochondrial permeability transition (MPT), as evidenced by the impaired phosphorylation of JNK, apoptosis signal-regulated kinase 1 (ASK1), and glycogen synthase kinase 3β (GSK3β). In addition, SPHK1 deficiency reduced the levels of histone deacetylase and promoted the acetylation of p65 and STAT1, thereby impairing the transcription of inflammatory genes. Supplementation with exogenous S1P significantly reversed the activation of the PERK-eIF2α-ATF4 pathway and ATF6 during ER stress as well as the activation of GSK3β, ASK1, and JNK during MPT. Both FTY720, a functional S1P receptor antagonist, and PF543, an SPHK1 inhibitor, significantly ameliorated APAP-induced liver injury and improved animal survival. Our study reveals a critical role for SPHK1 in mediating APAP-induced hepatotoxicity by promoting ER stress and MPT.

© 2018 Elsevier Ltd Taking full advantage of the indirect boundary element method (IBEM) and fast multi-pole expansion algorithm, this paper proposes a fast multi-pole indirect boundary element method (FM-IBEM) to solve the scattering of high-frequency seismic waves by three-dimensional (3-D) superficial irregularities or heterogeneity in a solid half-space. First, IBEM utilizes an exact dynamic Green's function for a full-space to construct the scattered wave field. Subsequently, by employing plane waves expansion of 3-D potential functions of compressional and shear waves, the multi-pole expansion and local expansion coefficients were derived. Implementation of FM-IBEM is presented in detail for wave-scattering problems. Numerical examples illustrate that the proposed FM-IBEM can reduce the memory required by more than an order of magnitude and also greatly improve the computing efficiency, retaining excellent accuracy as well. Ultimately, several high-frequency plane wave scattering problems of 3-D superficial irregularities in a solid half-space are illustrated, and several important scattering characteristics are described based on the high-precision numerical results.

Fractional-order fuzzy generalised predictive control (FFGPC) for a class of non-linear systems is studied. Based on the Grunwald-Letnikov fractional calculus, Laplace transform, and discretisation, a class of fractional-order non-linear systems are transformed to fit the standard controlled autoregressive integrating moving average (CARMA) model. With the help of the Takagi-Sugeno fuzzy linearisation theory, a linear CARMA model for the non-linear systems is represented. Then, a new FFGPC method is proposed for the fractional-order non-linear systems based on the obtained CARMA predictive model and generalised predictive control theory. Numerical simulations are implemented to verify the effectiveness and superiority of the new method. This work also provides a reference for the control of relevant fractional-order systems.

In this paper, an explicit representation of the N -fold degenerate Darboux transformation (DT) for the three component Kundu–Eckhaus equations, which can be viewed as a model to describe the effect of quintic nonlinearity on the ultra-short optical pulse propagation in non-Kerr media, has been derived. The DT is expressed by the initial eigenfunctions, spectral parameters and ‘seed’ solution. As applications of DT, the abundant and novel interactions between soliton and positon are discussed in detail, such as elastic interactions, inelastic interactions and bound states.

Leukocyte migration across the endothelial barrier plays an essential role in CNS inflammation. The migration process requires complex endothelial adhesion molecules concentrated at the junctions of endothelial cells. Recent findings suggest that cerebral endothelial cells play an active role in the pathogenesis of CNS inflammatory diseases. This review describes our current understanding of the effects of various inflammatory mediators of leukocyte migration on cerebral endothelial cells, the mechanisms underlying the leukocyte-endothelial cell interactions, and the crosstalk between endothelial cells and glial cells or platelets. These emerging mechanisms may provide new therapeutic strategies for a variety of CNS inflammatory diseases.

The phagocytosis of apoptotic cells by alveolar epithelial cells helps to eliminate airway inflammation. Insulin‑like growth factor 1 (IGF‑1) regulates cell metabolism and proliferation, and promotes cell survival, while it may also promote the proliferation and differentiation of alveolar epithelial cells during the repair of lung injury. The present study investigated the effect of IGF‑1 on the phagocytic activity of alveolar epithelial cells, a nonprofessional phagocyte. IGF‑1 was elevated in lung tissue and bronchoalveolar lavage fluid obtained from mice with ovalbumin‑induced asthma. IGF‑1 was reduced by 50% in the lung tissue and by nearly 100% in the bronchoalveolar lavage fluid in asthmatic mice established by depletion of alveolar macrophages using 2‑chloroadenosine. In addition, interleukin‑33 induced IGF‑1 production in primary alveolar macrophages. It was also observed that IGF‑1 inhibited the phagocytosis of fluorescent microspheres and apoptotic cells by MLE‑12 alveolar epithelial cells. Antibody blocking of IGF‑1 enhanced the phagocytosis of fluorescent microspheres and apoptotic cells, and significantly reduced inflammatory cell infiltration in airway and perivascular tissues. The elevated IGF‑1 level in the lungs of asthma model mice was mainly produced in alveolar macrophages. Taken together, the current study demonstrated that IGF‑1 inhibited phagocytosis by alveolar epithelial cells, and that IGF‑1 blockade enhanced the phagocytic activity and alleviated airway inflammation. These results support the potential use of IGF‑1 as a target in the treatment of asthma.

In this study, a robust finite time Takagi-Sugeno fuzzy control method for hydro-turbine governing system (HTGS) is investigated. Firstly, the mathematical model of HTGS is introduced, and on the basis of Takagi-Sugeno (T-S) fuzzy rules, the T-S fuzzy model of HTGS is presented. Secondly, based on finite time stability theory, a novel finite time Takagi-Sugeno fuzzy control method is designed for the stability control of HTGS. Thirdly, the relatively loose sufficient stability condition is acquired, which could be transformed into a group of linear matrix inequalities (LMIs) via Schur complement as well as the strict mathematical derivation is given. Furthermore, the control method could resist random disturbances, which shows the good robustness. Simulation results indicate the designed finite time T-S fuzzy control scheme works well compared with the conventional method. The approach proposed in this paper is easy to implement and also provides reference for relevant hydropower systems.

This paper studies the application of frequency distributed model for finite-time control of a class of fractional-order nonlinear systems. Firstly, a class of fractional-order nonlinear systems with model uncertainties and external disturbances are introduced, and a new frequency distributed model with theoretical inference is presented. Secondly, a novel fast terminal sliding surface is proposed and its stability to origin is proved based on the frequency distributed model and Lyapunov stability theory. Furthermore, based on finite-time stability and sliding mode control theory, a robust control law to ensure the occurrence of the sliding motion in a finite time is designed for stabilization of the fractional-order nonlinear systems. Finally, two typical examples of three-dimensional nonlinear fractional-order Lorenz system and four-dimensional nonlinear fractional-order Chen system are employed to demonstrate the validity of the proposed method.

A novel fractional order Takagi–Sugeno (T–S) fuzzy control method for a class of fractional order non-linear systems is proposed in this study. On the basis of the fractional order interval theory, the generalised T–S fuzzy model for a class of uncertain fractional order non-linear systems is presented. By using fractional order Lyapunov stability theorem, the more relaxed and practical sufficient stability conditions which are presented as a new set of linear matrix inequalities are put forward, which are guaranteed by rigorous mathematical derivation. The proposed control scheme is developed for fractional order non-linear systems stabilisation in the presence of random disturbances. Typical instances including the fractional order three-dimensional (3D) non-linear system and the fractional order 4D non-linear Lorenz hyperchaos are implemented. Simulation results indicate the designed fractional order T–S fuzzy control scheme works well compared with the existing method.

Infection in male and female genital tracts can lead to infertility. The underlying mechanisms of this process remain unclear. Toll-like receptors (TLRs) recognize conserved structures and respond to pathogens by initiating signals that activate inflammatory gene transcription. Here, we demonstrate that TLR activation in sperm reduces sperm motility via signalling through myeloid differentiation factor 88 (MyD88), phosphatidylinositol 3-kinase (PI3K), and glycogen synthase kinase (GSK)-3α. Upon TLR activation, phosphorylated forms of PI3K and GSK3α were detected in the mitochondria, and the mitochondrial membrane potential was impaired in sperm. In addition, mitochondrial ATP levels were decreased after TLR agonist stimulation. Furthermore, blocking PI3K or GSK3α activation abrogated these effects and reversed the TLR-induced reduction in sperm motility. These results identify a previously unrecognized TLR signalling pathway that leads to dysfunctional sperm mitochondria, which reduce sperm motility. Our study reveals a novel mechanism by which pathogenic infection affects sperm motility and possibly leads to infertility.