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In this paper, a new honeycomb plate box-type hollow roof structure is prepared. The failure mode and mechanical properties of the box-type hollow roof structure were analyzed by bearing capacity test and numerical analysis. The validity of the numerical analysis model is verified by comparing the results of bearing capacity test with the results of the complete coordinated model and the coupled model analysis. The results show that the failure mode of the specimen is tensile failure of the surface plate of the honeycomb plate with strengthened frame and buckling instability of the plate near the joint. The box-type hollow roof structure has good ductility. The results of static analysis and nonlinear buckling analysis of the honeycomb plate box-type hollow roof structure are carried out by coupling model are more consistent with the results of bearing capacity test.

This paper proposes the use of a novel modular joint to overcome the shortcomings of existing aluminium alloy gusset joints. Bearing capacity tests are performed on the bearing capacity of four sets of joints in the early stage, and the force characteristics and failure mechanism of the novel modular joint are summarized. On this basis, this study conducts theoretical research on the design method of this new type of joint. According to the four failure modes that occurred in the experiment, namely, the bending failure of the aluminium alloy beam, the shear failure of the bolt group, the tensile and shear failure of the modular unit, and the local buckling failure of the unit bottom plate, a formula for calculating the ultimate bearing capacity of each component is provided. According to the working mechanism of modular joints, theoretical formulas for the ultimate flexural bearing capacity and initial stiffness of the joints are derived according to the three-part bending moments produced by each component. Based on a power function model, a prediction formula is fitted to the bending moment-rotation curve of the new joint and compared with the measured values of the joint and 22 numerical models. The results show that the average errors of the two sets of theoretical formulas are only 2.85% and 4.5%, fully verifying their validity and reliability. The results provide a theoretical basis for the engineering design and application of this type of joint.

Joints are the most critical component of reticulated shell structures, and their hysteretic performance is crucial to the mechanical properties of the whole reticulated shell structure under seismic action. Therefore, the hysteretic behaviour of aluminium alloy flower-gusset composite joint for an out-of-plane bending moment was studied by experiments and numerical analysis. The results show that the hysteretic curves of flower-gusset composite joints and gusset joints contain four stages: an elastic stage, a bolt slip stage, a hole wall pressure-stiffness degradation stage and a failure stage. The hysteretic performance of the new flower-gusset composite joint is obviously better than that of the traditional plate joint. With the increase in the thickness of the cover plate, the bending stiffness of the flower-gusset composite joint increases significantly, while the rotational deformation decreases. Then, a restoring force model of the flower-gusset composite joint is proposed through theoretical analysis based on experiments and numerical analysis.

WD repeat domain 5 (WDR5) is a prominent target for pharmacological inhibition in cancer through its scaffolding role with various oncogenic partners such as MLL and MYC. WDR5-related drug discovery efforts center on blocking these binding interfaces or degradation have been devoted to developing small-molecule inhibitors or degraders of WDR5 for cancer treatment. Nevertheless, the precise role of WDR5 in these cancer cells has not been well elucidated genetically. Here, by using an MLL-AF9 murine leukemia model, we found that genetically deletion of Wdr5 impairs cell growth and colony forming ability of MLL-AF9 leukemia cells in vitro or ex vivo and attenuates the leukemogenesis in vivo as well, which acts through direct regulation of ribosomal genes. Pharmacological inhibition of Wdr5 recapitulates genetic study results in the same model. In conclusion, our current study demonstrated the first genetic evidence for the indispensable role of Wdr5 in MLL-r leukemogenesis in vivo, which supports therapeutically targeting WDR5 in MLL-rearranged leukemia by strengthening its disease linkage genetically and deepening insights into its mechanism of action.

To improve the mechanical properties of Trabecular Beetle Elytron Plates (TBEPs, a type of biomimetic sandwich structure inspired by the beetle elytron) under transverse loads, three-point bending tests are performed to investigate the influence of the trabecular and chamfer radii of the core structure on the mechanical performance of TBEPs manufactured by 3D printing technology. The results show that the three-point bending performance of TBEPs can be improved by setting reasonable trabecular and chamfer radii; however, excessive increases in these radii can cause a decline in the mechanical performance. For the reason, these two structural parameters can enhance the deformation stiffness of the whole structure and the connection property between the core and skin, which is also the mechanical reason why Prosopocoilus inclinatus beetle elytra have thick, short trabeculae with a large chamfer radius. However, when these radii increase to a certain extent, the cracks are ultimately controlled between two adjacent trabeculae, and the failure of the plate is determined by the skin rather than the core structure. Therefore, this study suggests a reasonable range for trabecular and chamfer radii, and indicates that TBEPs are better suited for engineering applications that have high compression requirements and general bending requirements.

Establishment of immune tolerance is crucial to protect humans against asthma. Promyelocytic leukemia zinc finger (PLZF) is an emerging suppressor of inflammatory responses. CCL21-CCR7 signaling mediates tolerance development. However, whether PLZF and CCL21-CCR7 are required for the development of asthma tolerance is unknown. Here, we found that Zbtb16 (coding PLZF) and Ccl21 were upregulated in OVA-induced asthma tolerance (OT) lungs by RNA-seq. PLZF physically interacted with GATA3 and its expression was higher in GATA3+ Th2 cells and ILC2s in OT lungs. Zbtb16-knockdown in lymphocytes promoted the differentiation of CD3e+ CD4+ T cells, particularly those producing IL-4 and IL-5. Moreover, iNKT cells with high expression of PLZF were recruited into the lungs via draining lymph nodes during tolerance. Blockade of CCL21-CCR7 signaling in OT mice decreased the PLZF+ cell population, abolished CCR7-induced PLZF+ iNKT recruitment to the lungs, enhanced Th2responses and exacerbated lung pathology. In OT mice, respiratory syncytial virus (RSV) infection impeded PLZF+ cell and CCR7+ PLZF+ iNKT cellrecruitment to the lungs and increased airway resistance. Collectively, these results indicate that PLZF could interact with GATA3 and restrain differentiation of IL-4- and IL-5-producing T cells, iNKT cells with high PLZF expression are recruited to the lungs via CCL21-CCR7 signaling to facilitate the development of asthma tolerance.

To improve the applications of beetle elytron plates (BEPs, which are biomimetic sandwich plates inspired by beetle elytra), the flexural performance and its synergistic mechanism of multibody molded BEPs were investigated via cantilever testing and finite element method (FEM). The results are summarized as follows. (1) Although debonding damage causes failure of the multibody molded BEPs and honeycomb plate and the reasonable range of trabecular size for BEPs is narrow, both the optimal loading capacity per mass and failure deformation of the BEPs are over two times those of the honeycomb plate. (2) A flexural synergistic mechanism is revealed in the trabecular-honeycomb core structure of BEPs; this mechanism causes the maximum deformation of core structure to gradually transfer from the honeycomb wall to the trabeculae with the increase in η (the ratio of the trabecular radius to the distance between the center points of two trabeculae), which means the different stretching behaviors in these core structures. (3) Unlike the compressive mechanism of BEPs, by controlling and balancing the deformation degrees of the trabeculae and honeycomb walls, the flexural mechanism achieves a minimum core deformation and an optimal flexural performance. These results suggest a qualitative relationship between the deformation behavior of trabecular-honeycomb core structure and bending performance of the whole BEP, and provide a solid foundation for subsequent research and the considerable application potential of this biomimetic sandwich structure in many fields.

Airway epithelial cells (AECs) participate in allergic airway inflammation by producing mediators in response to allergen stimulation. Whether ovalbumin (OVA) challenge promotes exosome release from AECs (OVA‐challenged AEC‐derived exosomes (OAEs)), thereby affecting airway inflammation, as well as the underlying mechanisms, is unknown. Our study showed that AECs released an increased number of exosomes after OVA challenge, and the expression of Plexin B2 (PLXNB2; a natural CD100 ligand) was increased by a massive 85.7‐fold in OAEs than in PBS‐treated AEC‐derived exosomes (PAEs). CD100+F4/80+ macrophages engulfed OAEs to trigger the transcription of pro‐inflammatory chemokines and cytokines. Plxnb2 transcripts increased in asthmatic lungs, and similarly, PLXNB2 protein was highly enriched in exosomes purified from asthmatic bronchoalveolar lavage (BAL) fluid. Furthermore, aspiration of PLXNB2 or OAEs increased the recruitment of lung neutrophils, monocytes, eosinophils and dendritic cells in OVA‐challenged mice. Mechanistically, OAE aspiration enhanced the cleavage of CD100 by MMP14, which manifested as an increase in the soluble CD100 (sCD100) level in BAL fluid and lung homogenates. Knockdown of Mmp14 in macrophages prevented the cleavage of CD100 and reduced Ccl2, Ccl5 and Cxcl2 transcription. These data indicate that PLXNB2‐containing OAEs aggravate airway asthmatic inflammation via cleavage of CD100 by MMP14, suggesting potential therapeutic targets of OAE‐mediated asthma exacerbations.

Vagal circuit-α7 nicotinic acetylcholine receptor (α7nAChR, coded by Chrna7) signaling can modulate lung proinflammatory responses. Arginase 1 (ARG1) plays a crucial role in the resolution of lung inflammation. However, whether vagal-α7nAChR signaling can regulate lung inflammation and ARG1 expression during an influenza infection is elusive. Here, we found that lung and spleen IL-4(+) cells and lung ARG1 expression were reduced; however, bronchoalveolar lavage (BAL) protein and leukocytes and lung inflammatory cytokines were increased in PR8 (A/Puerto Rico/8/1934, H1N1)-infected vagotomized mice when compared to the control. In PR8-infected α7nAChR-deficient mice, lung Arg1, Il10, and Socs3 expression and BAL Ly6C(+)CD206(+) cells were reduced. PR8-infected Chrna7(+/+) recipient mice reconstituted with Chrna7(−/−) bone marrow had a lower survival as compared to PR8-infected Chrna7(+/+) recipient mice reconstituted with Chrna7(+/+) bone marrow. Mechanistically, the activation of α7nAChR by its agonist GTS-21 could enhance IL-4-induced Arg1 expression, reduced Nos2, and TNF-α expression in PR8-infected bone marrow-derived macrophages (BMDM). Stimulation with IL-4 increased phosphorylation of STAT6 and activation of α7nAChR increased STAT6 binding with the ARG1 promoter and relieved IL-4-induced H3K27me3 methylation by increasing JMJD3 expression in PR8-infected BMDM. Inhibition of JMJD3 increased H3K27me3 methylation and abolished α7nAChR activation and IL-4 induced ARG1 expression. Activation of α7nAChR also reduced phosphorylation of AKT1 and contained FOXO1 in the nucleus. Knockdown of Foxo1a reduced α7nAChR activation and IL-4 induced Arg1 expression in PR8-infected BMDM. Therefore, vagal-α7nAChR signaling is a novel therapeutic target for treating lung inflammatory responses during an influenza infection.

Background Proliferation and transdifferentiation of lung stem cells (LSCs) could promote lung injury repair. The distal airways of the lung are innervated by the vagus nerve. Vagal-alpha7 nicotinic acetylcholine receptor (α7nAChR) signaling plays a key role in regulating lung infection and inflammation; however, whether this pathway could regulate LSCs remains unknown. Methods LSCs (Sca1+CD45−CD31− cells) were isolated and characterized according to a previously published protocol. α7nAChR knockout mice and wild-type littermates were intratracheally challenged with lipopolysaccharide (LPS) to induce lung injury. A cervical vagotomy was performed to study the regulatory effect of the vagus nerve on LSCs-mediated lung repair. α7nAChR agonist or fibroblast growth factor 10 (FGF10) was intratracheally delivered to mice. A single-cell suspension of lung cells was analyzed by flow cytometry. Lung tissues were collected for histology, quantitative real-time polymerase chain reaction (RT-PCR), and immunohistochemistry. Results We found that LSCs maintained multilineage differentiation ability and transdifferentiated into alveolar epithelial type II cells (AEC2) following FGF10 stimulation in vitro. Vagotomy or α7nAChR deficiency reduced lung Ki67+ LSCs expansion and hampered the resolution of LPS-induced lung injury. Vagotomy or α7nAChR deficiency decreased lung FGF10 expression and the number of AEC2. The α7nAChR agonist-GTS-21 reversed the reduction of FGF10 expression in the lungs, as well as the number of Ki67+ cells, LSCs, Ki67+ LSCs, and AEC2 in LPS-challenged vagotomized mice. Supplementation with FGF10 counteracted the loss of Ki67+ LSCs and AEC2 in LPS-challenged α7nAChR knockout mice. Conclusions The vagus nerve deploys α7nAChR to enhance LSCs proliferation and transdifferentiation and promote lung repair in an FGF10-dependent manner during LPS-induced lung injury.

Mesenchymal stem cells (MSCs) have been used in cell-based therapies for a variety of disorders. Some factors such as inflammatory mediators in the diseased area might damage the survival of MSCs and affect their efficacy. Pyroptosis is a form of programmed necrosis as a response for immune cells to cytosolic pathogenic stimuli. Whether MSCs develop pyroptosis under pathological stimulation, its underlying mechanism and biological significance are still unclear. Here, we found that LPS, flagellin, dsDNA, nigericin (NIG), or LPS combined with nigericin (LPS/NIG) could not induce pyroptosis in adipose-tissue-derived mesenchymal stem cells (ASCs). However, when applied the culture media collected from LPS/NIG-induced pyroptotic bone marrow-derived macrophages (BMDMs) to incubate ASCs, ASCs developed pyroptosis. Inhibition of caspases or deletion of Caspase-1/11 in ASCs did not affect the pyroptotic macrophage media-triggered ASC pyroptosis while ablation of Caspase-1/11 abolished BMDM pyroptosis induced by LPS/NIG. Media collected from LPS/NIG stimulated Gsdmd−/− or Caspase-1/11−/− BMDMs could not induce pyroptosis of ASCs. In addition, RNA-seq analysis showed that interferon (IFN)-stimulated genes were upregulated in pyroptotic ASCs. Adding IFNβ could boost LPS/NIG stimulated BMDM media-induced ASC pyroptosis. Surprisingly, the pyroptotic ASCs had a lower bactericidal ability to P. Aeruginosa. Taken together, induction of ASC pyroptosis requires gasdermin D or caspase-1/11-dependent mediators and IFNβ from pyroptotic macrophages.

In order to study the progressive collapse resistance of the panel-rod composite latticed shell, a static test was performed on two latticed shells with the same size, one of which was removed a key member. The results of experiments and numerical simulations show that the composite reticulated shells were damaged due to the fracture of some members and the shearing of some rivets. Compared with the complete latticed shell, the bearing capacity of the latticed shell which was removed a key member did not decrease too much, but its displacement of the joints increased significantly. The phenomenon indicated that the removal of the key member had a certain effect on the progressive collapse resistance of the composite latticed shell. The key members of the composite latticed shell must be locally strengthened.

In this paper, two types of the composite XX-type lattice sandwich structure (XX (Ⅰ) and XX (Ⅱ)) were made of panels (medium-density fiberboard and plywood) and core (birch) by using a type of insertion-glue method. An out-of-plane compressive test and a short beam shear test were carried out to investigate the failure modes, mechanical and energy absorption properties of the composite XX-type lattice sandwich structure. Results showed that the compression and short beam shear failure modes of composite XX-type lattice sandwich structure were mainly the shear failure of the core and the failure of panels. The sandwich structure with the core diameter of 8 mm had good compression property. The XX (Ⅱ)-type lattice sandwich structure of the combination of Plywood + birch had better compression, short beam shear, and energy absorption properties. The combination of MDF + birch was more suitable for the compressive theoretical model.

To develop functional honeycomb plates (HPs) with great thermal performance, This paper uses a heat flow meter to determine the equivalent thermal conductivity λ E of honeycomb plates (HPs) positioned horizontally under cold-above/hot-below conditions and combined with theoretical calculations, the influence mechanism of their geometric parameters on their heat transfer performance were investigated with different thicknesses h and cell wall lengths of 8 mm and 16 mm (HP8 and HP16, respectively). The results show that the thermal insulation performance of HPs with different cell side lengths varies with the plate thickness. HP8 presented a better thermal insulation performance when h = 40–60 mm. Based on this, the concepts of matching honeycomb structure and matching convection and the suggestions that according to the needs of a project, HP8 or HP16 can be reasonably selected, and the stacking of two kinds of plates can be optimized were first proposed. And it can be obtained that if the experimental λ E results of a HP are applied to a beetle elytron plate with the same thickness and honeycomb structure size, the heat insulation of the beetle elytron plate (BEP) would be superior to that of the HP. This paper lays a theoretical foundation for the research and development of multifunctional BEPs with heat insulation properties was verified. Finally, the internal influence mechanism of the difference in temperature distribution on the upper and lower surfaces and the three-dimensional size of the honeycomb cells on the matching honeycomb structure and matching convection.

α7 nicotinic acetylcholine receptor (α7 nAChR, coded by Chrna7) is indispensable in dampening proinflammatory responses. However, whether α7 nAChR plays a role in regulating bleomycin (BLM)-induced lung fibrosis is less investigated. Here, we challenged wild-type and Chrna7−/− mice with BLM intratracheally to elicit lung fibrosis. Taking advantage of this model, we measured body weight loss, lung fibrogenic genes (Acta2, Col1a1, Fsp1 and Fstl1), histology, Masson’s trichrome staining, hydroxyproline levels and expression of α-SMA at protein levels in the BLM-challenged lung to evaluate the severity of lung fibrosis. We also pretreated human fibroblasts (MRC5 cell line) and isolated mouse lung fibroblasts with GTS-21 (an α7 nAChR agonist) to study its effects on TGF-β-stimulated profibrotic profiles. We found that lung Chrna7 expression and CD4+CHAT+ cells (choline acetyltransferase, an enzyme for local acetylcholine synthesis) were elevated 12-fold and 4.5-fold, respectively, in the early stage of lung fibrosis. Deletion of Chrna7 prevented body-weight loss and reduced lung fibrogenic genes (Acta2, Colla1, Fsp1 and Fstl1) and Arg 1 (coding arginase 1). Deletion of Chrna7 attenuated lung arginase 1+Ly6C+ cells, Masson’s trichrome staining, hydroxyproline levels and expression of α-SMA at protein levels in BLM-challenged mice. Mechanistically, activation of α7 nAChR in human fibroblasts increased TGF-β-induced phosphorylation of Smad2/3 and transcription of fibrogenic genes (Acta2, Colla1). In isolated mouse lung fibroblasts, activation of α7 nAChR also enhanced TGF-β-induced transcription of fibrogenic genes; however, deletion of Chrna7 diminished these effects. Taken together, deficiency of α7 nAChR could suppress the development of BLM-induced lung fibrosis. Thus, α7 nAChR might be a novel therapeutic target for treating lung fibrosis.

Long-span space structures are particularly sensitive to their self-weight. In this paper, a honeycomb plate with a high strength and light weight is reliably connected to a single-layer aluminium alloy lattice shell to form a new type of combined lattice shell structure, which substantially improves the overall stiffness and stability of the lattice shell without a plate. The bending performance of the aluminium alloy honeycomb panel-beam combined grid structure (AAH combined grid structure) plays a key role in the stability of the combined lattice shell structure. Therefore, the bending performance of the AAH combined grid structure was studied through six groups of tests and refined finite element models. Then, the calculation formula for the equivalent bending stiffness of the AAH combined grid structure was obtained through a theoretical analysis. The results show that the contribution of the honeycomb structure to the stiffness of the structure is very obvious, and the proposed formula provides the theoretical basis and a practical method for the engineering design of new aluminium alloy combined lattice shell structures in the future.

This article proposes a new type of single-layer combined lattice shell (NSCLS); which is based on aluminum alloy honeycomb panels. Six models with initial geometric defect were designed and precision made using numerical control equipment. The stability of these models was tested. The results showed that the stable bearing capacity of NSCLS was approximately 16% higher than that of a lattice shell with the same span without a reinforcing plate. At the same time; the properties of the NSCLS were sensitive to defects. When defects were present; its stable bearing capacity was decreased by 12.3% when compared with the defect-free model. The model with random defects following a truncated Gaussian distribution could be used to simulate the distribution of defects in the NSCLS. The average difference between the results of the nonlinear analysis and the experimental results was 5.7%. By calculating and analyzing nearly 20,000 NSCLS; the suggested values of initial geometric defect were presented. The results of this paper could provide a theoretical basis for making and revising the design codes for this new combined lattice shell structure.

Vagal circuits-α7 nAChR (α7 nicotinic acetylcholine receptor, coded by Chrna7) signaling utilizes spleen as a hub to dampen systemic inflammatory responses. Vagal innervations also extend to the distal airways and alveoli. Vagotomy and deficiency of α7 nAChR deteriorate E. coli and lipopolysaccharide (LPS)-induced acute lung inflammatory responses; however, the underlying mechanisms remain elusive. Here, we hypothesized that vagal circuits would limit splenic release and lung recruitment of α7 nAChR+CD11b+ cells (CD11b is coded by Itgam, a surface marker of monocytes and neutrophils) via phosphorylation of AKT1 and that this process would define the severity of lung injury. Using both E. coli and LPS-induced lung injury mouse models, we found that vagotomy augmented splenic egress and lung recruitment of α7 nAChR+CD11b+ cells, and consequently worsened lung inflammatory responses. Rescue of vagotomy with an α7 nAChR agonist preserved α7 nAChR+CD11b+ cells in the spleen, suppressed recruitment of these cells to the lung and attenuated lung inflammatory responses. Vagal signals via α7 nAChR promoted serine473 phosphorylation of AKT1 in α7 nAChR+CD11b+ cells and stabilized these cells in the spleen. Deletion of Akt1 enhanced splenic egress and lung recruitment of α7 nAChR+CD11b+ cells, which elicited neutrophil-infiltrated lung inflammation and injury. Vagotomy and double deletion of Chrna7 and Itgam reduced serine473 phosphorylation of AKT1 in the spleen and BAL (bronchoalveolar lavage) Ly6CintGr1hi neutrophils and Ly6Chi monocytes, and they facilitated the recruitment of neutrophils and monocytes to the airspaces of E. coli-injured lungs. Double deletion of Chrna7 and Itgam increased lung recruitment of monocytes and/or neutrophils and deteriorated E. coli and LPS-induced lung injury. Thus, signals of vagal circuits engaging with AKT1 in α7 nAChR+CD11b+ cells attenuate E. coli and LPS-induced acute lung inflammatory responses. Targeting this signaling pathway could provide novel therapeutic strategies for treating acute lung injury.

This study investigates the shear capacity of aluminum alloy honeycomb sandwich plates connected by high-strength, ordinary, or self-tapping bolts. For that purpose, experimental tests and finite elements are carried out. The failure of a high-strength bolt connector is driven by bending deformations developed in the bolt that deform connection plate and pad openings. In the case of ordinary bolt connectors, stress concentration on the bolt shear surface causes a large shear deformation that finally leads to failure. In the case of self-tapping bolt connectors, the insufficient mechanical bite force of the screw thread yields the bolt misalignment and concentrates shear deformation. As a result, the high-strength bolt connector is the most efficient design solution. If the bolt hole edge distance is more than 1.5 times as much as the bolt diameter, the connection performance becomes insensitive to this parameter. The practical formula for evaluating the connector shear capacity is derived from experimental data.

In this review, we first analyzed the current status of cholinergic anti-inflammatory pathway and then put forward a novel regulatory machinery-pulmonary parasympathetic inflammatory reflex, which is composed by lung vagal sensors at afferent arm, α7 nAChR (α7 nicotinic acetylcholine receptors)-expressing cells at efferent arm and the brain information integrating center. This modulatory circuit might loop the lungs, immune and nervous systems and play a very important role in regulating lung infection, inflammation and immunity through the neural innervations and signals when the lungs encounter pathogenic challenges.

Background The neural system can finely tune immune system, especially pro- or anti-inflammatory responses of monocytes/macrophages. To maintain immune homeostasis, monocytes/macrophages are supposed to be primed by α7 nAChR agonist to establish anti-inflammatory memory. Aim To study whether activation of α7 nAChR would elicit anti-inflammatory memory in splenic monocytes in vivo and J774 monocytes in vitro . Design Laboratory study. Methods The wildtype mice were sacrificed 4 or 12 h after receiving intravenous injection of GTS-21. The splenocytes were isolated and stimulated with LPS for 4 h to detect Ly6C hi TNF-α + monocytes by flow cytometry. In the in vitro study, J774 monocytes received priming with GTS-21, washing GTS-21 out and resting, and thereafter stimulating with TLR ligands. The TNF-α protein and Tnfα , Il1β and il6 mRNAs were measured to evaluate anti-inflammatory responses. The H3K9ac, H4K5ac, H4K8ac, Acetyl-CBP, CBP (CREB-binding protein), PCAF (P300/CBP-associated factor) and Acetyl-NF-kB levels were measured in GTS-21-primed monocytes. Results Activation of α7 nAChR by GTS-21 suppressed TNF-α production in splenic Ly6C hi monocytes. In vivo -GTS-21-primed splenic Ly6C hi monocytes passed on anti-inflammatory feature if stimulated with LPS in vitro . J774 monocytes primed with GTS-21 developed anti-inflammatory trait in response to LPS (TLR4), Poly:IC (TLR3) and R848 (TLR7/8) ligands. In GTS-21-primed monocytes, H3K9ac, H4K5ac, H4K8ac, Acetyl-CBP, CBP, PCAF and Acetyl-NF-kB were reduced 4 h after washing and resting. In the nuclear extract, PCAF, Acetyl-NF-kB, p-NF-kB and p-STAT3 were decreased in LPS-stimulated GTS-21 primed J774 monocytes 4 h after washing and resting. Conclusions Monocytes primed by α7 nAChR agonist developed anti-inflammatory memory.

Vagal circuits-α7 nAChR (α7 nicotinic acetylcholine receptor, coded by Chrna7) signaling utilizes spleen as a hub to dampen systemic inflammatory responses. Vagal innervations also extend to the distal airways and alveoli. Vagotomy and deficiency of α7 nAChR deteriorate E. coli and lipopolysaccharide (LPS)-induced acute lung inflammatory responses; however, the underlying mechanisms remain elusive. Here, we hypothesized that vagal circuits would limit splenic release and lung recruitment of α7 nAChR+CD11b+ cells (CD11b is coded by Itgam, a surface marker of monocytes and neutrophils) via phosphorylation of AKT1 and that this process would define the severity of lung injury. Using both E. coli and LPS-induced lung injury mouse models, we found that vagotomy augmented splenic egress and lung recruitment of α7 nAChR+CD11b+ cells, and consequently worsened lung inflammatory responses. Rescue of vagotomy with an α7 nAChR agonist preserved α7 nAChR+CD11b+ cells in the spleen, suppressed recruitment of these cells to the lung and attenuated lung inflammatory responses. Vagal signals via α7 nAChR promoted serine473 phosphorylation of AKT1 in α7 nAChR+CD11b+ cells and stabilized these cells in the spleen. Deletion of Akt1 enhanced splenic egress and lung recruitment of α7 nAChR+CD11b+ cells, which elicited neutrophil-infiltrated lung inflammation and injury. Vagotomy and double deletion of Chrna7 and Itgam reduced serine473 phosphorylation of AKT1 in the spleen and BAL (bronchoalveolar lavage) Ly6CintGr1hi neutrophils and Ly6Chi monocytes, and they facilitated the recruitment of neutrophils and monocytes to the airspaces of E. coli-injured lungs. Double deletion of Chrna7 and Itgam increased lung recruitment of monocytes and/or neutrophils and deteriorated E. coli and LPS-induced lung injury. Thus, signals of vagal circuits engaging with AKT1 in α7 nAChR+CD11b+ cells attenuate E. coli and LPS-induced acute lung inflammatory responses. Targeting this signaling pathway could provide novel therapeutic strategies for treating acute lung injury.

To solve the problem of critical buckling in the structural analysis and design of the new long-span hollow core roof architecture proposed in this paper (referred to as a "honeycomb panel structural system" (HSSS)), lateral compression tests and finite element analyses were employed in this study to examine the lateral compressive buckling performance of this new type of honeycomb panel with different length-to-thickness ratios. The results led to two main conclusions: (1) Under the experimental conditions that were used, honeycomb panels with the same planar dimensions but different thicknesses had the same compressive stiffness immediately before buckling, while the lateral compressive buckling load-bearing capacity initially increased rapidly with an increasing honeycomb core thickness and then approached the same limiting value; (2) The compressive stiffnesses of test pieces with the same thickness but different lengths were different, while the maximum lateral compressive buckling loads were very similar. Overall instability failure is prone to occur in long and flexible honeycomb panels. In addition, the errors between the lateral compressive buckling loads from the experiment and the finite element simulations are within 6%, which demonstrates the effectiveness of the nonlinear finite element analysis and provides a theoretical basis for future analysis and design for this new type of spatial structure.