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Increasing spread by SARS-CoV-2 Omicron variants challenges existing vaccines and broadly reactive neutralizing antibodies (bNAbs) against COVID-19. Here we determine the diversity, potency, breadth and structural insights of bNAbs derived from memory B cells of BNT162b2-vaccinee after homogeneous Omicron BA.1 breakthrough infection. The infection activates diverse memory B cell clonotypes for generating potent class I/II or III bNAbs with new epitopes mapped to receptor-binding domain (RBD). The top eight bNAbs neutralize wildtype and BA.1 potently but display divergent IgH/IgL sequences and neuralization profiles against other variants of concern (VOCs). Two of them (P2D9 and P3E6) belonging to class III NAbs display comparable potency against BA.4/BA.5, although structural analysis reveals distinct modes of action. P3E6 neutralizes all variants tested through a unique bivalent interaction with two RBDs. Our findings provide new insights into hybrid immunity on BNT162b2-induced diverse memory B cells in response to Omicron breakthrough infection for generating diverse bNAbs with distinct structural basis.

XianLing GuBao Capsule (XLGB) is often used to treat osteoarthritis (OA), osteoporosis, fractures, and other musculoskeleton disorders. However, the molecular mechanism of XLGB for treating OA is still unclear.This study set out to uncover the molecular mechanism underlying the treatment of osteoarthritis with XLGB.Disease genes were obtained from CTD, DisGeNET, and GeneCards databases, and XLGB drug targets were obtained from ETCM and target genes predicted by XLGB metabolic components reported in the literature. Then we used the Venn diagram viewer to extract disease and drug intersection genes as potential therapeutic genes for Protein-protein interaction (PPI), GO terminology, and KEGG pathway analysis. Subsequently, we performed qRT-PCR, Western blot and histological analysis to validate the therapeutic effect of XLGB against OA and its molecular mechanism.A total of 1039 OA genes and 949 XLGB target genes were collected, and finally 188 potential therapeutic target genes were obtained. PPI network analysis indicated that the main target genes for XLGB to treat OA include Akt1, Mapk3, Il-6, Il-1β, Ptgs2, Mmp9, etc. The results of KEGG and GO enrichment analysis suggested that XLGB may treat OA by anti-inflammatory and reducing extracellular matrix degradation. In vitro, XLGB down-regulated the expressions of Mmp3, Mmp9, Mmp12, Mmp13, Cox-2, Il-6, increased the expression of Collagen II and Sox9. Mechanistically, XLGB inhibits the activation of PI3K/AKT/NF-κB and MAPK pathways. Moreover, the results of animal experiments indicated that XLGB reduced cartilage destruction, bone resorption, and synovitis in osteoarthritic rats.XLGB has a protective effect against OA by suppressing PI3K/AKT/NF-κB and MAPK signaling. Our study provides a theoretical basis for XLGB in the treatment of osteoarthritis.

The strikingly high transmissibility and antibody evasion of SARS-CoV-2 Omicron variant have posted great challenges on the efficacy of current vaccines and antibody immunotherapy.Here, we screened 34 BNT162b2-vaccinees and cloned a public broadly neutralizing antibody (bNAb) ZCB11 from an elite vaccinee. ZCB11 neutralized all authentic SARS-CoV-2 variants of concern (VOCs), including Omicron and OmicronR346K with potent IC50 concentrations of 36.8 and 11.7 ng/mL, respectively. Functional analysis demonstrated that ZCB11 targeted viral receptor-binding domain (RBD) and competed strongly with ZB8, a known RBD-specific class II NAb. Pseudovirus-based mapping of 57 naturally occurred single mutations or deletions revealed that only S371L resulted in 11-fold neutralization resistance, but this phenotype was not observed in the Omicron variant. Furthermore,prophylactic ZCB11 administration protected lung infection against both the circulating pandemic Delta and Omicron variants in golden Syrian hamsters. These results demonstrated that vaccine-induced ZCB11 is a promising bNAb for immunotherapy against pandemic SARS-CoV-2 VOCs.

Registration of a series of the two-dimensional electron microscope (EM) images of the brain tissue into volumetric form is an important technique that can be used for neuronal circuit reconstruction. However, complex appearance changes of neuronal morphology in adjacent sections bring difficulty in finding correct correspondences, making serial section neural image registration challenging. To solve this problem, we consider whether there are such stable "markers" in the neural images to alleviate registration difficulty. In this paper, we employ the spherical deformation model to simulate the local neuron structure and analyze the relationship between registration accuracy and neuronal structure shapes in two adjacent sections. The relevant analysis proves that regular circular structures in the section images are instrumental in seeking robust corresponding relationships. Then, we design a new serial section image registration framework driven by this neuronal morphological model, fully utilizing the characteristics of the anatomical structure of nerve tissue and obtaining more reasonable corresponding relationships. Specifically, we leverage a deep membrane segmentation network and neural morphological physical selection model to select the stable rounded regions in neural images. Then, we combine feature extraction and global optimization of correspondence position to obtain the deformation field of multiple images. Experiments on real and synthetic serial EM section neural image datasets have demonstrated that our proposed method could achieve more reasonable and reliable registration results, outperforming the state-of-the-art approaches in qualitative and quantitative analysis.

Summary: Asthma is a complex pulmonary disorder with multiple pathological mechanisms. A key pathological feature of chronic asthma is airway remodeling, which is largely attributed to airway smooth muscle (ASM) hyperplasia that contributes to thickening of the airway wall and further drives asthma pathology. The cellular processes that mediate ASM cell proliferation are not completely elucidated. Using multiple approaches, we demonstrate that the adapter protein Abi1 (Abelson interactor 1) is upregulated in ∼50% of ASM cell cultures derived from patients with asthma. Loss-of-function studies demonstrate that Abi1 regulates the activation of Jak2 (Janus kinase 2) and STAT3 (signal transducers and activators of transcription 3) as well as the proliferation of both nonasthmatic and asthmatic human ASM cell cultures. These findings identify Abi1 as a molecular switch that activates Jak2 kinase and STAT3 in ASM cells and demonstrate that a dysfunctional Abi1-associated pathway contributes to the progression of asthma.

The alignment of a 2D microscopic image stack to create a 3D image volume is an indispensable aspect of serial section electron microscopy (EM) technology, which could restore the original 3D integrity of biological tissues destroyed by chemical fixation and physical dissection. However, due to the similar texture intrasection and complex variations intersections of neural images, previous registration methods usually failed to yield reliable correspondences. And this also led to misalignment and impeded restoring the z-axis anatomical continuity of the neuron volume. In this article, inspired by human behaviors in finding correspondences, which use the topological relationship of image contents, we developed a spatial attention-based registration method for serial EM images to improve registration accuracy. Our approach combined the U-Net framework with spatial transformer networks (STN) to regress corresponding transformation maps in an unsupervised training fashion. The spatial attention (SA) module was incorporated into the U-Net architecture to increase the distinctiveness of image features by modeling its topological relationship. Experiments are conducted on both simulated and real data sets (MAS and RegCremi). Quantitative and qualitative comparisons demonstrate that our approach results in state of art accuracy (using the evaluation index of NCC, SSIM, Dice, Landmark error) and providing smooth and reliable transformation with less texture blur and unclear boundary than existing techniques. Our method is able to restore image stacks for visualization and quantitative analysis of EM image sequences.

In this paper, the thiol-modified paraffin/silica microencapsulated phase change materials (MEPCM) was synthesized using tetraethoxysilane (TEOS) and (3-mercaptopropyl)-trimethoxysilane (MPTMS) by interfacial co-hydrolysis and co-polycondensation as the aim of improving the thermal stability and suspension stability. The effect of MPTMS was analyzed by SEM, TEM, FT-IR, DSC, TGA, the leakage test and gravity sedimentation test. The most satisfied sample (S3) showed a high thermal storage density of 125.82 J/g, along with an encapsulation efficiency of 65.74%. It also appeared excellent thermal stability after 1000 cycles with 94.11% latent enthalpy remained and kept 99.48% mass after heating at 80 °C more than 150 min. Beneficial from the hydrophobicity regulation by the thiol functional group, the MEPCM exhibited the good suspension stability for 14 days without any surfactant. The modified MEPCM was used to prepare latent functionally thermal fluids (LFTF), which presented 41% improvement of the heat transfer performance when 2wt% MEPCM was added. In addition, a layer of copper nanoparticles was successfully synthesized on the surface of MEPCM for the thermal conductivity enhancement. Therefore, the modified MEPCM provided a new sight on the interfacial modification of MEPCM and has a significant potential for new type thermal fluids.

Spectroscopic properties play a significant role during the design and development of novel luminescent materials. In this work, quantum cutting (QC) luminescent materials KYF4:Tb3+,Yb3+ phosphors were successfully synthesized by sol–gel method. The crystal structure, morphology, fluorescence spectra, and decay curves were investigated by X-ray diffractometer (XRD), scanning electron microscope (SEM) and spectrofluorometer. The Judd-Ofelt (J-O) parameters, Ωλ (λ = 2, 4, 6), were directly derived from the emission spectra and decay curves, attributed to the transition intensities of Tb3+ ions were dependent on the J-O parameters. Then, the radiative and nonradiative transition rates, fluorescent branching ratios, cross-relaxation rates and lifetimes of QC luminescence were calculated based on the obtained J-O parameters. Moreover, the rate equation models of QC luminescence were established and the time-dependent population densities in excited levels of Tb3+ ions and Yb3+ ions were simulated. Finally, the dynamic processes of QC luminescence were discussed carefully and the corresponding theoretical quantum efficiency was estimated. Our studies would provide an insight into the QC luminescence and give theoretical guidance for developing novel luminescent materials.

Background Pulmonary fibrosis is a progressive disease characterized by structural distortion of the lungs. Transforming growth factor-beta (TGF-beta) is a key cytokine implicated in the pathogenesis of pulmonary fibrosis. TGF-beta-induced myofibroblast differentiation characterized by expression of smooth muscle alpha-actin and extracellular matrix proteins is a key process in pathogenesis of fibrotic disease. Tannic acid is a natural polyphenol with diverse applications. In this study, we investigated the effect of tannic acid on myofibroblast differentiation and pulmonary fibrosis in cultured cells and in bleomycin model of the disease. Methods Primary cultured human lung fibroblasts (HLF) were used. The relative levels of proteins were determined by Western blotting. HLF contraction was measured by traction microscopy. Bleomycin-induced pulmonary fibrosis in mice was used as the disease model. Results Tannic acid inhibited TGF-beta-induced expression of collagen-1 and smooth muscle alpha-actin (SMA) as well as force generation by HLF. Tannic acid did not affect initial phosphorylation of Smad2 in response to TGF-beta, but significantly inhibited sustained Smad2 phosphorylation, which we recently described to be critical for TGF-beta-induced myofibroblast differentiation. Accordingly, tannic acid inhibited Smad-dependent gene transcription in response to TGF-beta, as assessed using luciferase reporter for the activity of Smad-binding elements. Finally, in mouse model of bleomycin-induced pulmonary fibrosis, therapeutic application of tannic acid resulted in a significant reduction of lung fibrosis, decrease in collagen-1 content and of Smad2 phosphorylation in the lungs. Conclusions This study demonstrates the anti-fibrotic effect of tannic acid in vitro and in vivo through a regulation of sustained Smad2 phosphorylation. Electronic supplementary material The online version of this article (10.1186/s12931-019-1141-8) contains supplementary material, which is available to authorized users.

The pandemic of coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become the most formidable challenge to humanity in this century. The research and development of COVID-19 vaccines, which are believed to be the most effective tools to control this pandemic, has been a topic of critical importance, not only in the field of biomedicine but also in the entire international community. Here, we introduce the concepts related to COVID-19 vaccines, including their development process, clinical trials, designs and types. On this basis, we further summarize the research, development, and application of vaccines in different regions of the world, and describe the vaccines according to their respective regions. Finally, we discuss existing and emerging challenges, strategies and prospects of in the development and application of COVID-19 vaccines.

To control the spread of COVID-19, governments in different countries and regions implemented various types of lockdown and outdoor restrictions. The research aimed to describe and compare the health status of Chinese people both domestically and abroad in this global health crisis. An online questionnaire survey was distributed to Chinese mainland citizens living in Hubei (the lockdown province), outside Hubei, and those living abroad in 2020. A total of 1000 respondents were recruited and reported worse health status compared with Chinese population norms. People living in Hubei reported worse health status than those living outside Hubei but revealed better health status than overseas respondents. It was clear that the pandemic as well as strict lockdown and outdoor restriction policies affected Chinese people’s health. It is important for the Chinese government to be aware of the negative impact of such strict policies and to take measures to reduce the panic of society when implementing similar policies in the future. It also implies that governments in other countries should promote social support for those who live far from home and actively call for support for non-discriminatory attitudes toward ethnic minorities.

Phase change materials play a vital role in the field of thermal management field, in particular for the microencapsulated protocols owing to its large specific area, enhanced thermal stability and controlled volume variation. However, its sophisticated preparation process associated with complex chemical or physical events still heavily hinders the advance application. Herein, microencapsulation of phase change materials through an facile in-situ copolymerization of N-(tert-butyl)acrylamide, divinylbenzene and para-quaternary ammonium functionalized styrene has been studied. The ratio of core/shell, oil/water ratio and the different monomers were investigated towards the encapsulation efficiency and morphology of the as prepared microcapsules. Chemical composition, morphology of the microcapsules were analyzed by Fourier-transform infrared spectroscopy, X-ray diffraction instrument, thermal gravimetric analysis, scanning electron microscopy and transmission electron microscopy. Thermo-physical characteristics, such as leakage-proof performance, latent heat capacity and phase change temperature were also studied. This study, for the first time, using a quaternary ammonium functionalized styrene based amphipathic monomer, which was designed to be able to stay at the interface of oil and water, as one of the shell materials with the purpose of attaining a high encapsulation rate. As a result, the encapsulation efficiency of our protocol can achieve to 84.50% without observation of any PCMs leakage. Additionally, it was noteworthy that this study offers a facile way to construct PCMs microcapsule, which only needs a simple and rough mixing and filtration, thanks to the self-assembly characteristic of this amphipathic monomer.

Development of the mammalian heart is a complex process that involves the specification and differentiation of cardiovascular progenitor cells, their migration to the organ-forming region, interactions and signaling within and between tissues, and later growth and functional maturation of the organ. Normal heart structure and function rely on the precise expression and regulation of the transcription factor network during organogenesis. Over the last three decades, intensive studies from a number of invertebrate and vertebrate species have identified multiple genes encoding cardiac transcription factors, including GATA4/5/6, Nkx2-5, Tbx5, SRF, Mef2c, FOG, and HAND2, which are required for cardiogenesis. Defective expression or interactions between cardiac transcription factors underlie a significant portion of congenital heart disease. In this chapter, we summarize the current understanding of the functions of GATA transcription factors, especially GATA4, GATA5, and GATA6, in cardiovascular development and the molecular interactions of GATA factors with other transcription factors. The association of GATA transcription factors with cardiovascular disease is also discussed.

Gata5 is a transcription factor expressed in the lung, but its physiological role is unknown. To test whether and how Gata5 regulates airway constrictor responsiveness, we studied Gata5(-/-), Gata5(+/-), and wild-type mice on the C57BL/6J background. Cholinergic airway constrictor responsiveness was assessed invasively in mice without and with induction of allergic airway inflammation through ovalbumin sensitization and aerosol exposure. Gata5-deficient mice displayed native airway constrictor hyperresponsiveness (AHR) in the absence of allergen-induced inflammation. Gata5-deficient mice retained their relatively greater constrictor responsiveness even in ovalbumin-induced experimental asthma. Gata5 deficiency did not alter the distribution of cell types in bronchoalveolar lavage fluid, but bronchial epithelial mucus metaplasia was more prominent in Gata5(-/-) mice after allergen challenge. Gene expression profiles revealed that apolipoprotein E (apoE) was the fifth most down-regulated transcript in Gata5-deficient lungs, and quantitative RT-PCR and immunostaining confirmed reduced apoE expression in Gata5(-/-) mice. Quantitative RT-PCR also revealed increased IL-13 mRNA in the lungs of Gata5-deficient mice. These findings for the first time show that Gata5 regulates apoE and IL-13 expression in vivo and that its deletion causes AHR. Gata5-deficient mice exhibit an airway phenotype that closely resembles that previously reported for apoE(-/-) mice: both exhibit cholinergic AHR in native and experimental asthma states, and there is excessive goblet cell metaplasia after allergen sensitization and challenge. The Gata5-deficient phenotype also shares features that were previously reported for IL-13-treated mice. Together, these results indicate that Gata5 deficiency induces AHR, at least in part, by blunting apoE and increasing IL-13 expression.

The adsorption and reaction of NO on clean and O-precovered Cu(111) has been studied using X-ray photoelectron spectroscopy and temperature-programmed desorption spectroscopy. By varying NO exposure and annealing temperature, two different types of chemisorbed oxygen species, with O 1s binding energies (BE) of 531.0 (O531) and 529.7 eV (O529), were prepared on Cu(111). In the presence of O531 species, the relative occupation of different NO adsorption states was largely affected, and most of the adsorbed NO(a) underwent dissociative desorption, releasing N2O and N2 upon heating. In contrast, in the presence of O529 species, the dissociative desorption of NO(a) was largely suppressed. Furthermore, the O529 species show a more significant blocking effect on NO adsorption than the chemisorbed O531 species. Our results reveal that the effect of precovered oxygen species on the adsorption and reaction of NO on Cu(111) is closely related to the type of oxygen species and oxygen coverage.

The interaction of atomic hydrogen and H2O with stoichiometric and partially reduced CeO2(111) thin films deposited on a Cu(111) substrate was investigated by temperature programmed desorption and ...

We have studied the interaction of ethylene on Co(0001) in detail by X-ray photoelectron spectroscopy (XPS) and ultraviolet photoelectron spectroscopy (UPS). At 130 K, the chemisorption and decompo...

We have comprehensively investigated the reactivity of hydroxyls on FeOx(111) monolayer islands with different amounts of oxygen vacancy concentrations grown on Pt(111) by means of X-ray photoelectron spectroscopy, temperature-programmed desorption/reaction spectroscopy, and low energy electron diffraction. Hydroxyls on FeOx(111) monolayer islands are capable of oxidizing CO(a) on Pt(111) at the FeOx(111)-Pt(111) interface at low temperatures and such an interfacial oxidation of CO by hydroxyls to produce CO2 is not suppressed by either excess CO(a) or excess H(a) on FeOx(111)/Pt(111) inverse model catalyst surface. However, the reactivity of hydroxyls is controlled by the oxygen vacancy concentration in FeOx(111) monolayer islands. With the increase of oxygen vacancy concentration, reaction pathways of hydroxyls on FeOx(111) monolayer islands to produce H2O are thermodynamically suppressed, which thus opens other hydroxyls-involved reaction pathways including the interfacial oxidation of CO to produce CO...

Airway smooth muscle (ASM) hypertrophy is a cardinal feature of severe asthma, but the underlying molecular mechanisms remain uncertain. Forced protein kinase B/Akt 1 activation is known to induce myocyte hypertrophy in other muscle types, and, since a number of mediators present in asthmatic airways can activate Akt signaling, we hypothesized that Akt activation could contribute to ASM hypertrophy in asthma. To test this hypothesis, we evaluated whether Akt activation occurs naturally within airway myocytes in situ, whether Akt1 activation is sufficient to cause hypertrophy of normal airway myocytes, and whether such hypertrophy is accompanied by excessive accumulation of contractile apparatus proteins (contractile phenotype maturation). Immunostains of human airway sections revealed concordant activation of Akt (reflected in Ser473 phosphorylation) and of its downstream effector p70S6Kinase (reflected in Thr389 phosphorylation) within airway muscle bundles, but there was no phosphorylation of the alternative Akt downstream target glycogen synthase kinase (GSK) 3β. Artificial overexpression of constitutively active Akt1 (by plasmid transduction or lentiviral infection) caused a progressive increase in size and protein content of cultured canine tracheal myocytes and increased p70S6Kinase phosphorylation but not GSK3β phosphorylation; however, constitutively active Akt1 did not cause disproportionate overaccumulation of smooth muscle (sm) α-actin and SM22. Furthermore, mRNAs encoding sm-α-actin and SM22 were reduced. These results indicate that forced Akt1 signaling causes hypertrophy of cultured airway myocytes without inducing further contractile phenotypic maturation, possibly because of opposing effects on contractile protein gene transcription and translation, and suggest that natural activation of Akt1 plays a similar role in asthmatic ASM.

The reactivity of surface hydroxyls on FeO(111) monolayer films on Pt(111) with different oxygen vacancy concentrations has been investigated by means of X-ray photoelectron spectroscopy, thermal desorption spectroscopy, low energy electron diffraction, and density functional theory calculations. Surface hydroxyls on the FeO(111) monolayer films undergo two types of surface reactions: one type is surface reactions to form H2O and create oxygen vacancies; the other is surface reactions to form H2. Surface reactions to form H2O and create oxygen vacancies are preferred for surface hydroxyls on the stoichiometric FeO(111) monolayer film but get suppressed with the increasing of the oxygen vacancy concentration on the FeO(111) monolayer film. On the FeO0.67(111) monolayer film, surface hydroxyls prefer surface reactions to form H2. The accompanying DFT calculation results demonstrate that the thermodynamically favorable reaction between two OH(a) switches from the surface reaction to form H2O and oxygen vacan...

Chemisorption and surface reactions of C2H4, CO, and H2 on clean and graphite carbon-modified Co(0001) surfaces have been investigated by thermal desorption spectroscopy, X-ray photoelectron spectroscopy, and low-energy electron diffraction. The chemisorption and decomposition behaviors of C2H4 depend largely on the vacant sites available on clean Co(0001) at 130 K. C2H4 chemisorbs dissociatively to produce C2H2(a) and H(a) at low exposures but both dissociatively and molecularly to produce C2H4(a), C2H2(a), and H(a) at large exposures. Upon heating, some C2H4(a) desorbs and vacates surface sites, which results in the simultaneous decomposition of C2H4(a) into C2H3(a) and H(a). At 350 K, C2H3(a) either undergoes further dehydrogenation into C2H2(a) and H(a) or hydrogenates to produce C2H4. C2H2(a) then completely dehydrogenates to graphite carbon and H2 at 424 K. Graphite carbon modified Co(0001) surfaces were prepared by the thermal decomposition of C2H4 on clean Co(0001). The graphite carbon exerts both...

We report our investigation of the interaction of NO2 with the Au(997) vicinal surface by high-resolution photoelectron spectroscopy using synchrotron radiation as the excitation source. At 170 K, both core-level and valence-band photoemission results illustrate the decomposition of NO2 on the Au(997) surface at low NO2 exposures, forming coadsorbed NO(a) and O(a) species. After annealing at 300 K, NO(a) desorbs from Au(997) whereas O(a) remains on the surface. Upon annealing at 750 K, we observe no signal for adsorbed oxygen on Au(997). These results clearly demonstrate that thermal decomposition of NO2 is an effective method to generate oxygen adatoms on Au(997) under ultrahigh-vacuum conditions.

We have investigated the adsorption of water on a Co(0001) surface by means of temperature-programmed desorption (TPD), X-ray photoelectron spectroscopy (XPS), and low-energy electron diffraction (LEED). At 130 K, the interaction between adsorbed water (H2O(a)) and Co(0001) is quite weak, and water adsorption forms an intact, nonwetting, and three-dimensional layer on Co(0001). The monolayer and multilayer of H2O(a) could be distinguished by XPS, and they desorb molecularly upon heating but only giving a single water desorption peak. An ordered p(2 × 2) LEED pattern was observed at low exposures of water. At room temperature, water adsorbs dissociatively on Co(0001), forming chemisorbed atomic oxygen (O(a)) and atomic hydrogen (H(a)). Upon heating, H(a) recombines into H2 desorbing from the surface, whereas O(a) remains on the surface. The interaction of water with Co(0001) is greatly influenced by the presence and nature of the oxygen species on Co(0001). Water adsorption on Co(0001) precovered with 0.45...

Breathing (especially deep breathing) antagonises development and persistence of airflow obstruction during bronchoconstrictor stimulation. Force fluctuations imposed on contracted airway smooth muscle (ASM) in vitro result in its relengthening, a phenomenon called force fluctuation-induced relengthening (FFIR). Because breathing imposes similar force fluctuations on contracted ASM within intact lungs, FFIR represents a likely mechanism by which breathing antagonises bronchoconstriction. While this bronchoprotective effect appears to be impaired in asthma, corticosteroid treatment can restore the ability of deep breaths to reverse artificially induced bronchoconstriction in asthmatic subjects. It has previously been demonstrated that FFIR is physiologically regulated through the p38 mitogen-activated protein kinase (MAPK) signalling pathway. While the beneficial effects of corticosteroids have been attributed to suppression of airway inflammation, the current authors hypothesised that alternatively they might exert their action directly on ASM by augmenting FFIR as a result of inhibiting p38 MAPK signalling. This possibility was tested in the present study by measuring relengthening in contracted canine tracheal smooth muscle (TSM) strips. The results indicate that dexamethasone treatment significantly augmented FFIR of contracted canine TSM. Canine tracheal ASM cells treated with dexamethasone demonstrated increased MAPK phosphatase-1 expression and decreased p38 MAPK activity, as reflected in reduced phosphorylation of the p38 MAPK downstream target, heat shock protein 27. These results suggest that corticosteroids may exert part of their therapeutic effect through direct action on airway smooth muscle, by decreasing p38 mitogen-activated protein kinase activity and thus increasing force fluctuation-induced relengthening.