Myocd regulates airway smooth muscle cell remodeling in response to chronic asthmatic injury.

Abnormal growth of airway smooth muscle cells is one of the key features in asthmatic airway remodeling, which is associated with asthma severity. The mechanisms underlying inappropriate airway smooth muscle cell growth in asthma remain largely unknown. Myocd has been reported to act as a key transcriptional coactivator in promoting airway-specific smooth muscle development in fetal lungs. Whether Myocd controls airway smooth muscle remodeling in asthma has not been investigated. Mice with lung mesenchyme-specific deletion of Myocd after lung development were generated, and a chronic asthma model was established by sensitizing and challenging the mice with ovalbumin for a prolonged period. Comparison of the asthmatic pathology between the Myocd knockout mice and the wild-type controls revealed that abrogation of Myocd mitigated airway smooth muscle cell hypertrophy and hyperplasia, accompanied by reduced peri-airway inflammation, decreased fibrillar collagen deposition on airway walls, and attenuation of abnormal mucin production in airway epithelial cells. Our study indicates that Myocd is a key transcriptional coactivator involved in asthma airway remodeling. Inhibition of Myocd in asthmatic airways may be an effective approach to breaking the vicious cycle of asthmatic progression, providing a novel strategy in treating severe and persistent asthma. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Semi-Embedding Zn-Co3O4 Derived from Hybrid ZIFs into Wood-Derived Carbon for High-Performance Supercapacitors.

Transition metal oxides (TMOs) can provide high theoretical capacitance due to the change of multiple valence states of transition metals. However, their intrinsic drawbacks, including poor electrical conductivity, lower energy density, and huge volume expansion, will result in the pulverization of electrode materials and restricted electrochemical kinetics, thus leading to poor rate capability and rapid capacity fading. Composite electrodes based on transition metal oxides and carbon-based materials are considered to be promising candidates for overcoming these limitations. Herein, we reported a preparation method of hybrid ZIFs derived Zn-doped Co3O4/carbon (Zn-Co3O4/C-230) particles semi-embedded in wood-derived carbon skeleton for integrated electrodes. A large specific surface area, excellent conductivity, and electrochemical stability provide a larger electrochemical activity and potential window for the electrode. Prepared Zn-Co3O4@CW-230 electrode (0.6 mm thick) displays ultrahigh area specific capacitances of 7.83 and 6.46 F cm-2 at the current densities of 5 and 30 mA cm-2, respectively. Moreover, a symmetric supercapacitor assembled by two identical Zn-Co3O4@CW-230 electrodes delivers a superior area-specific capacitance of 2.61 F cm-2 at the current densities of 5 mA cm-2 and great energy densities of 0.36 mWh cm-2 (6.0 mWh cm-3) at 2.5 mW cm-2, while maintaining 97.3% of initial capacitance over 10,000 cycles. It notably outperforms those of most carbon-based metal oxides, endowing the Zn-Co3O4@CW-230 with extensive prospects for practical application.

Abrogation of mesenchyme-specific TGF-ß signaling results in lung malformation with prenatal pulmonary cysts in mice.

The TGF-ß signaling pathway plays a pivotal role in controlling organogenesis during fetal development. Although the role of TGF-ß signaling in promoting lung alveolar epithelial growth has been determined, mesenchymal TGF-ß signaling in regulating lung development has not been studied in vivo due to a lack of genetic tools for specifically manipulating gene expression in lung mesenchymal cells. Therefore, the integral roles of TGF-ß signaling in regulating lung development and congenital lung diseases are not completely understood. Using a Tbx4 lung enhancer-driven Tet-On inducible Cre transgenic mouse system, we have developed a mouse model in which lung mesenchyme-specific deletion of TGF-ß receptor 2 gene (Tgfbr2) is achieved. Reduced airway branching accompanied by defective airway smooth muscle growth and later peripheral cystic lesions occurred when lung mesenchymal Tgfbr2 was deleted from embryonic day 13.5 to 15.5, resulting in postnatal death due to respiratory insufficiency. Although cell proliferation in both lung epithelium and mesenchyme was reduced, epithelial differentiation was not significantly affected. Tgfbr2 downstream Smad-independent ERK1/2 may mediate these mesenchymal effects of TGF-ß signaling through the GSK3ß-ß-catenin-Wnt canonical pathway in fetal mouse lung. Our study suggests that Tgfbr2-mediated TGF-ß signaling in prenatal lung mesenchyme is essential for lung development and maturation, and defective TGF-ß signaling in lung mesenchyme may be related to abnormal airway branching morphogenesis and congenital airway cystic lesions.

Mesenchymal folliculin is required for alveolar development: implications for cystic lung disease in Birt-Hogg-Dubé syndrome.

BACKGROUND: Pulmonary cysts and spontaneous pneumothorax are presented in most patients with Birt-Hogg-Dubé (BHD) syndrome, which is caused by loss of function mutations in the folliculin (FLCN) gene. The pathogenic mechanisms underlying the cystic lung disease in BHD are poorly understood. METHODS: Mesenchymal Flcn was specifically deleted in mice or in cultured lung mesenchymal progenitor cells using a Cre/loxP approach. Dynamic changes in lung structure, cellular and molecular phenotypes and signalling were measured by histology, immunofluorescence staining and immunoblotting. RESULTS: Deletion of Flcn in mesoderm-derived mesenchymal cells results in significant reduction of postnatal alveolar growth and subsequent alveolar destruction, leading to cystic lesions. Cell proliferation and alveolar myofibroblast differentiation are inhibited in the Flcn knockout lungs, and expression of the extracellular matrix proteins Col3a1 and elastin are downregulated. Signalling pathways including mTORC1, AMP-activated protein kinase, ERK1/2 and Wnt-ß-catenin are differentially affected at different developmental stages. All the above changes have statistical significance (p<0.05). CONCLUSIONS: Mesenchymal Flcn is an essential regulator during alveolar development and maintenance, through multiple cellular and molecular mechanisms. The mesenchymal Flcn knockout mouse model provides the first in vivo disease model that may recapitulate the stages of cyst development in human BHD. These findings elucidate the developmental origins and mechanisms of lung disease in BHD.

Mesenchyme-specific deletion of Tgf-ß1 in the embryonic lung disrupts branching morphogenesis and induces lung hypoplasia.

Proper lung development depends on the precise temporal and spatial expression of several morphogenic factors, including Fgf10, Fgf9, Shh, Bmp4, and Tgf-ß. Over- or under-expression of these molecules often leads to aberrant embryonic or postnatal lung development. Herein, we deleted the Tgf-ß1 gene specifically within the lung embryonic mesenchymal compartment at specific gestational stages to determine the contribution of this cytokine to lung development. Mutant embryos developed severe lung hypoplasia and died at birth due to the inability to breathe. Despite the markedly reduced lung size, proliferation and differentiation of the lung epithelium was not affected by the lack of mesenchymal expression of the Tgf-ß1 gene, while apoptosis was significantly increased in the mutant lung parenchyma. Lack of mesenchymal expression of the Tgf-ß1 gene was also associated with reduced lung branching morphogenesis, with accompanying inhibition of the local FGF10 signaling pathway as well as abnormal development of the vascular system. To shed light on the mechanism of lung hypoplasia, we quantified the phosphorylation of 226 proteins in the mutant E12.5 lung compared with control. We identified five proteins, Hrs, Vav2, c-Kit, the regulatory subunit of Pi3k (P85), and Fgfr1, that were over- or under-phosphorylated in the mutant lung, suggesting that they could be indispensable effectors of the TGF-ß signaling program during embryonic lung development. In conclusion, we have uncovered novel roles of the mesenchyme-specific Tgf-ß1 ligand in embryonic mouse lung development and generated a mouse model that may prove helpful to identify some of the key pathogenic mechanisms underlying lung hypoplasia in humans.

Inactivation of Tsc2 in Mesoderm-Derived Cells Causes Polycystic Kidney Lesions and Impairs Lung Alveolarization.

The tuberous sclerosis complex (TSC) proteins are critical negative regulators of the mammalian/mechanistic target of rapamycin complex 1 pathway. Germline mutations of TSC1 or TSC2 cause TSC, affecting multiple organs, including the kidney and lung, and causing substantial morbidity and mortality. The mechanisms of organ-specific disease in TSC remain incompletely understood, and the impact of TSC inactivation on mesenchymal lineage cells has not been specifically studied. We deleted Tsc2 specifically in mesoderm-derived mesenchymal cells of multiple organs in mice using the Dermo1-Cre driver. The Dermo1-Cre-driven Tsc2 conditional knockout mice had body growth retardation and died approximately 3 weeks after birth. Significant phenotypes were observed in the postnatal kidney and lung. Inactivation of Tsc2 in kidney mesenchyme caused polycystic lesions starting from the second week of age, with increased cell proliferation, tubular epithelial hyperplasia, and epithelial-mesenchymal transition. In contrast, Tsc2 deletion in lung mesenchyme led to decreased cell proliferation, reduced postnatal alveolarization, and decreased differentiation with reduced numbers of alveolar myofibroblast and type II alveolar epithelial cells. Two major findings thus result from this model: inactivation of Tsc2 in mesoderm-derived cells causes increased cell proliferation in the kidneys but reduced proliferation in the lungs, and inactivation of Tsc2 in mesoderm-derived cells causes epithelial-lined renal cysts. Therefore, Tsc2-mTOR signaling in mesenchyme is essential for the maintenance of renal structure and for lung alveolarization.

Switching freely between superluminal and subluminal light propagation in a monolayer MoS2 nanoresonator.

We theoretically propose a feasible scheme to advance or slow the propagation of light in a monolayer MoS2 nanoresonator (NR). The scheme allows one to easily turn on or off the fast (superluminal) and slow (subluminal) light effects and switch freely between fast and slow light propagation by only adjusting the frequency or intensity of the pump field. As the exciton interacts strongly with the phonons in MoS2, the slow light effect will appear along with a large dispersion with a very steep negative slope and a sharp absorption peak. Especially, the maximal group velocity index of the slow light in the monolayer MoS2 NR can reach two orders of magnitude larger than that in a carbon nanotube resonator. These results provide a new way to measure the exciton-phonon coupling strength and may prove useful in device applications such as optical switching and optical signal processing.

BMP signaling is essential in neonatal surfactant production during respiratory adaptation.

Deficiency in pulmonary surfactant results in neonatal respiratory distress, and the known genetic mutations in key components of surfactant only account for a small number of cases. Therefore, determining the regulatory mechanisms of surfactant production and secretion, particularly during the transition from prenatal to neonatal stages, is essential for better understanding of the pathogenesis of human neonatal respiratory distress. We have observed significant increase of bone morphogenetic protein (BMP) signaling in neonatal mouse lungs immediately after birth. Using genetically manipulated mice, we then studied the relationship between BMP signaling and surfactant production in neonates. Blockade of endogenous BMP signaling by deleting Bmpr1a (Alk3) or Smad1 in embryonic day 18.5 in perinatal lung epithelial cells resulted in severe neonatal respiratory distress and death, accompanied by atelectasis in histopathology and significant reductions of surfactant protein B and C, as well as Abca3, whereas prenatal lung development was not significantly affected. We then identified a new BMP-Smad1 downstream target, Nfatc3, which is known as an important transcription activator for surfactant proteins and Abca3. Furthermore, activation of BMP signaling in cultured lung epithelial cells was able to promote endogenous Nfatc3 expression and also stimulate the activity of an Nfatc3 promoter that contains a Smad1-binding site. Therefore, our study suggests that the BMP-Alk3-Smad1-Nfatc3 regulatory loop plays an important role in enhancing surfactant production in neonates, possibly helping neonatal respiratory adaptation from prenatal amniotic fluid environment to neonatal air breathing.

Genetic variation, pathogenicity, and immunogenicity of highly pathogenic porcine reproductive and respiratory syndrome virus strain XH-GD at different passage levels.

Porcine reproductive and respiratory syndrome (PRRS) is one of the most economically important infectious diseases of swine worldwide. Immunization with an attenuated vaccine is considered an effective method for reducing the economic losses resulting from porcine reproductive and respiratory syndrome virus (PRRSV) infection. Several studies have shown that PRRSV can be attenuated by passage in Marc-145 cells, but it is still not clear whether this attenuation influences the immunogenicity of PRRSV and what the mechanism of attenuation is. In order to study the mechanism of attenuation and immunogenicity of highly pathogenic (HP) PRRSV, the HP-PRRSV strain XH-GD was serially 122 times passaged in Marc-145 cells. Genomic sequence comparisons were made at selected passages. To explore the differences in pathogenicity and immunogenicity at different passages, three passages (P5, P62 and P122) were selected for an animal challenge experiment, which showed that passage in Marc-145 cells resulted in attenuation of the virus. After 122 passages, 35 amino acid changes were observed in the structural proteins and non-structural proteins. The animal challenge experiment showed that pathogenicity decreased with increasing passage number. The N antibody level and specific neutralizing (SN) antibody titers also decreased with increasing passage number in the late stage of the animal experiment. This study indicated that the virulence of XH-GD was decreased by passage in Marc-145 cells and that overattenuation might influence the immunogenicity of virus. These results might contribute to our understanding of the mechanism of attenuation.

A novel profibrotic mechanism mediated by TGFß-stimulated collagen prolyl hydroxylase expression in fibrotic lung mesenchymal cells.

Idiopathic pulmonary fibrosis is a severe chronic lung disease with a high mortality rate. Excessive TGFß signalling is recognized as a central player in lung fibrosis. However, the related mechanisms remain unclear. Herein we used a novel Tbx4 lung enhancer-driven Tet-On transgenic system to inhibit TGFß signalling in mouse lung-resident mesenchymal cells at different stages of bleomycin-induced fibrosis, by conditionally knocking out TGFß receptor II or expressing a dominant-negative TGFß receptor II. Abrogation of mesenchymal TGFß signalling markedly attenuated bleomycin-induced fibrotic pathology, which was independent of altered early inflammation. Furthermore, a novel TGFß downstream target gene P4HA3 (an α-subunit of collagen prolyl hydroxylase) was identified, and its expression was significantly increased in fibroblastic foci of both bleomycin-induced fibrotic mouse lungs and idiopathic pulmonary fibrosis patients' lungs. The relationship between activated TGFß signalling, up-regulation of P4HA3 and increased hydroxyproline/collagen production was further verified in cultured lung fibroblasts. Moreover, inhibition of collagen prolyl hydroxylase by pyridine-2,5-dicarboxylate attenuated TGFß-stimulated collagen production in both cultured fibroblasts and bleomycin-induced mouse lung fibrosis. These data indicate that increased expression and activity of collagen prolyl hydroxylase is one of the important mechanisms underlying TGFß-mediated profibrotic effects. Inhibition of collagen prolyl hydroxylase may be a new, promising approach for preventing and treating pulmonary fibrosis.

Mesenchymal adenomatous polyposis coli plays critical and diverse roles in regulating lung development.

BACKGROUND: Adenomatous polyposis coli (Apc) is a tumor suppressor that inhibits Wnt/Ctnnb1. Mutations of Apc will not only lead to familial adenomatous polyposis with associated epithelial lesions, but will also cause aggressive fibromatosis in mesenchymal cells. However, the roles of Apc in regulating mesenchymal cell biology and organogenesis during development are unknown. RESULTS: We have specifically deleted the Apc gene in lung mesenchymal cells during early lung development in mice. Loss of Apc function resulted in immediate mesenchymal cell hyperproliferation through abnormal activation of Wnt/Ctnnb1, followed by a subsequent inhibition of cell proliferation due to cell cycle arrest at G0/G1, which was caused by a mechanism independent of Wnt/Ctnnb1. Meanwhile, abrogation of Apc also disrupted lung mesenchymal cell differentiation, including decreased airway and vascular smooth muscle cells, the presence of Sox9-positive mesenchymal cells in the peripheral lung, and excessive versican production. Moreover, lung epithelial branching morphogenesis was drastically inhibited due to disrupted Bmp4-Fgf10 morphogen production and regulation in surrounding lung mesenchyme. Lastly, lung mesenchyme-specific Apc conditional knockout also resulted in altered lung vasculogenesis and disrupted pulmonary vascular continuity through a paracrine mechanism, leading to massive pulmonary hemorrhage and lethality at mid-gestation when the pulmonary circulation should have started. CONCLUSIONS: Our study suggests that Apc in lung mesenchyme plays central roles in coordinating the proper development of several quite different cellular compartments including lung epithelial branching and pulmonary vascular circulation during lung organogenesis.

Lack of exposure of H10N8 avian influenza virus among veterinarians in Guangdong Province, China.

We conducted a retrospective seroepidemiological study for H10N8 avian influenza infection among 400 veterinarians sampled from February 2013 to August 2013 in Guangdong Province, China. None of the veterinarians had evidence of previous infection with the emergent H10N8 AIV. Although there is no evidence of H10N8-infected veterinarian before the first human index case of H10N8 infection in southern China, a more rigorous and long-term surveillance remained essential for early warning of novel reassortant viruses and interspecies transmission events.

High power tandem-pumped thulium-doped fiber laser.

We propose a cascaded tandem pumping technique and show its high power and high efficient operation in the 2-µm wavelength region, opening up a new way to scale the output power of the 2-µm fiber laser to new levels (e.g. 10 kW). Using a 1942 nm Tm(3+) fiber laser as the pump source with the co- (counter-) propagating configuration, the 2020 nm Tm(3+) fiber laser generates 34.68 W (35.15W) of output power with 84.4% (86.3%) optical-to-optical efficiency and 91.7% (92.4%) slope efficiency, with respect to launched pump power. It provides the highest slope efficiency reported for 2-µm Tm(3+)-doped fiber lasers, and the highest output power for all-fiber tandem-pumped 2-µm fiber oscillators. This system fulfills the complete structure of the proposed cascaded tandem pumping technique in the 2-µm wavelength region (~1900 nm → ~1940 nm → ~2020 nm). Numerical analysis is also carried out to show the power scaling capability and efficiency of the cascaded tandem pumping technique.

Sparse serological evidence of H5N1 avian influenza virus infections in domestic cats, northeastern China.

Today the cross-species transmission of avian influenza viruses (AIV) are a great concern. A number of AIV strains are now enzootic among poultry, with H9N2 and highly pathogenic H5N1 AIV strains prevalent in China. H5N1 strains have been recognized to infect zoo and domestic feline species. In this serological study we sought to examine evidence that H5N1 strains have infected domestic cats in northeastern China. In 2013, we conducted a cross-sectional serological study of 916 healthy cats in Heilongjian, Jilin, and Liaonin Provinces. Sera were screened with a hemagglutinin inhibition (HI) assay and seropositive specimens (HI ≥ 1:20) were further evaluated with a microneutralization (MN) assay against a clade 2.3.2 H5N1 AIV, a H9N2 AIV, A (H1N1)pdm09, and a canine H3N2 virus. While ∼2% of cats had elevated HI assays against H5N1, no elevations were confirmed (MN ≥ 1:80). These data serve as baseline for future surveillance for AIV infections among domestic cats. Conducting such surveillance seems important for geographical areas recognized as endemic for AIVs. This is especially true for countries such as China where domestic cats and poultry are often in close contact.

High signal-to-noise ratio, single-frequency 2 µm Brillouin fiber laser.

A high optical signal-to-noise ratio (OSNR) single-frequency 2 µm Brillouin fiber laser (BFL) with watt-level output and high transfer efficiency is demonstrated for the first time to the best of our knowledge. The Brillouin pump is constructed with a two-stage thulium-doped fiber amplifier (TDFA) seeded by a 2 µm laser diode, providing 4.02 W average power with 1 MHz linewidth. Using an optimized length of 14 m for the Brillouin ring cavity, the BFL works stably in single-mode region with 8 kHz linewidth because of the linewidth narrowing effect. The transfer efficiency is 51% with 1.08 W output power and 62 dB OSNR for 3.22 W pump power.

Spatial-temporal targeting of lung-specific mesenchyme by a Tbx4 enhancer.

BACKGROUND: Reciprocal interactions between lung mesenchymal and epithelial cells play essential roles in lung organogenesis and homeostasis. Although the molecular markers and related animal models that target lung epithelial cells are relatively well studied, molecular markers of lung mesenchymal cells and the genetic tools to target and/or manipulate gene expression in a lung mesenchyme-specific manner are not available, which becomes a critical barrier to the study of lung mesenchymal biology and the related pulmonary diseases. RESULTS: We have identified a mouse Tbx4 gene enhancer that contains conserved DNA sequences across many vertebrate species with lung or lung-like gas exchange organ. We then generate a mouse line to express rtTA/LacZ under the control of the Tbx4 lung enhancer, and therefore a Tet-On inducible transgenic system to target lung mesenchymal cells at different developmental stages. By combining a Tbx4-rtTA driven Tet-On inducible Cre expression mouse line with a Cre reporter mouse line, the spatial-temporal patterns of Tbx4 lung enhancer targeted lung mesenchymal cells were defined. Pulmonary endothelial cells and vascular smooth muscle cells were targeted by the Tbx4-rtTA driver line prior to E11.5 and E15.5, respectively, while other subtypes of lung mesenchymal cells including airway smooth muscle cells, fibroblasts, pericytes could be targeted during the entire developmental stage. CONCLUSIONS: Developmental lung mesenchymal cells can be specifically marked by Tbx4 lung enhancer activity. With our newly created Tbx4 lung enhancer-driven Tet-On inducible system, lung mesenchymal cells can be specifically and differentially targeted in vivo for the first time by controlling the doxycycline induction time window. This novel system provides a unique tool to study lung mesenchymal cell lineages and gene functions in lung mesenchymal development, injury repair, and regeneration in mice.

Self-healable electrically conducting wires for wearable microelectronics.

Electrically conducting wires play a critical role in the advancement of modern electronics and in particular are an important key to the development of next-generation wearable microelectronics. However, the thin conducting wires can easily break during use, and the whole device fails to function as a result. Herein, a new family of high-performance conducting wires that can self-heal after breaking has been developed by wrapping sheets of aligned carbon nanotubes around polymer fibers. The aligned carbon nanotubes offer an effective strategy for the self-healing of the electric conductivity, whereas the polymer fiber recovers its mechanical strength. A self-healable wire-shaped supercapacitor fabricated from a wire electrode of this type maintained a high capacitance after breaking and self-healing.

High performance supercapacitors deploying cube-templated tracheid cavities of wood-derived carbon.

Wood-derived carbon, with its strong tracheid array structure, is an ideal material for use as a self-supporting electrode in supercapacitors. By leveraging the inherent through pore structure and surface affinity found in wood tracheids, we successfully engineered a highly spatially efficient cube-templated porous carbon framework inside carbonized wood tracheid cavities through precise control over precursor crystallization temperatures. This innovative cubic channel architecture effectively maximizes up to (79 ± 1)% of the cavity volume in wood-derived carbon while demonstrating exceptional hydrophilicity and high conductivity properties, facilitating the development of supercapacitors with enhanced areal/volumetric capacitances (2.65F cm-2/53.0F cm-3 at 5.0 mA cm-2) as well as superior areal/volumetric energy densities (0.37 mWh cm-2/7.36 mWh cm-3 at 2.5 mW cm-2). The fabrication of these cube-templated channels with high cube filling content is not only simple and precisely controllable, but also environmentally friendly. The proposed method eliminates the conventional acid-base treatment process for pore formation, facilitating the rapid development and practical implementation of thick electrodes with superior performance in supercapacitors. Moreover, it offers a universal research approach for the commercialization of wood-derived thick electrodes.

Self-supported porous wood carbon electrode with a MoC/carbon nanocage composite for application in a high-performance supercapacitor.

The rational design and synthesis of carbon nanocages with highly complex porous structures are continuously facing challenges in the development of high-performance supercapacitors (SCs). The electrochemical performance characteristics of electrodes rely on their compositions and fabrication methods. Here, we propose a universal and efficient approach for the in-situ synthesis of zeolitic imidazolate framework-8 (ZIF-8) on porous carbonized wood, where the selective utilization of hexacarbonyl molybdenum protects the structural integrity of the ZIF-8 precursor, preventing collapse during thermal treatment. The subsequent pyrolysis process leads to the formation of small-sized molybdenum carbide (MoC) which are embedded in carbon nanocages (CN). The composite electrode consists of MoC/CN embedded in a porous carbonized wood (PCW), and it shows area-specific capacity of 9.7F cm-2 and 9.4 F cm-2 at 5 mA cm-2 and 30 mA cm-2, respectively. Subsequently, the symmetric supercapacitor, with two MoC/CN@PCW electrodes exhibits a areal specific capacitance of 2.7 F cm-2 at 5 mA cm-2. Moreover, this supercapacitor maintains an capacitance retention rate of 98.5 % after 12,000 discharge cycles. The supercapacitor exhibits a power density of 6.5 mW cm-2, resulting in an energy density of 0.864 mWh cm-2. Therefore, the utilization of wood-based electrodes holds promise for energy storage systems.

Defective mesenchymal Bmpr1a-mediated BMP signaling causes congenital pulmonary cysts.

Abnormal lung development can cause congenital pulmonary cysts, the mechanisms of which remain largely unknown. Although the cystic lesions are believed to result directly from disrupted airway epithelial cell growth, the extent to which developmental defects in lung mesenchymal cells contribute to abnormal airway epithelial cell growth and subsequent cystic lesions has not been thoroughly examined. In the present study, we dissected the roles of BMP receptor 1a (Bmpr1a)-mediated BMP signaling in lung mesenchyme during prenatal lung development and discovered that abrogation of mesenchymal Bmpr1a disrupted normal lung branching morphogenesis, leading to the formation of prenatal pulmonary cystic lesions. Severe deficiency of airway smooth muscle cells and subepithelial elastin fibers were found in the cystic airways of the mesenchymal Bmpr1a knockout lungs. In addition, ectopic mesenchymal expression of BMP ligands and airway epithelial perturbation of the Sox2-Sox9 proximal-distal axis were detected in the mesenchymal Bmpr1a knockout lungs. However, deletion of Smad1/5, two major BMP signaling downstream effectors, from the lung mesenchyme did not phenocopy the cystic abnormalities observed in the mesenchymal Bmpr1a knockout lungs, suggesting that a Smad-independent mechanism contributes to prenatal pulmonary cystic lesions. These findings reveal for the first time the role of mesenchymal BMP signaling in lung development and a potential pathogenic mechanism underlying congenital pulmonary cysts.