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• Abiraterone-resistant PC-3 cells alter prostate gland morphogenesis, drug response, immune response, and angiogenesis. • BPNS reduce proliferation and migration of the abiraterone-resistant prostate cancer cells. • BPNS mediate the genes related to cancer cell proliferation, metastasis, and oncogenic signaling pathways. • BPNS control MMP, ATF, and Notch families in abiraterone-resistant PC-3 cells. [Display omitted] Prostate cancer is the second most common cause of cancer-related deaths in men and is common in most developed countries. Androgen deprivation therapy (ADT) that uses abiraterone acetate (AA) is an effective second-line treatment for prostate cancer. However, approximately 20–40% of patients develop primary resistance to abiraterone post-treatment. In this study, we aimed to understand the molecular mechanisms underlying the development of abiraterone resistance in prostate cancer cells and the potential use of black phosphorus nanosheets (BPNS) for treating abiraterone-resistant prostate cancer. We first established abiraterone-resistant prostate cancer PC-3 cells and found that these cells have higher migration ability than normal prostate cancer cells. Using comparative transcriptomic and bioinformatics analyses between abiraterone-sensitive PC-3 and abiraterone-resistant PC-3 cells, we highlighted the differentially expressed genes (DEGs) involved in the biological processes related to prostate gland morphogenesis, drug response, immune response, angiogenesis. We further studied the therapeutic effects of BPNS. Our results show that BPNS reduced the proliferation and migration of abiraterone-resistant PC-3 cells. Bioinformatics analysis, including gene ontology, Kyoto encyclopedia of genes and genomes enrichment analysis, and ingenuity pathway analysis (IPA) of the DEGs, suggested that BPNS treatment controlled cancer cell proliferation, metastasis, and oncogenic signaling pathways. Furthermore, the IPA gene network highlighted the involvement of the MMP family, ATF, and notch families in the anti-prostate cancer function of BPNS. Our findings suggest that BPNS may have a chemotherapeutic function in treating abiraterone-resistant prostate cancer. [ABSTRACT FROM AUTHOR]

There is restricted research on the sensitive characteristic and detection ability analysis of semi-airborne frequency domain electromagnetic system at present. However, it is critical to the optimal design of the observation scheme, and it may be beneficial for the optimal selection of the record region and increasing the resolution of apparent resistivity imaging. So it is necessary to analyze the sensitive characteristic of the semi-airborne frequency domain system. In this paper, the primary electric field based on the closed-form expression of the electromagnetic field in the underground excited by a horizontal electric dipole is calculated, each element of the underground will be regarded as a current source, and the secondary magnetic field can be obtained based on tensor Green's function. The sensitivity is defined by the contribution of each element to the total secondary magnetic field at the receiving point, and the sensitivity distribution characteristic of the related region is analyzed. Numerical experiments reveal that the region with high sensitivity can produce a strong relative anomaly, and the contribution of the region with sensitivity near zero is almost negligible. To verify the analysis for sensitive characteristics and detectability, we have conducted a field test, after the design of the observation scheme, the data obtained reflects the underground fault zone well. Thus, the relationship between detectability and sensitivity is worth studying. • The sensitivity distribution characteristic of the related region for semi-airborne frequency domain system is analyzed. • The related region is analyzed with different combinations of the electrical, geometric and geological parameters. • The relationship between detectability and sensitive characteristics may help the optimal design of observation scheme. [ABSTRACT FROM AUTHOR]

Basic helix-loop-helix transcription factors (TFs), namely MYC2, MYC3, and MYC4, interact with Jasmonate Zim-domain proteins and are their direct targets. These TFs have been shown to function synergistically to control Arabidopsis growth and development. Our results showed similar MYC2 , MYC3, and MYC4 expression patterns during Arabidopsis seed development, which remained relatively high during seed mid-maturation. MYC2, MYC3, and MYC4 acted redundantly in seed size, weight control, and in regulating seed storage protein accumulation. Triple mutants produced the largest seeds and single and double mutants’ seeds were much larger than those of wild type. The weight of triple mutants’ seeds was significantly higher than that of wild-type seeds, which was accompanied by an increase in seed storage protein contents. Triple mutants’ seeds presented a marked decrease in 2S amounts relative to those in wild-type seeds. Liquid chromatography tandem mass spectra sequencing results indicated that both the relative abundance and the peptide number of CRA1 and CRU3 were greatly increased in triple mutants compared to wild type. The expression of 2S1 – 2S5 decreased and that of CRA1 and CRU3 increased in triple mutants relative to those in wild types during seed development, which might have contributed to the low 2S and high 12S contents in triple mutants. Our results contribute to understanding the function of MYC2, MYC3, and MYC4 on seed development, and provide promising targets for genetic manipulations of protein-producing crops to improve the quantity and quality of seed storage proteins. [ABSTRACT FROM AUTHOR]

Caleosins are a class of Ca binding proteins that appear to be ubiquitous in plants. Some of the main proteins embedded in the lipid monolayer of lipid droplets, caleosins, play critical roles in the degradation of storage lipids during germination and in lipid trafficking. Some of them have been shown to have histidine-dependent peroxygenase activity, which is believed to participate in stress responses in Arabidopsis. In the model plant Arabidopsis thaliana, caleosins have been examined extensively. However, little is known on a genome-wide scale about these proteins in other members of the Brassicaceae. In this study, 51 caleosins in Brassica plants and Arabidopsis lyrata were investigated and analyzed in silico. Among them, 31 caleosins, including 7 in A. lyrata, 11 in Brassica oleracea and 13 in Brassica napus, are herein identified for the first time. Segmental duplication was the main form of gene expansion. Alignment, motif and phylogenetic analyses showed that Brassica caleosins belong to either the H-family or the L-family with different motif structures and physicochemical properties. Our findings strongly suggest that L-caleosins are evolved from H-caleosins. Predicted phosphorylation sites were differentially conserved in H-caleosin and L-caleosins, respectively. 'RY-repeat' elements and phytohormone-related cis-elements were identified in different caleosins, which suggest diverse physiological functions. Gene structure analysis indicated that most caleosins (38 out of 44) contained six exons and five introns and their intron phases were highly conserved. Structurally integrated caleosins, such as BrCLO3-3 and BrCLO4-2, showed high expression levels and may have important roles. Some caleosins, such as BrCLO2 and BoCLO8-2, lost motifs of the calcium binding domain, proline knot, potential phosphorylation sites and haem-binding sites. Combined with their low expression, it is suggested that these caleosins may have lost function. [ABSTRACT FROM AUTHOR]

In this paper, we reported a novel far-red emitting phosphor Sr 9 Y 2 (WO 6) 4 : Mn4+ and alkaline earth metal Mg2+ ion co-doped phosphor Sr 9 Y 2 (WO 6) 4 : Mn4+, Mg2+. Systematical studies on its crystal structure and luminescence properties are carried out. X-ray powder diffraction confirmed that the pure phase Sr 9 Y 2 (WO 6) 4 : Mn4+ and Sr 9 Y 2 (WO 6) 4 : Mn4+, Mg2+ phosphors show a single phase. Upon 350 nm excitation, the phosphors could emit far-red emission in the range of 600–800 nm, peaking at 680 nm (14,706 cm−1) due to the 2E g →4A 2g transition, with broad spectra overlap with the absorption band of phytochrome P FR. The optimal doping concentration, concentration quenching mechanism, as well as the content and temperature dependent decay times of Sr 9 Y 2 (WO 6) 4 : Mn4+ phosphors are studied in detail. Impressively, Mg2+ dopant is found to strongly improve the luminescence of Mn4+ and the related mechanisms are deeply studied. Ultimately, a far-red light emitting diode lamp is fabricated by exciting a far red phosphor Sr 9 Y 2 (WO 6) 4 : 0.0025Mn4+, 0.01Mg2+ using a 365 nm n-UV illuminating LED chip. Our studies have shown that Sr 9 Y 2 (WO 6) 4 : Mn4+, Mg2+ phosphors have potential application in controlling or adjusting plant growth in plant-lighting. Image 1 • The charge compensation of Mg2+ was performed in the phosphor SYW: Mn4+. • We analyzed the crystal structure of SYW host at the first time. • The luminescence properties of SYW: Mn4+ and SYW: Mn4+, Mg2+ were systematically investigated. • The crystal field strength of SYW: Mn4+, Mg2+ with/without Mg2+ charge compensation were studied. • The SYW: Mn4+, Mg2+ phosphor was incorporated into a far-red LED lamp and its practicality was discussed. [ABSTRACT FROM AUTHOR]

Eu 2+ -doped near-infrared (NIR) emitting phosphors, known for their high efficiency, broadband emission and spectral tunability, have gained much attention. However, achieving efficient NIR emission based on Eu 2+ remains a challenge due to the co-existence of Eu 3+ , especially in materials (i.e. garnets and apatites) containing trivalent lanthanide cations. In this study, a Eu 2+ doped sulfureted NIR-emitting garnet phosphor Ca 3 (Sc, Eu) 2 Si 3 (O, S) 12 : Eu 2+ is successfully designed and synthesized. Notably, a strategy for regulating the initial valence state of dopants is proposed by using prepared EuS instead of the conventional Eu 2 O 3 as raw material, enhancing the NIR emission by 135 %. Moreover, a sulfuration strategy is further introduced to enhance the NIR-emitting intensity and internal quantum efficiency by 192 % and 167.8 %, and to improve thermal stability by 154 % at 120 °C. The luminescence origin of the unusual broadband NIR emission is re-examined through chemical unit co-substitution strategy by introducing [Al 3+ Hf 4+ ] to replace [Sc 3+ Si 4+ ] ion pairs. Meanwhile, the spectral regulation and the performance optimization mechanism are systematically discussed. Finally, a green light pumped NIR LED device with a photoelectric efficiency of 9.43 %@100 mA and output power of 22.74 mW@100 mA is fabricated, showing remarkable potential in nondestructive testing and biomedical imaging applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To analyze the epidemiological characteristics of measles, mumps, and rubella (MMR) between 2014 and 2021 and identify potential strategies and measures for the prevention and control of MMR in China., Methods: Data on MMR was obtained from China's National Notifiable Disease Reporting System for the period from 2014 to 2021. Spatiotemporal distributions were analyzed using SaTScan; temporal trends were analyzed using JoinPoint; and clusters were visualized using ArcGIS., Results: A total of 1,808,067 cases of MMR were reported from 2014 to 2021 in China's mainland, most of which were children and students under the age of 20. The incidence of measles declined during 2014-2021, whereas that of mumps and rubella peaked in 2019. MMR-reported cases generally peaked from March to July; however, high numbers of mumps cases were reported from September to November in 2020-2021. Measles and rubella clusters predominantly occurred in Western China, whereas clusters of mumps were generally found in the southern region., Conclusion: The relatively heterogeneous epidemiological characteristics of MMR have highlighted the weaknesses and gaps in surveillance and timely control of MMR transmission in China's mainland. Real-time and intelligent monitoring data should be collected for evidence-based early interventions., (Copyright © 2024 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)

Introduction: The global incidence of dengue fever has increased significantly over the past two decades, and China faces a significant upward trend in dengue control challenges., Methods: Data were obtained from China's NNDRS from 2005 to 2023. Joinpoint regression software was used to analyze temporal trends, while SaTScan software was used to analyze spatial, seasonal, and spatiotemporal distributions. ArcGIS software was used to visualize clusters., Results: A total of 117,892 dengue cases were reported from 2005 to 2023, with significant fluctuation in annual reported cases. Dengue was not endemic in China. Autochthonous outbreaks most likely occurred in the southwestern, southeastern coastal, and inland areas of China. These outbreaks have occurred between June and November, generally peaking in September or October, around epidemiological week (EW) 40., Conclusions: Dengue challenges in China are increasing. Timely case monitoring, proactive control interventions, and staff mobilization should be implemented before June to ensure a timely response to autochthonous outbreaks., Competing Interests: No conflicts of interest., (Copyright and License information: Editorial Office of CCDCW, Chinese Center for Disease Control and Prevention 2024.)

Tailormade bottom-up synthesis of covalent organic frameworks (COFs) from various functional building blocks offer not only tunable topology and pore size but also multidimensional properties. High crystallinity is one of the prerequisites for their structures and associated physicochemical properties. Among different π-conjugated motifs for constructing COFs, pyrene-based tetragonal structures are effective in achieving highly ordered and crystalline states. In the present research, we demonstrated that the substitution of pyrene with 2,7-diazapyrene produces nearly "flat" structures of two-dimensional (2D) COF layers by controlling the torsional angle of linker molecules. Featuring finite pore diameters and excellent thermodynamic stability of ∼500 °C, ordered face-to-face (slipped AA) stacking arrangements were produced. Extended electrical conjugation spanning 2D frames with modest optical bandgaps ( E g ) of ∼2.1 eV shows the planar character of diazapyrene-based COFs. The stacking of the conjugated 2D frames with small E g values is also beneficial for the formation of highly stable conducting pathways in the crystalline state, which was confirmed by the results of the microwave conductivity measurements. Nitrogen centers in diazapyrene units also play a key role as the active sites for proton transfer, and the maximum proton conductivity of σ = 10 -2 S cm -1 was achieved along the cocontinuous nanopore structures surrounded by the active sites. Results show that tetragonal COFs based on diazapyrene can be used as a highly crystalline two-dimensional material with special electrical and proton-conducting capabilities.

Significant effort has been devoted to the development of materials that combine high electrical conductivity and permanent porosity. This paper discloses a diazaporphyrin-based hydrogen-bonded organic framework (HOF) with porosity and n-type semiconductivity. A 5,15-diazaporphyrin Ni(ii) complex with carboxyphenyl groups at the meso positions afforded a HOF due to hydrogen-bonding interactions between the carboxy groups and meso -nitrogen atoms. The thermal and chemical stabilities of the HOF were examined using powder X-ray diffraction analysis, and the charge-carrier mobility was determined to be 2.0 × 10 -7 m 2 V -1 s -1 using the flash-photolysis time-resolved microwave conductivity (FP-TRMC) method. An analogous diazaporphyrin, which does not form a HOF, exhibited mobility that was 20 times lower. The results presented herein highlight the crucial role of hydrogen-bonding networks in achieving conductive pathways that can tolerate thermal perturbation., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Introduction: Porcine reproductive and respiratory syndrome virus (PRRSV) causes substantial economic losses in the global swine industry. The current vaccine options offer limited protection against PRRSV transmission, and there are no effective commercial antivirals available. Therefore, there is an urgent need to develop new antiviral strategies that slow global PRRSV transmission., Methods: In this study, we synthesized a dicoumarol-graphene oxide quantum dot (DIC-GQD) polymer with excellent biocompatibility. This polymer was synthesized via an electrostatic adsorption method using the natural drug DIC and GQDs as raw materials., Results: Our findings demonstrated that DIC exhibits high anti-PRRSV activity by inhibiting the PRRSV replication stage. The transcriptome sequencing analysis revealed that DIC treatment stimulates genes associated with the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signalling pathway. In porcine alveolar macrophages (PAMs), DIC-GQDs induce TYK2, JAK1, STAT1, and STAT2 phosphorylation, leading to the upregulation of JAK1, STAT1, STAT2, interferon-β (IFN-β) and interferon-stimulated genes (ISGs). Animal challenge experiments further confirmed that DIC-GQDs effectively alleviated clinical symptoms and pathological reactions in the lungs, spleen, and lymph nodes of PRRSV-infected pigs., Discussion: These findings suggest that DIC-GQDs significantly inhibits PRRSV proliferation by activating the JAK/STAT signalling pathway. Therefore, DIC-GQDs hold promise as an alternative treatment for PRRSV infection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, Wang, Wang, Zhao, Hou, Wang, Dong, Zhou, Gao, Yao, Li and Liu.)

A major barrier to the impact of genomic diagnosis in patients with congenital malformations is the lack of understanding regarding how sequence variants contribute to disease pathogenesis and whether this information could be used to generate patient-specific therapies. Congenital diaphragmatic hernia (CDH) is among the most common and severe of all structural malformations; however, its underlying mechanisms are unclear. We identified loss-of-function sequence variants in the epigenomic regulator gene SIN3A in two patients with complex CDH. Tissue-specific deletion of Sin3a in mice resulted in defects in diaphragm development, lung hypoplasia, and pulmonary hypertension, the cardinal features of CDH and major causes of CDH-associated mortality. Loss of SIN3A in the lung mesenchyme resulted in reduced cellular differentiation, impaired cell proliferation, and increased DNA damage. Treatment of embryonic Sin3a mutant mice with anacardic acid, an inhibitor of histone acetyltransferase, reduced DNA damage, increased cell proliferation and differentiation, improved lung and pulmonary vascular development, and reduced pulmonary hypertension. These findings demonstrate that restoring the balance of histone acetylation can improve lung development in the Sin3a mouse model of CDH.

Background: Thrombosis is a serious condition in children and neonates. However, the risk factors for thrombosis have not been conclusively determined. This study aimed to identify the risk factors for thrombosis in children and neonates in Intensive Care Unit (ICU) through a meta-analysis to better guide clinical treatment., Methods: A systematic search of electronic databases (PubMed, Embase, Cochrane Library, WOS, CNKI, Wanfang, VIP) was conducted to retrieve studies from creation on 23 May 2022. Data on the year of publication, study design, country of origin, number of patients/controls, ethnicity, and type of thrombus were extracted. The publication bias and heterogeneity between studies were assessed, and pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using fixed or random effects models., Results: A total of 18 studies met the inclusion criteria. The incidence of thrombosis in children was 2% per year (95% CI 1%-2%, P < 0.01). Infection and sepsis (OR = 1.95, P < 0.01), CVC (OR = 3.66, [95%CL 1.78-7.51], P < 0.01), mechanical ventilation (OR = 2.1, [95%CL1.47-3.01], P < 0.01), surgery (OR = 2.25, [95%CL1.2-4.22], P < 0.01), respiratory distress (OR = 1.39, [95%CL0.42-4.63], P < 0.01), ethnicities (OR = 0.88, [95%CL 0.79-0.98], P = 0.78), gestational age (OR = 1.5, [95%CL1.34-1.68], P = 0.65)were identified as risk factors for thrombosis., Conclusions: This meta-analysis suggests that CVC, Surgery, mechanical ventilation, Infection/sepsis, gestational age, Respiratory distress, and different ethnicities are risk factors for thrombosis in children and neonates in ICU. These findings may help clinicians to identify high-risk patients and develop appropriate prevention strategies., Trial Registration: PROSPERO (CRD 42022333449)., (© 2023. The Author(s).)

In this study, Lactiplantibacillus plantarum ATCC14917 was used to ferment Ganoderma lucidum spore powder. Two polysaccharides were purified from unfermented (GLP) and fermented (FGLP) Ganoderma lucidum spore powder. The chemical structure and antioxidant activity of the polysaccharides were studied. Finally, the effect of GLP and FGLP on the oxidative stress regulation pathway in HepG2 cells was explored. The results showed that the main structural characteristics of Ganoderma lucidum polysaccharides remained unchanged during the fermentation. However, the average molecular weight ( M w ) of Ganoderma lucidum polysaccharides decreased from 1.12 × 10 5  Da to 0.89 × 10 5  Da. Besides this, the contents of mannose, galactose, and glucuronic acid increased, while the contents of xylose and glucose were decreased. In addition, the content of uronic acid was raised, and the apparent structure was changed from smooth and hard to porous and loose. In antioxidant studies, intracellular ROS and MDA contents in the oxidative stress model were decreased, and T -AOC content was increased under GLP and FGLP intervention. In the investigation of the regulation pathway, Nrf-1 gene expression was up-regulated, and Keap1 gene expression was down-regulated under GLP and FGLP intervention. The antioxidant genes NQO1 and NO-1 expressions were increased to activate the activities of antioxidant enzymes CAT, SOD and GSH-PA to resist oxidative stress. Compared with GLP, FGLP has a stronger regulatory role in this pathway, thus showing more potent antioxidant activity. This experiment is beneficial to the further utilization of Ganoderma lucidum spore powder., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

Medical image segmentation is fundamental and essential for the analysis of medical images. Although prevalent success has been achieved by convolutional neural networks (CNN), challenges are encountered in the domain of medical image analysis by two aspects: 1) lack of discriminative features to handle similar textures of distinct structures and 2) lack of selective features for potential blurred boundaries in medical images. In this paper, we extend the concept of contrastive learning (CL) to the segmentation task to learn more discriminative representation. Specifically, we propose a novel patch-dragsaw contrastive regularization (PDCR) to perform patch-level tugging and repulsing. In addition, a new structure, namely uncertainty-aware feature re- weighting block (UAFR), is designed to address the potential high uncertainty regions in the feature maps and serves as a better feature re- weighting. Our proposed method achieves state-of-the-art results across 8 public datasets from 6 domains. Besides, the method also demonstrates robustness in the limited-data scenario. The code is publicly available at https://github.com/lzh19961031/PDCR&#95;UAFR-MIShttps://github.com/lzh19961031/PDCR&#95;UAFR-MIS.

Mallotus paniculatus (Lam.) Müll. Arg. 1865 ( Euphorbiaceae ) is a shrub or small tree with medicinal properties that is distributed across Southeast Asia. In this study, we sequenced the complete chloroplast genome of M. paniculatus to study phylogenetic relationships within the family Euphorbiaceae Juss. The complete chloroplast genome of M. paniculatus was 164,455 bp in length, with an overall GC content of 35.3%. It was found to consist of a long single copy region of 89,021 bp, a small single copy region of 18,524 bp, and a pair of inverted repeats of 28,455 bp. Results indicated that the chloroplast genome contains a total of 131 genes, including 78 protein-coding genes, 37 tRNA genes, eight rRNA genes, and eight pseudogenes. The phylogenetic tree showed that M. paniculatus is closely related to Mallotus japonicus and Mallotus peltatus ., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Deletion and mutation of the Smad4 gene are favorable events for the progression of colon cancer, which is related to the negative regulation of vascular endothelial growth factor C (VEGF-C). However, the regulatory mechanism between Smad4 and VEGF-C remains unclear. We reported first that Smad4 can increase the transcription of miR-128-3p, a microRNA targeting VEGF-C mRNA, resulting in a negative correlation between Smad4 and VEGF-C. Moreover, we found that Smad4 combined with Smad3 can positively regulate VEGF-C during colon cancer metastasis through binding to VEGF-C gene promoter. Further, results revealed a mechanism that long noncoding RNA (lncRNA) ASLNC07322 increased specifically in metastatic colon cancer and decreased miR-128-3p as a sponge, leading to a subsequent elevation of VEGF-C. In a word, there are two pathways in the progression of colon cancer, including Smad4/miR-128-3p/VEGF-C and Smad4/VEGF-C pathways in non-metastatic and metastatic colon cancer, respectively. ASLNC07322 crucially controlled this negative and positive regulatory transformation between them. Additionally, ASLNC07322 knockdown combined with Smad4 overexpression could efficiently inhibit lymphatic endothelial cells (LECs) proliferation and tube formation in vitro, as well as tumor growth and lymphangiogenesis in vivo. These data explained the underlying mechanism of Smad4 contribution on VEGF-C expression during metastasis where ASLNC07322 functions vitally as a switch in colon cancer., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Asthma remains an important cause of morbidity and mortality with an incidence that continues to rise. Despite the importance of this disease, the mechanisms by which the host develops allergic airways disease remain poorly understood. The development of allergic airways disease appears to be contingent on activation of both the innate and adaptive immune system, but little is known about the cross-talk between these two systems. The extracellular matrix protein mindin (Spondin 2) has been previously demonstrated to have functional roles in both the innate and adaptive immunological responses. Previous work supports that pulmonary challenge with fungal-associated allergenic proteinase (FAP) induces an innate allergic response. We hypothesized that mindin would modify the biological response to FAP. Saline or FAP was administered by oropharyngeal aspiration to C57BL/6 wild type or mindin-null mice every 4 days for a total of five exposures. FAP exposed C57BL/6 mice developed enhanced airway hyperresponsiveness (AHR) to methacholine challenge and increased neutrophils and eosinophils in the bronchoalveolar lavage as compared to saline exposed controls. These responses were significantly reduced in mindin-null mice exposed to FAP. FAP challenge was associated with a broad induction of cytokines (IL-1β, TNFα, Th1, Th2, and IL-17), chemokines, and growth factors, which were reduced in mindin-null mice exposed to FAP. RNA expression in lung monocytes for representative M1 and M2 activation markers were increased by FAP, but were independent of mindin. Our observations support that challenge with FAP results in activation of both innate and adaptive immune signaling pathways in a manner partially dependent on mindin. These findings suggest a potential role for the extracellular matrix protein mindin in cross-talk between the innate and adaptive immune systems.

Bullous pemphigoid (BP) is an autoimmune skin-blistering disease characterized by the presence of autoantibodies against the hemidesmosomal proteins BP230 and BP180. In the IgG passive transfer mouse model of BP, subepidermal blistering is triggered by anti-BP180 antibodies and depends on the complement system, mast cell (MC) degranulation, and neutrophil infiltration. In this study, we have identified the signaling events that connect the activation of the complement system and MC degranulation. We found that mice deficient in MCs or the C5a receptor (C5aR) injected with pathogenic anti-BP180 IgG failed to develop subepidermal blisters and exhibited a drastic reduction in p38 MAPK phosphorylation compared with WT mice. Local reconstitution with MCs from WT but not C5aR-deficient mice restored high levels of p38 MAPK phosphorylation and subepidermal blistering in MC-deficient mice. Local injection of recombinant C5a induced phosphorylation of p38 MAPK in WT but not MC-deficient mice. Cultured mouse MCs treated with recombinant C5a exhibited a significant increase in p38 MAPK phosphorylation and MC degranulation. Taken together, these data demonstrate that C5a interacts with C5aR on MCs and that this C5a-C5aR interaction triggers activation of the p38 MAPK pathway, subsequent MC degranulation, and ultimately BP blistering.

Ozone is a common urban environmental air pollutant and significantly contributes to hospitalizations for respiratory illness. The mechanisms, which regulate ozone-induced bronchoconstriction, remain poorly understood. Hyaluronan was recently shown to play a central role in the response to noninfectious lung injury. Therefore, we hypothesized that hyaluronan contributes to airway hyperreactivity (AHR) after exposure to ambient ozone. Using an established model of ozone-induced airways disease, we characterized the role of hyaluronan in airway hyperresponsiveness. The role of hyaluronan in response to ozone was determined by using therapeutic blockade, genetically modified animals, and direct challenge to hyaluronan. Ozone-exposed mice demonstrate enhanced AHR associated with elevated hyaluronan levels in the lavage fluid. Mice deficient in either CD44 (the major receptor for hyaluronan) or inter-alpha-trypsin inhibitor (molecule that facilitates hyaluronan binding) show similar elevations in hyaluronan but are protected from ozone-induced AHR. Mice pretreated with hyaluronan-binding peptide are protected from the development of ozone-induced AHR. Overexpression of hyaluronan enhances the airway response to ozone. Intratracheal instillation of endotoxin-free low molecular weight hyaluronan induces AHR dependent on CD44, whereas instillation of high molecular weight hyaluronan protects against ozone-induced AHR. In conclusion, we demonstrate that hyaluronan mediates ozone-induced AHR, which is dependent on the fragment size and both CD44 and inter-alpha-trypsin inhibitor. These data support the conclusion that pulmonary matrix can contribute to the development of airway hyperresponsiveness.

Objective: To investigate the role of extracellular signal-regulated kinase (ERK) 1/2 and Elk1 in pulmonary disease induced by crocidolite asbestos fiber., Method: Western blotting and Immunoprecipitation were used to detect the expression of phosphorylated ERK1/2 and Elk1 in human bronchial airway A549 cell line stimulated by crocidolite., Results: The expression of phosphorylated ERK1/2 and Elk1 were striking higher than those of the control, the differences were significant (P < 0.05)., Conclusion: Phosphorylated ERK1/2 and Elk1 probably involved in the process of the diseases induced by crocidolite.