Plasma sCD146 is a potential biomarker for acute exacerbation of chronic obstructive pulmonary disease.

This study examined the levels of soluble CD146 (sCD146) in plasma samples from patients with chronic obstructive pulmonary disease (COPD) and assessed the relationship between sCD146 and the severity of COPD. A total of 97 COPD patients were recruited from 20 medical centers in Jiangsu, China, including 13 stable subjects and 84 exacerbated subjects. The plasma sCD146 level in exacerbated subjects (28.77 ± 10.80 ng/mL) was significantly lower than that in stable subjects (38.84 ± 15.00 ng/mL). In the high sCD146 group, the proportion of subjects with modified Medical Research Council (mMRC) scores of 0-1 was higher, the proportion of subjects with the Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 4 was lower, and the proportion of subjects with ≥1 hospitalizations in the past year was lower. The plasma sCD146 level was negatively correlated with the COPD Assessment Test (CAT) score (r = -0.2664, p = 0.0087). Logistic regression analysis showed that sCD146 was an independent risk factor for acute exacerbation of COPD (AECOPD). Receiver operating characteristic (ROC) analysis suggested that sCD146 combined with sex, age, pulmonary function, and acute exacerbations in the past year had clinical value for the accurate identification of AECOPD, with an area under the ROC curve (AUC) of 0.908 (95% CI: 0.810-1.000, p < 0.001). In addition, there was a significant negative correlation between plasma sCD146 and S100A9 (r = -0.3939, p < 0.001).

LincR-PPP2R5C Promotes Th2 Cell Differentiation Through PPP2R5C/PP2A by Forming an RNA-DNA Triplex in Allergic Asthma.

PURPOSE: The roles and mechanisms of long noncoding RNAs (lncRNAs) in T helper 2 (Th2) differentiation from allergic asthma are poorly understood. We aimed to explore a novel lncRNA, LincR-protein phosphatase 2 regulatory subunit B' gamma (PPP2R5C), in Th2 differentiation in a mouse model of asthma. METHODS: LincR-PPP2R5C from RNA-seq data of CD4+ T cells of asthma-like mice were validated and confirmed by quantitative reverse transcription polymerase chain reaction, northern blotting, nuclear and cytoplasmic separation, and fluorescence in situ hybridization (FISH). Lentiviruses encoding LincR-PPP2R5C or shRNA were used to overexpress or silence LincR-PPP2R5C in CD4+ T cells. The interactions between LincR-PPP2R5C and PPP2R5C were explored with western blotting, chromatin isolation by RNA purification assay, and fluorescence resonance energy transfer. An ovalbumin-induced acute asthma model in knockout (KO) mice (LincR-PPP2R5C KO, CD4 conditional LincR-PPP2R5C KO) was established to explore the roles of LincR-PPP2R5C in Th2 differentiation. RESULTS: LncR-PPP2R5C was significantly higher in CD4+ T cells from asthmatic mice ex vivo and Th2 cells in vitro. The lentivirus encoding LincR-PPP2R5C suppressed Th1 differentiation; in contrast, the short hairpin RNA (shRNA) lentivirus decreased LincR-PPP2R5C and Th2 differentiation. Mechanistically, LincR-PPP2R5C deficiency suppressed the phosphatase activity of the protein phosphatase 2A (PP2A) holocomplex, resulting in a decline in Th2 differentiation. The formation of an RNA-DNA triplex between LincR-PPP2R5C and the PPP2R5C promoter enhanced PPP2R5C expression and activated PP2A. LincR-PPP2R5C KO and CD4 conditional KO decreased Th2 differentiation, airway hyperresponsiveness and inflammatory responses. CONCLUSIONS: LincR-PPP2R5C regulated PPP2R5C expression and PP2A activity by forming an RNA-DNA triplex with the PPP2R5C promoter, leading to Th2 polarization in a mouse model of acute asthma. Our data presented the first definitive evidence of lncRNAs in the regulation of Th2 cells in asthma.

CD146 deficiency aggravates chronic obstructive pulmonary disease via the increased production of S100A9 and MMP-9 in macrophages.

Chronic obstructive pulmonary disease (COPD) is a leading cause of global death. As a molecule beyond adhesion, CD146 is involved in COPD pathogenesis. However, the mechanisms of CD146 in COPD remain largely elusive. We hypothesized that CD146 regulates the production of matrix metalloproteinase-9 (MMP-9) in macrophages and thereby contributes to COPD. Here, we constructed a murine model of COPD using lipopolysaccharide (LPS) and porcine pancreatic elastase (PPE). In COPD-like mice, LPS and PPE decreased the pulmonary expression of CD146. MMP-9 expression and bioactivity were increased in CD146 knockout COPD-like mice. In vitro, LPS decreased CD146 expression in macrophages. With or without LPS challenge, CD146-defective macrophages produced more MMP-9. Transcriptome analysis based on next-generation sequencing (NGS) revealed that S100A9 regulated MMP-9 production in CD146-defective macrophages. Targeting S100A9 with paquinimod decreased lung inflammation and alleviated alveolar destruction in COPD-like mice. Collectively, our study suggests that CD146 negatively regulates MMP-9 production in macrophages via the S100A9 pathway in COPD.

Proline is increased in allergic asthma and promotes airway remodeling.

Proline and its synthesis enzyme pyrroline-5-carboxylate reductase 1 (PYCR1) are implicated in epithelial-mesenchymal transition (EMT), yet how proline and PYCR1 function in allergic asthmatic airway remodeling via EMT has not yet been addressed to our knowledge. In the present study, increased levels of plasma proline and PYCR1 were observed in patients with asthma. Similarly, proline and PYCR1 in lung tissues were high in a murine allergic asthma model induced by house dust mites (HDMs). Pycr1 knockout decreased proline in lung tissues, with reduced airway remodeling and EMT. Mechanistically, loss of Pycr1 restrained HDM-induced EMT by modulating mitochondrial fission, metabolic reprogramming, and the AKT/mTORC1 and WNT3a/ß-catenin signaling pathways in airway epithelial cells. Therapeutic inhibition of PYCR1 in wild-type mice disrupted HDM-induced airway inflammation and remodeling. Deprivation of exogenous proline relieved HDM-induced airway remodeling to some extent. Collectively, this study illuminates that proline and PYCR1 involved with airway remodeling in allergic asthma could be viable targets for asthma treatment.

Discovery of aphid-transmitted Rice tiller inhibition virus from native plants through metagenomic sequencing.

A major threat to rice production is the disease epidemics caused by insect-borne viruses that emerge and re-emerge with undefined origins. It is well known that some human viruses have zoonotic origins from wild animals. However, it remains unknown whether native plants host uncharacterized endemic viruses with spillover potential to rice (Oryza sativa) as emerging pathogens. Here, we discovered rice tiller inhibition virus (RTIV), a novel RNA virus species, from colonies of Asian wild rice (O. rufipogon) in a genetic reserve by metagenomic sequencing. We identified the specific aphid vector that is able to transmit RTIV and found that RTIV would cause low-tillering disease in rice cultivar after transmission. We further demonstrated that an infectious molecular clone of RTIV initiated systemic infection and causes low-tillering disease in an elite rice variety after Agrobacterium-mediated inoculation or stable plant transformation, and RTIV can also be transmitted from transgenic rice plant through its aphid vector to cause disease. Finally, global transcriptome analysis indicated that RTIV may disturb defense and tillering pathway to cause low tillering disease in rice cultivar. Thus, our results show that new rice viral pathogens can emerge from native habitats, and RTIV, a rare aphid-transmitted rice viral pathogen from native wild rice, can threaten the production of rice cultivar after spillover.

Fine particulate matter (PM2.5) induces inhibitory memory alveolar macrophages through the AhR/IL-33 pathway.

Fine particulate matter (PM2.5) concentrations have decreased in the past decade. The adverse effects of acute PM2.5 exposure on respiratory diseases have been well recognized. To explore the long-term effects of PM2.5 exposure on chronic obstructive pulmonary disease (COPD), mice were exposed to PM2.5 for 7 days and rest for 21 days, followed by challenges with lipopolysaccharide (LPS) and porcine pancreatic elastase (PPE). Unexpectedly, PM2.5 exposure and rest alleviated the disease severity and airway inflammatory responses in COPD-like mice. Although acute PM2.5 exposure increased airway inflammation, rest for 21 days reversed the airway inflammatory responses, which was associated with the induction of inhibitory memory alveolar macrophages (AMs). Similarly, polycyclic aromatic hydrocarbons (PAHs) in PM2.5 exposure and rest decreased pulmonary inflammation, accompanied by inhibitory memory AMs. Once AMs were depleted, pulmonary inflammation was aggravated. PAHs in PM2.5 promoted the secretion of IL-33 from airway epithelial cells via the aryl hydrocarbon receptor (AhR)/ARNT pathway. High-throughput mRNA sequencing revealed that PM2.5 exposure and rest drastically changed the mRNA profiles in AMs, which was largely rescued in IL-33-/- mice. Collectively, our results indicate that PM2.5 may mitigate pulmonary inflammation, which is mediated by inhibitory trained AMs via IL-33 production from epithelial cells through the AhR/ARNT pathway. We provide the rationale that PM2.5 plays complicated roles in respiratory disease.

Whole genome resequencing identifies local adaptation associated with environmental variation for redband trout.

Aquatic ectotherms are predicted to harbour genomic signals of local adaptation resulting from selective pressures driven by the strong influence of climate conditions on body temperature. We investigated local adaptation in redband trout (Oncorhynchus mykiss gairdneri) using genome scans for 547 samples from 11 populations across a wide range of habitats and thermal gradients in the interior Columbia River. We estimated allele frequencies for millions of single nucleotide polymorphism loci (SNPs) across populations using low-coverage whole genome resequencing, and used population structure outlier analyses to identify genomic regions under divergent selection between populations. Twelve genomic regions showed signatures of local adaptation, including two regions associated with genes known to influence migration and developmental timing in salmonids (GREB1L, ROCK1, SIX6). Genotype-environment association analyses indicated that diurnal temperature variation was a strong driver of local adaptation, with signatures of selection driven primarily by divergence of two populations in the northern extreme of the subspecies range. We also found evidence for adaptive differences between high-elevation desert vs. montane habitats at a smaller geographical scale. Finally, we estimated vulnerability of redband trout to future climate change using ecological niche modelling and genetic offset analyses under two climate change scenarios. These analyses predicted substantial habitat loss and strong genetic shifts necessary for adaptation to future habitats, with the greatest vulnerability predicted for high-elevation desert populations. Our results provide new insight into the complexity of local adaptation in salmonids, and important predictions regarding future responses of redband trout to climate change.

Exosomes in malignant pleural effusion from lung cancer patients impaired the cytotoxicity of double-negative T cells.

CD3+CD4-CD8- double-negative T (DNT) cells are new weapons in cancer immunotherapy. Here, we explored DNT cells in malignant pleural effusions (MPEs) from lung cancer patients. DNT cells, especially TCRαß+CD56- DNT cells, were increased in MPE from lung cancer patients. DNT cells highly expressed PD-1, TRAIL, NKG2D and DNAM-1. In contrast, FasL was barely detected in DNT cells. Compared with non-MPE cells, MPE-derived DNT cells expressed much higher levels of PD-1 and TRAIL. DNT cells from healthy peripheral blood donors potentially killed lung cancers, which was decreased by MPE supernatant. Exosomes from MPE supernatant expressed PD-1 and CEACAM1 and impaired the cytotoxicity of DNT cells. Blocking PD-1 and TIM3 rescued the cytotoxicity of DNT cells treated with MPE-derived exosomes. Overall, we demonstrated that the frequency of DNT cells in MPE from lung cancer patients was increased and that MPE-derived exosomes impaired the cytotoxicity of DNT cells via the PD-1/PD-L1 and CEACAM1/TIM3 pathways.

Picture book reading on the development of preschoolers in rural areas of China: Effects on language, inhibition, and theory of mind.

Studies have shown that book reading intervention may scaffold children's language development. However, whether book reading interventions are equally effective for children's cognitive development in a Chinese rural school setting remains to be explored. We conducted a four-month book reading intervention to address these issues in rural Chinese areas. A total of three hundred twenty-one children aged between 2.56 and 6.47 years (M = 4.66 ages, SD = 0.80) were assigned to three groups as follows: (a) control group without donated picture books; (b) active reading control group with donated picture books; and (c) intervention group with a 4-month instructed picture book reading intervention. The findings indicate that the available books could produce significant positive changes in the development of receptive language (F (1,191) = 14.46, p < 0.01) and inhibitory control (F (1,190) = 7.64, p = 0.01) of rural children. However, a 4-month intervention was noneffective at boosting participants' performance on these tasks (F (1,203) = 0.07~2.73, p > 0.10). The results discussed the possible explanations, implications for behavioral intervention researchers, and suggestions for social service organizations or public institutions.

KIF2A decreases IL-33 production and attenuates allergic asthmatic inflammation.

BACKGROUND: The microtubule-dependent molecular motor protein Kinesin Family Member 2A (KIF2A) is down-regulated in asthmatic human airway epithelium. However, little is known about the roles of KIF2A as well as the possible underlying mechanisms in asthma. METHODS: House dust mite (HDM) extract was administered to establish a murine model of asthma. The expression of KIF2A, IL-33 and the autophagy pathways were detected. The plasmid pCMV-KIF2A was used to overexpress KIF2A in the airway epithelial cells in vitro and in vivo. IL-4, IL-5, IL-33 and other cytokines in bronchoalveolar lavage fluid (BALF) and lung tissues homogenates were measured. RESULTS: In response to the challenge of house dust mite (HDM) in vitro and in vivo, airway epithelial cells displayed decreased production of KIF2A. Meanwhile, autophagy and IL-33 were increased in HMD-treated epithelial cells. Mechanistically, KIF2A decreased autophagy via suppressing mTORC1 pathway in HDM-treated epithelial cells, which contributed to the reduced production of IL-33. Moreover, in vivo KIF2A transfection reduced IL-33 and autophagy in the lung, leading to the attenuation of allergic asthma. CONCLUSION: KIF2A suppressed mTORC1-mediated autophagy and decreased the production of epithelial-derived cytokine IL-33 in allergic airway inflammation. These data indicate that KIF2A may be a novel target in allergic asthma.

Chloroquine Attenuates Asthma Development by Restoring Airway Smooth Muscle Cell Phenotype Via the ROS-AKT Pathway.

Switching of airway smooth muscle (ASM) cell phenotype from differentiated-contractile to dedifferentiated-proliferative/synthetic state often occurs in asthmatic subjects with airway dysfunction. Evidence has been provided that chloroquine (an agonist of bitter taste receptors) presented benefits to ASM cell function implicated in asthma. However, the underlying mechanism is unclear. House dust mite (HDM)-sensitized mice were administered with chloroquine or dexamethasone before challenge. BALF and lung tissue were obtained for cell counting, histological analysis or ELISA. Primary cultured ASM cells were stimulated with transforming growth factor (TGF)-ß1 or H2O2. Cells and supernatant were collected for the detection of ASM phenotype, ROS level, and proinflammatory cytokine production. In HDM-sensitized mice, chloroquine attenuated airway hyperresponsiveness (AHR), inflammation and remodeling with an inhibition of immunoglobulin E, IL-4/-13, and TGF-ß1 in BALF. ASM cell proliferation (PCNA), hypertrophy (α-SMA), and parasecretion (MMP-9 and MMP-13) were strongly suppressed by chloroquine, hinting the rebalance of the heterogeneous ASM populations in asthmatic airway. Our data in vitro indicated that chloroquine markedly restrained maladaptive alteration in ASM phenotype in concert with a remission of ROS. Using H2O2 and PI3K inhibitor (LY294002), we found that the inhibition of oxidative stress level and ROS-AKT signal by chloroquine may serve as a potential mechanism that dedicates to the restoration of the phenotypic imbalance in ASM cells. Overall, the present findings suggested that chloroquine improves asthmatic airway function by controlling ASM cell phenotype shift, sketching a novel profile of chloroquine as a new therapeutic candidate for airway remodeling.

Applying genomics in assisted migration under climate change: Framework, empirical applications, and case studies.

The rate of global climate change is projected to outpace the ability of many natural populations and species to adapt. Assisted migration (AM), which is defined as the managed movement of climate-adapted individuals within or outside the species ranges, is a conservation option to improve species' adaptive capacity and facilitate persistence. Although conservation biologists have long been using genetic tools to increase or maintain diversity of natural populations, genomic techniques could add extra benefit in AM that include selectively neutral and adaptive regions of the genome. In this review, we first propose a framework along with detailed procedures to aid collaboration among scientists, agencies, and local and regional managers during the decision-making process of genomics-guided AM. We then summarize the genomic approaches for applying AM, followed by a literature search of existing incorporation of genomics in AM across taxa. Our literature search initially identified 729 publications, but after filtering returned only 50 empirical studies that were either directly applied or considered genomics in AM related to climate change across taxa of plants, terrestrial animals, and aquatic animals; 42 studies were in plants. This demonstrated limited application of genomic methods in AM in organisms other than plants, so we provide further case studies as two examples to demonstrate the negative impact of climate change on non-model species and how genomics could be applied in AM. With the rapidly developing sequencing technology and accumulating genomic data, we expect to see more successful applications of genomics in AM, and more broadly, in the conservation of biodiversity.

IL-33/ST2 axis deficiency exacerbates neutrophil-dominant allergic airway inflammation.

OBJECTIVE: The IL-33/ST2 axis has been extensively investigated in type 2 eosinophilic inflammation. Here, we aimed to investigate the role of the IL-33/ST2 axis in neutrophil-dominant allergic airway inflammation. METHODS: House-dust mite (HDM) extract and lipopolysaccharide (LPS) were administered to establish a murine model of neutrophil-dominant allergic airway inflammation. The formation of neutrophilic extracellular traps (NETs) in the lung tissues was demonstrated by immunofluorescence imaging. Mature IL-33 in bronchoalveolar lavage fluid (BALF) was detected by Western blotting. The neutrophilic chemokine KC produced by bone marrow-derived macrophages (BMDMs) or primary alveolar epithelial cells was measured with a commercial ELISA kit. RESULTS: In the present study, we observed neutrophilic inflammation and tight junction damage in the lungs of mice sensitised with HDM and LPS. Furthermore, sensitisation with HDM and LPS resulted in the formation of NETs, accompanied by increased levels of mature IL-33 in the BALF. Moreover, LPS damaged the epithelial tight junction protein occludin directly or indirectly by inducing NET formation. Surprisingly, IL-33 deficiency augmented neutrophilia and epithelial barrier injury in the lungs of mice after sensitisation with HDM and LPS. Similarly, the absence of ST2 exacerbated the neutrophilic inflammatory response, decreased the expression of occludin and exacerbated the severity of neutrophil-dominant allergic airway inflammation in an HDM/LPS-induced mouse model. Mechanistically, BMDMs and alveolar epithelial cells from IL-33- or ST2-deficient mice tended to produce higher levels of the neutrophilic chemokine KC. CONCLUSIONS: These results demonstrated that the IL-33/ST2 axis may play a protective role in neutrophil-dominant allergic airway inflammation.

Whole genome resequencing reveals genomic regions associated with thermal adaptation in redband trout.

Adaptation to local environments involves evolution of ecologically important traits and underlying physiological processes. Here, we used low coverage whole-genome resequencing (lcWGR) on individuals to identify genome regions involved in thermal adaptation in wild redband trout Oncorhynchus mykiss gairdneri, a subspecies of rainbow trout that inhabits ecosystems ranging from cold montane forests to high elevation deserts. This study includes allele frequency-based analyses for selective sweeps among populations, followed by multiple association tests for specific sets of phenotypes measured under thermal stress (acute and chronic survival/mortality; high or low cardiac performance groups). Depending on the groups in each set of analyses, sequencing reads covered 43%-75% of the genome at ≥15× and each analysis included millions of SNPs across the genome. In tests for selective sweeps among populations, a total of six chromosomal regions were significant. The further association tests for specific phenotypes revealed that the region on chromosome 4 was consistently the most significant and contains the cerk gene (ceramide kinase). This study provides insight into a potential genetic mechanism of local thermal adaptation and suggests cerk may be an important candidate gene. However, further validation of this cerk gene is necessary to determine if the association with cardiac performance results in a functional role to influence thermal performance when exposed to high water temperatures and hypoxic conditions.

Epithelial-Mesenchymal Transition in Asthma Airway Remodeling Is Regulated by the IL-33/CD146 Axis.

Epithelial-mesenchymal transition (EMT) is essential in asthma airway remodeling. IL-33 from epithelial cells is involved in pulmonary fibrosis. CD146 has been extensively explored in cancer-associated EMT. Whether IL-33 regulates CD146 in the EMT process associated with asthma airway remodeling is still largely unknown. We hypothesized that EMT in airway remodeling was regulated by the IL-33/CD146 axis. House dust mite (HDM) extract increased the expression of IL-33 and CD146 in epithelial cells. Increased expression of CD146 in HDM-treated epithelial cells could be blocked with an ST2-neutralizing antibody. Moreover, HDM-induced EMT was dependent on the CD146 and TGF-ß/SMAD-3 signaling pathways. IL-33 deficiency decreased CD146 expression and alleviated asthma severity. Similarly, CD146 deficiency mitigated EMT and airway remodeling in a murine model of chronic allergic airway inflammation. Furthermore, CD146 expression was significantly elevated in asthma patients. We concluded that IL-33 from HDM extract-treated alveolar epithelial cells stimulated CD146 expression, promoting EMT in airway remodeling in chronic allergic inflammation.

DNA Geminivirus Infection Induces an Imprinted E3 Ligase Gene to Epigenetically Activate Viral Gene Transcription.

Flowering plants and mammals contain imprinted genes that are primarily expressed in the endosperm and placenta in a parent-of-origin manner. In this study, we show that early activation of the geminivirus genes C2 and C3 in Arabidopsis (Arabidopsis thaliana) plants, encoding a viral suppressor of RNA interference and a replication enhancer protein, respectively, is correlated with the transient vegetative expression of VARIANT IN METHYLATION5 (VIM5), an endosperm imprinted gene that is conserved in diverse plant species. VIM5 is a ubiquitin E3 ligase that directly targets the DNA methyltransferases MET1 and CMT3 for degradation by the ubiquitin-26S proteasome proteolytic pathway. Infection with Beet severe curly top virus induced VIM5 expression in rosette leaf tissues, possibly via the expression of the viral replication initiator protein, leading to the early activation of C2 and C3 coupled with reduced symmetric methylation in the C2-3 promoter and the onset of disease symptoms. These findings demonstrate how this small DNA virus recruits a host imprinted gene for the epigenetic activation of viral gene transcription. Our findings reveal a distinct strategy used by plant pathogens to exploit the host machinery in order to inhibit methylation-mediated defense responses when establishing infection.

JAcked Responses Go Viral: Hormonal Regulation of Antiviral RNAi.

Little is known about the mechanism that regulates the core steps of antiviral RNA interference (RNAi) pathway in plants and animals. In this issue of Cell Host & Microbe, Yang et al. (2020) provide compelling evidence for the regulation of antiviral RNAi by the jasmonate hormone signaling in plants.

MiR-1165-3p Suppresses Th2 Differentiation via Targeting IL-13 and PPM1A in a Mouse Model of Allergic Airway Inflammation.

PURPOSE: CD4⁺T cells are essential in the pathogenesis of allergic asthma. We have previously demonstrated that microRNA-1165-3p (miR-1165-3p) was significantly reduced in T-helper type (Th) 2 cells and that miR-1165-3p was a surrogate marker for atopic asthma. Little is known about the mechanisms of miR-1165-3p in the regulation of Th2-dominated allergic inflammation. We aimed to investigate the associations between Th2 differentiation and miR-1165b-3p in asthma as well as the possible mechanisms. METHODS: CD4⁺ naïve T cells were differentiated into Th1 or Th2 cells in vitro. MiR-1165-3p was up-regulated or down-regulated using lentiviral systems during Th1/Th2 differentiation. In vivo, the lentiviral particles with the miR-1165-3p enhancer were administered by tail vein injection on the first day of a house dust mite -induced allergic airway inflammation model. Allergic inflammation and Th1/Th2 differentiation were routinely monitored. To investigate the potential targets of miR-1165-3p, biotin-microRNA pull-down products were sequenced, and the candidates were further verified with a dual-luciferase reporter assay. The roles of a target protein phosphatase, Mg2+/Mn2+-dependent 1A (PPM1A), in Th2 cell differentiation and allergic asthma were further explored. Plasma PPM1A was determined by ELISA in 18 subjects with asthma and 20 controls. RESULTS: The lentivirus encoding miR-1165-3p suppressed Th2-cell differentiation in vitro. In contrast, miR-1165-3p silencing promoted Th2-cell development. In the HDM-induced model of allergic airway inflammation, miR-1165-3p up-regulation was accompanied by reduced airway hyper-responsiveness, serum immunoglobulin E, airway inflammation and Th2-cell polarization. IL-13 and PPM1A were the direct targets of miR-1165-3p. The expression of IL-13 or PPM1A was inversely correlated with that of miR-1165-3p. PPM1A regulated the signal transducer and activator of transcription and AKT signaling pathways during Th2 differentiation. Moreover, plasma PPM1A was significantly increased in asthmatic patients. CONCLUSIONS: MiR-1165-3p negatively may regulate Th2-cell differentiation by targeting IL-13 and PPM1A in allergic airway inflammation.

Airway invasive aspergillosis with organizing pneumonia: a case report and review of literature.

Organizing pneumonia (OP) is a distinct clinical and pathologic entity. This condition can be cryptogenic (COP) or secondary to other known causes (secondary OP, SOP). Concomitant occurrence of invasive pulmonary aspergillosis (IPA) with SOP is unusual. Here, we report a case where SOP was a presenting feature in a patient with diagnosed IPA. A previously healthy 62-year-old man presented to the hospital with a month of intermittent fever accompanied by cough and expectoration. According to computed tomography (CT), sputum culture, and transbronchial lung biopsy, he was diagnosed as IPA. Despite undergoing voriconazole and dexamethasone therapy, the patient's condition did not improve after three weeks of therapy. CT-guided percutaneous lung biopsy performed in the left upper lung showed invasive airway aspergillosis with organizing pneumonia. Two months after the combination therapy of voriconazole and methylprednisolone, the CT scan indicated the pulmonary consolidations were almost entirely resolved. To the best of our knowledge, this is the first case of successful non-surgical treatment of IPA with SOP. In a review of the literature, we aimed to highlight the possibility of invasive airway aspergillosis concurrent with secondary organizing pneumonia. Physicians should be aware of the possibility of SOP in the case of IPA.

Fine Particulate Matter (PM2.5) Promotes CD146 Expression in Alveolar Epithelial Cells and Cryptococcus neoformans Pulmonary Infection.

Air pollution is a leading cause of increasing infectious lung diseases. Pulmonary cryptococcosis is a fatal fungal pneumonia in acquired immunodeficiency syndrome patients. In some cases, the pathogen Cryptococcus neoformans also develops dormant nodules in immunocompetent individuals. In the present study, we demonstrated that fine particulate matter (PM2.5) increased CD146 expression in alveolar epithelial cells and promoted C. neoformans pulmonary infection. Aryl hydrocarbon receptor (AhR) signaling was required for increased expression of CD146 in epithelial cells treated with PM2.5. In a murine model of pulmonary infection, PM2.5 promoted fungal infection, and CD146 deficiency decreased the fugal burden of C. neoformans. Our study may highlight the importance of air pollution to lung mycosis and CD146 as a target for preventing infectious lung diseases.