3D Conjugated Hole Transporting Materials for Efficient and Stable Perovskite Solar Cells and Modules.

The orthogonal structure of the widely used hole transporting material (HTM) 2,2',7,7'-tetrakis(N, N-di-p-methoxyphenylamino)-9,9'-spirobifluorene (Spiro-OMeTAD) imparts isotropic conductivity and excellent film-forming capability. However, inherently weak intra- and inter-molecular π-π interactions result in low intrinsic hole mobility. Herein, a novel HTM, termed FTPE-ST, with a twist conjugated dibenzo(g,p)chrysene core and coplanar 3,4-ethylenedioxythiophene (EDOT) as extended donor units, is designed to enhance π-π interactions, without compromising on solubility. The three-dimensional (3D) configuration provides the material multi-direction charge transport as well as excellent solubility even in 2-methylanisole, and its large conjugated backbone endows the HTM with a high hole mobility. Moreover, the sulfur donors in EDOT units coordinate with lead ions on the perovskite surface, leading to stronger interfacial interactions and the suppression of defects at the perovskite/HTM interface. As a result, perovskite solar cells (PSCs) employing FTPE-ST achieve a champion power conversion efficiency (PCE) of 25.21% with excellent long-time stability, one of the highest PCEs for non-spiro HTMs in n-i-p PSCs. In addition, the excellent film-forming capacity of the HTM enables the fabrication of FTPE-ST-based large-scale PSCs (1.0 cm2) and modules (29.0 cm2), which achieve PCEs of 24.21% (certificated 24.17%) and 21.27%, respectively.

A Multifunctional Dye Molecule as the Interfacial Layer for Perovskite Solar Cells.

In perovskite solar cells (PSCs), defects in the interface and mismatched energy levels can damage the device performance. Improving the interface quality is an effective way to achieve efficient and stable PSCs. In this work, a multifunctional dye molecule, named ThPCyAc, was designed and synthesized to be introduced in the perovskite/HTM interface. On one hand, various functional groups on the acceptor unit can act as Lewis base to reduce defect density and suppress nonradiative combinations. On the other hand, the stepwise energy-level alignment caused by ThPCyAc decreases the accumulation of interface carriers for facilitating charge extraction and transmission. Therefore, based on the ThPCyAc molecule, the devices exhibit elevated open-circuit voltage and fill factor, resulting in the best power conversion efficiency (PCE) of 23.16%, outperforming the control sample lacking the interface layer (PCE = 21.49%). Excitingly, when attempting to apply it as a self-assembled layer in inverted devices, ThPCyAc still exhibits attractive behavior. It is worth noting that these results indicate that dye molecules have great potential in developing multifunctional interface materials to obtain higher-performance PSCs.

Dopant-Free Pyrene-Based Hole Transporting Material Enables Efficient and Stable Perovskite Solar Cells.

Dopant-free hole transporting materials (HTMs) is significant to the stability of perovskite solar cells (PSCs). Here, we developed a novel star-shape arylamine HTM, termed Py-DB, with a pyrene core and carbon-carbon double bonds as the bridge units. Compared to the reference HTM (termed Py-C), the extension of the planar conjugation backbone endows Py-DB with typical intermolecular π-π stacking interactions and excellent solubility, resulting in improved hole mobility and film morphology. In addition, the lower HOMO energy level of the Py-DB HTM provides efficient hole extraction with reduced energy loss at the perovskite/HTM interface. Consequently, an impressive power conversion efficiency (PCE) of 24.33 % was achieved for dopant-free Py-DB-based PSCs, which is the highest PCE for dopant-free small molecular HTMs in n-i-p configured PSCs. The dopant-free Py-DB-based device also exhibits improved long-term stability, retaining over 90 % of its initial efficiency after 1000 h exposure to 25 % humidity at 60 °C. These findings provide valuable insights and approaches for the further development of dopant-free HTMs for efficient and reliable PSCs.

Tuft cells are required for a rhinovirus-induced asthma phenotype in immature mice.

Infection of immature mice with rhinovirus (RV) induces an asthma-like phenotype consisting of type 2 inflammation, mucous metaplasia, eosinophilic inflammation, and airway hyperresponsiveness that is dependent on IL-25 and type 2 innate lymphoid cells (ILC2s). Doublecortin-like kinase 1-positive (DCLK1+) tuft cells are a major source of IL-25. We sought to determine the requirement of tuft cells for the RV-induced asthma phenotype in wild-type mice and mice deficient in Pou2f3, a transcription factor required for tuft cell development. C57BL/6J mice infected with RV-A1B on day 6 of life and RV-A2 on day 13 of life showed increased DCLK1+ tuft cells in the large airways. Compared with wild-type mice, RV-infected Pou2f3-/- mice showed reductions in IL-25 mRNA and protein expression, ILC2 expansion, type 2 cytokine expression, mucous metaplasia, lung eosinophils, and airway methacholine responsiveness. We conclude that airway tuft cells are required for the asthma phenotype observed in immature mice undergoing repeated RV infections. Furthermore, RV-induced tuft cell development provides a mechanism by which early-life viral infections could potentiate type 2 inflammatory responses to future infections.

Suppression of TRIM19 by arterivirus nonstructural protein 1 promotes viral replication.

Tripartite motif (TRIM)-containing proteins are a family of regulatory proteins that can participate in the induction of antiviral cytokines and antagonize viral replication. Promyelocytic leukemia (PML) protein is known as TRIM19 and is a major scaffold protein organizing the PML nuclear bodies (NBs). PML NBs are membrane-less organelles in the nucleus and play a diverse role in maintaining cellular homeostasis including antiviral response. Porcine reproductive and respiratory syndrome virus (PRRSV), a member virus of the family Arteriviridae, inhibits type I interferon (IFN) response during infection, and nonstructural protein 1 (nsp1) of the virus has been identified as a potent IFN antagonist. We report that the numbers of PML NBs per nucleus were significantly downregulated during infection of PRRSV. The overexpression of all six isoforms of PML suppressed the PRRSV replication, and conversely, the silencing of PML gene expression enhanced the PRRSV replication. The suppression of PML NBs by the nsp1 protein was common in other member viruses of the family, represented by equine arteritis virus, lactate dehydrogenase elevating virus of mice, and simian hemorrhagic fever virus. Our study unveils a conserved viral strategy in arteriviruses for innate immune evasion.

Methylene-Bridged Dimerization by Cu-Catalyzed Deconstructive C-C Cleavage of Oxacycloalkane.

Herein, we demonstrate the successful utilization of copper catalysis and oxygen oxidation for consecutive C(sp3)-C(sp3) bond cleavage in alkyl cyclic ethers. A key step involves a copper-oxygen autoxidation process, generating in situ alkoxy radicals and triggering sequential C-C bond cleavage. This ß-oxidative cleavage strategy enables the use of cyclic ethers as valuable C1 building blocks for the synthesis of bridged methylene dimers. This reaction holds promise for inspiring alternative methods targeting inert C(sp3)-C(sp3) bond cleavage.

Extending the π-Conjugated System in Spiro-Type Hole Transport Material Enhances the Efficiency and Stability of Perovskite Solar Modules.

Hole transport materials (HTMs) are a key component of perovskite solar cells (PSCs). The small molecular 2,2',7,7'-tetrakis(N,N-di-p-methoxyphenyl)-amine-9,9'-spirobifluorene (spiro-OMeTAD, termed "Spiro") is the most successful HTM used in PSCs, but its versatility is imperfect. To improve its performance, we developed a novel spiro-type HTM (termed "DP") by substituting four anisole units on Spiro with 4-methoxybiphenyl moieties. By extending the π-conjugation of Spiro in this way, the HOMO level of the HTM matches well with the perovskite valence band, enhancing hole mobility and increasing the glass transition temperature. DP-based PSC achieves high power conversion efficiencies (PCEs) of 25.24 % for small-area (0.06 cm2 ) devices and 21.86 % for modules (designated area of 27.56 cm2 ), along with the certified efficiency of 21.78 % on a designated area of 27.86 cm2 . The encapsulated DP-based devices maintain 95.1 % of the initial performance under ISOS-L-1 conditions after 2560 hours and 87 % at the ISOS-L-3 conditions over 600 hours.

Han's technique: a new reduction technique for acute anterior shoulder dislocation.

INTRODUCTION: Acute anterior shoulder dislocation (AASD) is the most common joint dislocation. Here, we introduced a new reduction technique for AASD, named "Han's technique" (or "Touch overhead technique"). METHODS: Patients diagnosed with AASD were treated with "Han's technique" in the orthopaedic department of our hospital from October 2018 to November 2020. An orthopedic surgeon performed the reduction maneuver without any anesthesia or sedation throughout the reduction process. The fundamental information and related data were recorded, including patients' age, sex, dislocation side, previous dislocations history, reduction time, number of attempts at reduction, success rate of the reduction, intensity of pain during reduction using the 10-point visual analogue scale score (VAS), any complications, with or without the fracture and neurovascular examination results. RESULTS: Forty-one patients with AASD were involved in our study. Thirty-nine cases (95%) were primary dislocation. Eleven patients (27%) were complicated with large tubercle fracture and one patient (2%) complicated with inferior glenoid fractures. All patients were successfully reduced by Han's technique with mean reduction time was 138 s. The pain score during the reduction operation is only1.83 ± 0.83 points. No neurovascular injury or iatrogenic fracture was found after reduction in all patients. CONCLUSIONS: Han's technique (or Touch overhead technique) is a simple, safe, effective, mild and easy to master which can be operated by one surgeon without anesthesia or sedation for AASD.

M2 Macrophages promote IL-33 expression, ILC2 expansion and mucous metaplasia in response to early life rhinovirus infections.

Wheezing-associated rhinovirus (RV) infections are associated with asthma development. We have shown that infection of immature mice with RV induces type 2 cytokine production and mucous metaplasia which is dependent on IL-33 and type 2 innate lymphoid cells (ILC2s) and intensified by a second heterologous RV infection. We hypothesize that M2a macrophages are required for the exaggerated inflammation and mucous metaplasia in response to heterologous RV infection. Wild-type C57Bl/6J mice and LysMCre IL4Rα KO mice lacking M2a macrophages were treated as follows: (1) sham infection on day 6 of life plus sham on day 13 of life, (2) RV-A1B on day 6 plus sham on day 13, (3) sham on day 6 and RV-A2 on day 13, or (4) RV-A1B on day 6 and RV-A2 on day 13. Lungs were harvested one or seven days after the second infection. Wild-type mice infected with RV-A1B at day 6 showed an increased number of Arg1- and Retnla-expressing lung macrophages, indicative of M2a polarization. Compared to wild-type mice infected with RV on day 6 and 13 of life, the lungs of LysMCre IL4Rα KO mice undergoing heterologous RV infection showed decreased protein abundance of the epithelial-derived innate cytokines IL-33, IL-25 and TSLP, decreased ILC2s, decreased mRNA expression of IL-13 and IL-5, and decreased PAS staining. Finally, mRNA analysis and immunofluorescence microscopy of double-infected LysMCre IL4Rα KO mice showed reduced airway epithelial cell IL-33 expression, and treatment with IL-33 restored the exaggerated muco-inflammatory phenotype. Conclusion: Early-life RV infection alters the macrophage response to subsequent heterologous infection, permitting enhanced IL-33 expression, ILC2 expansion and intensified airway inflammation and mucous metaplasia.

A N-Ethylcarbazole-Terminated Spiro-Type Hole-Transporting Material for Efficient and Stable Perovskite Solar Cells.

The development of stable and efficient hole-transporting materials (HTMs) is critical for the commercialization of perovskite solar cells (PSCs). Herein, a novel spiro-type HTM was designed and synthesized where N-ethylcarbazole-terminated groups fully substituted the methoxy group of spiro-OMeTAD, named spiro-carbazole. The developed molecule exhibited a lower highest occupied molecular orbital level, higher hole mobility, and extremely high glass transition temperature (Tg =196 °C) compared with spiro-OMeTAD. PSCs with the developed molecule exhibited a champion power conversion efficiency (PCE) of 22.01 %, which surpassed traditional spiro-OMeTAD (21.12 %). Importantly, the spiro-carbazole-based device had dramatically better thermal, humid, and long-term stability than spiro-OMeTAD.

[GAO Wei-bin's clinical experience of electric eye acupuncture and stagnant-moving needling for ophthalmopathy].

Professor GAO Wei-bin's clinical experience of electric eye acupuncture and stagnant-moving needling for ophthalmopathy was introduced. The indications of electric eye acupuncture and stagnant-moving needling include external ophtalmoplegia and visual impairment. Professor GAO has proposed new acupoints at the ocular muscles attachment of eyeball, and put forward five experience points: Shangming point, Neiming point, Xiaming point, Waiming point and Tijian point. The points are selected according to different pathological changes of ocular muscles. In the treatment of ophthalmopathy, the tendons and vessels are often regulated at the same time. Neiming point, Shangming point, Xiaming point and Qiuhou point are the main points, with Fengchi (GB 20) and Gongxue (Extra) as the matching points. In addition, attention is paid to the application of stagnant-moving needling and electroacupuncture (continuous dense wave, frequency of 50 Hz).

Qing`e Pill Inhibits Osteoblast Ferroptosis via ATM Serine/Threonine Kinase (ATM) and the PI3K/AKT Pathway in Primary Osteoporosis.

Osteoporosis (OP) is an aging-related disease that is the main etiology of fragility fracture. Qing'e Pill (QEP) is a mixture of traditional Chinese medicine (TCM) consisting of Eucommia ulmoides Oliv., Psoralea corylifolia L., Juglans regia L., and Allium sativum L. QEP has an anti-osteoporosis function, but the underlying mechanism remains unclear. In this study, online databases were employed to determine the chemical compounds of QEP and potential target genes in osteoporosis. Potential pathways associated with genes were defined by Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) databases. A compound-target-disease network was constructed. Hub genes screened through Cytoscape were intersected with the FerrDB database. The potential key genes were validated in HFOB 1.19 cells, and rat models were ovariectomized through Western blot, RT-qPCR, ELISA, HE staining, immunohistochemistry, and immunofluorescence analyses. The intersection targets of QEP and osteoporosis contained 121 proteins, whereas the target-pathway network included 156 pathways. We filtered five genes that stood out in the network analysis for experimental verification. The experiments validated that QEP exerted therapeutic effects on osteoporosis by inhibiting ferroptosis and promoting cell survival via the PI3K/AKT pathway and ATM. In conclusion, combining the application of network analysis and experimental verification may provide an efficient method to validate the molecular mechanism of QEP on osteoporosis.

The pediatric proximal ulna: a radiographic study.

INTRODUCTION: The proximal ulna has been comprehensively described in the anatomic literature and imaging studies. However, to the best of our knowledge, the anatomy of the proximal ulna in children has not been fully described in the literature. METHODS: The present study was conducted on 189 children aged between 0 and 12 years (4.7 ± 2.7) by analysis of lateral X-rays of the forearm. Proximal ulna dorsal angulation (PUDA), tip-to-apex (TTA), and total ulnar length (TUL) were measured. The correlation between age and the various X-ray measurements was recorded and then compared with gender differences and adult measurements. Three orthopedic surgeons independently examined the X-ray films and confirmed the reliability of the original observations through intra-group correlation coefficients. RESULTS: There was a strong positive correlation between age and TUL (r = 0.834), and a moderately negative correlation between age and PUDA (r = - 0.405). No significant differences were observed between different genders (p > 0.05). Compared with adults, all measurements were smaller except for PUDA, all such measurements statistically significantly different between children and adults (p < 0.05). Interobserver and intraobserver reliability were "very good" for TUL (0.81-1.00), and "good" for PUDA, TTA, and TTA% (0.61-0.80). CONCLUSIONS: Good understanding of the anatomy of the pediatric proximal ulna will help to increase the knowledge base in pediatric orthopedic surgeons allowing them to provide improved treatment of fractures. Restoration of the correct forearm anatomy should result in superior clinical and functional results.

Deficient inflammasome activation permits an exaggerated asthma phenotype in rhinovirus C-infected immature mice.

Compared to other RV species, RV-C has been associated with more severe respiratory illness and is more likely to occur in children with a history of asthma or who develop asthma. We therefore inoculated 6-day-old mice with sham, RV-A1B, or RV-C15. Inflammasome priming and activation were assessed, and selected mice treated with recombinant IL-1ß. Compared to RV-A1B infection, RV-C15 infection induced an exaggerated asthma phenotype, with increased mRNA expression of Il5, Il13, Il25, Il33, Muc5ac, Muc5b, and Clca1; increased lung lineage-negative CD25+CD127+ST2+ ILC2s; increased mucous metaplasia; and increased airway responsiveness. Lung vRNA, induction of pro-inflammatory type 1 cytokines, and inflammasome priming (pro-IL-1ß and NLRP3) were not different between the two viruses. However, inflammasome activation (mature IL-1ß and caspase-1 p12) was reduced in RV-C15-infected mice compared to RV-A1B-infected mice. A similar deficiency was found in cultured macrophages. Finally, IL-1ß treatment decreased RV-C-induced type 2 cytokine and mucus-related gene expression, ILC2s, mucous metaplasia, and airway responsiveness but not lung vRNA level. We conclude that RV-C induces an enhanced asthma phenotype in immature mice. Compared to RV-A, RV-C-induced macrophage inflammasome activation and IL-1ß are deficient, permitting exaggerated type 2 inflammation and mucous metaplasia.

Medial cortical positive support: A key factor for the postoperative stability of proximal humerus fractures.

ABSTRACT: Treatments for proximal humerus fractures (PHFs) often fail to achieve anatomical reduction. The purpose of this study was to evaluate the role of positive medial cortical support (PMCS) in the nonanatomical reduction of PHFs.A retrospective analysis was performed of 78 patients with PHFs who underwent surgery from August 2014 to September 2017 and whose treatments did not achieve anatomical reduction. Based on the results of standard AP radiographs of the shoulders 3, 6, and 12 months after surgery, the patients were divided into PMCS or negative medial cortical support (NMCS) groups. The postsurgical change in head-shaft angle (HSA) between the 2 groups was compared. Shoulder joint function and visual analog scale (VAS) scores of the 2 groups were also compared at the same time.Of the 78 patients analyzed, 37 were in the PMCS group and, 41 in the NMCS group. There was no statistically significant difference in any of the characteristics of the 2 groups (P > .05), or in postsurgical HSA. However, the HSA of the 2 groups had become significantly different (P < .05) 3, 6, and 12 months following surgery. The changes in HSA of the 2 groups were different at various time points (P < .05). One year after surgery, the shoulder function score of the PMCS group was significantly better than that of the NMCS group, as was the VAS score (both P < .05).Patients whose surgery for PHF does not achieve anatomical reduction during surgery can undergo PMCS to achieve improved results, postoperatively. NMCS should be avoided as far as possible.

[Research progress in the integration of machine learning and acupunctology].

Machine learning is a newly emerged discipline. It develops rapidly and has been penetrated into all walks of life and made great achievements in medical field. The introduction of machine learning in the field of acupuncture and moxibustion should fully play the advantages of targeted therapy of acupuncture and moxibustion, optimize the resource allocation of traditional Chinese medicine and accurately serve the clinic rather than only limited to data mining and analysis. In the paper, through the analysis of the relevant literature in recent years, the combination of acupuncture-moxibustion with machine learning was discussed from the aspects of acupoint selection and prescription, clinical teaching application of acupuncture and moxibustion, the prediction on acupuncture curative effect, etc. Moreover, on the base of multidisciplinary intersection and by means of machine learning, the exploration was given on the future direction of acupuncture and moxibustion.

Rhinovirus C Infection Induces Type 2 Innate Lymphoid Cell Expansion and Eosinophilic Airway Inflammation.

Rhinovirus C (RV-C) infection is associated with severe asthma exacerbations. Since type 2 inflammation is an important disease mechanism in asthma, we hypothesized that RV-C infection, in contrast to RV-A, preferentially stimulates type 2 inflammation, leading to exacerbated eosinophilic inflammation. To test this, we developed a mouse model of RV-C15 airways disease. RV-C15 was generated from the full-length cDNA clone and grown in HeLa-E8 cells expressing human CDHR3. BALB/c mice were inoculated intranasally with 5 x 106 ePFU RV-C15, RV-A1B or sham. Mice inoculated with RV-C15 showed lung viral titers of 1 x 105 TCID50 units 24 h after infection, with levels declining thereafter. IFN-α, ß, γ and λ2 mRNAs peaked 24-72 hrs post-infection. Immunofluorescence verified colocalization of RV-C15, CDHR3 and acetyl-α-tubulin in mouse ciliated airway epithelial cells. Compared to RV-A1B, mice infected with RV-C15 demonstrated higher bronchoalveolar eosinophils, mRNA expression of IL-5, IL-13, IL-25, Muc5ac and Gob5/Clca, protein production of IL-5, IL-13, IL-25, IL-33 and TSLP, and expansion of type 2 innate lymphoid cells. Analogous results were found in mice treated with house dust mite before infection, including increased airway responsiveness. In contrast to Rorafl/fl littermates, RV-C-infected Rorafl/flIl7rcre mice deficient in ILC2s failed to show eosinophilic inflammation or mRNA expression of IL-13, Muc5ac and Muc5b. We conclude that, compared to RV-A1B, RV-C15 infection induces ILC2-dependent type 2 airway inflammation, providing insight into the mechanism of RV-C-induced asthma exacerbations.

Early-life heterologous rhinovirus infections induce an exaggerated asthma-like phenotype.

BACKGROUND: Early-life wheezing-associated respiratory tract infection by rhinovirus (RV) is a risk factor for asthma development. Infants are infected with many different RV strains per year. OBJECTIVE: We previously showed that RV infection of 6-day-old BALB/c mice induces a mucous metaplasia phenotype that is dependent on type 2 innate lymphoid cells (ILC2s). We hypothesized that early-life RV infection alters the response to subsequent heterologous infection, inducing an exaggerated asthma-like phenotype. METHODS: Wild-type BALB/c mice and Rorafl/flIl7rcre mice lacking ILC2s were treated as follows: (1) sham on day 6 of life plus sham on day 13 of life, (2) RV-A1B on day 6 plus sham on day 13, (3) sham on day 6 plus RV-A2 on day 13, and (4) RV-A1B on day 6 plus RV-A2 on day 13. RESULTS: Mice infected with RV-A1B at day 6 and sham at day 13 showed an increased number of bronchoalveolar lavage eosinophils and increased expression of IL-13 mRNA but not expression of IFN-γ mRNA (which is indicative of a type 2 immune response), whereas mice infected with sham on day 6 and RV-A2 on day 13 of life demonstrated increased IFN-γ expression (which is a mature antiviral response). In contrast, mice infected with RV-A1B on day 6 before RV-A2 infection on day 13 showed increased expression of IL-13, IL-5, Gob5, Muc5b, and Muc5ac mRNA; increased numbers of eosinophils and IL-13-producing ILC2s; and exaggerated mucus metaplasia and airway hyperresponsiveness. Compared with Rorafl/fl mice, Rorafl/flIl7rcre mice showed complete suppression of bronchoalveolar lavage eosinophils and mucous metaplasia. CONCLUSION: Early-life RV infection alters the response to subsequent heterologous infection, inducing an intensified asthma-like phenotype that is dependent on ILC2s.

IL-1ß prevents ILC2 expansion, type 2 cytokine secretion, and mucus metaplasia in response to early-life rhinovirus infection in mice.

BACKGROUND: Early-life wheezing-associated respiratory infection with human rhinovirus (RV) is associated with asthma development. RV infection of 6-day-old immature mice causes mucous metaplasia and airway hyperresponsiveness which is associated with the expansion of IL-13-producing type 2 innate lymphoid cells (ILC2s) and dependent on IL-25 and IL-33. We examined regulation of this asthma-like phenotype by IL-1ß. METHODS: Six-day-old wild-type or NRLP3-/- mice were inoculated with sham or RV-A1B. Selected mice were treated with IL-1 receptor antagonist (IL-1RA), anti-IL-1ß, or recombinant IL-1ß. RESULTS: Rhinovirus infection induced Il25, Il33, Il4, Il5, Il13, muc5ac, and gob5 mRNA expression, ILC2 expansion, mucus metaplasia, and airway hyperresponsiveness. RV also induced lung mRNA and protein expression of pro-IL-1ß and NLRP3 as well as cleavage of caspase-1 and pro-IL-1ß, indicating inflammasome priming and activation. Lung macrophages were a major source of IL-1ß. Inhibition of IL-1ß signaling with IL-1RA, anti-IL-1ß, or NLRP3 KO increased RV-induced type 2 cytokine immune responses, ILC2 number, and mucus metaplasia, while decreasing IL-17 mRNA expression. Treatment with IL-1ß had the opposite effect, decreasing IL-25, IL-33, and mucous metaplasia while increasing IL-17 expression. IL-1ß and IL-17 each suppressed Il25, Il33, and muc5ac mRNA expression in cultured airway epithelial cells. Finally, RV-infected 6-day-old mice showed reduced IL-1ß mRNA and protein expression compared to mature mice. CONCLUSION: Macrophage IL-1ß limits type 2 inflammation and mucous metaplasia following RV infection by suppressing epithelial cell innate cytokine expression. Reduced IL-1ß production in immature animals provides a mechanism permitting asthma development after early-life viral infection.

Rhinovirus Attributes that Contribute to Asthma Development.

Early-life wheezing-associated infections with human rhinovirus (HRV) are strongly associated with the inception of asthma. The immune system of immature mice and humans is skewed toward a type 2 cytokine response. Thus, HRV-infected 6-day-old mice but not adult mice develop augmented type 2 cytokine expression, eosinophilic inflammation, mucous metaplasia, and airway hyperresponsiveness. This asthma phenotype depends on interleukin (IL)-13-producing type 2 innate lymphoid cells, the expansion of which in turn depends on release of the innate cytokines IL-25, IL-33, and thymic stromal lymphopoietin from the airway epithelium. In humans, certain genetic variants may predispose to HRV-induced childhood asthma.