Irreversible destruction of bronchi and alveoli can lead to multiple incurable lung diseases. Identifying lung stem/progenitor cells with regenerative capacity and utilizing them to reconstruct functional tissue is one of the biggest hopes to reverse the damage and cure such diseases. Here we showed that a rare population of SOX9+ basal cells (BCs) located at airway epithelium rugae can regenerate adult human lung. Human SOX9+ BCs can be readily isolated by bronchoscopic brushing and indefinitely expanded in feeder-free condition. Expanded human SOX9+ BCs can give rise to alveolar and bronchiolar epithelium after being transplanted into injured mouse lung, with air-blood exchange system reconstructed and recipient’s lung function improved. Manipulation of lung microenvironment with Pirfenidone to suppress TGF-β signaling could further boost the transplantation efficiency. Moreover, we conducted the first autologous SOX9+ BCs transplantation clinical trial in two bronchiectasis patients. Lung tissue repair and pulmonary function enhancement was observed in patients 3–12 months after cell transplantation. Altogether our current work indicated that functional adult human lung structure can be reconstituted by orthotopic transplantation of tissue-specific stem/progenitor cells, which could be translated into a mature regenerative therapeutic strategy in near future.Electronic supplementary materialThe online version of this article (10.1007/s13238-018-0506-y) contains supplementary material, which is available to authorized users.

In this paper, tetraphenylethylene (TPE) units, a well-known aggregation-induced emission (AIE) active group, are utilized to construct the hyperbranched polymer HP-TPE-Cz with carbazole moieties, a good hole-transporting and electroluminescent group, through an ''A 2 + B 4 '' approach by using a one-pot Suzuki polycondensation reaction. For comparison, its analog linear polymer LP-TPE-Cz, also constructed from these two moieties, was prepared. These two polymers exhibit interesting aggregation-induced emission enhanced (AIEE) behavior and act as explosive chemosensors with high sensitivity both as nanoparticles and in solid state, due to the presence of TPE units. Also, the HP-TPE-Cz PLED device exhibited a remarkably enhanced current efficiency (2.13 cd A À1 ) and luminescence efficiency (5914 cd m À2 ), compared with its analog linear polymer LP-TPE-Cz (1.04 cd A À1 , 1654 cd m À2 ).

Berberine, a natural isoquinoline alkaloid isolated from the berberis species, has a wide array of biological properties such as anti-inflammatory, antibacterial, antifungal, and antihelminthic effects. We evaluated the antiviral effect of berberine against influenza A/FM1/1/47 (H1N1) in vivo and in vitro. The results showed that berberine strongly suppressed viral replication in A549 cells and in mouse lungs. Meanwhile, berberine relieved pulmonary inflammation and reduced necrosis, inflammatory cell infiltration, and pulmonary edema induced by viral infection in mice when compared with vehicle-treated mice. Berberine suppressed the viral infection-induced up-regulation of TLR7 signaling pathway, such as TLR7, MyD88, and NF-κB (p65), at both the mRNA and protein levels. Furthermore, berberine significantly inhibited the viral infectioninduced increase in Th1/Th2 and Th17/Treg ratios as well as the production of inflammatory cytokines. Our data provide new insight into the potential of berberine as a therapeutic agent for viral infection via its antiviral activity.

Interleukin 23 (IL-23) is a new member of the IL-12 family that plays a critical role in promoting the proliferation of memory T helper 1 cells. The heterodimerized IL-23 receptor is composed of a shared IL-12 receptor beta 1 (IL-12Rbeta1) and an IL-12Rbeta2-related molecule called IL-23R. The standard form of IL-23R is encoded by at least 12 exons. Here, we demonstrate that at least six spliced isoforms of IL-23R (IL-23R1 to 6) can be generated through alternative splicing. The splicing strategies for the IL-23R gene are complicated and most often result in the deletion of exon 7 and/or exon 10. Translation prediction revealed that these spliced variants result in either premature termination to give rise to a diverse form of receptor ectodomain, or a frameshift to generate various lengths of the IL-23R endodomain. Differential expressions of IL-23R spliced variants are observed in natural killer and CD3+ CD4+ T cells. The expressions of these spliced variants are also prevalently and complicatedly regulated in tumor cell lines. Interestingly, only IL-23R2 and/or IL-23R4 variants are predominantly detected in certain human lung carcinomas, but not in their resected normal margin tissues. Thus, our results indicate that the regulation of alternative splicing on the IL-23R gene is complicated, and the preferential expression of certain IL-23R spliced variants may be a contributive factor to the pathogenesis of certain cancers.

Inorganic nanoparticles with unique physical properties have been explored as nanomedicines for brain tumor treatment. However, the clinical applications of the inorganic formulations are often hindered by the biological barriers and failure to be bioeliminated. The size of the nanoparticle is an essential design parameter which plays a significant role to affect the tumor targeting and biodistribution. Here, we report a feasible approach for the assembly of gold nanoparticles into ~80 nm nanospheres as a drug delivery platform for enhanced retention in brain tumors with the ability to be dynamically switched into the single formulation for excretion. These nanoassemblies can target epidermal growth factor receptors on cancer cells and are responsive to tumor microenvironmental characteristics, including high vascular permeability and acidic and redox conditions. Anticancer drug release was controlled by a pH-responsive mechanism. Intracellular L-glutathione (GSH) triggered the complete breakdown of nanoassemblies to single gold nanoparticles. Furthermore, in vivo studies have shown that nanospheres display enhanced tumor-targeting efficiency and therapeutic effects relative to single-nanoparticle formulations. Hence, gold nanoassemblies present an effective targeting strategy for brain tumor treatment.