In this task, you're given a paragraph from the research paper and your task is to generate a suitable title for the research paper based on the given paper. Under 100 words is a good title length.

Example Input: Influenza infection and pneumonia are known to cause much of their mortality by inducing acute respiratory distress syndrome (ARDS), which is the most severe form of acute lung injury (ALI). Angiotensin-converting enzyme 2 (ACE2), which is a negative regulator of angiotensin II in the renin-angiotensin system, has been reported to have a crucial role in ALI. Downregulation of ACE2 is always associated with the ALI or ARDS induced by avian influenza virus, severe acute respiratory syndrome-coronavirus, respiratory syncytial virus and sepsis. However, the molecular mechanism of the decreased expression of ACE2 in ALI is unclear. Here we show that avian influenza virus H5N1 induced the upregulation of miR-200c-3p, which was then demonstrated to target the 3′-untranslated region of ACE2. Then, we found that nonstructural protein 1 and viral RNA of H5N1 contributed to the induction of miR-200c-3p during viral infection. Additionally, the synthetic analog of viral double-stranded RNA (poly (I:C)), bacterial lipopolysaccharide and lipoteichoic acid can all markedly increase the expression of miR-200c-3p in a nuclear factor-κB-dependent manner. Furthermore, markedly elevated plasma levels of miR-200c-3p were observed in severe pneumonia patients. The inhibition of miR-200c-3p ameliorated the ALI induced by H5N1 virus infection in vivo, indicating a potential therapeutic target. Therefore, we identify a shared mechanism of viral and bacterial lung infection-induced ALI/ARDS via nuclear factor-κB-dependent upregulation of miR-200c-3p to reduce ACE2 levels, which leads increased angiotensin II levels and subsequently causes lung injury.
Example Output: miRNA-200c-3p is crucial in acute respiratory distress syndrome

Example Input: It is reported that bacterial colonization of the airway in neonates affects the likelihood and severity of subsequent wheezing in childhood. This study aimed to explore the impact of bacterial colonization on the severity of virus-induced wheezing, and accompanying airway inflammation. Nasopharyngeal aspirates (NPAs) from 68 hospitalized children with bronchiolitis and 85 children with recurrent wheezing were obtained. Eleven common respiratory viruses were sought by PCR and/or direct fluorescence assay. Bacteria were isolated from NPAs by routine culture methods. Cell numbers and concentrations of cytokines/chemokines in the NPAs were measured, and nucleated cells were characterized. The frequency of bacterial colonization in children with recurrent wheezing was significantly higher than in children with an initial attack of bronchiolitis. Bacterial colonization accompanying virus infection had no effect on clinical manifestations, duration of hospitalization, concentrations of cytokines/chemokines (except interleukin-10 (IL-10)) or cellularity in the children with bronchiolitis; however, among the children with recurrent wheezing, those who had coexistent non-invasive bacterial colonization and virus infection presented more frequent cyanosis, longer duration of hospitalization, a higher concentration of IL-10 and a higher percentage of neutrophils in NPAs than those with virus infection but without bacterial colonization. Bacterial colonization was common in children with virus-induced wheezing, particularly in the situation of recurrent wheezing. To some extent, bacterial colonization accompanying virus infection may contribute to the severity of the wheezing because of its impact on airway inflammation.
Example Output: Impact of bacterial colonization on the severity, and accompanying airway inflammation, of virus-induced wheezing in children

Example Input: Peptide based-vaccines are becoming one of the most widely investigated prophylactic and therapeutic health care interventions against a variety of diseases, including cancer. However, the lack of a safe and highly efficient adjuvant (immune stimulant) is regarded as the biggest obstacle to vaccine development. The incorporation of a peptide antigen in a nanostructure-based delivery system was recently shown to overcome this obstacle. Nanostructures are often formed from antigens conjugated to molecules such as polymers, lipids, and peptide, with the help of selfassembly phenomenon. This review describes the application of self-assembly process for the production of peptide-based vaccine candidates and the ability of these nanostructures to stimulate humoral and cellular immune responses. T stimulate a cytotoxic T lymphocyte response to eliminate cells that are already infected [8] [9] [10] . Therapeutic vaccines are a growing pharmaceutical sector. Sipuleucel-T (Provenge®) was approved by Food and Drug Administration (FDA) in 2010 for prostate cancer [11, 12] and talimogene laherparepvec (T-VEC) (Imlygic™) was introduced against metastatic melanoma in 2015 [13] [14] [15] . Despite their advantages, vaccines also have some drawbacks. Traditional vaccines based on attenuated and inactivated pathogens may revert to virulent form [16, 17] , cause autoimmunity or strong allergic responses [18, 19] . Additionally, the production and stability of this type of vaccine is often challenging. Subunit vaccines contain a small fragment of the whole pathogenic organism, for instance a recombinant protein, peptide, carbohydrate [20] [21] [22] [23] . Recombinant protein-based vaccines cause fewer adverse effects, but the difficulty with protein extraction and possible contamination during production are significant disadvantages. Recombinant vaccine can also trigger undesired immune responses. To avoid these obstacles minimal fragment of protein caring immunological information (peptide epitope) can be used for vaccine design [3] . However, peptide-based vaccines still have their own Achilles' heel. Peptides themselves are usually not immunogenic [3, 24] ; therefore, the use of immunostimulating agents (adjuvants) are essential for the success of this vaccine formulation [25] . Adjuvants are compounds that are able to evoke or enhance the immune response against co-delivered antigens [26] [27] [28] . A number of adjuvants have already been developed, for example Freund's adjuvant, lipid A, cholera toxin, aluminum salts, cytokines, liposomes, saponins, and CpG oligodeoxynucleotides [29] [30] [31] . However, the immunostimulating properties of these adjuvants are often poor or their toxicity is significant, therefore most of them are not suitable for human treatment. Thus, safer and more efficient adjuvants are urgently required [27] . Nanotechnology is one of the most quickly growing fields of science and engineering. It has been widely applied in materials, electronics, manufacturing, agricultural science, chemistry and bioscience [32] [33] [34] [35] [36] [37] . In bioscience, nanotechnology is used to create sensors, medical imaging and diagnostic tools, and for drug delivery. The most widely used nanostructures in this field are nanoparticles. Nanoparticles are often defined as particles with diameters ranging from 1 to 100 nm [24, 38] , while particles with diameter within the range of 100 to 1000 nm are considered sub-micro particles. However, following common understanding of "nano-size" range, nanostructures in this article are defined as any nanometer-sized object ranging from 1 to 1000 nm [39, 40] . Nanoparticles are especially useful in vaccine design. Many pathogens are within the nanometer range, nanoparticles are usually taken up efficiently by antigen-presenting cells (APCs) [41] . APCs are the key element of the primary innate immune system [42] and are responsible for triggering further adaptive immune responses. Therefore nanostructures often have immunostimulating properties and help to trigger immune reactions against the antigens they delivered (Fig. 1) [24, 43, 44] . Moreover, the surface of nanostructures can be modified with a specific targeting moiety for better APC recognition and uptake [45] [46] [47] . There are two main approaches to creating nanostructures: (1) mechanically breaking a large material into nanostructures, or (2) building up nanostructures from basic segments, often via a self-assembly process [48] . The first approach uses external forces like grinding, milling, or high pressure to break down the original material [49] [50] [51] . This process adds additional complexity to producing a nanostructure and the harsh conditions used to break down the initial component may damage the antigen. Nanostructures produced by this method typically have a low loading capacity and are often not biodegradable and thus may accumulate in the human tissues. Meanwhile, self-assembly-based strategies for production of nanoparticle vaccines can overcome these problems. Here, we highlight how the use of carrier-antigen conjugates forming self-assembling nanostructures can be effectively combined with the rational vaccine design. The formation of self-assembled nanoparticles from carrier-antigen (peptide epitopes) conjugates, and their ability to generate humoral/cellular immune responses are discussed (Fig. 1) . Extensive reviews on non-conjugated selfassembled antigen carrier, such as liposomes, can be found in the recent literature [52] [53] [54] [55] . Similarly, virus-like particles (VLPs), which are formed by self-assembly processes, have been reviewed extensively in the recent literature [56-58] and therefore are Fig. 1. Schematic representation of the self-assembled peptide subunit vaccines and the immune responses induced upon immunization with these nanostructures. G. Zhao et al.
Example Output:
Feature Article -Review The application of self-assembled nanostructures in peptide-based subunit vaccine development