Inhalable Nitric Oxide Delivery Systems for Pulmonary Arterial Hypertension Treatment.

Pulmonary arterial hypertension (PAH) is a severe medical condition characterized by elevated blood pressure in the pulmonary arteries. Nitric oxide (NO) is a gaseous signaling molecule with potent vasodilator effects; however, inhaled NO is limited in clinical practice because of the need for tracheal intubation and the toxicity of high NO concentrations. In this study, inhalable NO-releasing microspheres (NO inhalers) are fabricated to deliver nanomolar NO through a nebulizer. Two NO inhalers with distinct porous structures are prepared depending on the molecular weights of NO donors. It is confirmed that pore formation can be controlled by regulating the migration of water molecules from the external aqueous phase to the internal aqueous phase. Notably, open porous NO inhalers (OPNIs) can deliver NO deep into the lungs through a nebulizer. Furthermore, OPNIs exhibit vasodilatory and anti-inflammatory effects via sustained NO release. In conclusion, the findings suggest that OPNIs with highly porous structures have the potential to serve as tools for PAH treatment.

Potential lifetime effects caused by cellular uptake of nanoplastics: A review.

Plastics have been used for about 100 years, and daily-use products composed of plastics are now prevalent. As a result, humans are very easily exposed to the plastic particles generated from the daily-use plastics. However, studies on cellular uptake of nanoplastics in "human cells" have only recently begun to attract attention. In previous studies, definitions of nanoplastics and microplastics were vague, but recently, they have been considered to be different and are being studied separately. However, nanoplastics, unlike plastic particles of other sizes such as macro- and microplastics, can be absorbed by human cells, and thus can cause various risks such as cytotoxicity, inflammation, oxidative stress, and even diseases such as cancer82, 83. and diabetes (Fan et al., 2022; Wang et al., 2023). Thus, in this review, we defined microplastics and nanoplastics to be different and described the potential risks of nanoplastics to human caused by cellular uptake according to their diverse factors. In addition, during and following plastic product usage a substantial number of fragments of different sizes can be generated, including nanoplastics. Fragmentation of microplastics into nanoplastics may also occur during ingestion and inhalation, which can potentially cause long-term hazards to human health. However, there are still few in vivo studies conducted on the health effect of nanoplastics ingestion and inhalation.

Co-existing "spear-and-shield" air filter: Anchoring proteinaceous pathogen and self-sterilized nanocoating for combating viral pandemic.

Infectious pollutants bioaerosols can threaten human public health. In particular, the indoor environment provides a unique exposure situation to induce infection through airborne transmission like SARS-CoV-2. To prevent the infection from spreading, personal protective equipment or indoor air purification is necessary. However, it has been discovered that the conventional filter can become contaminated by pathogen-containing aerosols, meaning that advanced filtering and self-sterilization systems are required. Here, we fabricate a multilayered nanocoating around the fabric using laponite (LAP) with Cu2+ ions (LAP-Cu2+ nanocoating) two contradictory functions in one system: trapping proteinaceous pathogens and antibacterial effect. Due to the strong LAP-protein interaction, albumin and spike protein (S-protein) are trapped into the fabric when proteins are sprayed using a nebulizer. The protein-blocking performance of the nanocoated fabric is 9.55-fold higher than bare fabric. These trapping capacities are retained after rinsing and repeated adsorption cycles, showing reproducibility for air filtration. Even though the protein-binding occurred, the LAP-Cu2+ fabric indicates antibacterial effect. LAP-Cu2+ fabric has an equivalent air and water transmittance rate to that of bare fabric with a stability under physiological environment. Therefore, given its excellent "Spear-and-shield" functions, the proposed LAP-Cu2+ fabric shows great potential for use in filter and masks during the viral pandemic.

Broad-Spectrum Antiviral Activity of 3D8, a Nucleic Acid-Hydrolyzing Single-Chain Variable Fragment (scFv), Targeting SARS-CoV-2 and Multiple Coronaviruses In Vitro.

The virus behind the current pandemic, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the etiology of novel coronavirus disease (COVID-19) and poses a critical public health threat worldwide. Effective therapeutics and vaccines against multiple coronaviruses remain unavailable. Single-chain variable fragment (scFv), a recombinant antibody, exhibits broad-spectrum antiviral activity against DNA and RNA viruses owing to its nucleic acid-hydrolyzing property. The antiviral activity of 3D8 scFv against SARS-CoV-2 and other coronaviruses was evaluated in Vero E6 cell cultures. Viral growth was quantified with quantitative RT-qPCR and plaque assay. The nucleic acid-hydrolyzing activity of 3D8 was assessed through abzyme assays of in vitro viral transcripts and cell viability was determined by MTT assay. We found that 3D8 inhibited the replication of SARS-CoV-2, human coronavirus OC43 (HCoV-OC43), and porcine epidemic diarrhea virus (PEDV). Our results revealed the prophylactic and therapeutic effects of 3D8 scFv against SARS-CoV-2 in Vero E6 cells. Immunoblot and plaque assays showed the reduction of coronavirus nucleoproteins and infectious particles, respectively, in 3D8 scFv-treated cells. These data demonstrate the broad-spectrum antiviral activity of 3D8 against SARS-CoV-2 and other coronaviruses. Thus, it could be considered a potential antiviral countermeasure against SARS-CoV-2 and zoonotic coronaviruses.

Acceleration of Nitric Oxide Release in Multilayer Nanofilms through Cu(II) Ion Intercalation for Antibacterial Applications.

Implant-derived bacterial infection is a prevalent cause of diseases, and no antibacterial coating currently exists that is biocompatible and that does not induce multidrug resistance. To this end, nitric oxide (NO) has been emerging as an effective antimicrobial agent that acts on a broad range of bacteria and elicits no known resistance. Here, a method for accelerating NO release from multilayered nanofilms has been developed for facilitating antibacterial activity. A previously reported multilayered nanofilm (nbi film) was fabricated by alternative deposition of branched polyethyleneimine (BPEI) and alginate via the layer-by-layer assembly method. N-Diazeniumdiolate, a chemical NO donor, was synthesized at the secondary amine moiety of BPEI within the film (nbi/NO film). Cu(II) ions can be incorporated into the film by forming chelating compounds with unreacted amines that have not been converted to NO donors. The increase of the amine protonation state in the chelate caused destabilization of the NO donor by reducing hydrogen bonding between the deprotonated amine and the NO donor. Thus, the Cu(II) ion-embedding film presented accelerated NO release and was further subjected to antibacterial testing to demonstrate the correlation between the NO release rate and the antibacterial activity. This study aimed to establish a novel paradigm for NO-releasing material design based on multilayered nanofilms by presenting the correlation between the NO release rate and the antibacterial effect.

In planta transformation of Notocactus scopa cv. Soonjung by Agrobacterium tumefaciens.

Notocactus scopa cv. Soonjung was subjected to in planta Agrobacterium tumefaciens-mediated transformation with vacuum infiltration, pin-pricking, and a combination of the two methods. The pin-pricking combined with vacuum infiltration (20-30 cmHg for 15 min) resulted in a transformation efficiency of 67-100%, and the expression of the uidA and nptII genes was detected in transformed cactus. The established in planta transformation technique generated a transgenic cactus with higher transformation efficiency, shortened selection process, and stable gene expression via asexual reproduction. All of the results showed that the in planta transformation method utilized in the current study provided an efficient and time-saving procedure for the delivery of genes into the cactus genome, and that this technique can be applied to other asexually reproducing succulent plant species.