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RNA interference (RNAi) is a potent and specific post-transcriptional gene silencing process. Since its discovery, tremendous efforts have been made to translate RNAi technology into therapeutic applications for the treatment of different human diseases including respiratory diseases, by manipulating the expression of disease-associated gene(s). Similar to other nucleic acid-based therapeutics, the major hurdle of RNAi therapy is delivery. Pulmonary delivery is a promising approach of delivering RNAi therapeutics directly to the airways for treating local conditions and minimizing systemic side effects. It is a non-invasive route of administration that is generally well accepted by patients. However, pulmonary drug delivery is a challenge as the lungs pose a series of anatomical, physiological and immunological barriers to drug delivery. Understanding these barriers is essential for the development an effective RNA delivery system. In this review, the different barriers to pulmonary drug delivery are introduced. The potential of RNAi molecules as new class of therapeutics, and the latest preclinical and clinical studies of using RNAi therapeutics in different respiratory conditions are discussed in details. We hope this review can provide some useful insights for moving inhaled RNAi therapeutics from bench to bedside.

Multi-drug-resistant tuberculosis (MDR-TB) is a huge public health problem. The treatment regimen of MDR-TB requires prolonged chemotherapy with multiple drugs including second-line anti-TB agents associated with severe adverse effects. Capreomycin, a polypeptide antibiotic, is the first choice of second-line anti-TB drugs in MDR-TB therapy. It requires repeated intramuscular or intravenous administration five times per week. Pulmonary drug delivery is non-invasive with the advantages of local targeting and reduced risk of systemic toxicity. In this study, inhaled dry powder formulation of capreomycin targeting the lung was developed using spray drying technique. Among the 16 formulations designed, the one containing 25% capreomycin (w/w) and spray-dried at an inlet temperature of 90 °C showed the best overall performance with the mass median aerodynamic diameter (MMAD) of 3.38 μm and a fine particle fraction (FPF) of around 65%. In the pharmacokinetic study in mice, drug concentration in the lungs was approximately 8-fold higher than the minimum inhibitory concentration (MIC) (1.25 to 2.5 µg/mL) for at least 24 h following intratracheal administration (20 mg/kg). Compared to intravenous injection, inhaled capreomycin showed significantly higher area under the curve, slower clearance and longer mean residence time in both the lungs and plasma.

The delivery of therapeutics across biological membranes (e.g., mucosal barriers) by avoiding invasive routes (e.g., injection) remains a challenge in the pharmaceutical field. As such, there is the need to discover new compounds that act as drug permeability enhancers with a favorable toxicological profile. A valid alternative is represented by the class of sugar-based ester surfactants. In this study, sucrose and lactose alkyl aromatic and aromatic ester derivatives have been synthesized with the aim to characterize them in terms of their physicochemical properties, structure–property relationship, and cytotoxicity, and to test their ability as permeability enhancer agents across Calu-3 cells. All of the tested surfactants showed no remarkable cytotoxic effect on Calu-3 cells when applied both below and above their critical micelle concentration. Among the explored molecules, lactose p-biphenyl benzoate (URB1420) and sucrose p-phenyl benzoate (URB1481) cause a reversible ~30% decrease in transepithelial electrical resistance (TEER) with the respect to the basal value. The obtained result matches with the increased in vitro permeability coefficients (Papp) calculated for FTIC-dextran across Calu-3 cells in the presence of 4 mM solutions of these surfactants. Overall, this study proposes sucrose- and lactose-based alkyl aromatic and aromatic ester surfactants as novel potential and safe permeation enhancers for pharmaceutical applications.

Abstract & Objectives] This article aimed to study the grafting propagation techniques of red sandalwood (Pterocarpus santalinus) , so as to provide technical support for the effective propagation of seedlings of this precious Hongmu species. & Methods] Based on the analysis and comparison of the growth performance of the Hongmu tree species introduced to China, taking 1 to 2-year-old Pterocarpus indicus seedlings as rootstocYs and single-bud stems of P. santalinus as scions, grafting was carried out from January to April using three grafting propagation methods, cut grafting propagation, skin grafting propagation and oblique grafting propagation. & Results]The results of several years of experiments show that in early spring, P. santalinus could be propagated well using the grafting propagation methods of skin grafting propagation and oblique grafting propagation, with survival rate over 80%. Modern grafting techniques are mainly used to improve plant traits. [...]grafting is widely used in plant propagation and breeding of new varieties114-16'. The healing of grafting interface involves traumatic response, physiological and biochemical processes, cell and tissue differentiation, signal exchange between rootstock and scion and vascular bunde reconnection &24 _ 26'. [...]the key to the success of grafting is the affinity of the scion and the rootstock. According to special experiments in a few years or sporadic grafting practices, when F. indicus is use as rootstock for propagating P. santalinus, the dfinity between the rootstock and the scion is good, and the method is feasible.

[Objectives] This article aimed to study the grafting propagation techniques of red sandalwood (Pterocarpus santalinus), so as to provide technical support for the effective propagation of seedlings of this precious Hongmu species. [Methods] Based on the analysis and comparison of the growth performance of the Hongmu tree species introduced to China, taking 1 to 2-year-old  Pterocarpus indicus seedlings as rootstocks and single-bud stems of P. santalinus as scions, grafting was carried out from January to April using three grafting propagation methods, cut grafting propagation, skin grafting propagation and oblique grafting propagation. [Results] The results of several years of experiments show that in early spring, P. santalinus could be propagated well using the grafting propagation methods of skin grafting propagation and oblique grafting propagation, with survival rate over 80%. For rootstocks with young age or thin stems, the joint unions of the oblique grafting propagation healed well, without apparent protrusions, unlike those of skin grafting propagation. The survival rate of oblique grafting propagation that is fast and reliable was higher than that of cut grafting propagation. [Conclusions] It is feasible to use the grafting propagation methods to propagate P. santalinus seedlings. This is a traditional and innovative technology path in the in the propagation of high-quality seedlings of precious Hongmu trees, and can be promoted and applied in industrial practice.

Surface acoustic waves (SAWs) offer great potential for quantum information processing, optomechanics, acoustofludics, and acoustic tweezers. However, existing SAW chips lack the ability to control SAWs in a manner similar to current metamaterials, which can achieve versatile subwavelength-resolution manipulation of bulk acoustic waves. This study presents on-chip phased interdigital metamaterials (PIMs) featuring customized interdigital electrodes whose geometries are encoded with deep-subwavelength-resolution phase profiles, enabling versatile transformation of SAWs and manipulation of fluids and micro/nano-objects. Our on-chip PIMs can transform forward SAWs into waves with desired wavefronts and energy patterns, such as SAWs propagating in a specified direction, a SAW jet with energy confined in a wavelength, and twin jets. They also enable \"diode-like\" SAW transmission, allowing for routing the information carried by SAWs along a forward pathway while blocking backward communication. Additionally, SAWs generated by PIMs exhibit unique energy patterns, allowing for versatile active control of fluid streaming and micro/nano-object distributions.

Soybean has a palaeopolyploid genome with nearly 75% of the genes present in multiple copies. Although the CRISPR/Cas9 system has been employed in soybean to generate site-directed mutagenesis, a systematical assessment of mutation efficiency of the CRISPR/Cas9 system for the multiple-copy genes is still urgently needed. Here, we successfully optimize one sgRNA CRISPR/Cas9 system in soybean by testing the efficiency, pattern, specificity of the mutations at multiple loci of GmFAD2 and GmALS. The results showed that simultaneous site-directed mutagenesis of two homoeologous loci by one sgRNA, the mutation frequency in the T0 generation were 64.71% for GmPDS, 60.0% for GmFAD2 and 42.86% for GmALS, respectively. The chimeric and heterozygous mutations were dominant types. Moreover, association of phenotypes with mutation pattern at target loci of GmPDS11 and GmPDS18 could help us further demonstrate that the CRISPR/Cas9 system can efficiently generate target specific mutations at multiple loci using one sgRNA in soybean, albeit with a relatively low transformation efficiency.

The dielectric properties of Maillard reaction solutions (MRSs) formed between 10 amino acids [glycine (Gly), proline (Pro), cysteine (Cys), glutamine (Gln), lysine (Lys), methionine (Met), histidine (His), arginine (Arg), tyrosine (Tyr), and tryptophan (Try)] and glucose heated for 0–5 min using microwave irradiation were studied in the frequency range of 300–3000 MHz at 25.0 ± 0.5 °C. The critical frequencies of the MRSs were in the range of 0.81–1.98 GHz and increased as the heating time increased, with the exception of the MRS formed between Gln and glucose. The color difference (ΔE) of the MRSs increased as the heating time increased; alkaline amino acids exhibited the most significant change, reaching a maximum ΔE of 12.63 compared to non-polar and neutral polar amino acids. The penetration depth of the MRSs formed between alkaline amino acids and glucose decreased at 915 and 2450 MHz upon increasing the isoelectric point (pI) ( p  < 0.05). However, the penetration depth of non-polar and neutral polar amino acids increased upon increasing pI ( p  < 0.05). Non-polar amino acids required the highest energy [20.0 (± 0.20) × 10 −21  J], followed by neutral polar amino acids and alkaline amino acids [0.3 (± 0.01) × 10 −21  J]. The less energy required during the Maillard reaction, the easier the reaction could start. Finally, the real and imaginary parts of the Debye model were used to calculate the dielectric constant and dielectric loss factor of the MRSs formed between the amino acids and glucose and were in good agreement with the experimental values.

The aim of this study was to extract chitin and chitosan from shrimp shells by neutral protease‐assisted microwave multiple heating (one, two, three, and four) treatment. The structure and physicochemical properties of chitosan were characterized by scanning electron microscopy (SEM) and Fourier infrared spectroscopy (FTIR). The dielectric properties of chitosan acetate solution were determined by using a PNA‐L network analyzer, and the correlation between chitosan deacetylation degree and dielectric loss was further analyzed. The results show that the degree of deacetylation of chitosan increased from 84.9% to 90.8% with the increase in the number of microwave heating treatments. Furthermore, the chitosan prepared by multiple microwave heating was smoother. The dielectric constant of chitosan solution gradually decreases with the increase of frequency, and the dielectric loss first decreases and then increases. In addition, the dielectric loss of the chitosan solution increased with the degree of deacetylation of chitosan at 2450 MHz (R2 > 0.99). Therefore, enzyme‐assisted microwave extraction of chitosan can be used to obtain high‐quality chitosan under the condition of increasing the number of heating treatments. Enzyme‐assisted microwave extraction of chitosan can be used to obtain high‐quality chitosan under the condition of increasing the number of heating treatments.

Hybrid mapping is a powerful approach to efficiently identify and characterize genes regulated through mechanisms in cis. In this study, using reciprocal crosses of the phenotypically divergent Duroc and Lulai pig breeds, we perform a comprehensive multi-omic characterization of regulatory variation across the brain, liver, muscle, and placenta through four developmental stages. We produce one of the largest multi-omic datasets in pigs to date, including 16 whole genome sequenced individuals, as well as 48 whole genome bisulfite sequencing, 168 ATAC-Seq and 168 RNA-Seq samples. We develop a read count-based method to reliably assess allele-specific methylation, chromatin accessibility, and RNA expression. We show that tissue specificity was much stronger than developmental stage specificity in all of DNA methylation, chromatin accessibility, and gene expression. We identify 573 genes showing allele specific expression, including those influenced by parent-of-origin as well as allele genotype effects. We integrate methylation, chromatin accessibility, and gene expression data to show that allele specific expression can be explained in great part by allele specific methylation and/or chromatin accessibility. This study provides a comprehensive characterization of regulatory variation across multiple tissues and developmental stages in pigs. Here, the authors use multi-omic data to reveal how genetic and epigenetic variation affects gene expression in two pig breeds. The findings highlight strong tissue-specific regulation and identify genes with allele-specific expression.