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Background: With the intensification of population aging, osteoporosis has become one of the significant public health issues affecting human health. Currently available medications for treating osteoporosis are associated with various adverse effects and resistance issues. Oligonucleotide drugs show great potential. Effective delivery systems are essential to enhance the stability, bioavailability, and targeting of sRNA drugs. Lipid nanoparticles (LNPs) show promise as alternative osteoporosis therapeutics. This study explores the potential of LNPs as an effective delivery system to treat osteoporosis. Methods: LNPs were prepared using microfluidic techniques with varying lipid compositions, and characterized in terms of size, zeta potential, and entrapment efficiency (EE%). Dynamic light scattering (DLS) was employed to determine the size of the LNPs. The zeta potential was measured using electrophoretic light scattering. The pharmacodynamic effects and safety were then evaluated in a mouse model through intravenous administration. Results: Several lipid nanoparticle (LNP) formulations with different nitrogen/phosphorus ratios and different DMG-PEG2000 ratios were examined, and a lead candidate that supports delivery of sRNA in animal models of osteoporosis was identified. In OVX mice, LNP-sRNA significantly improved bone mineral density (BMD), trabecular microstructure, and biomechanical strength. Safety assessments revealed no systemic toxicity. It is shown that the optimized LNPs can serve as a promising delivery system to mediate sRNA delivery to bone tissue. Conclusions: After comparison of in vitro and in vivo properties, the optimized LNPs demonstrated good comprehensive performance as a delivery system for osteoporosis treatment. These results highlight the potential of the optimized LNPs as an ideal delivery system for osteoporosis, offering improved therapeutic efficacy and reduced systemic side effects.

MicroRNAs (miRNAs), a class of single-stranded non-coding RNA of about 22 nucleotides, are potent regulators of gene expression existing in both plants and animals. Recent studies showed that plant miRNAs could enter mammalian bloodstream via gastrointestinal tract, through which access a variety of tissues and cells of recipients to exert therapeutic effects. This intriguing phenomenon indicates that miRNAs of diet/plant origin may act as a new class of bioactive ingredients communicating with mammalian systems. In this review, in order to pinpoint the reason underlying discrepancies of miRNAs transmission from diet/plant to animals, the pathways that generate miRNAs and machineries involved in the functions of miRNAs in both kingdoms were outlined and compared. Then, the current controversies concerning cross-kingdom regulations and the potential mechanisms responsible for absorption and transfer of diet/plant-derived miRNAs were interpreted. Furthermore, the hormone-like action of miRNAs and the intricate interplay between miRNAs and hormones were implicated. Finally, how these findings may impact nutrition and medicine were briefly discussed.

(AB) is rising as a human pathogen of critical priority worldwide as it is the leading cause of opportunistic infections in healthcare settings and carbapenem-resistant AB is listed as a \"super bacterium\" or \"priority pathogen for drug resistance\" by the World Health Organization. Clinical isolates of were collected and tested for antimicrobial susceptibility. Among them, carbapenem-resistant and carbapenem-sensitive were subjected to prokaryotic transcriptome sequencing. The change of sRNA and mRNA expression was analyzed by bioinformatics and validated by quantitative reverse transcription-PCR. A total of 687 clinical isolates were collected, of which 336 strains of were resistant to carbapenem. Five hundred and six differentially expressed genes and nineteen differentially expressed sRNA candidates were discovered through transcriptomic profile analysis between carbapenem-resistant isolates and carbapenem-sensitive isolates. Possible binding sites were predicted through software for sRNA21 and , sRNA27 and , sRNA29 and , sRNA36 and , indicating a possible targeting relationship. A negative correlation was shown between sRNA21 and (r = -0.581, P = 0.007), sRNA27 and (r = -0.612, P = 0.004), sRNA29 and (r = -0.516, P = 0.020). This study preliminarily screened differentially expressed mRNA and sRNA in carbapenem-resistant , and explored possible targeting relationships, which will help further reveal the resistance mechanism and provide a theoretical basis for the development of drugs targeting sRNA for the prevention and treatment of carbapenem-resistant infection.

The present review represents an update on the fundamental role played by the Rho factor, which facilitates the process of Rho-dependent transcription termination in the prokaryotic world; it also provides a summary of relevant mutations in the Rho factor and the insights they provide into the functions carried out by this protein. Furthermore, a section is dedicated to the putative future use of Rho (the ‘taming’ of Rho) to facilitate biotechnological processes and adapt them to different technological contexts. Novel bacterial strains can be designed, containing mutations in the rho gene, that are better suited for different biotechnological applications. This process can obtain novel microbial strains that are adapted to lower temperatures of fermentation, shorter production times, exhibit better nutrient utilization, or display other traits that are beneficial in productive Biotechnology. Additional important issues reviewed here include epistasis, the design of TATA boxes, the role of small RNAs, and the manipulation of clathrin-mediated endocytosis, by some pathogenic bacteria, to invade eukaryotic cells.Key points• It is postulated that controlling the action of the prokaryotic Rho factor could generate major biotechnological improvements, such as an increase in bacterial productivity or a reduction of the microbial-specific growth rate.• The review also evaluates the putative impact of epistatic mechanisms on Biotechnology, both as possible responsible for unexpected failures in gene cloning and more important for the genesis of new strains for biotechnological applications• The use of clathrin-coated vesicles by intracellular bacterial microorganisms is included too and proposed as a putative delivery mechanism, for drugs and vaccines.