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The rapid advancements in gene therapy have opened up new possibilities for treating genetic disorders, including Duchenne muscular dystrophy, thalassemia, cystic fibrosis, hemophilia, and familial hypercholesterolemia. The utilization of the clustered, regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein (Cas) system has revolutionized the field of gene therapy by enabling precise targeting of genes. In recent years, CRISPR/Cas9 has demonstrated remarkable efficacy in treating cancer and genetic diseases. However, the susceptibility of nucleic acid drugs to degradation by nucleic acid endonucleases necessitates the development of functional vectors capable of protecting the nucleic acids from enzymatic degradation while ensuring safety and effectiveness. This review explores the biomedical potential of non-viral vector-based CRISPR/Cas9 systems for treating genetic diseases. Furthermore, it provides a comprehensive overview of recent advances in viral and non-viral vector-based gene therapy for genetic disorders, including preclinical and clinical study insights. Additionally, the review analyzes the current limitations of these delivery systems and proposes avenues for developing novel nano-delivery platforms. [ABSTRACT FROM AUTHOR]

Flexible polymer-based magnetoelectric (ME) materials have broad application prospects and are considered as a new research field. In this article, FeCoSiB thin films were deposited on poly(vinylidene fluoride-co-trifluoroethylene) (PVDF-TrFE) substrate by DC magnetron sputtering. The structure of PVDF-TrFE/FeCoSiB heterostructure thin films was similar to 2-2. Under a bias magnetic field of 70 Oe, the composites have a dramatically increased ME voltage coefficient as high as 111 V/cm⋅Oe at a frequency of about 85 kHz. The piezoelectric coefficient of PVDF-TrFE thin films is 34.87 pC/N. The surface morphology of PVDF-TrFE thin films were studied by FESEM, and the results of XRD and FTIR showed that the β-phase of PVDF-TrFE thin films was dominant. Meanwhile, the effects of different heating conditions on the crystallization and piezoelectric properties of PVDF-TrFE films were also studied. The flexible ME heterojunction composite has a significant ME voltage coefficient and excellent piezoelectric properties at room temperature, which allows it to be a candidate material for developing flexible magnetoelectric devices. [ABSTRACT FROM AUTHOR]

Diabetic foot ulceration is a common chronic diabetic complication. Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) have been widely used in regenerative medicine owing to their multipotency and easy availability. We developed poly(lactic-co-glycolic acid) (PLGA)-based scaffold to create hUC-MSC tissue sheets. In vitro immunostaining showed that hUC-MSC tissue sheets formed thick and solid tissue sheets with an abundance of extracellular matrix (ECM). Diabetic wounds in mice treated with or without either the hUC-MSC tissue sheet, hUC-MSC injection, or fiber only revealed that hUC-MSC tissue sheet transplantation promoted diabetic wound healing with improved re-epithelialization, collagen deposition, blood vessel formation and maturation, and alleviated inflammation compared to that observed in other groups. Taken collectively, our findings suggest that hUC-MSCs cultured on PLGA scaffolds improve diabetic wound healing, collagen deposition, and angiogenesis, and provide a novel and effective method for cell transplantation, and a promising alternative for diabetic skin wound treatment. [ABSTRACT FROM AUTHOR]

Nitraria sibirica is a shrub that can survive in extreme drought environments. The auxin-response factors (ARFs) are a class of transcription factors that are widely involved in plant growth and development, as well as in the regulation of stress resistance. However, the genome-wide identification of the ARF gene family and its responses to environmental stresses, especially drought stress, in N. sibirica has not yet been reported. Here, we identified a total of 12 ARF genes in the genome of N. sibirica, which were distributed over 10 chromosomes and divided into three clades. Intragenome synteny analysis revealed one collinear gene pair in the ARF gene family, i.e., NsARF9a and NsARF9b. Cis-acting element analysis showed that multiple hormones and stress-responsive cis-acting elements were found in the promoters of NsARFs, suggesting that NsARFs may be involved in multiple biological processes. Quantitative real-time PCR (qRT-PCR) showed that many NsARFs had tissue-specific expression patterns, with the highest expression of NsARF16 in the seedlings of N. sibirica. In addition, most of the NsARFs that were upregulated under drought were independent of endogenous ABA biosynthesis, whereas the response of NsARF5 and NsARF7a to drought was disrupted by the ABA-biosynthesis inhibitor fluridone. These studies provide a basis for further research into how NsARFs in N. sibirica respond to hormonal signaling and environmental stresses. [ABSTRACT FROM AUTHOR]

The calcineurin B-like-interacting protein kinase (CIPK) protein family plays a key role in the plant calcium ion-mediated signal transduction pathway, which regulates a plant's response to abiotic stress. Nitraria sibirica pall. (N. sibirica) is a halophyte with a strong tolerance for high salt environments, yet how it is able to deal with salt stress on a molecular level is still unknown. Due to their function as described in other plant species, CIPK genes are prime candidates for a role in salt stress signaling in N. sibirica. In this study, we identified and analyzed the phylogenetic makeup and gene expression of the N. sibirica CIPK gene family. A total of 14 CIPKs were identified from the N. sibirica genome and were clustered into seven groups based on their phylogeny. The promoters of NsCIPK genes contained multiple elements involved in hormonal and stress response. Synteny analysis identified a total of three pairs of synteny relationships between NsCIPK genes. Each gene showed its own specific expression pattern across different tissues, with the overall expression of CIPK6 being the lowest, and that of CIPK20 being the highest. Almost all CIPK genes tended to respond to salt, drought, and cold stress, but with different sensitivity levels. In this study, we have provided a general description of the NsCIPK gene family and its expression, which will be of great significance for further understanding of the NsCIPK gene family function. [ABSTRACT FROM AUTHOR]

Relevant, predictive normal, or disease model systems are of vital importance for drug development. The difference between nonhuman models and humans could contribute to clinical trial failures despite ideal nonhuman results. As a potential substitute for animal models, human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (CMs) provide a powerful tool for drug toxicity screening, modeling cardiovascular diseases, and drug discovery. Here, we review recent hiPSC-CM disease models and discuss the features of hiPSC-CMs, including subtype and maturation and the tissue engineering technologies for drug assessment. Updates from the international multisite collaborators/administrations for development of novel drug discovery paradigms are also summarized.

Developmental genetic studies of Antirrhinum majus demonstrated that two transcription factors from the MYB gene family, RADIALIS (RAD) and DIVIRICATA (DIV), interact through antagonism to regulate floral dorsoventral asymmetry. Interestingly, similar antagonistic interaction found among proteins of FSM1 (RAD-like) and MYBI (DIV-like) in Solanum lycopersicum is involved in fruit development. Here, we report the reconstruction of the phylogeny of I-box-like and R-R-type clades, where RAD - and DIV -like genes belong, respectively. We also examined the homology of these antagonistic MYB proteins using these phylogenies. The results show that there are likely three paralogs of RAD -/ I-box -like genes, RAD1, RAD2, and RAD3, which originated in the common ancestor of the core eudicots. In contrast, R-R -type sequences fall into two major clades, RR1 and RR2, the result of gene duplication in the common ancestor of both monocots and dicots. RR1 was divided into clades RR1A, RR1B, and RR1C, while RR2 was divided into clades RR2A/DIV1, RR2B/DIV2, and RR2C/DIV3. We demonstrate that among similar antagonistic interactions in An. Majus and So. lycopersicum , RAD -like genes originate from the RAD2 clade, while DIV -like genes originate from distantly related paralogs of the R-R-type lineage. The phylogenetic analyses of these two MYB clades lay the foundation for future comparative studies including testing the evolution of the antagonistic relationship of proteins., Competing Interests: The authors declare no conflict of interest.