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Although organic nanomaterials and inorganic nanoparticles possess inherent flexibility, facilitating functional modification, increased intracellular uptake and controllable drug release, their underlying cytotoxicity and lack of specificity still cause safety concerns. Owing to their merits, which include natural biocompatibility, structural stability, unsurpassed programmability, ease of internalization and editable functionality, tetrahedral DNA nanostructures show promising potential as an alternative vehicle for drug delivery and biomedical treatment. Here, we describe the design, fabrication, purification, characterization and potential biomedical applications of a self-assembling tetrahedral DNA nanostructure (TDN)–based multifunctional delivery system. First, relying on Watson-Crick base pairing, four single DNA strands form a simple and typical pyramid structure via one hybridization step. Then, the protocol details four different modification approaches, including replacing a short sequence of a single DNA strand by an antisense peptide nucleic acid, appending an aptamer to the vertex, direct incubation with small-molecular-weight drugs such as paclitaxel and wogonin and coating with protective agents such as cationic polymers. These modified TDN-based complexes promote the intracellular uptake and biostability of the delivered molecules, and show promise in the fields of targeted therapy, antibacterial and anticancer treatment and tissue regeneration. The entire duration of assembly and characterization depends on the cargo type and modification method, which takes from 2 h to 3 d. In this protocol, the authors describe the design, fabrication, purification, characterization and potential biomedical applications of a self-assembling TDN-based multifunctional delivery system.

Atoh7 has been believed to be essential for establishing the retinal ganglion cell (RGC) lineage, and Pou4f2 and Isl1 are known to regulate RGC specification and differentiation. Here we report our further study of the roles of these transcription factors. Using bulk RNA-seq, we identify genes regulated by the three transcription factors, which expand our understanding of the scope of downstream events. Using scRNA-seq on wild-type and mutant retinal cells, we reveal a transitional cell state of retinal progenitor cells (RPCs) co-marked by Atoh7 and other genes for different lineages and shared by all early retinal lineages. We further discover the unexpected emergence of the RGC lineage in the absence of Atoh7. We conclude that competence of RPCs for different retinal fates is defined by lineage-specific genes co-expressed in the transitional state and that Atoh7 defines the RGC competence and collaborates with other factors to shepherd transitional RPCs to the RGC lineage. Atoh7 is essential for retinal ganglion cell (RGC) genesis. Here the authors perform scRNAseq on embryonic mouse retina and conclude that Atoh7 defines a transitional state and that other factors also participate in establishing the RGC lineage.

Angiogenesis is crucial for tissue engineering, wound healing, and regenerative medicine. Nanomaterials constructed based on specific goals can be employed to activate endogenous growth factor‐related signaling. In this study, based on the conventional single‐stranded DNA self‐assembly into tetrahedral framework nucleic acids (tFNAs), the Apt02 nucleic acid aptamer and dimethyloxallyl glycine (DMOG) small molecule are integrated into a complex via a template‐based click chemistry reaction and toehold‐mediated strand displacement reaction. Thus, being able to simulate the VEGF (vascular endothelial growth factor) function and stabilize HIF (hypoxia‐inducible factor), a functional whole is constructed and applied to angiogenesis. Cellular studies demonstrate that the tFNAs‐Apt02 complex (TAC) has a conspicuous affinity to human umbilical vein endothelial cells (HUVECs). Further incubation with DMOG yields the tFNAs‐Apt02‐DMOG complex (TACD), which promotes VEGF secretion, in vitro blood vessel formation, sprouting, and migration of HUVECs. Additionally, TACD enhances angiogenesis by upregulating the VEGF/VEGFR and HIF signaling pathways. Moreover, in a diabetic mouse skin defect repair process, TACD increases blood vessel formation and collagen deposition, therefore accelerating wound healing. The novel strategy simulating VEGF and stabilizing HIF promotes blood‐vessel formation in vivo and in vitro and has the potential for broad applications in the vascularization field. Angiogenesis is crucial for tissue engineering, wound healing, and regenerative medicine. Here, a framework nucleic acid‐based nanomaterial is synthesized by combining tFNAs, DNA aptamer Apt02, and DMOG to enhance angiogenesis through upregulating the VEGF/VEGFR and HIF signaling in vitro and in vivo.

This research introduces a novel high-accuracy time-series forecasting method, namely the Time Neural Network (TNN), which is based on a kernel filter and time attention mechanism. Taking into account the complex characteristics of time-series data, such as non-linearity, high dimensionality, and long-term dependence, the TNN model is designed and implemented. The key innovations of the TNN model lie in the incorporation of the time attention mechanism and kernel filter, allowing the model to allocate different weights to features at each time point, and extract high-level features from the time-series data, thereby improving the model’s predictive accuracy. Additionally, an adaptive weight generator is integrated into the model, enabling the model to automatically adjust weights based on input features. Mainstream time-series forecasting models such as Recurrent Neural Networks (RNNs) and Long Short-Term Memory Networks (LSTM) are employed as baseline models and comprehensive comparative experiments are conducted. The results indicate that the TNN model significantly outperforms the baseline models in both long-term and short-term prediction tasks. Specifically, the RMSE, MAE, and R2 reach 0.05, 0.23, and 0.95, respectively. Remarkably, even for complex time-series data that contain a large amount of noise, the TNN model still maintains a high prediction accuracy.

The aim of this study was to estimate the influence of regenerated tobacco on the extraction of Cd from two acidic soils as well as to address the problem of how to deal with contaminated leaves following phytoextraction. Results showed that a coppicing tobacco led to a decline in Cd concentration in regenerated leaves and stalks when plants were grown in pots, but increased concentrations in regenerated lower and middle leaves when plants were grown under field conditions. The highest recorded bioconcentration factors in Chaling and Guanxi soil were 37.53 and 19.21 in lower leaves in the field, respectively. Total Cd extraction efficiency in practice (9.43% for Chaling soil and 6.24% for Guanxi soil) under field conditions confirmed our theoretical calculations (10.0% for Chaling soil and 6.73% for Guanxi soil). Use of a 0.5% hydrochloric acid(HCl) solution was sufficient to reduce Cd (98.4%) in tobacco leaves to permissible levels as required by the Hygienic Standard for Feeds in China (≤0.5 mg kg −1 ). Regenerated tobacco has the potential to allow cultivation of Cd contaminated farmland to produce animal feed, assist in lowering total Cd content of soil, and allow income generation for farmers.

Telomerase Cajal body protein 1 (TCAB1), which is involved in Cajal body maintenance, telomere elongation and ribonucleoprotein biogenesis, has been linked to cancer predisposition, including nasopharyngeal carcinoma (NPC), due to its oncogenic properties. However, there are no specific reports to date on the functional relevance of TCAB1 and Epstein–Barr virus (EBV), which is considered to be a risk factor for NPC. In this study, we first examined NPC clinical tissues and found a notable overexpression of TCAB1 in EBV-positive specimens. Secondly, on a cellular level, we also observed that TCAB1 expression rose gradually along with the increased duration of EBV exposure in NPC cell lines. Additionally, EBV infection promoted cell proliferation and telomerase activity, but the activation was significantly inhibited after TCAB1 knockdown. Moreover, depletion of TCAB1 caused both cell cycle arrest and apoptosis, and suppressed the activation of ataxia telangiectasia and Rad3 related protein (ATR) induced by EBV, resulting in accumulation of DNA damage. Taken together, we here demonstrate that up-regulated expression of TCAB1, induced by EBV in the development of NPC, is involved in stimulating telomerase activity and regulating the DNA damage response within the context of EBV infection.

Objectives Nephrolithiasis (kidney stones) is a common disease with the prevalence that is increasing globally. We previously found that trimethyltin (TMT), a by-product of plastic stabilisers, can inhibit the H+/K+ ATPase activity in renal intercalated cells and alter urinary pH, which is a known risk factor for nephrolithiasis. In this study, we conducted a cross-sectional analysis to evaluate the impact of chronic low level occupational TMT exposure on nephrolithiasis. Methods This study included 216 healthy workers with TMT exposure and 119 workers as controls with no TMT exposure. All study participants were administered a questionnaire and underwent a routine clinical examination including an ultrasonographic screening for kidney stones. Exposures were assessed by measuring TMT concentrations in personal air samples, blood and urine. Logistic regression analysis was used to estimate the ORs and 95% CIs for the risk of kidney stones. Results TMT exposed workers had a higher prevalence of kidney stones (18.06%) in comparison with control workers (5.88%). High TMT concentrations in personal air samples, blood and urines were positively associated with increased prevalence of kidney stones in workers exposed to TMT compared with controls workers (p-trend values=0.005, 0.008 and 0.002, respectively). The length of employment in plants with elevated TMT levels (duration of the exposure) was significantly associated with the increased prevalence of kidney stones (p trend=0.001). The ORs were 2.66 for <3 years, 3.73 for 3–<10 years and 7.89 for 10+ years of employment compared with control workers. Conclusions To our knowledge, this is the first report to demonstrate that occupational exposure to TMT is a potential risk factor for nephrolithiasis.

Several studies have explored the origin and development mechanism of oral lichen planus (OLP) with limited attention to the role of bacteria in the progression of this common oral disease. Here we utilized MiSeq sequencing of 16S rRNA gene amplicons to identify complex oral microbiota associated with OLP from saliva samples of two subtypes (reticular and erosive) of OLP patients and healthy controls. Our analyses indicated that the overall structure of the salivary microbiome was not significantly affected by disease status. However, we did observe evident variations in abundance for several taxonomic groups in OLP. Porphyromonas and Solobacterium showed significantly higher relative abundances, whereas Haemophilus , Corynebacterium , Cellulosimicrobium and Campylobacter showed lower abundances in OLP patients, as compared with healthy controls. In addition, we explored specific microbial co-occurrence patterns in OLP and revealed significantly fewer linkers of Streptococcus comprising species in erosive OLP. Furthermore, the disease severity and immune dysregulation were also genus-associated, including with Porphyromonas that correlated to disease scores and salivary levels of interleukin (IL)-17 and IL-23. Overall, this study provides a general description of oral microbiome in OLP and it will be useful for further investigation of their potential roles in the initiation and immune modulation of OLP.

The increasing integration of renewable energy sources into electrical grids has exacerbated power quality issues, necessitating advanced methods for the rapid detection and precise classification of power quality disturbances (PQDs). This study presents a novel PQD identification approach that integrates two-dimensional feature enhancement with a deep learning framework to address these challenges. The proposed method employs the relative position matrix (RPM) technique to transform PQD signals into visual representations, enhancing 2D feature extraction by capturing temporal dependencies and inter-point relationships through spatial arrangement. Building on this, Spatial Group-wise Enhance (SGE)-MobileViT, an advanced identification and classification technique that autonomously extracts image features, was introduced for accurate PQD detection. The SGE-MobileViT model incorporates an attention mechanism that adaptively adjusts the feature map significance, optimizing feature space scalability and enabling the effective capture of both local features and global contextual relationships. Experimental results demonstrated the model’s superior performance, achieving 99.17% classification accuracy in noiseless environments and maintaining high accuracy (95.13%, 97.00%, and 97.50%) at signal-to-noise ratios of 20 dB, 30 dB, and 50 dB, respectively. The robustness and practical applicability of SGE-MobileViT were further validated through comprehensive simulations and hardware platform implementations including an embedded system demonstration. This study offers a significant advancement in PQD identification, providing a reliable solution for power quality management in modern electrical grids with high renewable energy penetration.

Caries is one of the most prevalent and costly infectious diseases affecting humans of all ages. It is initiated by cariogenic supragingival dental plaques forming on saliva-coated tooth surfaces, yet the etiology remains elusive. To determine which microbial populations may predispose a patient to caries, we report here an in-depth and comprehensive view of the microbial community associated with supragingival dental plaque collected from the healthy teeth of caries patients and healthy adults. We found that microbial communities from caries patients had a higher evenness and inter-individual variations but simpler ecological networks compared to healthy controls despite the overall taxonomic structure being similar. Genera including Selenomonas, Treponema, Atopobium, and Bergeriella were distributed differently between the caries and healthy groups with disturbed co-occurrence patterns. In addition, caries and healthy subjects carried different Treponema, Atopobium, and Prevotella species. Moreover, distinct populations of 13 function genes involved in organic acid synthesis, glycan biosynthesis, complex carbohydrate degradation, amino acid synthesis and metabolism, purine and pyrimidine metabolism, isoprenoid biosynthesis, lipid metabolism, and co-factor biosynthesis were present in each of the healthy and caries groups. Our results suggested that the fundamental differences in dental plaque ecology partially explained the patients’ susceptibility to caries, and could be used for caries risk prediction in the future.