Search Results (326)

Photolithography is the mainstream technology used in micro/nanofabrication. While projection photolithography is widely used in production, with a resolution close to the wavelength of the light source, its processes are complicated and expensive. Moreover, in projection photolithography, scanning and splicing are required to achieve large-area exposure at the wafer level, which reduces throughput in production. Contact photolithography offers a cost-effective and parallel exposure solution, but achieving uniform resolution over large areas with micrometer or sub-micrometer resolution remains a challenge. In this study, we propose a conformal contact photolithography strategy based on a wafer-scale embedded elastomeric mask. By optimizing metal patterning and embedding transfer processes, we significantly improve the area (wafer-scale) and efficiency (lift-off and metal transfer process within seconds) of metal-embedded elastomeric mask fabrication. This method enables the rapid and cost-effective fabrication of large-area sub-micrometer-resolution structures, with broad applications in the production of sub-micrometer devices and academic research. Full article

Advances in technology have provided a better understanding of the genetic basis of neurodegenerative disorders and their underlying molecular pathophysiology. However, treating these disorders with conventional strategies is a major challenge. The approval of gene targeted therapy for spinal muscular atrophy (SMA) has laid the foundation for developing highly personalized therapies for other neurodegenerative disorders. As intensive research and efforts to advance gene targeted therapies continue, this review provides an overview of viral and non-viral vectors and delivery methods, as well as treatment strategies, including gene addition, replacement, editing, silencing, and splice modulation. Gene targeted approaches and clinical trials for SMA and amyotrophic lateral sclerosis (ALS) have demonstrated success, and additional studies are in progress. The design of efficient clinical trials which facilitate successful translation into clinical practice is of critical importance. Key considerations include the selection of appropriate disease models, understanding the natural history of the disease, and establishing well-defined outcome measures to assess prognosis of the disease and therapeutic efficacy. Finally, the precision of CRISPR-based gene editing offers the potential for one-time corrective therapies for monogenic disorders like SMA and SOD1-ALS. Full article

This work presents a compact broadband in-fiber polarization filter using gold-deposited square-lattice photonic crystal fiber (PCF) numerically. The finite element method (FEM) is utilized to analyze the transmission characteristics of this PCF. The simulation results indicate that when the cladding hole diameter is 1.5 μm, the large hole diameter is 2.1 μm, the long axis of elliptical holes is 1.96 μm, the short axis of elliptical holes is 0.98 μm, the pitch is 2 μm, and the gold layer thickness is 50 nm, the x-polarized mode can interact with two plasmonic modes, and two surface plasmon resonance (SPR) processes at two common communication windows can be achieved. The length of this PCF filter is set as 0.5 mm, exhibiting the maximum extinction ratio (ER) of −51.4 dB at 1.31 μm and −47.3 dB at 1.55 μm, and the operating bandwidth of >860 nm. Additionally, the estimated splice losses are ~2.22 dB at 1.31 μm and ~1.42 dB at 1.55 μm. It is expected that this small-size PCF-SPR filter, characterized by its efficient filtering performance and wide bandwidth, will serve as a promising candidate for building integrated networks that combine optical fiber communication, sensing, and computing capabilities. Full article

Background: Retinal and optic nerve disorders are a leading cause of irreversible visual impairment worldwide. Advances in molecular genetics—including next-generation sequencing, genome-wide association studies, and gene-based therapeutic technologies—have reshaped understanding of both inherited and complex retinal diseases. However, translating genetic discovery into sustained clinical benefit remains biologically and practically constrained. Methods: A structured literature search was conducted using PubMed and Scopus to identify relevant studies published between 2015 and 2025. The search focused on molecular genetics, epigenetic modulation, mitochondrial biology, and translational applications in inherited retinal dystrophies and selected complex retinal diseases, prioritizing high-impact original research and systematic reviews addressing diagnostic innovation and therapeutic development. Results: Inherited retinal dystrophies represent the most advanced model of precision ophthalmology, with diagnostic yields approaching 70–80% in well-characterized cohorts. Gene augmentation and genome-editing strategies have demonstrated proof-of-concept efficacy, yet clinical benefit depends on residual cellular viability, delivery efficiency, and durability of expression. Emerging platforms include AAV-mediated gene transfer, in vivo CRISPR-based editing, RNA-directed splice modulation, and mitochondrial-targeted approaches. Persistent barriers include unresolved non-coding and structural variants, variant interpretation uncertainty, and endpoint selection in clinical trials. In contrast, complex retinal diseases such as glaucoma, age-related macular degeneration, and pathological myopia reflect polygenic susceptibility interacting with environmental and aging-related factors. Although polygenic risk scores refine probabilistic prediction, their utility is limited by ancestry bias and incomplete predictive performance. Epigenetic and mitochondrial mechanisms further modulate disease expression but remain largely non-actionable in routine practice. Conclusions: Retinal genetics has progressed from gene discovery to early therapeutic implementation. Future advances will depend on improved variant detection, functional validation, biomarker-guided staging, and integration of genomics with imaging and longitudinal modeling to achieve durable and equitable precision ophthalmology. Full article

Duchenne muscular dystrophy (DMD) is a severe X-linked neuromuscular disease (NMD) caused by loss-of-function mutations in the DMD gene. RNA-based therapies, especially antisense oligonucleotides (ASO)-mediated exon skipping and adenosine deaminase acting on RNA (ADAR)-guided RNA editing, have emerged as complementary approaches that modulate pre-mRNA splicing or correct transcripts without altering genomic DNA. Current phosphorodiamidate morpholino oligomer (PMO) drugs targeting exons 51, 53, and 45 provide mutation-class-specific benefit. At the same time, next-generation delivery strategies (e.g., peptide-conjugated PMOs (PPMOs), antibody–oligonucleotide conjugates (AOC), and endosomal-escape vehicles) aim to improve skeletal, cardiac, and diaphragm exposure. In parallel, RNA editing strategies offer a route to correct select nonsense or missense variants at the base level and may, in principle, restore near-native dystrophin expression. Meaningful translation of these modalities requires predictive large-animal models. A genome-edited microminipig (MMP) bearing DMD exon-23 mutations faithfully recapitulates hallmark features of human DMD. That includes early locomotor deficits, elevated serum creatine kinase (CK) and cardiac troponin T, progressive myocardial fibrosis, and a decline in left-ventricular ejection fraction (LVEF), while maintaining a manageable lifespan of approximately 30 months suitable for long-term studies. In particular, the MMP model provides a practical platform for addressing the persistent challenge of efficient therapeutic delivery to the heart and diaphragm through longitudinal dosing, imaging, and biopsy. In this review, we synthesize clinical progress in exon skipping, outline the promise of RNA editing, and integrate recent insights from Duchenne muscular dystrophy model for microminipigs (DMD-MMPs) as an advanced surrogate for preclinical development and translational evaluation. Full article

Cashmere goats produce high-value fine fibers derived from secondary hair follicles; however, the molecular mechanisms underlying this trait remain incompletely understood. In this study, comparative transcriptome sequencing was performed on skin tissues from Inner Mongolian cashmere goats and normal goats to characterize gene expression differences associated with cashmere fiber production. High-quality RNA-seq data with strong mapping efficiency and reproducibility were obtained across all samples. Differential expression analysis identified 1543 significantly differentially expressed genes (DEGs) between cashmere and normal goats, including genes involved in hair follicle morphogenesis, epidermal differentiation, cell proliferation, and extracellular matrix organization. Multivariate analyses showed a clear transcriptomic separation between fleece types, indicating that fleece phenotype is the primary driver of variation in global gene expression. Functional enrichment revealed significant involvement of the Wnt, MAPK, and PI3K–Akt signaling pathways, and several biologically relevant regulators of hair follicle development and hair cycle control, including FGF5, SOX9, LHX2, and VDR, were differentially expressed. Gene fusion events were rare and showed no group specific patterns, whereas alternative splicing was widespread, with exon skipping as the predominant splicing event in goat skin. Overall, these results provide quantitative transcriptomic evidence linking signaling regulation, follicle development, and structural differentiation to secondary hair follicle activity and cashmere fiber formation, offering candidate genes and molecular pathways for functional validation and molecular breeding in cashmere goats. Full article

Next-generation sequencing (NGS) and antisense oligonucleotide (ASO) technologies are converging to transform the diagnosis and treatment of rare monogenic disorders. NGS enables comprehensive, single-test molecular diagnoses through targeted panels, whole-exome sequencing, and whole-genome sequencing, which together reveal pathogenic variants across coding, intronic, and structural domains. Integration with transcriptomic analyses, including RNA sequencing, further refines genotype–phenotype correlations and identifies splicing aberrations amenable to correction by ASOs. Therapeutic advances now span RNase H1-dependent gapmers for transcript knockdown, splice-modulating phosphorodiamidate morpholino oligomers (PMOs), and peptide/antibody-conjugated PMOs that enhance muscle and cardiac delivery. These platforms underpin the rise in N-of-1 ASO therapies—customized drugs developed for individual patients with unique pathogenic variants. Landmark cases such as Milasen and Atipeksen illustrate the clinical feasibility and ethical complexities of personalized RNA therapeutics, while updated FDA guidance supports expedited, patient-specific investigational pathways. Despite progress, challenges persist in delivery efficiency, long-term efficacy, and equitable access. Emerging approaches—including long-read sequencing, AI-driven oligo design, and improved delivery—promise to extend ASO precision and reach. This review synthesizes current advances linking genomic diagnosis to individualized RNA-targeted interventions, outlining how integrated NGS-ASO pipelines are reshaping the therapeutic landscape for rare genetic diseases. Full article

Adenoviral vectors are among the most efficient platforms for gene delivery; however, the level and pattern of transgene expression in these vectors are largely shaped by the viral genomic context. This review discusses the mechanisms of adenoviral transcription and alternative splicing and how they influence the expression of inserted expression cassettes. Particular attention is given to the role of insertion orientation and transgene placement within the E1 and E3 regions, as well as to the effects of viral regulatory elements, including the E1A enhancer. We analyze evidence on the use of insulating sequences to reduce nonspecific activation and improve the controllability of transgene expression. We also consider the use of endogenous adenoviral promoters—the major late promoter (MLP) and the E3 region promoter—and their contribution to enhanced transgene expression through late viral transcription. Overall, these findings support principles for the rational design of adenoviral vectors, both for high-level protein production and for building systems with regulated or tissue-specific expression. Full article

Due to their advantages of being low-cost, lightweight and flexible, and having wide shooting coverage, UAVs have played an important role in situational awareness in the fields of disaster prevention and mitigation, urban planning and management, etc. In these applications, UAV aerial photography is limited by the field of view, and high-definition panoramic images of the complete target area cannot be obtained. Image mosaic technology is essential, but an image mosaic using only a single UAV cannot meet the high real-time requirements for situational awareness. In response to the above problems, this paper proposes a multi-UAV fast aerial image mosaic method based on key frames. First, the multi-UAV area coverage flight strategy is determined according to the size of the task area and the UAV flight parameters; then, the field of view of the pod, the flight speed, and the flight altitude are used to determine the key frame extraction time period during the UAV aerial photography process. The image matching-rate calculation method is designed and the key frames are extracted during the extraction time period, and the key frames are returned to the ground visual puzzle system; in the ground visual puzzle system, the improved Laplacian pyramid method is used to quickly fuse and stitch the key frames extracted by each UAV to obtain a panoramic stitched map. The experiment shows that the method can quickly obtain high-precision real-scene map information of the task area. Compared with the single-UAV method and the multi-UAV full video stream-splicing method, this method greatly reduces the consumption of computing power and the requirements of communication bandwidth and improves the efficiency and real-time performance of panoramic map acquisition. Full article

Improving phosphorus use efficiency (PUE) in crops is critical for sustainable agriculture. Although the transcriptional regulation of phosphate starvation responses, centered on regulators such as the PHR1 and SPX proteins, is well established, the post-transcriptional mechanisms remain incompletely understood. This gap hinders a comprehensive view of how plants adapt to low-P conditions. This review synthesizes current knowledge on the gene regulatory networks involved in low-P adaptation in barley, with a specific focus on the emerging role of RNA processing. It highlights the limited knowledge of how alternative splicing contributes to this response. AS provides a rapid and energy-efficient means of fine-tuning gene expression, expanding proteome diversity and enabling more sophisticated adaptation mechanisms than the relatively binary “on/off” mode of transcriptional control. Several core regulators of AS, including serine–arginine-rich proteins and hnRNPs, have been identified, with the former discussed in detail and illustrated with key examples. Building on the advanced mechanistic insights into AS gained from model crops such as rice, this review proposes a predictive framework to prioritize research targets and experimental strategies. Such an approach can accelerate the discovery of analogous mechanisms in barley, thereby bridging a critical knowledge gap and advancing strategies to improve PUE in this important cereal crop. Full article

With production growth and improvements in production speed in modern industries, accurate anomaly detection is becoming increasingly important to improve quality inspection efficiency and help minimize production costs. Existing reconstruction-based methods achieve promising anomaly detection results in some scenarios. However, when large-scale anomalies exist, the generalization ability of these methods is limited, and it is difficult to reconstruct the anomalies effectively into normal areas, which may lead to unsatisfactory results. To address this issue, this paper proposes a novel network architecture called SeRNet, which comprises three components: a segmentation sub-network, a reconstruction sub-network, and a repair module. SeRNet addresses the challenge of large-scale anomaly reconstruction by utilizing the segmentation sub-network for pre-segmentation, the repair module for repairing the large-scale anomalies using normal images similar to the test images, and the reconstruction sub-network for processing small-scale anomalies and anomalies in the repaired splices. Additionally, this paper introduces two methods for generating pseudo-anomalies at different scales. SeRNet leverages the advantages of both the segmentation sub-network, which is effective at segmenting large-scale anomalies, and the reconstruction sub-network, which can effectively reconstruct small-scale anomalies. Experiments on the MVTec AD industrial dataset demonstrate that SeRNet delivers outstanding performance, achieving an image-level AUROC score of 99.6. Full article

This research presents a lens-based light collection system that integrates a handmade glass conical waveguide (GCW) with a single silica multimodal optical fiber (SMMF) and a concentrator Fresnel lens (FL). The GCW functions as a secondary optical element (SOE), effectively expanding the fiber’s receptive area and enabling efficient coupling of concentrated light. Calibrated ray-tracing simulations confirm that the complete FL + GCW + SMMF configuration maintains low transmission losses, thereby validating efficient coupling into the SMMF. Experimental results demonstrated a maximum net optical efficiency of 41% at an FL numerical aperture (NA) of 0.08, with GCW transmission reaching 60% and splice losses to the SMMF around 34%. With a luminous flux input of 155 lumens, the system delivered up to 63 lumens at the fiber output. Importantly, the FL + GCW + SMMF configuration combines reproducible fabrication, straightforward assembly, and reliable characterization, establishing a scalable pathway for daylight harvesting. The major contribution of this work is the demonstration that a simple, manufacturable GCW can substantially expand the effective collection area of multimodal fibers while preserving low optical losses, thereby bridging practical design with efficient energy transfer for sustainable photonics applications. Full article

Disease-specific diversity in RNA transcripts stems from RNA splicing, ribosomal abnormalities, and other factors. However, the mechanisms underlying the regulation of rRNA expression in the nucleolus and mRNA expression in the cytoplasm during cancer and neuronal differentiation remain largely unknown. In this article, we review current knowledge and discuss the regulatory mechanisms of rRNA and mRNA expression in human diseases using the splicing model of PUF60 (poly(U) binding splicing factor 60)—also known as FUSE-binding protein-interacting repressor (FIR) (FUBP1-interacting repressor), RoBPI, SIAHBP1, and VRJS (Gene ID: 22827). Noncoding RNAs, much like coding RNAs, have been found to be translated into proteins with significant physiological functions. Splicing is also involved in dominant ORF RNAs implicated in the expression of both noncoding and coding RNAs. Here, we analyze recent findings regarding gene splicing, ribosome formation, and the determination of selected ORFs (dominant ORFs) in a system modeled on FIR splicing in two databases (RefSeq and ENSEMBL). rRNA transcription affects ribosomes, whereas mRNA expression and splicing affect the intracellular proteome. Our objective is to develop efficient methods for identifying biomarkers for disease diagnosis and therapeutic targets. In the field of cancer treatment, therapeutic drugs targeting intracellular signaling have proven effective. Full article

Despite years of study, the biological role of the human proinsulin connecting peptide (C-peptide) remains poorly understood. Nevertheless, the C-peptide exhibits subdomains including conserved residues that are thought to have co-evolved with the insulin moiety of proinsulin. Genome-wide association studies in humans suggest that alterations of glycemic control may exhibit a possible linkage with the presence of certain C-peptide variants other than frame-shifts, stop codons, alternative splice variants, or the addition of an extra unpaired Cys residue. Although the C-peptide is ultimately excised from insulin, here, we have bioengineered missense mutations in the amino-terminal portion of the C-peptide (especially involving or near preproinsulin residues Q62,V63) that we find impair proinsulin folding and trafficking efficiency and, in this way, impair insulin biogenesis. We show that proinsulin bearing a C-peptide missense variant can also physically interact with co-expressed wildtype proinsulin, affecting the trafficking behavior of both proinsulin proteins in a manner that is directly related to the relative expression ratio of the variant and wildtype gene products. We conclude that in addition to other possible functions, the amino-terminal portion of the C-peptide influences proinsulin folding and trafficking and, in this way, affects human insulin production. Full article

To elucidate the physiological and molecular mechanisms underlying cold tolerance in the mangrove species Kandelia obovata Sheue & al, this study measured the antioxidant enzyme activities and photosynthetic pigment contents of two populations—cold-tolerant and -sensitive—under natural overwintering conditions. In addition, transcriptome sequencing was performed to analyze differentially expressed genes (DEGs), transcription factor families, single nucleotide polymorphisms (SNPs), and alternative splicing events. The results showed that catalase activity was significantly elevated in the cold-tolerant population, which enhanced the efficiency of hydrogen peroxide scavenging. In contrast, although the superoxide dismutase activity was relatively high in the cold-sensitive population, its downstream scavenging capacity was insufficient, resulting in an overall lower antioxidant efficiency. The KEGG enrichment analysis indicated that pathways such as phenylpropanoid biosynthesis, amino sugar metabolism, and plant hormone signal transduction might be involved in the response to low-temperature stress. Further analysis revealed that transcription factors such as WRKY, NAC, MYB, and ERF were differentially expressed at significant levels in the cold-tolerant population, suggesting that they may play important roles in low-temperature adaptation. In addition, the diversity of SNPs and alternative splicing events may enhance protein function and contribute to improved cold tolerance. In summary, the cold-tolerant K. obovata population achieves low-temperature tolerance through multiple mechanisms, including antioxidant defense, metabolic regulation, and transcriptional as well as post-transcriptional regulation. This study provides a theoretical basis for elucidating the molecular foundations of cold tolerance in K. obovata. Full article