Search Results (227)

Background: Spondylolysis is a stress fracture of the pars interarticularis, most common in adolescents and athletes involved in sports requiring repetitive spinal loading, extension, and rotation. The condition is often underdiagnosed due to delays in presentation and diagnosis, particularly among non-orthopedic providers. Aims: This review aims to summarize the current understanding of spondylolysis, focusing on its etiology, diagnosis, management strategies, and identify gaps in research for future exploration. Methods: A structured literature search was conducted in PubMed to identify studies relevant to pediatric and adolescent spondylolysis, spondylosis, and spondylolisthesis, particularly in the context of athletic injuries. The initial search yielded 143 citations. Applying filters for English language publications within the past five years reduced this to 125 citations. Limiting to populations that were aged 18 years and under returned 50 studies. After screening the titles and abstracts, 12 non-specific or irrelevant articles (including letters to the editor) were excluded, leaving a final dataset of 38 articles for detailed review. In addition, foundational and landmark studies outside this window were included to provide historical and conceptual context, bringing the total evidence base to 50 papers. Findings: Spondylolysis most commonly affects the L5 vertebra, with a higher incidence in male athletes. Conservative treatments like physical therapy and bracing are effective, especially when initiated early. However, the efficacy of bracing remains debated, with limited evidence on long-term clinical benefits. Surgical intervention is considered for severe or non-responsive cases. Diagnostic methods, including CT and MRI, are preferred, with emerging techniques like ultrasound showing potential for non-ionizing, cost-effective, early detection. Implications: Early diagnosis and treatment are crucial for preventing progression to spondylolisthesis. While conservative treatments often yield favorable outcomes, more research is needed to compare the effectiveness of bracing and pharmacological interventions. Future studies should focus on long-term outcomes, cost-effective, non-ionizing diagnostic methods, and the role of emerging therapies like regenerative medicine. A multi-disciplinary approach is vital for optimal patient care, particularly in young athletes. Full article

Gene editing technologies have revolutionized therapeutic development, offering potentially curative and preventative strategies for cardiovascular disease (CVD), which remains a leading global cause of morbidity and mortality. This review provides an introduction to the state-of-the-art gene editing tools—including ZFNs, TALENs, CRISPR/Cas9 systems, base editors, and prime editors—and evaluates their application in lipid metabolic pathways central to CVD pathogenesis. Emphasis is placed on targets such as PCSK9, ANGPTL3, CETP, APOC3, ASGR1, LPA, and IDOL, supported by findings from human genetics, preclinical models, and recent first-in-human trials. Emerging delivery vehicles (AAVs, LNPs, lentivirus, virus-like particles) and their translational implications are discussed. The review highlights ongoing clinical trials employing liver-targeted in vivo editing modalities (LivGETx-CVD) and provides insights into challenges in delivery, off-target effects, genotoxicity, and immunogenicity. Collectively, this review captures the rapid progress of LivGETx-CVD from conceptual innovation to clinical application, and positions gene editing as a transformative, single-dose strategy with the potential to redefine prevention and long-term management of dyslipidemia and atherosclerotic cardiovascular disease. Full article

In plants, cytidine-to-uridine (C-to-U) and uridine-to-cytidine (U-to-C) editing events are directed by pentatricopeptide repeat (PPR) proteins, modular RNA-binding factors that recognize their RNA targets through a predictable amino acid–nucleotide recognition code. Deciphering this code has enabled the rational design of synthetic PPR (synPPR) proteins with programmable RNA-binding specificity and robust stability in heterologous systems. Recent advances have extended these synthetic scaffolds to active RNA editors by fusing them to catalytically competent DYW deaminase domains, generating customizable enzymes capable of precise base conversion in bacteria, plants, and even human cells. This review summarizes current understanding of the structural and mechanistic principles underlying PPR-mediated RNA editing and highlights recent progress in the design and application of synPPR proteins. We discuss how synthetic PPR proteins have been used as programmable RNA stabilizers, translational regulators, and targeted C-to-U or U-to-C editors, as well as their emerging therapeutic potential in RNA-mediated diseases. The development of compact, cofactor-independent editors derived from early-diverging plant lineages further expands the versatility of this platform. Together, these efforts establish synthetic PPR proteins as a powerful and flexible class of RNA engineering tools with applications spanning basic research, biotechnology, and biomedicine. Continued refinement of targeting specificity, catalytic efficiency, and effector modularity will propel PPR-based editors toward broader use in synthetic biology and therapeutic RNA modulation. Full article

Cytosine base editors (CBEs) enable precise C-to-T (G-to-A) conversions in genomic DNA, offering significant potential for specific gene editing. This study compared the prototypical Base Editor 3 (BE3) and a modified variant, BE3-Y130F, which utilizes an hA3A deaminase with the Y130F mutation, focusing on their editing efficiency and editing window characteristics using bovine zygotes. Following in vitro fertilization (IVF), sgRNA and Cas9 mRNA were injected as a targeting efficiency control, which resulted in 100% editing with no wild-type sequence. Then, either BE3 or BE3-Y130F mRNA, synthesized via in vitro transcription, and an sgRNA targeting exon 4 of the MYO7A gene was injected into zygotes. Genomic DNA was extracted from both blastocysts and developmentally arrested embryos, and Sanger sequencing was performed to evaluate C-to-T conversion efficiency and editing window. Both BE3 and BE3-Y130F achieved 100% C-to-T conversion efficiency at the primary target cytosine. BE3 displayed a defined editing window, primarily affecting cytosines at positions 7 and 8, indicating a predictable profile. In contrast, BE3-Y130F maintained high efficiency but had a less clearly defined editing window, resulting in incomplete editing and a remaining cytosine on the target sequence. Full article

Evaluating the quality of fine-grained 3D shape editing, such as adjusting a vehicle’s roof length or wheelbase, is essential for assessing generative models but remains challenging. Most existing metrics depend on auxiliary regressors or large-scale human evaluations, which may introduce bias, reduce reproducibility, and increase evaluation cost. To address these issues, a reference-free metric for evaluating fine-grained 3D shape editing is proposed. The method is based on the Rich-Attribute Sufficiency Assumption (RASA), which posits that when a geometric attribute set is sufficiently comprehensive, models with the same attribute vector should exhibit nearly identical shapes. Following this assumption, the dataset itself serves as a validation source: each source model is edited to match a small set of target attribute vectors, and the post-editing similarity to the targets reflects the editor’s accuracy and stability. Reproducible indicators are defined, including mean similarity, variation across targets, and calibration with respect to attribute distance. Empirical validation demonstrates the effectiveness of the proposed metric, showing approximately 9% degradation under semantic perturbations and less than 2% variation across different target-sampling settings, confirming both its discriminative sensitivity and robustness. This framework provides a low-cost, regressor-free benchmark for fine-grained editing and establishes its applicability through an explicit assumption and evaluation protocol. Full article

The increasing need for precise testing in battery and electronic component development has driven the demand for modular and scalable laboratory systems. This paper presents the design and initial implementation of a LabVIEW-based measurement system tailored for ISO/IEC 17025-compliant testing environments. The system’s software architecture is modular and built around a Hardware Abstraction Layer, enabling the integration of various remotely controlled instruments, such as programmable power supplies, electronic loads, and climate chambers. LabVIEW’s object-oriented programming and multi-threaded execution environment allows synchronized control and real-time data acquisition. Test procedures are defined using a JSON-based sequence structure, supporting repeatable testing. A graphical editor provides an intuitive interface for configuring test steps, ensuring ease of use. The system is designed to support future expansion, including high-speed measurement modules and parallel test execution. This solution lays the foundation for a reliable and extensible automated testing platform that aligns with modern industrial and regulatory standards. Full article

This study presents a heterogeneous PLC-based distributed controller integrating an embedded logic-monitoring blackbox for real-time failover and fault detection in industrial control environments. Industrial automation and water treatment systems heavily rely on programmable logic controllers (PLCs) for process and equipment control. However, frequent failures, transient errors, and unknown malfunctions threaten system reliability and operational continuity. To address these issues, this study proposes a heterogeneous redundancy architecture consisting of a primary PLC and a standby distributed controller equipped with a logic-monitoring blackbox. The blackbox continuously monitors the I/O logic status of the primary PLC, records abnormal behaviors such as I/O faults, and enables the standby controller’s I/O to selectively execute failover operations. Unlike conventional homogeneous redundancy, which depends on identical hardware, the proposed approach adopts a Linux-based platform, offering advantages in flexibility, cost efficiency, and elimination of vendor lock-in. Furthermore, the standby controller integrates both a ladder editor and an HMI editor, allowing for direct on-site modification and editing of faulty I/O without external tools. Experimental validation was conducted using a laboratory testbed, while durability and electromagnetic compatibility (EMC) assessments were performed by an accredited institute to verify industrial applicability. Quantitatively, the mean time between failures (MTBF) increased by 17.2%, the average switchover latency was reduced to 41 ms, and the detection probability ($g$) reached 0.986 under multi-vendor configurations. All tests were performed under controlled industrial conditions using IEC 61508-compliant PLC testbeds. The results confirm that the proposed heterogeneous redundancy method significantly enhances fault detection capability, ensures rapid failover, and improves overall operational reliability in industrial automation systems. Full article

Background: Point mutations in mitochondrial DNA (mtDNA) cause a range of neurometabolic disorders that currently have no curative treatments. The m.8993T>G mutation in the Homo sapiens MT-ATP6 gene leads to neurogenic muscle weakness, ataxia, and retinitis pigmentosa (NARP) when heteroplasmy exceeds approximately 70%. Methods: We engineered a split DddA-derived cytosine base editor (DdCBE), each half fused to programmable TALE DNA-binding domains and a mitochondrial targeting sequence, to correct the m.8993T>G mutation in patient-derived induced pluripotent stem cells (iPSCs). Seven days after plasmid delivery, deep amplicon sequencing showed 35 ± 3% on-target C•G→T•A conversion at position 8993, reducing mutant heteroplasmy from 80 ± 2% to 45 ± 3% with less than 0.5% editing at ten predicted off-target loci. Results: Edited cells exhibited a 25% increase in basal oxygen consumption rate, a 50% improvement in ATP-linked respiration, and a 2.3-fold restoration of ATP synthase activity. Directed neural differentiation yielded 85 ± 2% Nestin-positive progenitors compared to 60 ± 2% in unedited controls. Conclusions: Edits remained stable over 30 days in culture. These results establish mitochondrial base editing as a precise and durable strategy to ameliorate biochemical and cellular defects in NARP patient cells. Full article

Inherited retinal diseases (IRDs) are a clinically and genetically heterogeneous spectrum of disorders that lead to progressive and irreversible vision loss. Gene therapy is the most promising emerging treatment for IRDs. While gene augmentation strategies have demonstrated clinical benefit and results within the first approved ocular gene therapy, their application is restricted by adeno-associated virus (AAV) packaging capacity and limited efficacy for dominant mutations. Recent breakthroughs in precision genome editing, particularly base editing (BE) and prime editing (PE), have provided alternatives capable of directly correcting pathogenic variants. BE enables targeted single-nucleotide conversions, whereas PE further allows for precise insertions and deletions, both circumventing the double-strand DNA cleavage or repair processes typically induced by conventional CRISPR–Cas editing systems, thereby offering advantages in post-mitotic retinal cells. Preclinical investigations across murine and non-human primate models have demonstrated the feasibility, molecular accuracy, and preliminary safety profiles of these platforms in targeting IRD-associated mutations. However, critical challenges remain before clinical application can be realized, including limited editing efficiency in photoreceptors, interspecies variability in therapeutic response, potential risks of off-target effects, and barriers in large-scale vector manufacturing. Moreover, the delivery of genome editors to the outer retina remains suboptimal, prompting intensive efforts in capsid engineering and the development of non-viral delivery systems. This review synthesizes the current progress in BE and PE optimization, highlights innovations in delivery platforms that encompass viral and emerging non-viral systems and summarizes the major barriers to clinical translation. We further discuss AI-driven strategies for the rational design of BE/PE systems, thereby outlining their future potential and perspectives in the treatment of IRDs. Full article

In this study, p-type NiO_x and Cu-doped NiO_x nanoparticles (NPs) were synthesized by a simple chemical precipitation method and used as hole transport layers (HTLs) for inverted perovskite solar cells (PSCs). The microstructural property, surface morphology, elemental composition, optical property, charge recombination, and surface topography of the NiO_x and Cu-NiO_x HTLs were comprehensively characterized. The results showed that the NiO_x and Cu-NiO_x NPs were uniformly coated on the substrates without pinholes or voids. Cu incorporation into NiO_x did not change its crystalline nature and considerably improved its electrical conductivity. The Cu-NiO_x HTLs exhibited superior photoluminescence quenching and the least lifetime decay, which indicated that Cu-NiO_x exhibited higher charge transport than NiO_x HTLs. The fabricated PSC performances were further analyzed using current density–voltage characteristics, external quantum efficiency, and electrochemical impedance spectroscopy. The PSCs with PEDOT:PSS, NiO_x, and 2% Cu-NiO_x HTLs exhibited power conversion efficiencies of 11.93%, 13.72%, and 15.54%, respectively. The 2% Cu-NiO_x HTL-based device showed the best performance compared with the PEDOT:PSS- and NiO_x-based devices. Academic Editors: Chunyang Zhang, Dou Zhang Full article

The solar system is a Basic Competency for grade VI students at SDN 06 Taluak IV Suku. This material encourages students to recognize planets and their characteristics in the solar system, thus requiring interactive learning media. This research develops solar system flashcard learning media based on AR technology to enhance learning interactivity. Using the MDLC method, the application was built with Unity Editor and Vuforia SDK for Android and iOS devices. The application utilizes marker-based and markerless tracking technology to display 3D models of the planets. Flashcards are equipped with engaging images and brief information, as well as a quiz feature for evaluation. Testing showed that the application successfully displayed 3D objects and interactive quiz features. The application is considered to have an attractive appearance, appropriate material, ease of use, and provides an in-depth learning experience about the solar system. Full article

Pulmonary fibrosis (PF) is a progressive and fatal lung disease characterized by irreversible alveolar destruction and pathological extracellular matrix (ECM) deposition. Currently approved agents (pirfenidone and nintedanib) slow functional decline but do not reverse established fibrosis or restore functional alveoli. Multifunctional bioscaffolds present a promising therapeutic strategy through targeted modulation of critical cellular processes, including proliferation, migration, and differentiation. This review synthesizes recent advances in scaffold-based interventions for PF, with a focus on their dual mechano-epigenetic regulatory functions. We delineate how scaffold properties (elastic modulus, stiffness gradients, dynamic mechanical cues) direct cell fate decisions via mechanotransduction pathways, exemplified by focal adhesion–cytoskeleton coupling. Critically, we highlight how pathological mechanical inputs establish and perpetuate self-reinforcing epigenetic barriers to regeneration through aberrant chromatin states. Furthermore, we examine scaffolds as platforms for precision epigenetic drug delivery, particularly controlled release of inhibitors targeting DNA methyltransferases (DNMTi) and histone deacetylases (HDACi) to disrupt this mechano-reinforced barrier. Evidence from PF murine models and ex vivo lung slice cultures demonstrate scaffold-mediated remodeling of the fibrotic niche, with key studies reporting substantial reductions in collagen deposition and significant increases in alveolar epithelial cell markers following intervention. These quantitative outcomes highlight enhanced alveolar epithelial plasticity and upregulating antifibrotic gene networks. Emerging integration of stimuli-responsive biomaterials, CRISPR/dCas9-based epigenetic editors, and AI-driven design to enhance scaffold functionality is discussed. Collectively, multifunctional bioscaffolds hold significant potential for clinical translation by uniquely co-targeting mechanotransduction and epigenetic reprogramming. Future work will need to resolve persistent challenges, including the erasure of pathological mechanical memory and precise spatiotemporal control of epigenetic modifiers in vivo, to unlock their full therapeutic potential. Full article

Base editing represents a major breakthrough in the field of genome editing in recent years. By fusing deaminases with the CRISPR/Cas system, it enables precise single-base modifications of DNA. This review systematically summarizes the development of base editing technologies, including cytosine base editors (CBEs), adenine base editors (ABEs), and glycosylase base editors (GBEs), with a particular focus on their applications in crop improvement as well as future trends and prospects. We highlight advances in the creation of novel germplasm with enhanced stress resistance and desirable agronomic traits through base editing in rice, wheat, maize, potato, and other crops, particularly for improving herbicide resistance, disease resistance, and grain quality. Furthermore, we analyze factors that influence base editing efficiency, noting that challenges remain, such as PAM sequence constraints, limited base conversion types, off-target effects, narrow editing windows, and efficiency variation. Future efforts should aim to optimize deaminase activity, expand PAM compatibility, and develop versatile tools to facilitate the broad application of base editing in molecular breeding. This review provides a timely reference for researchers and breeders, offering theoretical guidance and practical insights into harnessing base editing for crop genetic improvement. Full article

Avian genome editing has historically lagged behind mammalian research. This disparity is primarily due to a unique reproductive biology that precludes standard techniques like pronuclear injection. A pivotal breakthrough, however, came from the development of efficient in vitro culture systems for primordial germ cells (PGCs). This has established the chicken as a tractable and powerful model for genetic engineering. Our review chronicles the technological evolution this has enabled, from early untargeted methods to the precision of modern CRISPR-based systems. We then analyze the broad applications of these tools, which are now used to engineer disease resistance, enhance agricultural traits, and develop novel platforms such as surrogate hosts and oviduct bioreactors. Collectively, these advances have established PGC-based genome editing as a robust and versatile platform. Looking forward, emerging precision editors and the expansion of these techniques to other avian species are poised to drive the next wave of innovation in poultry science and biotechnology. Full article

Repairing the central nervous system (CNS) remains one of the most difficult obstacles to overcome in translational neurosciences. This is due to intrinsic growth inhibitors, extracellular matrix issues, the glial scar–form barrier, chronic neuroinflammation, and epigenetic silencing. The purpose of this review is to bring together findings from recent developments in genome editing and computational approaches, which center around the possible convergence of clustered regularly interspaced short palindromic repeats (CRISPR) platforms and artificial intelligence (AI), towards precision neuroregeneration. We wished to outline possible ways in which CRISPR-based systems, including but not limited to Cas9 and Cas12 nucleases, RNA-targeting Cas13, base and prime editors, and transcriptional regulators such as CRISPRa/i, can be applied to potentially reactivate axon-growth programs, alter inhibitory extracellular signaling, reprogram or lineage transform glia to functional neurons, and block oncogenic pathways in glioblastoma. In addition, we wanted to highlight how AI approaches, such as single-cell multi-omics, radiogenomic prediction, development of digital twins, and design of adaptive clinical trials, will increasingly be positioned to act as system-level architects that allow translation of complex datasets into predictive and actionable therapeutic approaches. We examine convergence consumers in spinal cord injury and adaptive neuro-oncology and discuss expanse consumers in ischemic stroke, Alzheimer’s disease, Parkinson’s disease, and rare neurogenetic syndromes. Finally, we discuss the ethical and regulatory landscape around beyond off-target editing and genomic stability of CRISPR, algorithmic bias, explainability, and equitable access to advanced neurotherapies. Our intent was not to provide a comprehensive inventory of possibilities but rather to provide a conceptual tool where CRISPR acts as a molecular manipulator and AI as a computational integrator, converging to create pathways towards precision neuroregeneration, personalized medicine, and adaptive neurotherapeutics that are ethically sound. Full article