Photoactive nanocatalysts as DTT-assisted BSA-AuNCs with enhanced oxidase-mimicking ability for sensitive fluorometric detection of antioxidants.

Redox imbalance and oxidative stress are increasingly recognized as significant factors in health disorders such as neurodegenerative disorders, premature aging and cancer. However, detecting antioxidant levels that is crucial for managing oxidative stress, can be challenging due to existing assays' limitations, such as insensitivity to thiol-containing antioxidants. This study presents a simple fluorescence-based assay for antioxidant detection employing the enhanced photocatalytic oxidase-like activity of dithiothreitol (DTT)-assisted bovine serum albumin (BSA)-stabilized gold nanoclusters (DTT@BSA-AuNCs). The reported nanozyme exhibits remarkable stability, versatility, and catalytic activity. Under LED irradiation, DTT@BSA-AuNCs generate singlet oxygen, which converts non-fluorescent thiamine to fluorescent thiochrome, utilizing dissolved oxygen for catalysis. Antioxidants inhibit thiochrome formation, leading to fluorescence quenching. This method enables sensitive detection of antioxidants such as ascorbic acid and glutathione with limits of detection of 0.08 µM and 0.32 µM, respectively, under neutral pH, outperforming previous studies. The assay successfully detects antioxidants in human saliva and cancer cell models. The DTT@BSA-AuNCs-based assay offers a cost-effective, sensitive, and straightforward approach for detecting antioxidants in biological samples, facilitating improved monitoring of oxidative stress in various diseases.

Relationship between phthalate exposure and kidney function in Taiwanese adults as determined through covariate-adjusted standardization and cumulative risk assessment.

Few studies have investigated the associations between phthalate exposure and kidney function indicators in adults by simultaneously performing covariate-adjusted creatinine standardization, cumulative risk assessment, and mixture analysis. Thus, we applied these methods simultaneously to investigate the aforementioned associations in an adult population. This cross-sectional study analyzed data (N = 839) from a community-based arm of the Taiwan Biobank. The levels of 10 urinary phthalate metabolites were measured and calculated as the sum of the molar concentrations of the dibutyl phthalate metabolite (ΣDBPm) and di(2-ethylhexyl) phthalate (DEHP) metabolite (ΣDEHPm). The hazard index (HI) and daily intake (DI) were estimated by measuring the urinary levels of the phthalate metabolite. Kidney function biomarkers were assessed by measuring the following: blood urea nitrogen (BUN), uric acid, the albumin-to-creatinine ratio (ACR), and the estimated glomerular filtration rate (eGFR). Generalized linear models were implemented to examine the associations between exposure to individual phthalates, HI scores, and kidney function biomarkers. We also employed Bayesian kernel machine regression (BKMR) to analyze the relationships between exposure to various combinations of phthalates and kidney function. ΣDEHPm levels were significantly and positively associated with BUN and ACR levels, and ΣDBPm levels were positively associated with ACR levels. In addition, eGFR was negatively associated with ΣDBPm and ΣDEHPm levels. In the BKMR model, a mixture of 10 phthalate metabolites was significantly associated with BUN, uric acid, ACR, and eGFR results. Higher DIDEHP and higher DIDnBP values were significantly associated with lower eGFRs and higher ACRs, respectively. Higher DIDiBP and DIDEP values were significantly associated with higher uric acid levels. A higher HI was significantly associated with lower eGFRs and higher ACRs. Our results suggest that exposure to environmental phthalates is associated with impaired kidney function in Taiwanese adults.

Outcomes after arthroscopic treatment for scaphoid nonunion using ipsilateral radius bone graft and a headless compression screw: a comparison between the patients with and without avascular necrosis.

PURPOSE: To determine whether avascular necrosis can affect clinical outcomes or the union incidence after arthroscopic bone grafting for the treatment of scaphoid nonunion. METHODS: This retrospective comparative study included thirty-four patients with scaphoid nonunion that underwent arthroscopic bone graft from the ipsilateral radius and internal fixation. The patients were divided into two cohorts (group A, with avascular necrosis, n = 15; group B, without avascular necrosis, n = 19) based on pre-operative magnetic resonance imaging findings. Additionally, the patients were grouped in accordance with the location of nonunion (waist, n = 27; proximal pole, n = 7). The mean follow-up was 20.7 months (range 12.0-40.0 months). Clinical outcomes, including the visual analog scale (VAS) pain score, grip strength, range of motion (ROM), Mayo Wrist Score (MWS), and Disabilities of the Arm, Shoulder, and Hand (DASH) score, were evaluated. Radiographic measurements for carpal bone alignment were assessed as well. RESULTS: Union rates did not differ between groups (group A, 93.3%; group B, 94.7%: p = 0.863), and the post-operative VAS pain score, ROM, and MWS were similar at follow-up for a minimum of one year. DASH and grip strength were significantly better in group B, but the intergroup differences were minimal (mean DASH 11.9 versus 9.6; mean grip strength 77.5% versus 95.4% of contralateral side). There was no significant intergroup difference in mean time to achieving union (group A, 14.9 weeks; group B, 14.6 weeks; p = 0.900). In post-operative radiographic assessments, no significant intergroup differences were noted in any of the parameters. Subgroup analysis regarding the location of nonunion showed there were no significant intergroup differences in union rates, mean time to achieving union, and clinical outcome measures at the last post-operative follow-up. CONCLUSIONS: Arthroscopic bone grafting and internal fixation in the treatment of scaphoid nonunion provided good union rates and satisfactory outcomes regardless of vascularity status.

Erythropoietin in Glaucoma: From Mechanism to Therapy.

Glaucoma can cause irreversible vision loss and is the second leading cause of blindness worldwide. The disease mechanism is complex and various factors have been implicated in its pathogenesis, including ischemia, excessive oxidative stress, neurotropic factor deprivation, and neuron excitotoxicity. Erythropoietin (EPO) is a hormone that induces erythropoiesis in response to hypoxia. However, studies have shown that EPO also has neuroprotective effects and may be useful for rescuing apoptotic retinal ganglion cells in glaucoma. This article explores the relationship between EPO and glaucoma and summarizes preclinical experiments that have used EPO to treat glaucoma, with an aim to provide a different perspective from the current view that glaucoma is incurable.

Circulating tumor cells: A step toward precision medicine in hepatocellular carcinoma.

Serum alpha-fetoprotein and radiologic imaging are the most commonly used tests for early diagnosis and dynamic monitoring of treatment response in hepatocellular carcinoma (HCC). However, the accuracy of these tests is limited, and they may not reflect the underlying biology of the tumor. Thus, developing highly accurate novel HCC biomarkers reflecting tumor biology is a clinically unmet need. Circulating tumor cells (CTCs) have long been proposed as a noninvasive biomarker in clinical oncology. Most CTC assays utilize immunoaffinity-based, size-based, and/or enrichment-free mechanisms followed by immunocytochemical staining to characterize CTCs. The prognostic value of HCC CTC enumeration has been extensively validated. Subsets of CTCs expressing mesenchymal markers are also reported to have clinical significance. In addition, researchers have been devoting their efforts to molecular characterizations of CTCs (e.g. genetics and transcriptomics) as molecular profiling can offer a more accurate readout and provide biological insights. As new molecular profiling techniques, such as digital polymerase chain reaction, are developed to detect minimal amounts of DNA/RNA, several research groups have established HCC CTC digital scoring systems to quantify clinically relevant gene panels. Given the versatility of CTCs to provide intact molecular and functional data that reflects the underlying tumor, CTCs have great potential as a noninvasive biomarker in HCC. Large-scale, prospective studies for HCC CTCs with a standardized protocol are necessary for successful clinical translation.

Nanoparticles-mediated CRISPR-Cas9 gene therapy in inherited retinal diseases: applications, challenges, and emerging opportunities.

Inherited Retinal Diseases (IRDs) are considered one of the leading causes of blindness worldwide. However, the majority of them still lack a safe and effective treatment due to their complexity and genetic heterogeneity. Recently, gene therapy is gaining importance as an efficient strategy to address IRDs which were previously considered incurable. The development of the clustered regularly-interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9) system has strongly empowered the field of gene therapy. However, successful gene modifications rely on the efficient delivery of CRISPR-Cas9 components into the complex three-dimensional (3D) architecture of the human retinal tissue. Intriguing findings in the field of nanoparticles (NPs) meet all the criteria required for CRISPR-Cas9 delivery and have made a great contribution toward its therapeutic applications. In addition, exploiting induced pluripotent stem cell (iPSC) technology and in vitro 3D retinal organoids paved the way for prospective clinical trials of the CRISPR-Cas9 system in treating IRDs. This review highlights important advances in NP-based gene therapy, the CRISPR-Cas9 system, and iPSC-derived retinal organoids with a focus on IRDs. Collectively, these studies establish a multidisciplinary approach by integrating nanomedicine and stem cell technologies and demonstrate the utility of retina organoids in developing effective therapies for IRDs.

The Latest Evidence of Erythropoietin in the Treatment of Glaucoma.

Erythropoietin (EPO) is a circulating hormone conventionally considered to be responsible for erythropoiesis. In addition to facilitating red blood cell production, EPO has pluripotent potential, such as for cognition improvement, neurogenesis, and anti-fibrotic, anti-apoptotic, anti-oxidative, and anti-inflammatory effects. In human retinal tissues, EPO receptors (EPORs) are expressed in the photoreceptor cells, retinal pigment epithelium, and retinal ganglion cell layer. Studies have suggested its potential therapeutic effects in many neurodegenerative diseases, including glaucoma. In this review, we discuss the correlation between glaucoma and EPO, physiology and potential neuroprotective function of the EPO/EPOR system, and latest evidence for the treatment of glaucoma with EPO.

Erythropoietin in Optic Neuropathies: Current Future Strategies for Optic Nerve Protection and Repair.

Erythropoietin (EPO) is known as a hormone for erythropoiesis in response to anemia and hypoxia. However, the effect of EPO is not only limited to hematopoietic tissue. Several studies have highlighted the neuroprotective function of EPO in extra-hematopoietic tissues, especially the retina. EPO could interact with its heterodimer receptor (EPOR/ßcR) to exert its anti-apoptosis, anti-inflammation and anti-oxidation effects in preventing retinal ganglion cells death through different intracellular signaling pathways. In this review, we summarized the available pre-clinical studies of EPO in treating glaucomatous optic neuropathy, optic neuritis, non-arteritic anterior ischemic optic neuropathy and traumatic optic neuropathy. In addition, we explore the future strategies of EPO for optic nerve protection and repair, including advances in EPO derivates, and EPO deliveries. These strategies will lead to a new chapter in the treatment of optic neuropathy.

Neuro-ophthalmological Presentation of Optic Neuritis in Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease.

Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a rare demyelinating autoimmune disorder of the central nervous system. MOGAD frequently manifests with severe, bilateral, and episodes of recurrent optic neuritis (ON) and is an important differential diagnosis to multiple sclerosis and aquaporin-4-IgG seropositive neuromyelitis optica spectrum disorders. Besides ON, the clinical manifestations of MOGAD commonly include transverse myelitis, acute disseminated encephalomyelitis, and brain stem encephalitis. In this review, we summarize the current knowledge of the neuro-ophthalmological presentation of MOGAD-ON. We describe epidemiological aspects, including the association with COVID-19 and other infections or vaccinations, clinical presentation, and imaging findings of MOGAD-ON in the acute stage and during remission. Furthermore, we report findings on prognosis, treatment response, and changes in ON-unaffected eyes. We touch upon findings on visual acuity, visual fields, and visual evoked potentials, as well as structural changes assessed with optical coherence tomography. Moreover, we explain how to differentiate MOGAD from its differential diagnoses, including other neuroinflammatory disorders (multiple sclerosis and neuromyelitis optica spectrum disorders), but also idiopathic intracranial hypertension.

Delayed Onset Bilateral Papilledema in a Young Boy's Eyes after Trauma.

Cerebral venous sinus thrombosis (CVST) is a rare venous thromboembolic disease that affects young adults in their thirties, with a female predilection. Head trauma accounts for only 1-3% of cases among possible etiologies. Here, we present a particular case of trauma-related CVST with delayed-onset symptoms and signs in a young boy. A 12-year-old boy presented to the emergency department with non-specific visual symptoms 11 days after head trauma. Apart from mild-grade disc swelling in the right eye and dyschromatopsia in both eyes, no significant findings were revealed during physical examinations and a non-contrast cranial computed tomography (CT) scan. Unfortunately, the patient suffered multiple seizure attacks the following day. Trauma-related CVST, complicated by delayed-onset increased intracranial pressure, and bilateral papilledema were finally diagnosed. Physicians need increased awareness of a possible CVST diagnosis if a patient with a history of head trauma shows persistent or worsening neurological symptoms despite negative results on serial non-contrast cranial CT scans.

Supramolecular Nanosubstrate-Mediated Delivery for CRISPR/Cas9 Gene Disruption and Deletion.

The clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein 9 (CRISPR/Cas9) is an efficient and precise gene-editing technology that offers a versatile solution for establishing treatments directed at genetic diseases. Currently, CRISPR/Cas9 delivery into cells relies primarily on viral vectors, which suffer from limitations in packaging capacity and safety concerns. These issues with a nonviral delivery strategy are addressed, where Cas9•sgRNA ribonucleoprotein (RNP) complexes can be encapsulated into supramolecular nanoparticles (SMNP) to form RNP⊂SMNPs, which can then be delivered into targeted cells via supramolecular nanosubstrate-mediated delivery. Utilizing the U87 glioblastoma cell line as a model system, a variety of parameters for cellular-uptake of the RNP-laden nanoparticles are examined. Dose- and time-dependent CRISPR/Cas9-mediated gene disruption is further examined in a green fluorescent protein (GFP)-expressing U87 cell line (GFP-U87). The utility of an optimized SMNP formulation in co-delivering Cas9 protein and two sgRNAs that target deletion of exons 45-55 (708 kb) of the dystrophin gene is demonstrated. Mutations in this region lead to Duchenne muscular dystrophy, a severe genetic muscle wasting disease. Efficient delivery of these gene deletion cargoes is observed in a human cardiomyocyte cell line (AC16), induced pluripotent stem cells, and mesenchymal stem cells.

Molecular Mechanisms Underlying Remodeling of Ductus Arteriosus: Looking beyond the Prostaglandin Pathway.

The ductus arteriosus (DA) is a physiologic vessel crucial for fetal circulation. As a major regulating factor, the prostaglandin pathway has long been the target for DA patency maintenance or closure. However, the adverse effect of prostaglandins and their inhibitors has been a major unsolved clinical problem. Furthermore, a significant portion of patients with patent DA fail to respond to cyclooxygenase inhibitors that target the prostaglandin pathway. These unresponsive medical patients ultimately require surgical intervention and highlight the importance of exploring pathways independent from this well-recognized prostaglandin pathway. The clinical limitations of prostaglandin-targeting therapeutics prompted us to investigate molecules beyond the prostaglandin pathway. Thus, this article introduces molecules independent from the prostaglandin pathway based on their correlating mechanisms contributing to vascular remodeling. These molecules may serve as potential targets for future DA patency clinical management.

An Update on Gene Therapy for Inherited Retinal Dystrophy: Experience in Leber Congenital Amaurosis Clinical Trials.

Inherited retinal dystrophies (IRDs) are a group of rare eye diseases caused by gene mutations that result in the degradation of cone and rod photoreceptors or the retinal pigment epithelium. Retinal degradation progress is often irreversible, with clinical manifestations including color or night blindness, peripheral visual defects and subsequent vision loss. Thus, gene therapies that restore functional retinal proteins by either replenishing unmutated genes or truncating mutated genes are needed. Coincidentally, the eye's accessibility and immune-privileged status along with major advances in gene identification and gene delivery systems heralded gene therapies for IRDs. Among these clinical trials, voretigene neparvovec-rzyl (Luxturna), an adeno-associated virus vector-based gene therapy drug, was approved by the FDA for treating patients with confirmed biallelic RPE65 mutation-associated Leber Congenital Amaurosis (LCA) in 2017. This review includes current IRD gene therapy clinical trials and further summarizes preclinical studies and therapeutic strategies for LCA, including adeno-associated virus-based gene augmentation therapy, 11-cis-retinal replacement, RNA-based antisense oligonucleotide therapy and CRISPR-Cas9 gene-editing therapy. Understanding the gene therapy development for LCA may accelerate and predict the potential hurdles of future therapeutics translation. It may also serve as the template for the research and development of treatment for other IRDs.

Identification of Novel Genomic-Variant Patterns of OR56A5, OR52L1, and CTSD in Retinitis Pigmentosa Patients by Whole-Exome Sequencing.

Inherited retinal dystrophies (IRDs) are rare but highly heterogeneous genetic disorders that affect individuals and families worldwide. However, given its wide variability, its analysis of the driver genes for over 50% of the cases remains unexplored. The present study aims to identify novel driver genes, disease-causing variants, and retinitis pigmentosa (RP)-associated pathways. Using family-based whole-exome sequencing (WES) to identify putative RP-causing rare variants, we identified a total of five potentially pathogenic variants located in genes OR56A5, OR52L1, CTSD, PRF1, KBTBD13, and ATP2B4. Of the variants present in all affected individuals, genes OR56A5, OR52L1, CTSD, KBTBD13, and ATP2B4 present as missense mutations, while PRF1 and CTSD present as frameshift variants. Sanger sequencing confirmed the presence of the novel pathogenic variant PRF1 (c.124_128del) that has not been reported previously. More causal-effect or evidence-based studies will be required to elucidate the precise roles of these SNPs in the RP pathogenesis. Taken together, our findings may allow us to explore the risk variants based on the sequencing data and upgrade the existing variant annotation database in Taiwan. It may help detect specific eye diseases such as retinitis pigmentosa in East Asia.

RNA Modifications and Epigenetics in Modulation of Lung Cancer and Pulmonary Diseases.

Lung cancer is the leading cause of cancer-related mortality worldwide, and its tumorigenesis involves the accumulation of genetic and epigenetic events in the respiratory epithelium. Epigenetic modifications, such as DNA methylation, RNA modification, and histone modifications, have been widely reported to play an important role in lung cancer development and in other pulmonary diseases. Whereas the functionality of DNA and chromatin modifications referred to as epigenetics is widely characterized, various modifications of RNA nucleotides have recently come into prominence as functionally important. N6-methyladosine (m6A) is the most prevalent internal modification in mRNAs, and its machinery of writers, erasers, and readers is well-characterized. However, several other nucleotide modifications of mRNAs and various noncoding RNAs have also been shown to play an important role in the regulation of biological processes and pathology. Such epitranscriptomic modifications play an important role in regulating various aspects of RNA metabolism, including transcription, translation, splicing, and stability. The dysregulation of epitranscriptomic machinery has been implicated in the pathological processes associated with carcinogenesis including uncontrolled cell proliferation, migration, invasion, and epithelial-mesenchymal transition. In recent years, with the advancement of RNA sequencing technology, high-resolution maps of different modifications in various tissues, organs, or disease models are being constantly reported at a dramatic speed. This facilitates further understanding of the relationship between disease development and epitranscriptomics, shedding light on new therapeutic possibilities. In this review, we summarize the basic information on RNA modifications, including m6A, m1A, m5C, m7G, pseudouridine, and A-to-I editing. We then demonstrate their relation to different kinds of lung diseases, especially lung cancer. By comparing the different roles RNA modifications play in the development processes of different diseases, this review may provide some new insights and offer a better understanding of RNA epigenetics and its involvement in pulmonary diseases.

Identification of DNA Damage Repair-Associated Prognostic Biomarkers for Prostate Cancer Using Transcriptomic Data Analysis.

In the recent decade, the importance of DNA damage repair (DDR) and its clinical application have been firmly recognized in prostate cancer (PC). For example, olaparib was just approved in May 2020 to treat metastatic castration-resistant PC with homologous recombination repair-mutated genes; however, not all patients can benefit from olaparib, and the treatment response depends on patient-specific mutations. This highlights the need to understand the detailed DDR biology further and develop DDR-based biomarkers. In this study, we establish a four-gene panel of which the expression is significantly associated with overall survival (OS) and progression-free survival (PFS) in PC patients from the TCGA-PRAD database. This panel includes DNTT, EXO1, NEIL3, and EME2 genes. Patients with higher expression of the four identified genes have significantly worse OS and PFS. This significance also exists in a multivariate Cox regression model adjusting for age, PSA, TNM stages, and Gleason scores. Moreover, the expression of the four-gene panel is highly correlated with aggressiveness based on well-known PAM50 and PCS subtyping classifiers. Using publicly available databases, we successfully validate the four-gene panel as having the potential to serve as a prognostic and predictive biomarker for PC specifically based on DDR biology.

Role of Extracellular Matrix in Pathophysiology of Patent Ductus Arteriosus: Emphasis on Vascular Remodeling.

The ductus arteriosus (DA) is a shunt vessel between the aorta and the pulmonary artery during the fetal period that is essential for the normal development of the fetus. Complete closure usually occurs after birth but the vessel might remain open in certain infants, as patent ductus arteriosus (PDA), causing morbidity or mortality. The mechanism of DA closure is a complex process involving an orchestration of cell-matrix interaction between smooth muscle cells (SMC), endothelial cells, and extracellular matrix (ECM). ECM is defined as the noncellular component secreted by cells that consists of macromolecules such as elastin, collagens, proteoglycan, hyaluronan, and noncollagenous glycoproteins. In addition to its role as a physical scaffold, ECM mediates diverse signaling that is critical in development, maintenance, and repair in the cardiovascular system. In this review, we aim to outline the current understandings of ECM and its role in the pathophysiology of PDA, with emphasis on DA remodeling and highlight future outlooks. The molecular diversity and plasticity of ECM present a rich array of potential therapeutic targets for the management of PDA.

Current Genetic Survey and Potential Gene-Targeting Therapeutics for Neuromuscular Diseases.

Neuromuscular diseases (NMDs) belong to a class of functional impairments that cause dysfunctions of the motor neuron-muscle functional axis components. Inherited monogenic neuromuscular disorders encompass both muscular dystrophies and motor neuron diseases. Understanding of their causative genetic defects and pathological genetic mechanisms has led to the unprecedented clinical translation of genetic therapies. Challenged by a broad range of gene defect types, researchers have developed different approaches to tackle mutations by hijacking the cellular gene expression machinery to minimize the mutational damage and produce the functional target proteins. Such manipulations may be directed to any point of the gene expression axis, such as classical gene augmentation, modulating premature termination codon ribosomal bypass, splicing modification of pre-mRNA, etc. With the soar of the CRISPR-based gene editing systems, researchers now gravitate toward genome surgery in tackling NMDs by directly correcting the mutational defects at the genome level and expanding the scope of targetable NMDs. In this article, we will review the current development of gene therapy and focus on NMDs that are available in published reports, including Duchenne Muscular Dystrophy (DMD), Becker muscular dystrophy (BMD), X-linked myotubular myopathy (XLMTM), Spinal Muscular Atrophy (SMA), and Limb-girdle muscular dystrophy Type 2C (LGMD2C).

Resistin Enhances Monocyte Chemoattractant Protein-1 Production in Human Synovial Fibroblasts and Facilitates Monocyte Migration.

BACKGROUND/AIMS: The adipocyte-secreting adipokine, resistin, may play a critical role in the modulation of inflammatory diseases. Migration and infiltration of mononuclear cells into inflammatory sites are critical events during the development of osteoarthritis (OA). Monocyte chemoattractant protein-1 (MCP-1), also known as chemokine ligand 2 (CCL2), plays a critical role in the regulation of monocyte migration and infiltration. In this study, we show how resistin promotes MCP-1 expression in OA synovial fibroblasts and monocyte migration. METHODS: We used qPCR to detect MCP-1 and miRNA expression. THP-1 migration was investigated by Transwell assay. The Western blotting was used to examine the resistinmediated signaling pathways. RESULTS: Resistin activated the phosphatidylinositol-3-kinase (PI3K), Akt and mammalian target of rapamycin (mTOR) signaling pathways, while PI3K, Akt and mTOR inhibitors or small interfering RNAs diminished resistin-induced MCP-1 expression and monocyte migration. We also demonstrate that resistin stimulates MCP-1mediated monocyte migration by suppressing microRNA (miR)-33a and miR-33b via the PI3K, Akt and mTOR signaling pathways. CONCLUSION: These results provide new insights into the mechanisms of resistin action that may have therapeutic implications for patients with OA.

In Situ Investigation of Defect-Free Copper Nanowire Growth.

The fabrication and placement of high purity nanometals, such as one-dimensional copper (Cu) nanowires, for interconnection in integrated devices have been among the most important technological developments in recent years. Structural stability and oxidation prevention have been the key issues, and the defect control in Cu nanowire growth has been found to be important. Here, we report the synthesis of defect-free single-crystalline Cu nanowires by controlling the surface-assisted heterogeneous nucleation of Cu atomic layering on the graphite-like loop of an amorphous carbon (a-C) lacey film surface. Without a metal-catalyst or induced defects, the high quality Cu nanowires formed with high aspect ratio and high growth rate of 578 nm/s. The dynamic study of the growth of heterogeneous nanowires was conducted in situ with a high-resolution transmission electron microscope. The study illuminates the new mechanism by heterogeneous nucleation control and laying the groundwork for better understanding of heterosurface-assisted nucleation of defect-free Cu nanowire on a-C lacey film.