Microinvasion in hepatocellular carcinoma: predictive factor and application for definition of clinical target volume for radiotherapy.

BACKGROUND: To investigate the correlation between microinvasion and various features of hepatocellular carcinoma (HCC), and to clarify the microinvasion distance from visible HCC lesions to subclinical lesions, so as to provide clinical basis for the expandable boundary of clinical target volume (CTV) from gross tumor volume (GTV) in the radiotherapy of HCC. METHODS: HCC patients underwent hepatectomy of liver cancer in our hospital between July 2019 and November 2021 were enrolled. Data on various features and tumor microinvasion distance were collected. The distribution characteristics of microinvasion distance were analyzed to investigate its potential correlation with various features. Tumor size compared between radiographic and pathologic samples was analyzed to clarify the application of pathologic microinvasion to identify subclinical lesions of radiographic imaging. RESULTS: The average microinvasion distance was 0.6 mm, with 95% patients exhibiting microinvasion distance less than 3.0 mm, and the maximum microinvasion distance was 4.0 mm. A significant correlation was found between microinvasion and liver cirrhosis (P = 0.036), serum albumin level (P = 0.049). Multivariate logistic regression analysis revealed that HCC patients with cirrhosis had a significantly lower risk of microinvasion (OR = 0.09, 95%CI = 0.02 ~ 0.50, P = 0.006). Tumor size was overestimated by 1.6 mm (95%CI=-12.8 ~ 16.0 mm) on radiographic size compared to pathologic size, with a mean %Δsize of 2.96% (95%CI=-0.57%~6.50%). The %Δsize ranged from - 29.03% to 34.78%. CONCLUSIONS: CTV expanding by 5.4 mm from radiographic GTV could include all pathologic microinvasive lesions in the radiotherapy of HCC. Liver cirrhosis was correlated with microinvasion and were independent predictive factor of microinvasion in HCC.

Synergistic Effect of 2-(Trifluoromethyl) Benzimidazole on the Stability and Performance of Perovskite Solar Cells.

The quality of the perovskite active layer directly impacts the photovoltaic performance of perovskite solar cells (PSCs). Unfortunately, perovskite films produced through solution methods often have a significant number of defects on their surface, which lead to a substantial degradation in the performance of devices. For this reason, a multifunctional additive 2-(trifluoromethyl) benzimidazole (TFMBI) is introduced into perovskite films. Based on the Lewis acid/base coordination principle, the TFMBI double site cooperatively passivates surface defects, inhibiting carrier non-radiative recombination. Simultaneously, the hydrophobic solid group (-CF3) of TFMBI covers the surface, establishing a moisture-oxygen barrier and improving the environmental stability of the devices. In consequence, the power conversion efficiency (PCE) of TFMBI-modified PSCs reached 23.16%, significantly higher than the pristine one with a PCE of 20.62%. Additionally, the unencapsulated target device retained 90.32% of its initial PCE even after being reserved in the air with a relative humidity of 20-30% for 60 days.

Generation of neural organoids for spinal-cord regeneration via the direct reprogramming of human astrocytes.

Organoids with region-specific architecture could facilitate the repair of injuries of the central nervous system. Here we show that human astrocytes can be directly reprogrammed into early neuroectodermal cells via the overexpression of OCT4, the suppression of p53 and the provision of the small molecules CHIR99021, SB431542, RepSox and Y27632. We also report that the activation of signalling mediated by fibroblast growth factor, sonic hedgehog and bone morphogenetic protein 4 in the reprogrammed cells induces them to form spinal-cord organoids with functional neurons specific to the dorsal and ventral domains. In mice with complete spinal-cord injury, organoids transplanted into the lesion differentiated into spinal-cord neurons, which migrated and formed synapses with host neurons. The direct reprogramming of human astrocytes into neurons may pave the way for in vivo neural organogenesis from endogenous astrocytes for the repair of injuries to the central nervous system.

SOX9 and SOX10 control fluid homeostasis in the inner ear for hearing through independent and cooperative mechanisms.

The in vivo mechanisms underlying dominant syndromes caused by mutations in SRY-Box Transcription Factor 9 (SOX9) and SOX10 (SOXE) transcription factors, when they either are expressed alone or are coexpressed, are ill-defined. We created a mouse model for the campomelic dysplasia SOX9Y440X mutation, which truncates the transactivation domain but leaves DNA binding and dimerization intact. Here, we find that SOX9Y440X causes deafness via distinct mechanisms in the endolymphatic sac (ES)/duct and cochlea. By contrast, conditional heterozygous Sox9-null mice are normal. During the ES development of Sox9Y440X/+ heterozygotes, Sox10 and genes important for ionic homeostasis are down-regulated, and there is developmental persistence of progenitors, resulting in fewer mature cells. Sox10 heterozygous null mutants also display persistence of ES/duct progenitors. By contrast, SOX10 retains its expression in the early Sox9Y440X/+ mutant cochlea. Later, in the postnatal stria vascularis, dominant interference by SOX9Y440X is implicated in impairing the normal cooperation of SOX9 and SOX10 in repressing the expression of the water channel Aquaporin 3, thereby contributing to endolymphatic hydrops. Our study shows that for a functioning endolymphatic system in the inner ear, SOX9 regulates Sox10, and depending on the cell type and target gene, it works either independently of or cooperatively with SOX10. SOX9Y440X can interfere with the activity of both SOXE factors, exerting effects that can be classified as haploinsufficient/hypomorphic or dominant negative depending on the cell/gene context. This model of disruption of transcription factor partnerships may be applicable to congenital deafness, which affects ∼0.3% of newborns, and other syndromic disorders.

Fluorogenic RNA aptamers to probe transcription initiation and co-transcriptional RNA folding by multi-subunit RNA polymerases.

Transcription is the first and most highly regulated step in gene expression. Experimental techniques for monitoring transcription are, thus, important for studying gene expression and gene regulation as well as for translational research and drug development. Fluorescence methods are often superior to other techniques for real-time monitoring of biochemical processes. Green fluorescent proteins have long served as valuable tools for studying the process of translation. Here we present two methods that utilize fluorescent light-up RNA aptamers (FLAPs), the RNA mimics of green fluorescent proteins, to monitoring transcription and co-transcriptional RNA folding. FLAPs adopt defined three-dimensional folds that bind low molecular weight compounds called fluorogens with concomitant increase in fluorescence by many folds. FLAPs provide a strong fluorescence signal with low background that allows monitoring of transcription in real time in vitro and in vivo. However, it takes several seconds for RNA polymerase to synthesize FLAPs and the subsequent folding of the fluorogen-binding platform takes additional seconds or minutes. Here we show that Broccoli-FLAP is well suited for monitoring the rate of transcription initiation in a multi-round setup that mitigates the slow rate of the FLAP maturation. Furthermore, we demonstrate that a relatively slow and inefficient folding of iSpinach-FLAP can be taken advantage of for monitoring the action of RNA folding chaperones.

Dual-specificity Tyrosine Phosphorylation-regulated Kinase Inhibitor ID-8 Promotes Human Somatic Cell Reprogramming by Activating PDK4 Expression.

BACKGROUND: Human induced pluripotent stem cells (hiPSCs) hold great potentials in disease modeling, drug screening and cell therapy. However, efficiency and costs of hiPSCs preparation still need to be improved. METHODS: We screened the compounds that target signaling pathways, epigenetic modifications or metabolic-process regulation to replace the growth factors. After small molecule treatment, TRA-1-60, which is a cell surface antigen expressed by human embryonic stem cells (hESCs), staining was performed to quantify the efficiency of somatic cell reprogramming. Next, small molecule cocktail-induced ESCs or iPSCs were examined with pluripotent markers expression. Finally, Genome-wide gene expression profile was analyzed by RNA-seq to illustrate the mechanism of human somatic cell reprogramming. RESULT: Here, we found that a dual-specificity tyrosine phosphorylation-regulated kinase (DYRK) inhibitor ID-8 robustly enhanced human somatic cell reprogramming by upregulation of pyruvate dehydrogenase kinase 4 (PDK4) and activation of glycolysis. Furthermore, we identified a novel growth-factor-free hiPSC generation system using small molecules ID-8 (I) and TGFß signal pathway agonist Kartogenin (K). Importantly, we developed IK medium combined with low-dose bFGF to support the long-term expansion of human pluripotent stem cells. IK-iPSCs showed pluripotency and normal karyotype. CONCLUSIONS: Our studies may provide a novel growth-factor-free culture system to facilitate the generation of hiPSCs for multiple applications in regenerative medicine. In Brief Xu et at. found that a dual-specificity tyrosine phosphorylation-regulated kinase (DYRK) inhibitor ID-8 robustly enhanced human somatic cell reprogramming by upregulation of PDK4 and activation of glycolysis. Furthermore, we established a novel growth-factor-free hiPSC generation system using small molecules ID-8/Kartogenin (IK). IK medium combined with Low-dose bFGF (IKB medium) supported the long-term expansion of human pluripotent stem cells. Highlights ID-8 Enhanced Reprogramming of Human Fibroblasts and Astrocytes Establishment of the Growth-factor-free Reprogramming System Using Small Molecule Compounds IK IKB Medium Maintained the Long-term Expansion of Human Pluripotent Stem Cells ID-8 Promoted Human Somatic Cell Reprogramming by Activating PDK4 Expression.

Alterations in the Retinal Vascular Network and Structure in Myelin Oligodendrocyte Glycoprotein Antibody-Associated Optic Neuritis: A Longitudinal OCTA Study.

PURPOSE: To investigate the longitudinal microstructural and microvascular changes in patients with myelin oligodendrocyte glycoprotein antibody-associated optic neuritis (MOG-ON) without new attacks. METHODS: We included 20 eyes of 12 MOG-ON patients without new attacks during the follow-up and 24 eyes of 12 age- and sex-matched healthy controls. RESULTS: The BCVA, retinal vessels and structure were significantly lower in MOG-ON eyes than in healthy eyes(all P < .05). In MOG-ON eyes, the BCVA (p = .408) and mean deviation (p = .854) were not significantly decreased at the follow-up visit. However, there were small, significant decreases in parafoveal vessel density (p = .026), peripapillary vessel density (p = .008), and RNFL thickness (p = .03), but not GCIPL thickness (p = .107). CONCLUSIONS: Ongoing deterioration was observed in RNFL thickness and parafoveal and peripapillary vessel density, but not GCIPL thinning, in MOG-ON eyes without a new attack of ON.

Changes in Retinal Perfusion in Leber's Hereditary Optic Neuropathy: An Optical Coherence Tomography-Angiography Study.

INTRODUCTION: We aimed to study the change in the retinal perfusion in Leber's hereditary optic neuropathy (LHON). METHODS: Fourteen patients (28 eyes) diagnosed with LHON and 14 healthy controls (28 eyes) were enrolled. The retinal vessel densities in the parafoveal and peripapillary areas were measured with optical coherence tomography-angiography. RESULTS: In the subacute LHON patients, the parafoveal superficial capillary plexus (SCP) and inner retinal thickness (IRT) were significantly reduced in all sectors compared with the controls (all p < 0.05), and the radial peripapillary capillary (RPC) network was significantly reduced in the temporal and inferior temporal sectors compared with the controls (p < 0.05). In the chronic LHON patients, the SCP and IRT were significantly lower in all sectors than in the controls (all p < 0.05), the RPC vessel density and thickness were significantly lower in all sectors than in the controls and lower in the temporal, superior temporal, inferior temporal, and nasal sectors than in the subacute-stage patients (all p < 0.05). CONCLUSION: The retinal structure and the perfusion of the macular and peripapillary areas are reduced in subacute LHON, and the retinal structure and the perfusion of the peripapillary area are further reduced in chronic LHON.

Comparison of the retinal vascular network and structure in patients with optic neuritis associated with myelin oligodendrocyte glycoprotein or aquaporin-4 antibodies: an optical coherence tomography angiography study.

OBJECTIVE: To compare the retinal vascular network and structure of optic neuritis associated with myelin oligodendrocyte glycoprotein antibodies (MOG-ON) or aquaporin-4 antibodies (AQP4-ON). METHODS: Nineteen patients with MOG-ON (29 eyes), 24 patients with AQP4-ON (43 eyes), and 25 healthy participants (50 eyes) were enrolled. The best-corrected visual acuity (BCVA), mean deviation (MD), retinal nerve fiber layer (RNFL) thickness, parafoveal ganglion cell and inner plexiform layer (GCIPL) thickness, and vessel densities in the peripapillary and parafoveal areas were measured. RESULTS: The BCVA, RNFL thickness, GCIPL thickness, and vessel densities in the peripapillary and parafoveal areas were significantly decreased in the AQP4-ON and MOG-ON eyes compared with healthy controls (all P < 0.05). There were no significant differences in the MD, RNFL thickness, GCIPL thickness, or vessel densities between the AQP4-ON and MOG-ON eyes (all P > 0.05). However, the BCVA was significantly worse in AQP4-ON eyes than in MOG-ON eyes (P = 0.001). The peripapillary vessel density was significantly correlated with the BCVA and MD in AQP4-ON eyes and with MD in MOG-ON eyes (all P < 0.05). CONCLUSIONS: MOG-ON and AQP4-ON are associated with severe visual dysfunction, as well as retinal structural and vascular damage. The extent of visual dysfunction was strongly correlated with the peripapillary vessel density. Although we found no significant difference in the MD between MOG-ON and AQP4-ON, which are characterized by comparable vascular and structural damage within the peripapillary and parafoveal areas, the BCVA was worse in AQP4-ON eyes than in MOG-ON eyes.

Alterations in the Retinal Vascular Network and Structure in MOG Antibody-Associated Disease: An Optical Coherence Tomography Angiography Study.

BACKGROUND: To determine retinal vessel density in patients with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). METHODS: Twenty-five patients with MOGAD and 20 healthy participants were enrolled. Patients with MOGAD were divided into myelin oligodendrocyte glycoprotein antibody (MOG-Ab)-positive eyes with a history of optic neuritis (ON; MOG-Ab-ON+ group) or without a history of ON (MOG-Ab-ON- group). Visual function, retinal vessel densities, and thickness were measured. RESULTS: The retinal nerve fiber layer, parafoveal ganglion cell and inner plexiform layers, and vessel densities in the peripapillary and parafoveal areas were significantly decreased in the MOG-Ab-ON+ eyes compared with healthy eyes and MOG-Ab-ON- eyes (all P < 0.05). An increasing number of ON episodes was associated with greater decreases in these variables (all P < 0.05). Visual field mean deviation was not significantly decreased in patients with a history of 1 or 2 episodes of ON, although the relative decreases in retinal nerve fiber layer thickness, parafoveal ganglion cell and inner plexiform layer thickness, peripapillary vessel density, and parafoveal vessel density reached 33.1%, 23.2%, 17.0%, and 11.5% (all P < 0.05), respectively, in eyes with 2 episodes of ON. The mean deviation was significantly correlated with peripapillary vessel density (P < 0.05) after adjustment for other variables. Best-corrected visual acuity was not significantly correlated with optical coherence tomography variables (all P > 0.05). CONCLUSIONS: MOG-Ab-associated ON was associated with significant decreases in retinal structure and vessel density, without significant deteriorations in visual function. The peripapillary vessel density might predict the visual outcomes in patients with MOG-Ab-associated ON.

The δ subunit and NTPase HelD institute a two-pronged mechanism for RNA polymerase recycling.

Cellular RNA polymerases (RNAPs) can become trapped on DNA or RNA, threatening genome stability and limiting free enzyme pools, but how RNAP recycling into active states is achieved remains elusive. In Bacillus subtilis, the RNAP δ subunit and NTPase HelD have been implicated in RNAP recycling. We structurally analyzed Bacillus subtilis RNAP-δ-HelD complexes. HelD has two long arms: a Gre cleavage factor-like coiled-coil inserts deep into the RNAP secondary channel, dismantling the active site and displacing RNA, while a unique helical protrusion inserts into the main channel, prying the ß and ß' subunits apart and, aided by δ, dislodging DNA. RNAP is recycled when, after releasing trapped nucleic acids, HelD dissociates from the enzyme in an ATP-dependent manner. HelD abundance during slow growth and a dimeric (RNAP-δ-HelD)2 structure that resembles hibernating eukaryotic RNAP I suggest that HelD might also modulate active enzyme pools in response to cellular cues.

Structure-Based Mechanisms of a Molecular RNA Polymerase/Chaperone Machine Required for Ribosome Biosynthesis.

Bacterial ribosomal RNAs are synthesized by a dedicated, conserved transcription-elongation complex that transcribes at high rates, shields RNA polymerase from premature termination, and supports co-transcriptional RNA folding, modification, processing, and ribosomal subunit assembly by presently unknown mechanisms. We have determined cryo-electron microscopy structures of complete Escherichia coli ribosomal RNA transcription elongation complexes, comprising RNA polymerase; DNA; RNA bearing an N-utilization-site-like anti-termination element; Nus factors A, B, E, and G; inositol mono-phosphatase SuhB; and ribosomal protein S4. Our structures and structure-informed functional analyses show that fast transcription and anti-termination involve suppression of NusA-stabilized pausing, enhancement of NusG-mediated anti-backtracking, sequestration of the NusG C-terminal domain from termination factor ρ, and the ρ blockade. Strikingly, the factors form a composite RNA chaperone around the RNA polymerase RNA-exit tunnel, which supports co-transcriptional RNA folding and annealing of distal RNA regions. Our work reveals a polymerase/chaperone machine required for biosynthesis of functional ribosomes.

Structural basis for the function of SuhB as a transcription factor in ribosomal RNA synthesis.

Ribosomal RNA synthesis in Escherichia coli involves a transcription complex, in which RNA polymerase is modified by a signal element on the transcript, Nus factors A, B, E and G, ribosomal protein S4 and inositol mono-phosphatase SuhB. This complex is resistant to ρ-dependent termination and facilitates ribosomal RNA folding, maturation and subunit assembly. The functional contributions of SuhB and their structural bases are presently unclear. We show that SuhB directly binds the RNA signal element and the C-terminal AR2 domain of NusA, and we delineate the atomic basis of the latter interaction by macromolecular crystallography. SuhB recruitment to a ribosomal RNA transcription complex depends on the RNA signal element but not on the NusA AR2 domain. SuhB in turn is required for stable integration of the NusB/E dimer into the complex. In vitro transcription assays revealed that SuhB is crucial for delaying or suppressing ρ-dependent termination, that SuhB also can reduce intrinsic termination, and that SuhB-AR2 contacts contribute to these effects. Together, our results reveal functions of SuhB during ribosomal RNA synthesis and delineate some of the underlying molecular interactions.

Bacterial indicator reduction in dairy manure using hybrid zero-valent iron (h-ZVI) system.

Novel and efficient animal wastewater treatment technologies of bacteria reduction are needed for preventing disease outbreak in animal herds and safeguarding environmental health. Zero-valent iron (ZVI) has been used to treat bacteria contaminated water for the past decades, but its passivation issue has been a major challenge. In this study, batch tests were performed to evaluate the effect of a hybrid zero-valent iron (h-ZVI) or a mixed ZVI/Fe3O4 media system on reduction of Escherichia coli (E. coli) levels. The h-ZVI media was created through a wet chemical process that uses nitrate to oxidize ZVI in the presence of externally added Fe2+ (aq.). Transforming ZVI into a h-ZVI system could overcome the passivation of ZVI and increase the reactivity of the media. The results demonstrated that E. coli cells in the bulk phase were removed rapidly by h-ZVI media. Majority of E. coli was attached (or adsorbed) to the surface of h-ZVI media within a few minutes, which suggested that adsorption was the dominant mechanism for bacterial removal in the initial phase. This adsorption was confirmed by fluorescence microscopy with CTC-DAPI double staining and transmission electron microscopy (TEM). Increasing contact time steadily inactivated E. coli; all cells were inactivated after 120 min of contact. The TEM results indicated that h-ZVI inactivated E. coli by causing direct damage on bacterial cell membrane. The results of this study strongly suggest that h-ZVI treatment can be used in water treatment industry where bacterial contamination is concerned.

Structural Basis for the Action of an All-Purpose Transcription Anti-termination Factor.

Bacteriophage λN protein, a model anti-termination factor, binds nascent RNA and host Nus factors, rendering RNA polymerase resistant to all pause and termination signals. A 3.7-Å-resolution cryo-electron microscopy structure and structure-informed functional analyses reveal a multi-pronged strategy by which the intrinsically unstructured λN directly modifies RNA polymerase interactions with the nucleic acids and subverts essential functions of NusA, NusE, and NusG to reprogram the transcriptional apparatus. λN repositions NusA and remodels the ß subunit flap tip, which likely precludes folding of pause or termination RNA hairpins in the exit tunnel and disrupts termination-supporting interactions of the α subunit C-terminal domains. λN invades and traverses the RNA polymerase hybrid cavity, likely stabilizing the hybrid and impeding pause- or termination-related conformational changes of polymerase. λN also lines upstream DNA, seemingly reinforcing anti-backtracking and anti-swiveling by NusG. Moreover, λN-repositioned NusA and NusE sequester the NusG C-terminal domain, counteracting ρ-dependent termination. Other anti-terminators likely utilize similar mechanisms to enable processive transcription.

Kinetics and mechanism of selenite reduction by zero valent iron under anaerobic condition activated and enhanced by dissolved Fe(II).

Batch test was conducted to investigate Se(IV) removal kinetics and mechanism by zero valent iron (ZVI) in presence of Fe(II) under anaerobic condition. Dissolved Fe(II) activated and enhanced Se(IV) reduction by ZVI, which also determined the removal efficiency, reduction rate, final corrosion products and their structures. Se(IV) was completely removed at initial Fe(II)/Se(IV) ≥ 1.0, and the specific rate constant significantly increased from 0.6 to 3.44 L h-1 m-2 with the augment of ratio from 1.0 to 1.4. At Fe(II)/Se(IV) < 1.0 (take 0.6 as an example), Raman, XPS, SEM-EDS and XRD results suggested that Se(IV) was reduced to amorphous Se(0) in forms of red suspended solids, amorphous FeSe and crystal maghemite (γ-Fe2O3) coated on ZVI surface. At Fe(II)/Se(IV) ≥ 1.0 (take 1.0 and 1.4 as examples), crystal FeSe and magnetite (Fe3O4) deposits formed on ZVI surface with a core-shell structure. Additionally, final pH increased due to Se(IV) reduction. This study suggested that traditional ZVI passivation problem could be overcome through the addition of excess dissolved Fe(II) under anaerobic condition, which also provided an alternative method to produce a reactive ammonia-free Fe3O4/ZVI/Fe(II) system.

A simple and novel method to enhance As (V) removal by zero valent iron and activated iron media through air injection at intervals.

A simple and novel method was developed at first time to enhance As (V) removal by zero valent iron (ZVI) and activated ZVI/Fe3O4 media (AIM) through air injection at intervals. Fe (II) was essential to trigger As (V) removal by ZVI and AIM, and magnetite did not improve As (V) removal. In presence of 0.5 mM Fe (II) under anaerobic condition, 10 g L-1 ZVI and AIM showed same As (V) removal efficiency including percentage, capacity and rate of >99.999%, 3.0 mg/g ZVI/AIM and 0.013 mg As (V)/(g · min), respectively. Compared to the passivation of ZVI and AIM after one-time air injection, As (V) removal efficiency was significantly improved by intermittent air injection with increased air volume and injection frequency. After third time of 1.0 mL air injection at 30 min intervals, As (V) removal percentage and capacity remained same remarkable values as that under anaerobic condition, but total removal rate was further improved to 0.033 mg As (V)/(g · min). XPS results indicated that As (V) was completely reduced to As (III) and As (0) by Fe (0) under anaerobic condition, but quick adsorption/co-precipitation of As (V) followed by reduction to As (III) and As (0) by Fe (0) was the main mechanism under aerobic condition. This study suggests the addition of Fe (II) followed by simple air injection at intervals harnesses the reactivity of traditional ZVI for arsenic removal.

Targeted next-generation sequencing extends the mutational spectrums for OPA1 mutations in Chinese families with optic atrophy.

Purpose: We aim to reveal the disease-causing mutations in 15 Chinese families with optic atrophy (OA). Methods: In total, 15 families with OA were recruited in the present study. Medical histories were carefully reviewed and comprehensive ophthalmic examinations were received by all recruited patients. Targeted next-generation sequencing (NGS) was selectively performed on all probands for mutation detection. Intrafamilial cosegregation and in-silico analyses were subsequently applied to predict the potential pathogenic effects of identified mutations. Results: All included patients presented bilateral vision loss. Their fundus photographs showed temporal or total pallor of the optic discs. Fourteen mutations in the optic atrophy 1 (OPA1) gene were revealed as disease-causing mutations for the 15 families, including eight novel (c.968A>G, c.193C>G, c.1071dupT, c.987_988del, c.2012+2T>G, c.1036-1G>C, c.2126A>G, and c.1036_1038del) and six recurrent (c.1499G>A, c.1800C>A, c.1034G>A, c.2873_2876del, c.112C>T, and c.804_805del) mutations. Conclusions: In conclusion, our study expands the mutational spectrum for the OPA1 gene and implies targeted NGS as an effective approach for the genetic diagnosis of OA, which might help to improve the clinical diagnosis for patients with OA.

Peripapillary and parafoveal vascular network assessment by optical coherence tomography angiography in aquaporin-4 antibody-positive neuromyelitis optica spectrum disorders.

BACKGROUND/AIMS: Current understanding of the alterations in the retinal vascular network in neuromyelitis optica spectrum disorders (NMOSDs) is limited. We aim to assess the peripapillary and parafoveal vessel density in aquaporin-4 antibody-positive NMOSD patients by optical coherence tomography (OCT) angiography. METHODS: A total of 55 aquaporin-4 antibody-positive NMOSD patients with or without a history of optic neuritis (ON) and 33 healthy controls underwent spectral domain OCT and OCT angiography. Clinical histories, Expanded Disability Status Scale score, visual functional system score (VFSS) and disease duration were collected. RESULTS: Peripapillary and parafoveal vessel density was significantly decreased in NMOSD eyes with or without a history of ON. The decrease in retinal vessel density could occur before ON and retinal nerve fibre layer (RNFL) atrophy. Peripapillary vessel density correlated well with the spectral domain OCT measurements and VFSS in NMOSD eyes with a history of ON. CONCLUSION: Subclinical primary retinal vasculopathy may occur in NMOSD prior to ON and RNFL atrophy. Peripapillary vessel density might be a sensitive predictor of visual outcomes in NMOSD patients with ON.

Clinical Characteristics of Pediatric Optic Neuritis With Myelin Oligodendrocyte Glycoprotein Seropositive: A Cohort Study.

BACKGROUND: The clinical characteristics of patients with pediatric optic neuritis with seropositive myelin oligodendrocyte glycoprotein antibodies in Asia have not been reported. METHODS: Patients ≤18 years-old with acute-onset optic neuritis were enrolled. Serum myelin oligodendrocyte glycoprotein and aquaporin-4 antibodies were detected and patients were followed for at least six months. The clinical features were evaluated among myelin oligodendrocyte glycoprotein-seropositive optic neuritis, aquaporin-4-seropositive optic neuritis, and double seronegative optic neuritis. Best-corrected visual acuity, thickness of optic disc retinal nerve fiber layer, and macular ganglion cell complex were measured by optical coherence tomography. RESULTS: Among myelin oligodendrocyte glycoprotein-optic neuritis, aquaporin-4-optic neuritis, and seronegative-optic neuritis, the percentages of best-corrected visual acuity measured better than 0.8 (20/25) at the six-month visit were 89.47%, 33.33%, and 82.26%, respectively, a rate that is significantly better in patients with myelin oligodendrocyte glycoprotein-optic neuritis and seronegative-optic neuritis (P = 0.02). The average peripapillary retinal nerve fiber layers were 58.03 ± 8.73 µm, 64.34 ± 12.88 µm, and 78.12 ± 13.34 µm for the patients with myelin oligodendrocyte glycoprotein-optic neuritis, aquaporin-4-optic neuritis, and seronegative-optic neuritis, respectively, which showed no statistical difference between patients with myelin oligodendrocyte glycoprotein-optic neuritis and aquaporin-4-optic neuritis (P = 0.089), but were both thinner than patients with seronegative-optic neuritis (P = 0.001). CONCLUSIONS: The recovery of visual acuity in patients with myelin oligodendrocyte glycoprotein-optic neuritis was as good as in patients with seronegative-optic neuritis, and the retinal nerve fiber layer of the optic nerve head showed thinning as severe as that of the patients with aquaporin-4-optic neuritis.