Early Detection of Optic Nerve Changes on Optical Coherence Tomography Using Deep Learning for Risk-Stratification of Papilledema and Glaucoma.

BACKGROUND: The use of artificial intelligence is becoming more prevalence in medicine with numerous successful examples in ophthalmology. However, much of the work has been focused on replicating the works of ophthalmologists. Given the analytical potentials of artificial intelligence, it is plausible that artificial intelligence can detect microfeatures not readily distinguished by humans. In this study, we tested the potential for artificial intelligence to detect early optic coherence tomography changes to predict progression toward papilledema or glaucoma when no significant changes are detected on optical coherence tomography by clinicians. METHODS: Prediagnostic optical coherence tomography of patients who developed papilledema (n = 93, eyes = 166) and glaucoma (n = 187, eyes = 327) were collected. Given discrepancy in average cup-to-disc ratios of the experimental groups, control groups for papilledema (n = 254, eyes = 379) and glaucoma (n = 441, eyes = 739) are matched by cup-to-disc ratio. Publicly available Visual Geometry Group-19 model is retrained using each experimental group and its respective control group to predict progression to papilledema or glaucoma. Images used for training include retinal nerve fiber layer thickness map, extracted vertical tomogram, ganglion cell thickness map, and ILM-RPE thickness map. RESULTS: Trained model was able to predict progression to papilledema with a precision of 0.714 and a recall of 0.769 when trained with retinal nerve fiber layer thickness map, but not other image types. However, trained model was able to predict progression to glaucoma with a precision of 0.682 and recall of 0.857 when trained with extracted vertical tomogram, but not other image types. Area under precision-recall curve of 0.826 and 0.785 were achieved for papilledema and glaucoma models, respectively. CONCLUSIONS: Computational and analytical power of computers have become an invaluable part of our lives and research endeavors. Our proof-of-concept study showed that artificial intelligence (AI) algorithms have the potential to detect early changes on optical coherence tomography for prediction of progression that is not readily observed by clinicians. Further research may help establish possible AI models that can assist with early diagnosis or risk stratification in ophthalmology.

Heightened sensitivity to high-calorie foods in children at risk for obesity: insights from behavior, neuroimaging, and genetics.

Pediatric obesity is a major public health concern. Genetic susceptibility and increased availability of energy-dense food are known risk factors for obesity. However, the extent to which these factors jointly bias behavior and neural circuitry towards increased adiposity in children remains unclear. While undergoing fMRI, 108 children (ages 5-11y) performed a food-specific go/no-go task. Participants were instructed to either respond ("go") or inhibit responding ("no-go") to images of food or toys. Half of the runs depicted high-calorie foods (e.g., pizza) whereas the other half depicted low-calorie foods (e.g., salad). Children were also genotyped for a DNA polymorphism associated with energy intake and obesity (FTO rs9939609) to examine the influence of obesity risk on behavioral and brain responses to food. Participants demonstrated differences in behavioral sensitivity to high- and low-calorie food images depending on task demands. Participants were slower but more accurate at detecting high- (relative to low-) calorie foods when responding to a neutral stimulus (i.e., toys) and worse at detecting toys when responding to high-calorie foods. Inhibition failures were accompanied by salience network activity (anterior insula, dorsal anterior cingulate cortex), which was driven by false alarms to food images. Children at a greater genetic risk for obesity (dose-dependent model of the FTO genotype) demonstrated pronounced brain and behavioral relationships such that genetic risk was associated with heightened sensitivity to high-calorie food images and increased anterior insula activity. These findings suggest that high-calorie foods may be particularly salient to children at risk for developing eating habits that promote obesity.

Facilitating deep learning through preprocessing of optical coherence tomography images.

BACKGROUND: While deep learning has delivered promising results in the field of ophthalmology, the hurdle to complete a deep learning study is high. In this study, we aim to facilitate small scale model trainings by exploring the role of preprocessing to reduce computational burden and accelerate learning. METHODS: A small subset of a previously published dataset containing optical coherence tomography images of choroidal neovascularization, drusen, diabetic macula edema, and normal macula was modified using Fourier transformation and bandpass filter, producing high frequency images, original images, and low frequency images. Each set of images was trained with the same model, and their performances were compared. RESULTS: Compared to that with the original image dataset, the model trained with the high frequency image dataset achieved an improved final performance and reached maximum performance much earlier (in fewer epochs). The model trained with low frequency images did not achieve a meaningful performance. CONCLUSION: Appropriate preprocessing of training images can accelerate the training process and can potentially facilitate modeling using artificial intelligence when limited by sample size or computational power.

Correlations between Clinical and Histopathologic Characteristics in Idiopathic Epiretinal Membrane.

PURPOSE: To investigate correlations between clinical and histopathologic characteristics of idiopathic epiretinal membrane (ERM). DESIGN: Retrospective interventional case series. PARTICIPANTS: In total, 87 eyes from 87 patients with idiopathic ERM who underwent pars plana vitrectomy with peeling of the ERM from 2019 to 2020 were included. METHODS: The outcomes of clinical ophthalmic examination, including measurement of best-corrected visual acuity (BCVA) and spectral-domain OCT (SD-OCT), before and after surgery were reviewed. Surgical specimens were fixed in formalin and embedded in paraffin for histologic and immunohistochemical analysis. MAIN OUTCOMES MEASURES: The association between morphological characteristics revealed on SD-OCT images and the cellular composition of the surgically excised ERM demonstrated with immunohistochemical staining were the main outcome measures. Changes in the BCVA and central macular thickness (CMT) were assessed through a comparison of preoperative and postoperative measurements. RESULTS: Based on SD-OCT morphological characteristics in the foveal area, 15 cases were classified into group 1A (mainly outer retinal thickening), 39 into group 1B (more tenting of the outer retina and distorted inner retina), and 33 into group 1C (prominent inner retina thickening). Overall, postoperative final BCVA and CMT at 1 year improved in all groups. Patients who presented with a better initial BCVA exhibited a more favorable final BCVA. Epiretinal membranes in group 1C demonstrated the greatest decrease in CMT compared with those in groups 1B and 1A, but the final CMT did not differ among the groups. A negative correlation between the density of hyalocytes (P = 0.003) and myofibroblasts (P = 0.047) was noted between the 3 groups. Total cell density and glial cell density of the ERMs were strongly associated with poor final BCVA and BCVA improvement. CONCLUSIONS: The present study provides new histopathologic information regarding the formation and progression of idiopathic ERM. Glial cell proliferation plays a predominant role in these processes. Epiretinal membranes with high cellularity and glial cell density may cause damage to the retina structure, resulting in poor postoperative visual outcomes. These findings provide additional evidence supporting early surgical intervention in patients with idiopathic ERM reported with visual disturbance.

The Black Necrotic Lesion Enhanced Fusarium graminearum Resistance in Wheat.

Fusarium head blight, mainly incited by Fusarium graminearum, is a devastating wheat disease worldwide. Diverse Fusarium head blight (FHB) resistant sources have been reported, but the resistance mechanisms of these sources remain to be investigated. FHB-resistant wheat germplasm often shows black necrotic lesions (BNLs) around the infection sites. To determine the relationship between BNL and FHB resistance, leaf tissue of a resistant wheat cultivar Sumai 3 was inoculated with four different F. graminearum isolates. Integrated metabolomic and transcriptomic analyses of the inoculated samples suggested that the phytohormone signaling, phenolamine, and flavonoid metabolic pathways played important roles in BNL formation that restricted F. graminearum extension. Exogenous application of flavonoid metabolites on wheat detached leaves revealed the possible contribution of flavonoids to BNL formation. Exogenous treatment of either salicylic acid (SA) or methyl jasmonate (MeJA) on wheat spikes significantly reduced the FHB severity. However, exogenous MeJA treatment prevented the BNL formation on the detached leaves of FHB-resistant wheat Sumai 3. SA signaling pathway influenced reactive oxygen species (ROS) burst to enhance BNL formation to reduce FHB severity. Three key genes in SA biosynthesis and signal transduction pathway, TaICS1, TaNPR1, and TaNPR3, positively regulated FHB resistance in wheat. A complex temporal interaction that contributed to wheat FHB resistance was detected between the SA and JA signaling pathways. Knowledge of BNLs extends our understanding of the molecular mechanisms of FHB resistance in wheat and will benefit the genetic improvement of wheat FHB resistance.

Step-wise diagnostic approach for patients with uveitis - Experts consensus in Taiwan.

Uveitis is a sight-threatening disease that can be associated with many different etiologies. Successful treatment of uveitis relies on accurate diagnosis and prompt efficient therapy. History taking, physical and ocular examinations, systemic evaluations, and response to treatment provide crucial information to differentiate possible etiologies involved in the pathophysiology of intraocular inflammation. This article provides recommendations for a step-wise approach to patients with uveitis in Taiwan based on an expert meeting and consensus. Systemic evaluations for uveitis should be performed step-by-step and include investigation of patients' general systemic conditions, ruling out infectious etiologies, and obtaining evidential biomarkers to diagnose a specific disease entity.

Visual outcomes and incidence of pseudophakic cystoid macular oedema in eyes with cataract and idiopathic epiretinal membrane after two-step sequential surgery.

OBJECTIVES: To determine whether pars plana vitrectomy (PPV) or cataract surgery should be performed first in concurrent epiretinal membrane (ERM) and cataract treatment with respect to visual outcome and pseudophakic cystoid macular oedema (PCMO) incidence. METHODS: Patients who underwent PPV and cataract surgery sequentially at a tertiary medical centre were retrospectively recruited. Best-corrected visual acuity (BCVA) and central macular thickness (CMT) measured from optical coherence tomography (OCT) images collected before and after each surgery were documented. OCT-defined PCMO incidence and its influence on visual outcomes were analysed. RESULTS: In total, 259 and 159 eyes received PPV (ERM-CATA) before and after cataract surgery (CATA-ERM), respectively. The ERM-CATA group had better final BCVA (logMAR: 0.274 vs. 0.558, p < 0.001) and greater BCVA gain (logMAR VA change: -0.379 vs. -0.220, p = 0.001) than did the CATA-ERM group. Baseline BCVA was positively correlated with final BCVA (p < 0.001), whereas baseline CMT, final CMT, and postoperative CMT changes were not. PCMO incidence did not differ significantly between the two groups (15.4% vs. 19.5%, p = 0.287), and final BCVA changes did not significantly differ between eyes with and without PCMO. PCMO incidence was much higher (29.40% vs. 16.30%, p = 0.008) in eyes with baseline CMT ≥ 500 µm. CONCLUSIONS: When managing ERM and cataract, PPV should be performed before cataract surgery to yield better visual outcomes. Both surgical sequences yield similar PCMO rates. Greater baseline CMT is a risk factor for PCMO after cataract surgery.

Effect of Zn-Rich Wheat Bran With Different Particle Sizes on the Quality of Steamed Bread.

Bran is the main by-product of wheat milling and the part of the grain with the highest Zn content. We investigated the effects of the particle sizes (coarse, D50 = 375.4 ± 12.3 µm; medium, D50 = 122.3 ± 7.1 µm; and fine, D50 = 60.5 ± 4.2 µm) and addition level (5-20%) of Zn-biofortified bran on the quality of flour and Chinese steamed bread. It was studied to determine if the Zn content of steamed bread could be enhanced without deleterious effects on quality. Dough pasting properties, such as peak viscosity, trough viscosity, final viscosity, breakdown, and setback, decreased significantly as the bran addition level was increased from 5 to 20% but did not significantly differ as a result of different bran particle sizes. Bran incorporation significantly increased hardness, gumminess, chewiness, and adhesiveness, whereas the springiness, cohesiveness, and specific volume of steamed bread decreased with the increase in bran addition. The optimal sensory score of steamed bread samples in the control and Zn fertilizer groups were obtained under 5% bran addition resulting in comparable flavor, and texture relative to control. Meanwhile, the Zn content of the steamed bread in the Zn fertilizer group was 40.2 mg/kg, which was 55.8% higher than that in the control group. Results indicated that adding the appropriate particle size and amount of bran would be an effective and practical way to solve the problem of the insufficient Zn content of steamed bread.

Scn2a severe hypomorphic mutation decreases excitatory synaptic input and causes autism-associated behaviors.

SCN2A, encoding the neuronal voltage-gated Na+ channel NaV1.2, is one of the most commonly affected loci linked to autism spectrum disorders (ASDs). Most ASD-associated mutations in SCN2A are loss-of-function mutations, but studies examining how such mutations affect neuronal function and whether Scn2a mutant mice display ASD endophenotypes have been inconsistent. We generated a protein truncation variant Scn2a mouse model (Scn2aΔ1898/+) by CRISPR that eliminates the NaV1.2 channel's distal intracellular C-terminal domain, and we analyzed the molecular and cellular consequences of this variant in a heterologous expression system, in neuronal culture, in brain slices, and in vivo. We also analyzed multiple behaviors in WT and Scn2aΔ1898/+ mice and correlated behaviors with clinical data obtained in human subjects with SCN2A variants. Expression of the NaV1.2 mutant in a heterologous expression system revealed decreased NaV1.2 channel function, and cultured pyramidal neurons isolated from Scn2aΔ1898/+ forebrain showed correspondingly reduced voltage-gated Na+ channel currents without compensation from other CNS voltage-gated Na+ channels. Na+ currents in inhibitory neurons were unaffected. Consistent with loss of voltage-gated Na+ channel currents, Scn2aΔ1898/+ pyramidal neurons displayed reduced excitability in forebrain neuronal culture and reduced excitatory synaptic input onto the pyramidal neurons in brain slices. Scn2aΔ1898/+ mice displayed several behavioral abnormalities, including abnormal social interactions that reflect behavior observed in humans with ASD and with harboring loss-of-function SCN2A variants. This model and its cellular electrophysiological characterizations provide a framework for tracing how a SCN2A loss-of-function variant leads to cellular defects that result in ASD-associated behaviors.

High-resolution genome-wide association study and genomic prediction for disease resistance and cold tolerance in wheat.

KEY MESSAGE: High-resolution genome-wide association study (GWAS) facilitated QTL fine mapping and candidate gene identification, and the GWAS based genomic prediction models were highly predictive and valuable in wheat genomic breeding. Wheat is a major staple food crop and provides more than one-fifth of the daily calories and dietary proteins for humans. Genome-wide association study (GWAS) and genomic selection (GS) for wheat stress resistance and tolerance related traits are critical to understanding their genetic architecture for improvement of breeding selection efficiency. However, the insufficient marker density in previous studies limited the utility of GWAS and GS in wheat genomic breeding. Here, we conducted a high-resolution GWAS for wheat leaf rust (LR), yellow rust (YR), powdery mildew (PM), and cold tolerance (CT) by genotyping a panel of 768 wheat cultivars using genotyping-by-sequencing. Among 153 quantitative trait loci (QTLs) identified, 81 QTLs were delimited to ≤ 1.0 Mb intervals with three validated using bi-parental populations. Furthermore, 837 stress resistance-related genes were identified in the QTL regions with 12 showing induced expression by YR and PM pathogens. Genomic prediction using 2608, 4064, 3907, and 2136 pre-selected SNPs based on GWAS and genotypic correlations between the SNPs showed high prediction accuracies of 0.76, 0.73, and 0.78 for resistance to LR, YR, and PM, respectively, and 0.83 for resistance to cold damage. Our study laid a solid foundation for large-scale QTL fine mapping, candidate gene validation and GS in wheat.

Deep learning and ensemble stacking technique for differentiating polypoidal choroidal vasculopathy from neovascular age-related macular degeneration.

Polypoidal choroidal vasculopathy (PCV) and neovascular age-related macular degeneration (nAMD) share some similarity in clinical imaging manifestations. However, their disease entity and treatment strategy as well as visual outcomes are very different. To distinguish these two vision-threatening diseases is somewhat challenging but necessary. In this study, we propose a new artificial intelligence model using an ensemble stacking technique, which combines a color fundus photograph-based deep learning (DL) model and optical coherence tomography-based biomarkers, for differentiation of PCV from nAMD. Furthermore, we introduced multiple correspondence analysis, a method of transforming categorical data into principal components, to handle the dichotomous data for combining with another image DL system. This model achieved a robust performance with an accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve of 83.67%, 80.76%, 84.72%, and 88.57%, respectively, by training nearly 700 active cases with suitable imaging quality and transfer learning architecture. This work could offer an alternative method of developing a multimodal DL model, improve its efficiency for distinguishing different diseases, and facilitate the broad application of medical engineering in a DL model design.

Genetic mapping of a novel powdery mildew resistance gene in wild emmer wheat from "Evolution Canyon" in Mt. Carmel Israel.

KEY MESSAGE: A single dominant powdery mildew resistance gene MlNFS10 was identified in wild emmer wheat and mapped within a 0.3cM genetic interval spanning a 2.1Mb physical interval on chromosome arm 4AL. Wheat powdery mildew caused by Blumeria graminis forma specialis tritici (Bgt) is a globally devastating disease. The use of powdery mildew resistance genes from wild relatives of wheat is an effective method of disease management. Our previous research has shown that disruptive ecological selection has driven the discrete adaptations of the wild emmer wheat population on the south facing slope (SFS) and north facing slope (NFS) at the microsite of "Evolution Canyon" at Mount Carmel, Israel and demonstrated that 16 accessions in the NFS population display high resistance to 11 powdery mildew isolates (collected from different wheat fields in China). Here, we constructed bi-parental population by crossing the accession NFS-10 (resistant to 22 Bgt races collected from China in seedling resistance screen) and the susceptible line SFS2-12. Genetic analysis indicated that NFS-10 carries a single dominant gene, temporarily designated MlNFS10. Ultimately, 13 markers were successfully located within the long arm of chromosome 4A, thereby delineating MlNFS10 to a 0.3 cM interval covering 2.1 Mb (729275816-731365462) in the Chinese Spring reference sequence. We identified disease resistance-associated genes based on the RNA-seq analysis of both parents. The tightly linked InDel marker XWsdau73447 and SSR marker XWsdau72928 were developed and used for marker-assisted selection when MlNFS10 was introgressed into a hexaploid wheat background. Therefore, MlNFS10 can be used for improvement of germplasm in breeding programs for powdery mildew resistant cultivars.

Role of BDNF in the development of an OFC-amygdala circuit regulating sociability in mouse and human.

Social deficits are common in many psychiatric disorders. However, due to inadequate tools for manipulating circuit activity in humans and unspecific paradigms for modeling social behaviors in rodents, our understanding of the molecular and circuit mechanisms mediating social behaviors remains relatively limited. Using human functional neuroimaging and rodent fiber photometry, we identified a mOFC-BLA projection that modulates social approach behavior and influences susceptibility to social anxiety. In humans and knock-in mice with a loss of function BDNF SNP (Val66Met), the functionality of this circuit was altered, resulting in social behavioral changes in human and mice. We further showed that the development of this circuit is disrupted in BDNF Met carriers due to insufficient BDNF bioavailability, specifically during a peri-adolescent timeframe. These findings define one mechanism by which social anxiety may stem from altered maturation of orbitofronto-amygdala projections and identify a developmental window in which BDNF-based interventions may have therapeutic potential.

Integrated metabolo-transcriptomics and functional characterization reveals that the wheat auxin receptor TIR1 negatively regulates defense against Fusarium graminearum.

Fusarium head blight (FHB) caused by Fusarium graminearum Schwabe (teleomorph Gibberella zeae (Schw.) Perch) results in large yield losses in annual global wheat production. Although studies have identified a number of wheat FHB resistance genes, a deeper understanding of the mechanisms underlying host plant resistance to F. graminearum is required for the control of FHB. Here, an integrated metabolomics and transcriptomics analysis of infected wheat plants (Triticum aestivum L.) enabled identification of 789 differentially accumulated metabolites, including flavonoids, phenolamides, tryptamine derivatives, and phytohormones, and revealed altered expression of more than 100 genes that function in the biosynthesis or regulation of these pathways. Our data regarding the effects of F. graminearum infection on flavonoids and auxin signaling led to follow-up experiments that showed that exogenous kaempferide and apigenin application on spikes increased wheat resistance to FHB, while exogenous auxin treatment increased FHB susceptibility. RNAi-mediated knockdown of the gene encoding the auxin receptor, TaTIR1, increased FHB resistance. Our data supported the use of TaTIR1 knockdown in controlling FHB. Our study provides insights on the wheat response to F. graminearum infection and its FHB resistance mechanisms while illustrating the potential of TaTIR1 knockdown in increasing FHB resistance during crop improvement programs.

The Use of Systemic Steroids in the Treatment of Herpes Zoster Ophthalmicus-Related Ophthalmoplegia: Case Report and Case Meta-analysis.

PURPOSE: The role of systemic steroids in the treatment of ophthalmoplegia in the setting of herpes zoster ophthalmicus (HZO) is controversial. We conducted a case report-based meta-analysis to investigate the role of systemic steroid in the recovery of efferent dysfunctions in HZO. DESIGN: Case-report based meta-analysis. METHOD: We report a case of herpes zoster ophthalmicus-related ophthalmoplegia (HZORO) in which systemic steroid led to complete resolution of external ophthalmoplegia. We further identified subjects from published cases of HZO-related ophthalmoplegia by searching PubMed and Google Scholar, which elicited 42 articles (49 cases) after excluding those younger than 18 years or with incomplete follow-up data. With the present case, a total of 50 cases are included in the analysis. Main outcome measure is the recovery of efferent dysfunction at the last known follow-up, coded as 1 for complete recovery or 0 for noncomplete recovery. We performed multivariable linear regression and Cox proportional hazards analysis to determine the contribution of steroid duration on the status of complete recovery. RESULTS: Multivariable linear regression showed significant association between duration of steroid treatment and status of complete recovery (P < .001). Cox proportional hazards analysis showed a hazard ratio of 1.1 (P = .04), indicating that longer treatment duration increased chance of complete recovery. Age, gender, and initial steroid dose did not contribute significantly to recovery status. CONCLUSION: Our meta-analysis suggests that extended steroid taper may aid the recovery of ophthalmoplegia in the setting of HZO and should be investigated further in the future.

Orbital Apex Syndrome Secondary to Invasive Aspergillus Infection: A Case Series and Literature Review.

BACKGROUND: Invasive fungal sinusitis carries high morbidity and mortality and often poses a diagnostic challenge. Orbital apex syndrome (OAS) is not an uncommon presentation in the setting of invasive fungal sinusitis. Delays in diagnosis and appropriate treatment can result in permanent visual dysfunction and, potentially, death. We present 2 cases of OAS secondary to invasive sinus aspergillosis, detailing the diagnostic process, treatment, and outcome for both patients. Subsequently, we present a review of the literature and combined analysis of our 2 patients plus 71 cases from previously published reports. METHODS: Literature review was performed to identify demographic, diagnostic, clinical, and treatment data of patients with OAS caused by Aspergillus species. RESULTS: The review resulted in 52 included articles with 71 patients, plus our 2 reported patients, leading to a total of 73 subjects included in the analysis. The average age of patients at presentation was 59.9 years. A combination of visual disturbance and pain (headache and/or periocular pain) was the most common presentation reported (46 cases; 63%). Diabetes mellitus was reported in 15 cases (21%), with more than half specifically noted to have poorly controlled diabetes. After diabetes, the second most common cause of immunocompromise was chronic steroid use (n = 13; 18%). Empiric antifungal treatment was started in 10 patients (14%), while 25 patients (34%) were first treated with systemic steroids due to a concern for an inflammatory etiology. Time to diagnosis from initial presentation was on average 7.4 weeks (range of 0.3-40 weeks). Approximately 78% of the cases (57 of 73) had biopsies with histology that confirmed Aspergillus fungal morphology, and 30/73 (41%) had diagnostic fungal cultures. The majority of the cases received monotherapy with intravenous (IV) amphotericin B (36 patients; 49%) and IV voriconazole (19 patients; 26%), with a combination of the 2 or more antifungal agents being used in 11 patients (15%). Forty patients (55%) showed signs of clinical improvement with treatment, while 33 (45%) patients did not experience any improvement or continued to deteriorate, and 23 (32%) died in the course of their reported follow-up. CONCLUSIONS: The present cases illustrate well the challenge in the diagnosis and treatment of OAS due to invasive sinus aspergillosis. Our review and analysis of 73 cases support the notion that a high index of suspicion leading to early biopsy with histology and fungal culture is paramount for diagnosis. Early empiric antifungal treatment and debridement can potentially reduce morbidity and mortality.

Flow signal change in polyps after anti-vascular endothelial growth factor therapy.

Optical coherence tomography angiography (OCTA) is a novel, non-invasive imaging tool used to detect vascular flow. The absence of a flow signal in OCTA in polyps revealed by indocyanine green angiography (ICGA) in patients with polypoidal choroidal vasculopathy (PCV) may indicate slow or compromised filling of blood flow from choroidal vessels. Naïve patients with PCV treated with intravitreal injections of aflibercept (IVI-A) were enrolled in this study to validate the hypothesis that baseline flow may affect the outcome of polyp regression in ICGA. The flow signal of polyps in OCTA was detected by manual segmentation in the corresponding location by ICGA. Polyps were defined as high-flow if both OCTA and ICGA showed positive findings, and low-flow if OCTA showed a negative flow signal in 3 consecutive horizontal scans at the polyp area shown in ICGA. A total of 24 polyps were identified in 13 PCV patients at baseline. Of these 24 polyps, 22 (91.7%) were high-flow and 2 (8.3%) were low-flow. After 3 monthly IVI-A, all low-flow polyps had complete regression in ICGA. Among 17 (77%) high-flow polyps at baseline that had regression after treatment, 10 (58.8%) became low-flow, while 5 (22.7%) persistent polyps remained high-flow. Flow signal of polyps as detected by OCTA could be a predictive factor for treatment response in patients with PCV. Monitoring changes in flow signal after treatment is clinically relevant.

A member of wheat class III peroxidase gene family, TaPRX-2A, enhanced the tolerance of salt stress.

BACKGROUND: Salt and drought are the main abiotic stresses that restrict the yield of crops. Peroxidases (PRXs) are involved in various abiotic stress responses. Furthermore, only few wheat PRXs have been characterized in the mechanism of the abiotic stress response. RESULTS: In this study, a novel wheat peroxidase (PRX) gene named TaPRX-2A, a member of wheat class III PRX gene family, was cloned and its response to salt stress was characterized. Based on the identification and evolutionary analysis of class III PRXs in 12 plants, we proposed an evolutionary model for TaPRX-2A, suggesting that occurrence of some exon fusion events during evolution. We also detected the positive selection of PRX domain in 13 PRXs involving our evolutionary model, and found 2 or 6 positively selected sites during TaPRX-2A evolution. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) results showed that TaPRX-2A exhibited relatively higher expression levels in root tissue than those exhibited in leaf and stem tissues. TaPRX-2A expression was also induced by abiotic stresses and hormone treatments such as polyethylene glycol 6000, NaCl, hydrogen peroxide (H2O2), salicylic acid (SA), methyljasmonic acid (MeJA) and abscisic acid (ABA). Transgenic wheat plants with overexpression of TaPRX-2A showed higher tolerance to salt stress than wild-type (WT) plants. Confocal microscopy revealed that TaPRX-2A-eGFP was mainly localized in cell nuclei. Survival rate, relative water content, and shoot length were higher in TaPRX-2A-overexpressing wheat than in the WT wheat, whereas root length was not significantly different. The activities of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) were enhanced in TaPRX-2A-overexpressing wheat compared with those in the WT wheat, resulting in the reduction of reactive oxygen species (ROS) accumulation and malondialdehyde (MDA) content. The expression levels of downstream stress-related genes showed that RD22, TLP4, ABAI, GST22, FeSOD, and CAT exhibited higher expressions in TaPRX-2A-overexpressing wheat than in WT under salt stress. CONCLUSIONS: The results show that TaPRX-2A plays a positive role in the response to salt stress by scavenging ROS and regulating stress-related genes.

High-Resolution Genome-wide Association Study Identifies Genomic Regions and Candidate Genes for Important Agronomic Traits in Wheat.

Wheat (Triticum aestivum) is a major staple food crop worldwide. Genetic dissection of important agronomic traits is essential for continuous improvement of wheat yield to meet the demand of the world's growing population. We conducted a large-scale genome-wide association study (GWAS) using a panel of 768 wheat cultivars that were genotyped with 327 609 single-nucleotide polymorphisms generated by genotyping-by-sequencing and detected 395 quantitative trait loci (QTLs) for 12 traits under 7 environments. Among them, 273 QTLs were delimited to ≤1.0-Mb intervals and 7 of them are either known genes (Rht-D, Vrn-B1, and Vrn-D1) that have been cloned or known QTLs (TaGA2ox8, APO1, TaSus1-7B, and Rht12) that were previously mapped. Eight putative candidate genes were identified for three QTLs that enhance spike seed setting and grain size using gene expression data and were validated in three bi-parental populations. Protein sequence analysis identified 33 putative wheat orthologs that have high identity with rice genes in QTLs affecting similar traits. Large r2 values for additive effects observed among the QTLs for most traits indicated that the phenotypes of these identified QTLs were highly predictable. Results from this study demonstrated that significantly increasing GWAS population size and marker density greatly improves detection and identification of candidate genes underlying a QTL, solidifying the foundation for large-scale QTL fine mapping, candidate gene validation, and developing functional markers for genomics-based breeding in wheat.

[Unnatural amino acid orthogonal translation: a genetic engineering technology for the development of new-type live viral vaccine].

Unnatural amino acid orthogonal translation machinery can insert unnatural amino acids at desired sites of protein through stop codon by means of foreign orthogonal translation system composed of aminoacyl-tRNA synthetase and orthogonal tRNA genes. This new genetic engineering technology is not only a new tool for biochemical researches of proteins, but also an epoch-making technology for the development of new-type live viral vaccines. The mutated virus containing premature termination codon in genes necessary for replication can be propagated in transgenic cells harboring unnatural amino acid orthogonal translation machinery in media with corresponding unnatural amino acid, but it cannot replicate in conventional host cells. This replication-deficient virus is a new-type of live viral vaccine that possesses advantages of high efficacy of traditional attenuated vaccine and high safety of killed vaccine. This article reviews the application and prospect of unnatural amino acid orthogonal translation machinery in the development of novel replication-deficient virus vaccines.