A novel NIR-II albumin-escaping probe for cerebral arteries and perfusion imaging in stroke mice model.

In order to guide the formulation of post-stroke treatment strategy in time, it is necessary to have real-time feedback on collateral circulation and revascularization. Currently used near-infrared II (NIR-II) probes have inherent binding with endogenous albumin, resulting in significant background signals and uncontrollable pharmacokinetics. Therefore, the albumin-escaping properties of the new probe, IR-808AC, was designed, which achieved timely excretion and low background signal, enabling the short-term repeatable injection for visualization of cerebral vessels and perfusion. We further achieved continuous observation of changes in collateral vessels and perfusion during the 7-d period in middle cerebral artery occlusion mice using IR-808AC in vivo. Furthermore, using IR-808AC, we confirmed that remote ischemic conditioning could promote collateral vessels and perfusion. Finally, we evaluated the revascularization after thrombolysis on time in embolic stroke mice using IR-808AC. Overall, our study introduces a novel methodology for safe, non-invasive, and repeatable assessment of collateral circulation and revascularization in real-time that is crucial for the optimization of treatment strategies.

Nanodrug delivery systems for regulating microglial polarization in ischemic stroke treatment: A review.

The incidence of ischemic stroke (IS) is rising in tandem with the global aging population. There is an urgent need to delve deeper into the pathological mechanisms and develop new neuroprotective strategies. In the present review, we discuss the latest advancements and research on various nanodrug delivery systems (NDDSs) for targeting microglial polarization in IS treatment. Furthermore, we critically discuss the different strategies. NDDSs have demonstrated exceptional qualities to effectively permeate the blood-brain barrier, aggregate at the site of ischemic injury, and target specific cell types within the brain when appropriately modified. Consequently, NDDSs have considerable potential for reshaping the polarization phenotype of microglia and could be a prospective therapeutic strategy for IS. The treatment of IS remains a challenge. However, this review provides a new perspective on neuro-nanomedicine for IS therapies centered on microglial polarization, thereby inspiring new research ideas and directions.

m6A-Mediated Upregulation of Imprinted in Prader-Willi Syndrome Induces Aberrant Apical-Basal Polarization and Oxidative Damage in RPE Cells.

Purpose: To reveal the clinical significance, pathological involvement and molecular mechanism of imprinted in Prader-Willi syndrome (IPW) in RPE anomalies that contribute to AMD. Methods: IPW expression under pathological conditions were detected by microarrays and qPCR assays. In vitro cultured fetal RPE cells were used to study the pathogenicity induced by IPW overexpression and to analyze its upstream and downstream regulatory networks. Results: We showed that IPW is upregulated in the macular RPE-choroid tissue of dry AMD patients and in fetal RPE cells under oxidative stress, inflammation and dedifferentiation. IPW overexpression in fetal RPE cells induced aberrant apical-basal polarization as shown by dysregulated polarized markers, disrupted tight and adherens junctions, and inhibited phagocytosis. IPW upregulation was also associated with RPE oxidative damages, as demonstrated by intracellular accumulation of reactive oxygen species, reduced cell proliferation, and accelerated cell apoptosis. Mechanically, N6-methyladenosine level of the IPW transcript regulated its stability with YTHDC1 as the reader. IPW mediated RPE features by suppressing MEG3 expression to sequester its inhibition on the AKT serine-threonine kinase (AKT)/mammalian target of rapamycin (mTOR) pathway. We also noticed that the mTOR inhibitor rapamycin suppresses the AKT/mTOR pathway to alleviate the IPW-induced RPE anomalies. Conclusions: We revealed that IPW overexpression in RPE induces aberrant apical-basal polarization and oxidative damages, thus contributing to AMD progression. We also annotated the upstream and downstream regulatory networks of IPW in RPE. Our findings shed new light on the molecular mechanisms of RPE dysfunctions, and indicate that IPW blockers may be a promising option to treat RPE abnormalities in AMD.

Oxygen-tolerant CO2 electroreduction over covalent organic frameworks via photoswitching control oxygen passivation strategy.

The direct use of flue gas for the electrochemical CO2 reduction reaction is desirable but severely limited by the thermodynamically favorable oxygen reduction reaction. Herein, a photonicswitching unit 1,2-Bis(5'-formyl-2'-methylthien-3'-yl)cyclopentene (DAE) is integrated into a cobalt porphyrin-based covalent organic framework for highly efficient CO2 electrocatalysis under aerobic environment. The DAE moiety in the material can reversibly modulate the O2 activation capacity and electronic conductivity by the framework ring-closing/opening reactions under UV/Vis irradiation. The DAE-based covalent organic framework with ring-closing type shows a high CO Faradaic efficiency of 90.5% with CO partial current density of -20.1 mA cm-2 at -1.0 V vs. reversible hydrogen electrode by co-feeding CO2 and 5% O2. This work presents an oxygen passivation strategy to realize efficient CO2 electroreduction performance by co-feeding of CO2 and O2, which would inspire to design electrocatalysts for the practical CO2 source such as flue gas from power plants or air.

Boosting CO2 Electroreduction over a Covalent Organic Framework in the Presence of Oxygen.

Herein, we propose an oxygen-containing species coordination strategy to boost CO2 electroreduction in the presence of O2. A two-dimensional (2D) conjugated metal-covalent organic framework (MCOF), denoted as NiPc-Salen(Co)2-COF that is composed of the Ni-phthalocyanine (NiPc) unit with well-defined Ni-N4-O sites and the salen(Co)2 moiety with binuclear Co-N2O2 sites, is developed and synthesized for enhancing the CO2RR under aerobic condition. In the presence of O2, one of the Co sites in the NiPc-Salen(Co)2-COF that coordinated with the intermediate of *OOH from ORR could decrease the energy barrier of the activation of CO2 molecules and stabilize the key intermediate *COOH of the CO2RR over the adjacent Co center. Besides, the oxygen species axially coordinated Ni-N4-O sites can favor in reducing the energy barrier of the intermediate *COOH formation for the CO2RR. Thus, NiPc-Salen(Co)2-COF exhibits high oxygen-tolerant CO2RR performance and achieves outstanding CO Faradaic efficiency (FECO) of 97.2 % at -1.0 V vs. the reversible hydrogen electrode (RHE) and a high CO partial current density of 40.3 mA cm-2 at -1.1 V in the presence of 0.5 % O2, which is superior to that in pure CO2 feed gas (FECO=94.8 %, jCO=19.9 mA cm-2). Notably, the NiPc-Salen(Co)2-COF achieves an industrial-level current density of 128.3 mA cm-2 in the flow-cell reactor with 0.5 % O2 at -0.8 V, which is higher than that in pure CO2 atmosphere (jCO=104.8 mA cm-2). It is worth noting that an excellent FECO of 86.8 % is still achieved in the presence of 5 % O2 at -1.0 V. This work provides an effective strategy to enable the CO2RR under O2 atmosphere by utilizing the *OOH intermediates of ORR to boost CO2 electroreduction.

Lactylation-driven FTO targets CDK2 to aggravate microvascular anomalies in diabetic retinopathy.

Diabetic retinopathy (DR) is a leading cause of irreversible vision loss in working-age populations. Fat mass and obesity-associated protein (FTO) is an N6-methyladenosine (m6A) demethylase that demethylates RNAs involved in energy homeostasis, though its influence on DR is not well studied. Herein, we detected elevated FTO expression in vitreous fibrovascular membranes of patients with proliferative DR. FTO promoted cell cycle progression and tip cell formation of endothelial cells (ECs) to facilitate angiogenesis in vitro, in mice, and in zebrafish. FTO also regulated EC-pericyte crosstalk to trigger diabetic microvascular leakage, and mediated EC-microglia interactions to induce retinal inflammation and neurodegeneration in vivo and in vitro. Mechanistically, FTO affected EC features via modulating CDK2 mRNA stability in an m6A-YTHDF2-dependent manner. FTO up-regulation under diabetic conditions was driven by lactate-mediated histone lactylation. FB23-2, an inhibitor to FTO's m6A demethylase activity, suppressed angiogenic phenotypes in vitro. To allow for systemic administration, we developed a nanoplatform encapsulating FB23-2 and confirmed its targeting and therapeutic efficiency in mice. Collectively, our study demonstrates that FTO is important for EC function and retinal homeostasis in DR, and warrants further investigation as a therapeutic target for DR patients.

Heart Rate Variability in Patients with Spontaneous Intracerebral Hemorrhage and its Relationship with Clinical Outcomes.

BACKGROUND: Although abnormal heart rate variability (HRV) is frequently observed in patients with spontaneous intracerebral hemorrhage (ICH), its time course and presentation of different indices remain unclear, and few studies have focused on its association with clinical outcomes. METHODS: We prospectively recruited consecutive patients with spontaneous ICH between June 2014 and June 2021. HRV was evaluated twice during hospitalization (within 7 days and 10-14 days after stroke). Time and frequency domain indices were calculated. A modified Rankin Scale score ≥ 3 at 3 months was defined as a poor outcome. RESULTS: Finally, 122 patients with ICH and 122 age- and sex-matched volunteers were included. Compared with controls, time domain and absolute frequency domain HRV parameters (total power, low frequency [LF], and high frequency [HF]) in the ICH group were significantly decreased within 7 days and 10-14 days. For relative values, normalized LF (LF%) and LF/HF were significantly higher, whereas normalized HF (HF%) was significantly lower, in the patient group than in the control group. Furthermore, LF% and HF% measured at 10-14 days were independently associated with 3-month outcomes. CONCLUSIONS: HRV values were impaired significantly within 14 days after ICH. Furthermore, HRV indices measured 10-14 days after ICH were independently associated with 3-month outcomes.

Organ-enriched gene expression during floral morphogenesis in wild barley.

Floral morphology varies considerably between dicots and monocots. The ABCDE model explaining how floral organ development is controlled was formulated using core eudicots and applied to grass crops. Barley (Hordeum. vulgare) has unique floral morphogenesis. Wild barley (H. vulgare ssp. spontaneum), which is the immediate ancestor of cultivated barley (H. vulgare ssp. vulgare), contains a rich reservoir of genetic diversity. However, the wild barley genes involved in floral organ development are still relatively uncharacterized. In this study, we generated an organ-specific transcriptome atlas for wild barley floral organs. Genome-wide transcription profiles indicated that 22 838 protein-coding genes were expressed in at least one organ. These genes were grouped into seven clusters according to the similarities in their expression patterns. Moreover, 5619 genes exhibited organ-enriched expression, 677 of which were members of 47 transcription factor families. Gene ontology analyses suggested that the functions of the genes with organ-enriched expression influence the biological processes in floral organs. The co-expression regulatory network showed that the expression of 690 genes targeted by MADS-box proteins was highly positively correlated with the expression of ABCDE model genes during floral morphogenesis. Furthermore, the expression of 138 genes was specific to the wild barley OUH602 genome and not the Morex genome; most of these genes were highly expressed in the glume, awn, lemma, and palea. This study revealed the global gene expression patterns underlying floral morphogenesis in wild barley. On the basis of the study findings, a molecular mechanism controlling floral morphology in barley was proposed.

Remote ischemic conditioning attenuates oxidative stress and inflammation via the Nrf2/HO-1 pathway in MCAO mice.

The protective effects of remote ischemic conditioning (RIC) on acute ischemic stroke have been reported. However, the protective mechanisms of RIC have not been fully elucidated. This study aimed to investigate whether RIC could reduce oxidative stress and inflammatory responses in middle cerebral artery occlusion (MCAO)-reperfusion mice via the nuclear factor-E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway. C57BL/6 mice were subjected to MCAO and underwent RIC twice daily at 1, 3, and 7 days after MCAO. ML385 was used to specifically inhibit Nrf2 in MCAO mice. Neurological deficit scores, infarct volume, and hematoxylin-eosin (HE) staining were assessed. Oxidative stress levels were assessed based on total antioxidant capacity (TAC), malonaldehyde (MDA), superoxide dismutase (SOD), and glutathione/glutathione disulfide (GSH/GSSG). mRNA levels were detected using real-time polymerase chain reaction (PCR), and protein levels were detected using western blotting and enzyme-linked immunosorbent assay (ELISA). Protein localization was investigated using immunofluorescence staining. RIC significantly reduced infarct volume and improved neurological function and histological changes after MCAO. RIC significantly increased TAC, SOD, and GSH/GSSG levels and decreased MDA levels. RIC significantly increased Nrf2 and HO-1 mRNA levels and decreased Keap1, NLRP3, and Cleaved Caspase-1 mRNA levels. RIC significantly increased Nrf2, HO-1, and NQO1 protein expression and decreased Keap1, NLRP3, Cleaved Caspase-1, Cleaved IL-1ß, IL-6, and TNF-α protein expression. RIC promoted the activation and translocation of Nrf2 into the nucleus. The protective effects of RIC were abolished by ML385 treatment. In conclusion, our findings suggest that RIC alleviates oxidative stress and inflammatory responses via the Nrf2/HO-1 pathway, which in turn improves neurobehavioral function. RIC may provide novel therapeutic options for acute ischemic stroke.

ALKBH5 causes retinal pigment epithelium anomalies and choroidal neovascularization in age-related macular degeneration via the AKT/mTOR pathway.

Retinal pigment epithelium (RPE) dysfunction and choroidal neovascularization (CNV) are predominant features of age-related macular degeneration (AMD), with an unclear mechanism. Herein, we show that RNA demethylase α-ketoglutarate-dependent dioxygenase alkB homolog 5 (ALKBH5) is up-regulated in AMD. In RPE cells, ALKBH5 overexpression associates with depolarization, oxidative stress, disturbed autophagy, irregular lipid homeostasis, and elevated VEGF-A secretion, which subsequently promotes proliferation, migration, and tube formation of vascular endothelial cells. Consistently, ALKBH5 overexpression in mice RPE correlates with various pathological phenotypes, including visual impairments, RPE anomalies, choroidal neovascularization (CNV), and interrupted retinal homeostasis. Mechanistically, ALKBH5 regulates retinal features through its demethylation activity. It targets PIK3C2B and regulates the AKT/mTOR signaling pathway with YTHDF2 as the N6-methyladenosine reader. IOX1, an ALKBH5 inhibitor, suppresses hypoxia-induced RPE dysfunction and CNV progression. Collectively, we demonstrate that ALKBH5 induces RPE dysfunction and CNV progression in AMD via PIK3C2B-mediated activation of the AKT/mTOR pathway. Pharmacological inhibitors of ALKBH5, like IOX1, are promising therapeutic options for AMD.

Circular RNA expression and the competitive endogenous RNA network in pathological, age-related macular degeneration events: A cross-platform normalization study.

Age-related macular degeneration (AMD) causes irreversible blindness in people aged over 50 worldwide. The dysfunction of the retinal pigment epithelium is the primary cause of atrophic AMD. In the current study, we used the ComBat and Training Distribution Matching method to integrate data obtained from the Gene Expression Omnibus database. We analyzed the integrated sequencing data by the Gene Set Enrichment Analysis. Peroxisome and tumor necrosis factor-α (TNF-α) signaling and nuclear factor kappa B (NF-κB) were among the top 10 pathways, and thus we selected them to construct AMD cell models to identify differentially expressed circular RNAs (circRNAs). We then constructed a competing endogenous RNA network, which is related to differentially expressed circRNAs. This network included seven circRNAs, 15 microRNAs, and 82 mRNAs. The Kyoto Encyclopedia of Genes and Genomes analysis of mRNAs in this network showed that the hypoxia-inducible factor-1 (HIF-1) signaling pathway was a common downstream event. The results of the current study may provide insights into the pathological processes of atrophic AMD.

Wheat Ym2 originated from Aegilops sharonensis and confers resistance to soil-borne Wheat yellow mosaic virus infection to the roots.

Wheat yellow mosaic virus (WYMV) is a pathogen transmitted into its host's roots by the soil-borne vector Polymyxa graminis. Ym1 and Ym2 genes protect the host from the significant yield losses caused by the virus, but the mechanistic basis of these resistance genes remains poorly understood. Here, it has been shown that Ym1 and Ym2 act within the root either by hindering the initial movement of WYMV from the vector into the root and/or by suppressing viral multiplication. A mechanical inoculation experiment on the leaf revealed that the presence of Ym1 reduced viral infection incidence, rather than viral titer, while that of Ym2 was ineffective in the leaf. To understand the basis of the root specificity of the Ym2 product, the gene was isolated from bread wheat using a positional cloning approach. The candidate gene encodes a CC-NBS-LRR protein and it correlated allelic variation with respect to its sequence with the host's disease response. Ym2 (B37500) and its paralog (B35800) are found in the near-relatives, respectively, Aegilops sharonensis and Aegilops speltoides (a close relative of the donor of bread wheat's B genome), while both sequences, in a concatenated state, are present in several accessions of the latter species. Structural diversity in Ym2 has been generated via translocation and recombination between the two genes and enhanced by the formation of a chimeric gene resulting from an intralocus recombination event. The analysis has revealed how the Ym2 region has evolved during the polyploidization events leading to the creation of cultivated wheat.

Absence of CEP78 causes photoreceptor and sperm flagella impairments in mice and a human individual.

Cone-rod dystrophy (CRD) is a genetically inherited retinal disease that can be associated with male infertility, while the specific genetic mechanisms are not well known. Here, we report CEP78 as a causative gene of a particular syndrome including CRD and male infertility with multiple morphological abnormalities of sperm flagella (MMAF) both in human and mouse. Cep78 knockout mice exhibited impaired function and morphology of photoreceptors, typified by reduced ERG amplitudes, disrupted translocation of cone arrestin, attenuated and disorganized photoreceptor outer segments (OS) disks and widen OS bases, as well as interrupted connecting cilia elongation and abnormal structures. Cep78 deletion also caused male infertility and MMAF, with disordered '9+2' structure and triplet microtubules in sperm flagella. Intraflagellar transport (IFT) proteins IFT20 and TTC21A are identified as interacting proteins of CEP78. Furthermore, CEP78 regulated the interaction, stability, and centriolar localization of its interacting protein. Insufficiency of CEP78 or its interacting protein causes abnormal centriole elongation and cilia shortening. Absence of CEP78 protein in human caused similar phenotypes in vision and MMAF as Cep78-/- mice. Collectively, our study supports the important roles of CEP78 defects in centriole and ciliary dysfunctions and molecular pathogenesis of such multi-system syndrome.

m6A modification of circSPECC1 suppresses RPE oxidative damage and maintains retinal homeostasis.

Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss in the elderly population with unclear pathogenic mechanism. Herein, we detect downregulated circSPECC1 expression in retinal pigment epithelium (RPE) of AMD patients. In RPE cells, circSPECC1 insufficiency leads to oxidative stress-induced ferroptosis, depolarization, and irregular lipid metabolism. Consistently, in mice, circSPECC1 deficiency induces visual impairments and RPE anomalies and interrupts retinal homeostasis. Mechanically, nuclear export of circSPECC1 transcript depends on its N6-methyladenosine (m6A) level with YTHDC1 as the reader. CircSPECC1 directly sponges miR-145-5p to block its interaction with CDKN1A. Overexpressing miR-145-5p aggravates RPE dysfunctions, mimicking circSPECC1 silencing effects. Retinal phenotypes induced by circSPECC1 insufficiency are alleviated by miR-145-5p inhibition and are aggravated by miR-145-5p overexpression. Collectively, circSPECC1, mediated by m6A modification and sponging miR-145-5p, resists oxidative stress injuries and maintains lipid metabolism in RPE. Pharmacological supplementation of circSPECC1 is a promising therapeutic option for atrophic retinopathies like AMD.

Platelet-to-lymphocyte ratio at 24h after thrombolysis is a prognostic marker in acute ischemic stroke patients.

Background: The changes in the platelet-to-lymphocyte ratio (PLR) before and after recombinant tissue plasminogen activator (rtPA) treatment and the time point at which the PLR is a potentially valuable prognostic predictor in patients wit ischemic stroke remain largely unknown. Therefore, the purpose of this study was to explore the characteristics of the PLR and evaluate their effects on clinical outcomes before and 24 h after rtPA treatment. Methods: This study included 741 consecutive patients with acute ischemic stroke who underwent intravenous thrombolysis with rtPA. We collected data on demographics, vascular risk factors, medication history, and other clinical information pertaining to all patients. Specifically, blood samples for PLR measurement were collected on admission and 24 h after stroke. The outcome was assessed by using the Modified Rankin Scale (mRS) at 3 months and whether death occurred within 3 months or not. Univariate and multivariate logistic regression analysis was used to assess the association of the PLR with the risks of poor outcome (mRS>2) and death. An individualized prediction model was established to predict poor outcome. Results: Of the 741 patients, 255 (34.4%) had poor outcome, and 43 (5.8%) died. The PLR significantly increased 24 h after rtPA in patients with poor outcome and death. Logistic analysis revealed that higher PLR 24 h after rtPA was independently associated with increased risks of poor outcome and death. However, the PLR on admission was not associated with the risks of poor outcome and death. The individualized prediction model for poor outcome based on the 24-h PLR exhibited favorable discrimination (areas under the curves of the training and validation groups: 0.743 and 0.729, respectively), calibration (P > 0.05), and clinical usefulness. Conclusions: We found the PLR to be a variable that potentially predicts the risks of poor outcome and death in patients with acute ischemic stroke 24 h after rtPA; however, it cannot make the same prediction on admission.

The Role of N6-Methyladenosine Modification in Microvascular Dysfunction.

Microvascular dysfunction (MVD) has long plagued the medical field despite improvements in its prevention, diagnosis, and intervention. Microvascular lesions from MVD increase with age and further lead to impaired microcirculation, target organ dysfunction, and a mass of microvascular complications, thus contributing to a heavy medical burden and rising disability rates. An up-to-date understanding of molecular mechanisms underlying MVD will facilitate discoveries of more effective therapeutic strategies. Recent advances in epigenetics have revealed that RNA methylation, an epigenetic modification, has a pivotal role in vascular events. The N6-methylation of adenosine (m6A) modification is the most prevalent internal RNA modification in eukaryotic cells, which regulates vascular transcripts through splicing, degradation, translation, as well as translocation, thus maintaining microvascular homeostasis. Conversely, the disruption of the m6A regulatory network will lead to MVD. Herein, we provide a review discussing how m6A methylation interacts with MVD. We also focus on alterations of the m6A regulatory network under pathological conditions. Finally, we highlight the value of m6A regulators as prognostic biomarkers and novel therapeutic targets, which might be a promising addition to clinical medicine.

Prognostic values of serum alkaline phosphatase and globulin levels in patients undergoing intravenous thrombolysis.

Background: In previous studies, alkaline phosphatase (ALP) level was a prognostic factor for patients with ischemic stroke, and globulin level was associated with hemorrhagic transformation (HT) after intravenous thrombolysis (IVT). However, the association between these serum biomarkers and prognosis in patients with acute ischemic stroke (AIS) who undergo IVT remains unclear. This study aimed to investigate the characteristics of serum ALP and globulin levels after IVT and to assess the relationship between these serum biomarkers and prognosis. Materials and methods: This retrospective study used a prospectively collected database. We included patients with AIS who received recombinant tissue plasminogen activator (rt-PA) IVT. Demographic information, vascular risk factors, laboratory test results, and other stroke-related data were collected for analysis. Clinical outcomes included HT and 3-month poor outcome (modified Rankin Scale scores ≥ 2) after IVT. The association of ALP and globulin levels with HT and poor outcome was investigated using multivariate logistic regression analysis. An individualized prediction model based on ALP and globulin levels for functional outcomes was established. Results: We enrolled 750 patients in this study; 452 patients (60.3%) had poor outcome, and 117 patients (15.6%) had HT after IVT. After adjusting for all confounders, serum globulin level [OR = 1.055; 95% confidence intervals (CI): 1.006-1.107; P = 0.028] was independently associated with HT in patients with IVT. Serum ALP (OR = 1.009; 95% CI: 1.002-1.016; P = 0.010) and globulin levels (OR = 1.062; 95% CI: 1.020-1.107; P = 0.004) were associated with 3-month poor outcome in these patients. The constructed individualized prediction model for the 3-month poor outcome comprised the National Institutes of Health Stroke Scale (NIHSS) score, Trial of Org 10172 in Acute Stroke Treatment (TOAST), history of antihypertensive therapy, ALP and globulin levels. The area under the curve of the training and validation sets were 0.726 and 0.706, respectively, revealing that the model had good discriminating power. The P-values for the Hosmer-Lemeshow test in the training and validation sets were 0.978 and 0.148, respectively, indicating the model had good calibration. Conclusion: This study found that higher serum globulin levels were independently associated with HT. Additionally, higher serum ALP and globulin levels were independently associated with a poor outcome in patients after IVT.

A novel Nance-Horan syndrome mutation identified by next-generation sequencing in a Chinese family.

AIM: To identify the disease-causing mutation in a four-generation Chinese family diagnosed with Nance-Horan syndrome (NHS). METHODS: A Chinese family, including four affected patients and four healthy siblings, was recruited. All family members received ophthalmic examinations with medical histories provided. Targeted next-generation sequencing approach was conducted on the two affected males to screen for their disease-causing mutations. RESULTS: Two male family members diagnosed with NHS manifested bilateral congenital cataracts microcornea, strabismus and subtle facial and dental abnormalities, while female carriers presented posterior Y-sutural cataracts. A novel frameshift mutation (c.3916_3919del) in the NHS gene was identified. This deletion was predicted to alter the reading frame and generate a premature termination codon after a new reading frame. CONCLUSION: The study discovers a new frameshift mutation in a Chinese family with NHS. The findings broaden the spectrum of NHS mutations that can cause NHS in Chinese patients.

Genome-Wide Analysis of Snf2 Gene Family Reveals Potential Role in Regulation of Spike Development in Barley.

Sucrose nonfermenting 2 (Snf2) family proteins, as the catalytic core of ATP-dependent chromatin remodeling complexes, play important roles in nuclear processes as diverse as DNA replication, transcriptional regulation, and DNA repair and recombination. The Snf2 gene family has been characterized in several plant species; some of its members regulate flower development in Arabidopsis. However, little is known about the members of the family in barley (Hordeum vulgare). Here, 38 Snf2 genes unevenly distributed among seven chromosomes were identified from the barley (cv. Morex) genome. Phylogenetic analysis categorized them into 18 subfamilies. They contained combinations of 21 domains and consisted of 3 to 34 exons. Evolution analysis revealed that segmental duplication contributed predominantly to the expansion of the family in barley, and the duplicated gene pairs have undergone purifying selection. About eight hundred Snf2 family genes were identified from 20 barley accessions, ranging from 38 to 41 genes in each. Most of these genes were subjected to purification selection during barley domestication. Most were expressed abundantly during spike development. This study provides a comprehensive characterization of barley Snf2 family members, which should help to improve our understanding of their potential regulatory roles in barley spike development.

FOVEAL AVASCULAR ZONE VOLUME: A New Index Based on Optical Coherence Tomography Angiography Images.

PURPOSE: To propose a new clinical evaluation index, foveal avascular zone (FAZ) volume, and analyze its statistical significance. METHODS: A semiautomatic method is proposed to measure the FAZ volume in optical coherence tomography angiography images as follows: The region of interest was flattened and annotated axially. The labeled pixels in the restored region of interest were counted as the FAZ volume. Linear regression and the independent samples t-test were performed for the statistical analysis. RESULTS: Sixty-one normal, 64 high myopia, and 42 diabetic retinopathy eyes were imaged using optical coherence tomography angiography. For normal eyes, the FAZ volume correlates inversely with central macular thickness (superficial: P = 0.004; deep: P < 0.001) and positively with area (P < 0.001). For high myopia eyes, the deep plexus FAZ (P = 0.34) and total FAZ (P = 0.38) volumes show no significant difference, whereas the superficial plexus FAZ volume is significantly larger than control (P < 0.001). For diabetic retinopathy eyes, the superficial plexus FAZ (P = 0.001), deep plexus FAZ (P = 0.014), and total volumes (P = 0.002) are significantly larger than control. CONCLUSION: The FAZ volume is proposed for depicting the 3D structure of the FAZ. It shows greater sensitivity for vascular alteration that makes it meaningful for clinical analysis.