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Leber’s hereditary optic neuropathy (LHON) is a debilitating mitochondrial disease associated with mutations in mitochondrial DNA (mtDNA). Unfortunately, the available treatment options for LHON patients are limited due to challenges in mitochondrial replacement. In our study, we reprogramming LHON urine cells into induced pluripotent stem cells (iPSCs) and differentiating them into neural progenitor cells (NPCs) and neurons for disease modeling. Our research revealed that LHON neurons exhibited significantly higher levels of mtDNA mutations and reduced mitochondrial function, confirming the disease phenotype. However, through co-culturing LHON iPSC-derived NPCs with mesenchymal stem cells (MSCs), we observed a remarkable rescue of mutant mtDNA and a significant improvement in mitochondrial metabolic function in LHON neurons. These findings suggest that co-culturing with MSCs can enhance mitochondrial function in LHON NPCs, even after their differentiation into neurons. This discovery holds promise as a potential therapeutic strategy for LHON patients.

AimsTo investigate the clinical characteristics of Leber hereditary optic neuropathy (LHON) with mtDNA primary mutations to better understand features associated with prognosis.MethodsThis study enrolled 1540 LHON patients from 1516 unrelated families genetically confirmed by Sanger or whole-mitochondrial sequencing between 1997 and 2022. The spectrum of variants was summarised and compared in different ethnic groups. Clinical data from outpatients were collected, including onset age, disease course, optic disc categories and the corresponding visual acuity.ResultsOf the 1516 LHON families, 13 pathogenic mtDNA variants were detected, in which the proportion of m.11778G>A, m.3460G>A and m.3635G>A was significantly different from non-East Asians (p<0.0001). About 95% (1075/1131) of patients were between 8 and 40 years old at onset, with a median onset age of 16. The eyes of m.14484T>C patients presented with better visual acuity and slower progression across patients with different onset ages and initial severity. Eyes (N=439) with available fundus images were divided into four categories (C1–C4). The progression grades were derived from the category and the corresponding time course, where a higher grade (C3–C4 within 1 year) was associated with greater visual impairment than a lower grade (C1–C2 over 1 year) (p=4.60E-05) . A prognostic matrix showed that later onset and a higher progression grade are associated with higher risk of blindness.ConclusionCompared with non-East Asians, Chinese LHON patients had higher proportions of m.11778G>A and m.3635G>A and lower m.3460G>A mutations. A novel progression grade derived from optic disc category was proposed. The prognostic matrix indicated that lower grade and younger-onset age are the most favourable prognostic factors.

The Asian community — the second largest non-European ethnic community in New Zealand — plays an important role in combatting the COVID-19 pandemic, evidenced by their active advocation for border control and mass masking. Despite the long history of racial discrimination against the Asian population, the Asian community has experienced certain degrees of racial discrimination associated with the stigmatisation as the cause of the COVID-19 outbreak in New Zealand. Based on data from a quantitative online survey with 402 valid responses within the Asian communities across New Zealand and the in-depth interviews with 19 Asian people in Auckland, New Zealand, this paper will illustrate Asian people’s experience of racial discrimination and stigmatisation during the pandemic in the country. The survey shows that since the outbreak of COVID-19, under a quarter of the participants reported experiencing discrimination, and a third reported knowing an immediate contact who had experienced discrimination. However, when looking beyond their immediate social circle, an even higher proportion reported noticing racism and stigmatisation through the traditional or social media due to COVID-19. Major variations of the degree of racial discrimination experienced are determined by three demographic variables: ethnicity, age, and region. The in-depth interviews largely echoed the survey findings and highlighted a strong correlation between the perceived racial discrimination among the local Asian community and the stigmatisation associated with COVID-19. These findings are important for improving the way we manage future pandemics and other disasters within the context of the UN Sendai Framework for Disaster Risk Reduction.

Fine-grained entity typing (FGET) is an important natural language processing (NLP) task. It is to assign fine-grained semantic types of a type taxonomy (e.g., Person/artist/actor) to entity mentions. Fine-grained entity semantic types have been successfully applied in many natural language processing applications, such as relation extraction, entity linking and question answering. The key challenge for FGET is how to deal with label noises that disperse in corpora since the corpora are normally automatically annotated. Various type taxonomies, typing methods and representation learning approaches for FGET have been proposed and developed in the past two decades. This paper systematically categorizes and reviews these various typing methods and representation learning approaches to provide a reference for future studies on FGET. We also present a comprehensive review of type taxonomies, resources, applications for FGET and methods for automatically generating FGET training corpora. Furthermore, we identify the current trends in FGET research and discuss future research directions for FGET. To the best of our knowledge, this is the first comprehensive review of FGET.

AimsTo elucidate genetic background of early-onset high myopia (eoHM) and characteristics of ARR3-associated MYP26.MethodsVariants in 14 genes reported to contribute to eoHM, including ARR3, were selected from exome sequencing data set and classified into different categories following American College of Medical Genetics and Genomics guidelines based on in silico prediction, associated phenotypes, confirmation and cosegregation analysis. The available clinical data of individuals were summarised.ResultsPathogenic and likely pathogenic variants in three of 14 genes were identified in 52 of 928 families with eoHM, including 29 in ARR3, 22 in OPN1LWand 1 in LRPAP1. For ARR3, 24 pathogenic variants (16 truncation and 8 missense) were identified in 66 women and 12 men, in whom 64 women and 4 men had eoHM by X-linked female-limited inheritance. Refraction ranged from −5.00 to −28.75 diopter (−12.58±4.83). Mild-to-moderately reduced cone responses were recorded in 76.9% (10/13) of patients with electroretinogram recordings. Most patients (75.9%, 41/54) had mild myopic fundus changes (C0 to C1). Genotype–phenotype analysis suggested that the myopic retinopathy degree was correlated with age and the variant’s nature. Peripheral retinal degeneration was observed in 38.5% (5/13) patients using wide-field examinations.ConclusionThis study reveals ARR3as the most frequently implicated gene for Mendelian eoHM. Truncations and highly scored missense variants in ARR3are pathogenic. Myopia due to ARR3mutations is transmitted in X-linked female-limited inheritance, manifests with mild cone impairment and slowly progresses to pathologic myopia. Identification of the most common cause for Mendelian eoHM provides a valuable starting point into the molecular mechanism of myopia.

Aim: Asians are the second largest and fastest growing non-European population in New Zealand but are under-researched in terms of their COVID-19 pandemic response. The paper aims to illustrates Asians’ risk perceptions and knowledge of COVID-19, and self-protection practices to avoid infection and prevent community transmission. Subject and methods: An online survey was used to collect data and received 402 valid responses. Data analyses included: 1) a descriptive analysis by using Chi-square tests and a Kruskal-Wallis rank sum tests to explore associations between responses and the four demographic variables (i.e. age, gender, country of origin/ethnicity, and region); and 2) a correlation analysis between different survey objectives. Results: The descriptive analysis of the survey found that while ethnicity (within the Asian category) was the most influential variable that resulted in varying responses to many questions, gender and age were other two important variables in influencing the answering patterns. The correlation analysis found a positive correlation between the perceived ‘dangerousness’ of COVID-19 and respondents’ overall compliance behaviour to New Zealand authorities’ recommendations to prevent spread of COVID-19. Conclusion: The majority of the respondents provided correct answers to the questions about the vulnerable populations, symptoms, asymptomatic transmission and potential sequelae of COVID-19; however, their understanding of the availability of a cure for, and the incubation period of COVID-19 was not consistent with the official information. The research also found that the higher perceived dangerousness of COVID-19, the better compliance to self-protection practices among the surveyed population.

Background/aimsX-linked retinoschisis (XLRS), associated with RS1, is the most common type of X-linked retinopathy in children. This study aimed to identify clinical and genetic features of retinoschisis in 120 families with RS1variants in China.MethodsRS1variants were collected from our in-house exome data and were predicted by multiple-step bioinformatics analysis. Clinical data of 122 patients from 120 families with potential pathogenic RS1variants were analysed and summarised, respectively.ResultTotally, 79 hemizygous variants (53 missense, 25 truncation and 1 indel), were detected. All except one (78/79, 98.7%), including 22 novels, were classified as potential pathogenic and detected exclusively in 120 families with retinoschisis. Clinical data demonstrated an average age of presentation at 5 years (1 month–41 years). Macular changes were classified as macular schisis (87.5%), macular atrophy (10.7%), normal (0.9%) and unclassified (0.9%). Patients with macular atrophy had older age but similar visual acuity compared with macular schisis. Peripheral retinal changes included flat retinoschisis (52.4%), bullous retinoschisis (BRS) (10.7%) and normal-like (36.9%) patients. Spontaneous regression was observed in two patients with BRS on follow-up examination. Visual acuity in the peripheral retinoschisis group was worse than that without peripheral retinoschisis.ConclusionAlmost all rare RS1variants were potential pathogenic. All patients with RS1pathogenic variants showed detectable characteristics in the macula and/or peripheral retina. Our data on RS1variants and associated clinical phenotypes may be of value for clinical diagnosis and genetic test of retinoschisis.

The recovery of platinum group metals (PGMs) from spent automotive catalysts (SACs) is a promising solution to alleviate PGMs resource shortage and reduce environmental pollution caused by SACs. Nevertheless, the traditional iron capture method requires high smelting temperatures for effective PGMs recovery, leading to significant energy consumption. Therefore, experimenting with lower temperatures to achieve efficient recovery is both beneficial and challenging. The introduction of Sn for the Fe-Sn co-capture of Pt and Pd has been proven to be effective. However, the unique behavior and mechanism of Sn in capturing Rh remain unclear. In this paper, we conduct a detailed study on Sn's behavior in capturing Rh. Rh exhibits a different trend compared to Pt/Pd. Specifically, Sn demonstrates a significantly stronger ability to capture Rh than Pt/Pd, and its effectiveness surpasses that of Fe. Under optimized slag types and smelting conditions, the recovery efficiencies for Pt, Pd, and Rh increased by 20.55 %, 13.04 %, and 21.57 % respectively, compared to traditional single metal iron trapping, reaching 94.14 %, 93.42 %, and 93.76 %. DFT calculations indicate that the lattice substitution energy for PGMs entering the Sn lattice is lower than that for Fe, thus the introduction of Sn enhances the metal trap's ability to capture PGMs. This work provides an in-depth understanding of how the introduction of Sn enhances the recovery of PGMs, particularly Rh. It offers new theoretical guidance for efficiently recovering PGMs from SACs, benefiting the comprehensive recovery and utilization of PGMs.

Glycogen storage disease type 1b (GSD1b) is a rare genetic disorder, resulting from mutations in the SLC37A4 gene located on chromosome 11q23.3. Although the SLC37A4 gene has been identified as the pathogenic gene for GSD1b, the complete variant spectrum of this gene remains to be fully elucidated. In this study, we present three patients diagnosed with GSD1b through genetic testing. We detected five variants of the SLC37A4 gene in these three patients, with three of these mutations (p. L382Pfs*15, p. G117fs*28, and p. T312Sfs*13) being novel variants not previously reported in the literature. We also present a literature review and general overview of the currently reported SLC37A4 gene variants. Our study expands the mutation spectrum of SLC37A4, which may help enable genetic testing to facilitate prompt diagnosis, appropriate intervention, and genetic counseling for affected families.

BackgroundLeber congenital amaurosis (LCA) is the earliest and most severe form of inherited retinal dystrophies. In approximately 56% of Chinese probands, genetic defects can be detected in known LCA-causing genes. In this study, the objective was to identify pathogenic variants in two unsolved Chinese families with LCA.MethodsTo identify the genetic defect, whole-exome sequencing (WES) and clinical analysis was performed in both probands with LCA as well as in 3011 in-house controls with other hereditary eye diseases. The expression profiles, as well as the phenotype analysis of knockdown zebrafish model and knockout mice model, were performed to investigate the function of USP45in photoreceptors.ResultsBy analysing WES data based on allele frequencies of in-house controls, population allele frequencies and in silico prediction tools, two rare homozygous mutations in USP45were identified in two unrelated families. Immunohistochemistry of USP45 in the human and zebrafish retinal sections revealed enriched expression in the inner segments of photoreceptors. The knockdown of usp45transcript in zebrafish led to abnormal retinal development with effects on photoreceptors, which could be successfully rescued by wild-type usp45mRNA. Moreover, targeted knockout of Usp45in mice caused abnormal electroretinography responses, similar to that seen in patients with LCA.ConclusionsOur study implicates that biallelic mutations in USP45are associated with the occurrence of LCA. Moreover, our results indicate that USP45is indispensable to the maintenance of photoreceptor function.

IMPORTANCE: Mutations in CNGA3 are the most common cause of achromatopsia and cone-rod dystrophies. OBJECTIVE: To identify CNGA3 mutations in patients with cone dystrophies or Leber congenital amaurosis. DESIGN, SETTING, AND PARTICIPANTS: Clinical data and genomic DNA in 267 Chinese probands from 138 families with cone dystrophies and 129 families with Leber congenital amaurosis collected at the Zhongshan Ophthalmic Center, Guangzhou, China. MAIN OUTCOMES AND MEASURES: Variants in CNGA3 and associated phenotypes, assessed by Sanger sequencing of CNGA3, bioinformatics of variants, and segregation analysis. RESULTS: Homozygous or compound heterozygous mutations in CNGA3, including 26 novel and 13 known mutations, were identified in 46 probands from 138 families with cone dystrophies, but none were found in any of the probands from 129 families with Leber congenital amaurosis. The 46 probands with CNGA3 mutations could be further classified as likely having achromatopsia (18 probands) and cone-rod dystrophies (28 probands) based on electroretinographic recordings. Analysis of family members in 17 of 46 families demonstrated good segregation of the disease with the CNGA3 mutations. CONCLUSIONS AND RELEVANCE: To our knowledge, this study is the first systemic analysis of CNGA3 in Chinese patients and expands the mutational spectrum and associated phenotypes. Our results suggest that CNGA3 mutations are a common cause of cone-rod dystrophies and achromatopsia in the Chinese population. These data indicate that CNGA3-associated cone dystrophies may be a common form of early-onset severe retinal dystrophies. Therapeutic potential such as gene therapy targeting this gene may benefit some children with early-onset severe retinal dystrophies.

Ozone is a model abiotic elicitor of reactive oxygen species (ROS). ROS are important oxidative signaling molecules coordinating plant development and responses to biotic and abiotic stresses. Recently, microRNAs have been described as important players in regulating stress responses in plants. In this research we examined the miRNAs that are differentially expressed early in response to ozone in the Arabidopsis thalianaecotype Col-0 that is tolerant to this oxidant. We used a plant miRNA array to identify 22 miRNA families that are differentially expressed within one hour of ozone fumigation. Majority of these miRNAs were also reported in response to UV-B stress. Analysis of the miRNA target genes showed a strong negative correlation to the miRNA expression. In silico promoter analysis of miRNA genes identified several stress responsive cis-elements that were enriched in the promoters of ozone responsive genes. Majority of the target genes of ozone responsive miRNAs were associated with developmental processes. Based on these results we suggest that post-transcriptional gene regulation via miRNAs may aid in resource allocation by downregulating developmental processes to cater to the oxidative stress demands on plants.

Abstract: DNA methylation, a major event in epigenetics, plays an essential role in the control of gene expression. Increasing evidence suggests that long and short non-coding RNAs are involved extensively in plants to direct the establishment, spread, and removal of DNA cytosine methylation throughout their genomes. Yet, little has been known about the role of microRNAs (miRNAs) in DNA methylation although the role of small interfering RNAs (siRNAs) in DNA methylation has been well established. Several recent studies, however, provided the evidence for miRNA-directed DNA methylation in plants, and the working mechanisms still need to be fully explored. In this review, we highlight the key features of miRNA-directed DNA methylation in plants and provide insight into the complexities of such an event in plants. The interaction between miRNAs and the epigenetic machinery and the future potential research questions are briefly discussed.

OBJECTIVE To identify the genetic locus for X-linked nonsyndromic high myopia in a large Chinese family. METHODS Phenotypic information and DNA samples were collected from 19 individuals in a Chinese family; 7 had high myopia and 12 were unaffected. We performed a linkage scan on the X chromosome and sequenced several candidate genes. RESULTS High myopia in this family, presenting since early childhood and ranging from −6.00 to −15.00 diopters of sphere, is consistent with an X-linked recessive trait. The presence of a normal optic disc and the absence of color visual defects and other systemic abnormalities indicated that high myopia in this family is nonsyndromic. Our linkage analysis mapped the disease locus to Xq28, a 6.1-cM region between DXS8069 and Xqter, with 2-point logarithm of odds scores greater than 2.0 for 5 markers and a maximum logarithm of odds score of 3.59 at θ = 0 for 2 markers. Sequence analysis of coding and adjacent intronic regions of GPR50, PRRG3, CNGA2, and BGN did not identify any potential causative mutation. CONCLUSIONS Nonsyndromic high myopia in a Chinese family was mapped to the MYP1 region, which confirmed and refined this region for high myopia. In addition, our results suggest that color visual defects and optic disc hypoplasia are not necessary signs of high myopia attributed to the MYP1 region. CLINICAL RELEVANCE MYP1 is a common and the best locus for positional cloning of the gene responsible for high myopia. Our results suggest that MYP1 is also responsible for nonsyndromic high myopia.Arch Ophthalmol. 2010;128(11):1473-1479--

In September 2021, Immigration New Zealand (INZ) announced the offer of a one-off residence visa category – the 2021 Resident Visa, to over 165,000 temporary migrant workers and their family members living in the country. The offer was a response to the backlog and growing numbers of applications that INZ was unable to attend to largely because of the lockdown during the COVID-19 pandemic. Drawing on relevant statistical data, news media reports and available academic publications, this research note examines how New Zealand’s sanitization policies during the pandemic affected the lives of temporary migrant workers who hold various work visas.

The penetrance of Leber's hereditary optic neuropathy (LHON) in families with primary mitochondrial DNA (mtDNA) mutations is very complex. Matrilineal and nuclear genetic background, as well as environmental factors, have been reported to be involved in different affected pedigrees. Here we describe two large Chinese families that show a striking difference in the penetrance of LHON, in which 53.3% and 15.0% of members were affected (P<0.02), respectively. Analysis of the complete mtDNA genome of the two families revealed the presence of the primary mutation G11778A and several other variants suggesting the same haplogroup status G2a. The family with higher penetrance contained a previously described secondary mutation G13708A, which presents a polymorphism in normal Chinese samples and does not affect in vivo mitochondrial oxidative metabolism as described in a previous study. Evolutionary analysis failed to indicate any putatively pathogenic mutation that cosegregated with G11778A in these two pedigrees. Our results suggest that the variable penetrance of LHON in the two Chinese families is independent of both their mtDNA haplotype background and a secondary mutation G13708A. As a result, it is likely that unknown nuclear gene involvement and/or other factors contribute to the strikingly different penetrance of LHON.