PLPPR4 haploinsufficiency causes neurodevelopmental disorders by disrupting synaptic plasticity via mTOR signalling.

Phospholipid phosphatase related 4 (PLPPR4), a neuron-specific membrane protein located at the postsynaptic density of glutamatergic synapses, is a putative regulator of neuronal plasticity. However, PLPPR4 dysfunction has not been linked to genetic disorders. In this study, we report three unrelated patients with intellectual disability (ID) or autism spectrum disorder (ASD) who harbour a de novo heterozygous copy number loss of PLPPR4 in 1p21.2p21.3, a heterozygous nonsense mutation in PLPPR4 (NM_014839, c.4C > T, p.Gln2*) and a homozygous splice mutation in PLPPR4 (NM_014839: c.408 + 2 T > C), respectively. Bionano single-molecule optical mapping confirmed PLPPR4 deletion contains no additional pathogenic genes. Our results suggested that the loss of function of PLPPR4 is associated with neurodevelopmental disorders. To test the pathogenesis of PLPPR4, peripheral blood mononuclear cells obtained from the patient with heterozygous deletion of PLPPR4 were induced to specific iPSCs (CHWi001-A) and then differentiated into neurons. The neurons carrying the deletion of PLPPR4 displayed the reduced density of dendritic protrusions, shorter neurites and reduced axon length, suggesting the causal role of PLPPR4 in neurodevelopmental disorders. As the mTOR signalling pathway was essential for regulating the axon maturation and function, we found that mTOR signalling was inhibited with a higher level of p-AKT, p-mTOR and p-ERK1/2, decreased p-PI3K in PLPPR4-iPSCs neurons. Additionally, we found silencing PLPPR4 disturbed the mTOR signalling pathway. Our results suggested PLPPR4 modulates neurodevelopment by affecting the plasticity of neurons via the mTOR signalling pathway.

Novel compound heterozygous synonymous and missense variants in the MYO7A gene identified by next-generation sequencing in a Chinese family with nonsyndromic hearing loss.

BACKGROUND: Variants in the MYO7A gene are increasingly identified among patients suffering from Usher syndrome type 1B (USH1B). However, such mutations are less commonly detected among patients suffering from nonsyndromic hearing loss (NSHL), including autosomal recessive deafness (DFNB2) and autosomal dominant deafness (DFNA11). This research attempts to clarify the genetic base of DFNB2 in a Chinese family and determine the pathogenicity of the identified mutations. METHOD: Targeted next-generation sequencing (TGS) of 127 known deafness genes was performed for the 14-year-old proband. Then, Sanger sequencing was performed on the available family members. A minigene splicing assay was performed to verify the impact of the novel MYO7A synonymous variant. After performing targeted next-generation sequencing (TGS) of 127 existing hearing loss-related genes in a 14-year-old proband, Sanger sequencing was carried out on the available family members. Then, to confirm the influence of the novel MYO7A synonymous variants, a minigene splicing assay was performed. RESULTS: Two heteroallelic mutants of MYO7A (NM_000260.3) were identified: a maternally inherited synonymous variant c.2904G > A (p.Glu968=) in exon 23 and a paternally inherited missense variant c.5994G > T (p.Trp1998Cys) in exon 44. The in vitro minigene expression indicated that c.2904G > A may result in skipping of exon 23 resulting in a truncated protein. CONCLUSIONS: We reported a novel missense (c.5994G > T) and identified, for the first time, a novel pathogenic synonymous (c.2904G > A) variant within MYO7A in a patient with DFNB2. These findings enrich our understanding of the MYO7A variant spectrum of DFNB2 and can contribute to accurate genetic counseling and diagnosis of NSHL patients.

[Analysis of ARID1B gene variants in two Chinese pedigrees with Coffin-Siris syndrome].

OBJECTIVE: To explore the genetic basis for two Chinese pedigrees affected with Coffin-Siris syndrome (CSS). METHODS: Whole exome sequencing (WES) was carried out for the probands. Candidate variants were verified by Sanger sequencing of the probands and their family members. RESULTS: The two probands were respectively found to harbor a heterozygous c.5467delG (p.Gly1823fs) variant and a heterozygous c.5584delA (p.Lys1862fs) variant of the ARID1B gene, which were both of de novo in origin and unreported previously. Based on the guidelines of American College of Medical Genetics and Genomics, both variants were predicted to be pathogenic (PVS1+PS2+PM2). CONCLUSION: The c.5467delG (p.Gly1823fs) and c.5545delA (p.Lys1849fs) variants of the ARID1B genes probably underlay the CSS in the two probands. Above results have enabled genetic counselling and prenatal diagnosis for the pedigrees.

Genetic analysis and prenatal diagnosis of 20 Chinese families with oculocutaneous albinism.

BACKGROUND: Oculocutaneous albinism (OCA) is a group of heterogeneous genetic disorders characterized by abnormal melanin synthesis in the hair, skin, and eyes. OCA exhibits obvious genetic and phenotypic heterogeneity. Molecular diagnosis of causal genes can be of help in the classification of OCA subtypes and the study of OCA pathogenesis． METHODS: In this study, Sanger sequencing and whole exome sequencing were used to genetically diagnose 20 nonconsanguineous Chinese OCA patients. In addition, prenatal diagnosis was provided to six OCA families. RESULTS: Variants of TYR, OCA2, and HPS1 were detected in 85%, 10%, and 5% of affected patients, respectively. A total of 21 distinct variants of these three genes were identified. Exons 1 and 2 were the hotspot regions of the TYR variants, and c.895C > A and c.896G > A were the hotspot variants. We also found seven novel variants: c.731G > A, c.741C > A, c.867C > A, and c.1037-2A > T in TYR, c.695dupT and c.1054A > G in OCA2, and c.9C > A in HPS1. Genetic tests on six fetuses revealed three carrier fetuses, two normal fetuses, and one affected fetus. The follow-up results after birth were consistent with the results of prenatal diagnosis (one fetus terminated during pregnancy was not followed up). CONCLUSIONS: This study expands our understanding of the genotypic spectrum of the Chinese OCA population. The findings indicate that prenatal diagnosis can provide important information for genetic counseling.

The variations in human orphan G protein-coupled receptor QRFPR affect PI3K-AKT-mTOR signaling.

BACKGROUND: QRFPR is a recently identified member of the G protein-coupled receptor and is an orphan receptor for 26Rfa, which plays important role in the regulation of many physiological functions. METHODS: Here, we employed whole exome sequencing (WES) to examine the patients with intellectual disability (ID) and difficulty in feeding. We performed SIFT and PolyPhen2 predictions for the variants. The structure model was built from scratch by I-TASSER. Here, results derived from a number of cell-based functional assays, including shRNA experiment, intracellular Ca2+ measurement, the expression of PI3 K-AKT-mTOR, and phosphorylation. The functional effect of QRFPR variants on PI3K-AKT-mTOR signaling was evaluated in vitro transfection experiments. RESULT: Here, we identified two QRFPR variants at c.202 T>C (p.Y68H) and c.1111C>T (p.R371W) in 2 unrelated individuals. Structural analysis revealed that p.Y68H and p.R371W variants may affect the side chain structure of adjacent amino acids causing reduced binding of QRFPR to 26Rfa. The results show that QRFPR stimulated by 26Rfa leading to the transient rise of intracellular Ca2+ . The QRFPR variations p.Y68H and p.R371 W can reduce the mobilization of intracellular Ca2+ . The phosphorylation levels of the PI3K, Akt, and mTOR were significantly up- or downregulated by QRFPR overexpression or silencing, respectively. The QRFPR variations inhibited PI3K-AKT-mTOR signaling, resulting in downregulation of p-mTOR. CONCLUSIONS: Our findings suggest that QRFPR acts as important role in neurodevelopment, and the effects of QRFPR are likely to be mediated by the Ca2+ -dependent PI3K-AKT-mTOR pathways. Importantly, these findings provide a foundation for future elucidation of GPCR-mediated signaling and the physiological implications.

Mast cell and autoimmune diseases.

Mast cells are important in innate immune system. They have been appreciated as potent contributors to allergic reaction. However, increasing evidence implicates the important role of mast cells in autoimmune disease like rheumatoid arthritis and multiple sclerosis. Here we review the current stage of knowledge about mast cells in autoimmune diseases.

Regulatory Effect of Iguratimod on the Balance of Th Subsets and Inhibition of Inflammatory Cytokines in Patients with Rheumatoid Arthritis.

OBJECTIVE: To expand upon the role of iguratimod (T-614) in the treatment of rheumatoid arthritis (RA), we investigated whether the Th1, Th17, follicular helper T cells (Tfh), and regulatory T cells (Treg) imbalance could be reversed by iguratimod and the clinical implications of this reversal. METHODS: In this trial, 74 patients were randomized into iguratimod-treated (group A) and control (broup B) group for a 24-week treatment period. In the subsequent 28 weeks, both groups were given iguratimod. Frequencies of Th1, Th17, Tfh, and Treg were quantified using flow cytometry, and serum cytokines were detected by enzyme-linked immunosorbent assay. mRNA expression of cytokines and transcriptional factor were quantified by RT-PCR. The composite Disease Activity Score, erythrocyte sedimentation rate, and C-reactive protein were assessed at each visit. RESULT: The clinical scores demonstrated effective suppression of disease after treatment with iguratimod. In addition, iguratimod downregulated Th1, Th17-type response and upregulated Treg. Furthermore, the levels of Th1, Th17, and Tfh associated inflammatory cytokines and transcription factors were reduced after treatment with iguratimod, while the levels of Treg associated cytokines and transcription factors were increased.

Efficient segmentation of fetal brain MRI based on the physical resolution.

BACKGROUND: The image resolution of fetal brain magnetic resonance imaging (MRI) is a critical factor in brain development measures, which is mainly determined by the physical resolution configured in the MRI sequence. However, fetal brain MRI are commonly reconstructed to 3D images with a higher apparent resolution, compared to the original physical resolution. PURPOSE: This work is to demonstrate that accurate segmentation can be achieved based on the MRI physical resolution, and the high apparent resolution segmentation can be achieved by a simple deep learning module. METHODS: This retrospective study included 150 adult and 80 fetal brain MRIs. The adult brain MRIs were acquired at a high physical resolution, which were downsampled to visualize and quantify its impacts on the segmentation accuracy. The physical resolution of fetal images was estimated based on MRI acquisition settings and the images were downsampled accordingly before segmentation and restored using multiple upsampling strategies. Segmentation accuracy of ConvNet models were evaluated on the original and downsampled images. Dice coefficients were calculated, and compared to the original data. RESULTS: When the apparent resolution was higher than the physical resolution, the accuracy of fetal brain segmentation had negligible degradation (accuracy reduced by 0.26%, 1.1%, and 1.8% with downsampling factors of 4/3, 2, and 4 in each dimension, without significant differences from the original data). Using a downsampling factor of 4 in each dimension, the proposed method provided 7× smaller and 10× faster models. CONCLUSION: Efficient and accurate fetal brain segmentation models can be developed based on the physical resolution of MRI acquisitions.

Associations between the choroid plexus and tau in Alzheimer's disease using an active learning segmentation pipeline.

BACKGROUND: The cerebrospinal fluid (CSF), primarily generated by the choroid plexus (ChP), is the major carrier of the glymphatic system. The alternations of CSF production and the ChP can be associated with the Alzheimer's disease (AD). The present work investigated the roles of the ChP in the AD based on a proposed ChP image segmentation pipeline. METHODS: A human-in-the-loop ChP image segmentation pipeline was implemented with intermediate and active learning datasets. The performance of the proposed pipeline was evaluated on manual contours by five radiologists, compared to the FreeSurfer and FastSurfer toolboxes. The ChP volume and blood flow were investigated among AD groups. The correlations between the ChP volume and AD CSF biomarkers including phosphorylated tau (p-tau), total tau (t-tau), amyloid-ß42 (Aß42), and amyloid-ß40 (Aß40) was investigated using three models (univariate, multiple variables, and stepwise regression) on two datasets with 806 and 320 subjects. RESULTS: The proposed ChP segmentation pipeline achieved superior performance with a Dice coefficient of 0.620 on the test dataset, compared to the FreeSurfer (0.342) and FastSurfer (0.371). Significantly larger volumes (p < 0.001) and higher perfusion (p = 0.032) at the ChP were found in AD compared to CN groups. Significant correlations were found between the tau and the relative ChP volume (the ChP volume and ChP/parenchyma ratio) in each patient groups and in the univariate regression analysis (p < 0.001), the multiple regression model (p < 0.05 except for the t-tau in the LMCI), and in the step-wise regression model (p < 0.021). In addition, the correlation coefficients changed from - 0.32 to - 0.21 along with the AD progression in the multiple regression model. In contrast, the Aß42 and Aß40 shows consistent and significant associations with the lateral ventricle related measures in the step-wise regression model (p < 0.027). CONCLUSIONS: The proposed pipeline provided accurate ChP segmentation which revealed the associations between the ChP and tau level in the AD. The proposed pipeline is available on GitHub ( https://github.com/princeleeee/ChP-Seg ).

The Impact of Intraocular Pressure Changes on Corneal Biomechanics in Primary Open-angle Glaucoma.

PURPOSE: To investigate the relationship between intraocular pressure (IOP) changes and corneal biomechanical properties, determine the quantitative relationship between IOP changes and corneal biomechanical properties in patients with glaucoma and observe the differences among different types of glaucoma when the effects of high-level IOP were excluded. DESIGN: Prospective clinical cohort study. METHODS: Setting: Institutional. PATIENTS: Treatment-naive patients with primary open-angle glaucoma or ocular hypertension (OHT) were included. OBSERVATION PROCEDURES: IOP was measured using a Goldmann applanation tonometer. Corneal biomechanics were evaluated using a corneal indentation device and corneal visualization Scheimpflug technology. Medication therapy was used for IOP reduction. Repeated measurements were taken at the baseline visit and each week thereafter within a month. Paired t tests were used to compare IOP and corneal biomechanical metrics before and after IOP-lowering therapy. One-way analysis of variance was employed to investigate potential differences across groups, with a Bonferroni post hoc correction administered for multiple intergroup comparisons. MAIN OUTCOME MEASURES: Corneal biomechanical parameters following IOP changes. RESULTS: Eighty-one participants (mean age, 41.63 ± 17.33 years) were included in this study. The cohort comprised 20 patients with normal-tension glaucoma (NTG), 47 with high-tension glaucoma (HTG), and 14 with OHT. The baseline corneal stiffness (88.58 ± 18.30 N/m) and corneal modulus (0.71 ± 0.16 MPa) were greater than the post-IOP reduction values (67.15 ± 9.24 N/m and 0.54 ± 0.08 MPa, respectively; P < .001). The relationships between changes in IOP and changes in corneal biomechanical parameters were Δ corneal stiffness = 2.06*ΔIOP+6.47 (P < .001) and Δ corneal modulus = 0.017*ΔIOP+0.051 (P < .001). After IOP reduction, the mean corneal stiffness at the 4th week in the NTG group was significantly lower (60.97 ± 6.36 N/m) than that in the HTG (67.25 ± 9.01 N/m) and OHT (75.62 ± 6.52 N/m, P < .001) groups. Additionally, the stiffness of HTG patients was lower than that of OHT patients (P = .003). CONCLUSIONS: Changes in IOP have an impact on corneal biomechanical parameters. Decreases in corneal stiffness and modulus were observed after IOP reduction. When the effect of high-level IOP was excluded, corneal biomechanics varied according to the type of glaucoma. The HTG corneas were softer than the OHT corneas, and the NTG corneas were even softer.

Classification and sources of extremely severe sandstorms mixed with haze pollution in Beijing.

Air quality has significantly improved in China; however, new challenges emerge when dust weather is combined with haze pollution during spring in northern China. On March 15, 2021, an extremely severe sandstorm occurred in Beijing, with hourly maximum PM10 and PM2.5 concentrations reaching 5267.7 µg m-3 and 963.9 µg m-3, respectively. Continuous sandstorm events usually lead to complicated pollution status in spring. Three pollution types were identified disregarding the time sequence throughout March. The secondary formation type was dominant, with high ratios of PM2.5/PM10 (mean 74%) and PM1/PM2.5 (mean 52%). This suggests that secondary transformations are the primary cause of heavy pollution, even during the dry seasons. Sandstorm type resulted in dramatic PM10 levels, with a noticeable decrease in PM2.5/PM10 levels (27%), although PM2.5 levels remain high. The transitional pollution type was distinguished by an independent increase in PM10 levels, although PM2.5 and PM1 levels differed from the PM10 levels. Throughout March, the sulfur oxidation rate varied considerably, with high levels during most periods (mean 0.52). A strong correlation indicated that relative humidity was the primary variable promoting the formation of secondary sulfate. Sandstorms promote heterogeneous reactions by providing abundant reaction surfaces from mineral particles, therefore aggravating secondary pollution. The sandstorm air mass from the northwest passing through the sand sources of Mongolia carried not only crustal matter but also organic components, such as bioaerosols, resulting in a sharp increase in the organic carbon in PM2.5.

Neuroinflammation and brain-peripheral interaction in ischemic stroke: A narrative review.

Excessive immune activation within the lesion site can be observed after stroke onset. Such neuroinflammation within the brain parenchyma represents the innate immune response, as well as the result of the additional interactions between peripheral and resident immune cells. Accumulative studies have illustrated that the pathological process of ischemic stroke is associated with resident and peripheral immunity. The infiltration of peripheral immune cells within the brain parenchyma implicitly contributes to secondary brain injuries. Therefore, better understanding of the roles of resident and peripheral immune reactions toward ischemic insult is necessary. In this review, we summarized the interaction between peripheral and resident immunity on systemic immunity and the clinical outcomes after stroke onset and also discussed various potential immunotherapeutic strategies.

Novel Wet Electrospinning Inside a Reactive Pre-Ceramic Gel to Yield Advanced Nanofiber-Reinforced Geopolymer Composites.

Electrospinning is a versatile approach to generate nanofibers in situ. Yet, recently, wet electrospinning has been introduced as a more efficient way to deposit isolated fibers inside bulk materials. In wet electrospinning, a liquid bath is adopted, instead of a solid collector, for fiber collection. However, despite several studies focused on wet electrospinning to yield polymer composites, few studies have investigated wet electrospinning to yield ceramic composites. In this paper, we propose a novel in-situ fabrication approach for nanofiber-reinforced ceramic composites based on an enhanced wet-electrospinning method. Our method uses electrospinning to draw polymer nanofibers directly into a reactive pre-ceramic gel, which is later activated to yield advanced nanofiber-reinforced ceramic composites. We demonstrate our method by investigating wet electrospun Polyacrylonitrile and Poly(ethylene oxide) fiber-reinforced geopolymer composites, with fiber weight fractions in the range 0.1-1.0 wt%. Wet electrospinning preserves the amorphous structure of geopolymer while changing the molecular arrangement. Wet electrospinning leads to an increase in both the fraction of mesopores and the overall porosity of geopolymer composites. The indentation modulus is in the range 6.76-8.90 GPa and the fracture toughness is in the range 0.49-0.76 MPam with a clear stiffening and toughening effect observed for Poly(ethylene oxide)-reinforced geopolymer composites. This work demonstrates the viability of wet electrospinning to fabricate multifunctional nanofiber-reinforced composites.

Unbalanced emission reductions and adverse meteorological conditions facilitate the formation of secondary pollutants during the COVID-19 lockdown in Beijing.

During the coronavirus disease 2019 (COVID-19) lockdown in 2020, severe haze pollution occurred in the North China Plain despite the significant reduction in anthropogenic emissions, providing a natural experiment to explore the response of haze pollution to the reduction of human activities. Here, we study the characteristics and causes of haze pollution during the COVID-19 outbreak based on comprehensive field measurements in Beijing during January and February 2020. After excluding the Spring Festival period affected by fireworks activities, we found the ozone concentrations and the proportion of sulfate and nitrate in PM2.5 increased during the COVID-19 lockdown compared with the period before the lockdown, and sulfate played a more important role. Heterogeneous chemistry and photochemistry dominate the formation of sulfate and nitrate during the whole campaign, respectively, and the heterogeneous formation of nitrate at night was enhanced during the lockdown. The coeffects of more reductions in NOx than VOCs, weakened titration of NO, and increased temperature during the lockdown led to the increase in ozone concentrations, thereby promoting atmospheric oxidation capacity and photochemistry. In addition, the increase in relative humidity during the lockdown facilitated heterogeneous chemistry. Our results indicate that unbalanced emission reductions and adverse meteorological conditions induce the formation of secondary pollutants during the COVID-19 lockdown haze, and the formulation of effective coordinated emission-reduction control measures for PM2.5 and ozone pollution is needed in the future, especially the balanced control of NOx and VOCs.

Wide Corneal Epithelial Thickness Mapping in Eyes With Topical Antiglaucoma Therapy Using Optical Coherence Tomography.

Purpose: The purpose of this study was to assess the corneal epithelial thickness (CET) of the 9-mm diameter zone in patients treated using topical antiglaucoma medications and to evaluate the factors associated with CET changes. Methods: Seventy-five patients treated using topical antiglaucoma medications and 65 healthy subjects were included in this cross-sectional study. Each patient completed the Ocular Surface Disease Index (OSDI) questionnaire and underwent examinations including the Schirmer I test, tear breakup time (TBUT), and fluorescein staining. CET mapping of the 9-mm diameter zone was performed using RTVue XR. The CET of the different analyzed zones was compared between groups. The relationship between CET and confounding factors was investigated. Results: The patient group had a significantly shorter TBUT, shorter Schirmer I test, and greater fluorescein staining than those of the control group (all P < 0.05). The mean CET of patients with glaucoma was significantly lower than that of controls in the central, paracentral, mid-peripheral, and peripheral zones (all P < 0.001). Age affected the CET in the paracentral, mid-peripheral, and peripheral zones (all P < 0.01). The number of medications affected the CET in the central, paracentral, and mid-peripheral zones (all P < 0.05). The duration of treatment affected the CET in the central and peripheral zones (all P < 0.05). Conclusions: Use of topical IOP-lowering medications leads to epithelial thinning in the 9-mm diameter zone in glaucomatous eyes. Epithelial protection should be considered in older patients and patients treated with multiple medications from the early stages of long-term topical antiglaucoma therapy. Translational Relevance: The 9-mm diameter CET mapping by using widefield optical coherence tomography (OCT) can be a valuable and convenient method to assess the ocular surface damage in patients with topical antiglaucoma therapy.

Corneal Stiffness and Modulus of Normal-Tension Glaucoma in Chinese.

PURPOSE: To assess and compare the corneal biomechanics of normal-tension glaucoma (NTG), high-tension glaucoma (HTG), and normal controls based on stiffness and modulus. The correlations among central corneal thickness (CCT), visual field, retinal nerve fiber layer (RNFL) thickness, and corneal biomechanics in glaucoma eyes were also evaluated. DESIGN: A prospective, cross-sectional, comparative study. METHODS: This study included 334 eyes of 108 NTG patients, 113 HTG patients, and 113 control subjects at Zhongshan Ophthalmic Center, Sun Yat-Sen University. Corneal biomechanics were evaluated using a corneal indentation device (CID) and corneal visualization Scheimpflug technology (Corvis ST). Visual field and RNFL thickness were obtained using standard automated perimetry and spectral-domain optical coherence tomography. One-way analyses of variance with Bonferroni post hoc tests and a multivariable linear regression analysis with adjustment were conducted. Correlations among corneal biomechanical parameters, CCT, visual field, and RNFL thickness were analyzed. RESULTS: The corneal stiffness of the NTG patients (71.0 ± 10.9 N/m) was significantly lower than that of the HTG patients (77.3 ± 15.6 N/m; P = .001) and the CCT- and IOP-matched normal controls (75.6 ± 11.0 N/m; P = .023). The patients in the NTG group had lower corneal stiffness than those in the control group (ß = -4.88, 95% CI -9.002, -0.758; P = .020) after adjusting for confounders. Stiffness was positively correlated with CCT in the NTG group (P = .028) but not in the HTG group (P = .509). There was no significant correlation (P > .05) between corneal biomechanics, visual field, or RNFL thickness. CONCLUSIONS: The corneas of NTG patients were softer than those of HTG patients and controls, as assessed by CID, which were associated with thinner CCT. These might suggest different ocular biomechanical properties in NTG and HTG.

Prenatal diagnosis of 7 cases with uniparental disomy by utilization of single nucleotide polymorphism array.

BACKGROUND: The phenotypes of uniparental disomy (UPD) are variable, which may either have no clinical impact, lead to clinical signs and symptoms. Molecular analysis is essential for making a correct diagnosis. This study involved a retrospective analysis of 4512 prenatal diagnosis samples and explored the molecular characteristics and prenatal phenotypes of UPD using a single nucleotide polymorphism (SNP) array. RESULTS: Out of the 4512 samples, a total of seven cases of UPD were detected with an overall frequency of 0.16%. Among the seven cases of UPD, two cases are associated with chromosomal aberrations (2/7), four cases (4/7) had abnormal ultrasonographic findings. One case presented with iso-UPD (14), and two case presented with mixed hetero/iso-UPD (15), which were confirmed by Methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) as maternal UPD (15) associated with Prader-Willi syndrome (PWS). Four cases had iso-UPD for chromosome 1, 3, 14, and 16, respectively; this is consistent with the monosomy rescue mechanism. Another three cases presented with mixed hetero/isodisomy were consistent with a trisomy rescue mechanism. CONCLUSION: The prenatal phenotypes of UPD are variable and molecular analysis is essential for making a correct diagnosis and genetic counselling of UPD. The SNP array is a useful genetic test in prenatal diagnosis cases with UPD.

A Novel Indentation Assessment to Measure Corneal Biomechanical Properties in Glaucoma and Ocular Hypertension.

Purpose: To evaluate the ability of the new in vivo corneal indentation device (CID) to measure corneal biomechanical properties. Methods and Results: In total, 186 eyes from 46 healthy subjects, 107 patients with primary open-angle glaucoma, and 33 patients with ocular hypertension were enrolled in a cross-sectional study. Measurements were performed using corneal visualization Scheimpflug technology (Corvis ST) and the CID. The deformation amplitude (DA), inward applanation time, inward applanation velocity (A1V), outward applanation time (A2T), outward applanation velocity (A2V), highest concavity time, DA ratio, max inverse radius (MIR), integrated radius, and stiffness parameter A1 were included as Corvis ST parameters, and stiffness and modulus were included as CID parameters. Associations between the Corvis ST and CID parameters and correlations between central corneal thickness and corneal biomechanical parameters were analyzed. The stiffness was significantly correlated with all the Corvis ST parameters (P < 0.05). The modulus was significantly correlated with the DA, A1V, A2T, A2V, highest concavity time, and MIR (P < 0.05). The DA, inward applanation time, A1V, A2T, A2V, DA ratio, MIR, integrated radius, and stiffness parameter A1 values and both CID-derived values were significantly correlated with central corneal thickness (P < 0.05). Conclusions: Parameters derived from the CID and Corvis ST demonstrated agreement in the measurement of corneal biomechanical properties. The stiffness and modulus can characterize in vivo corneal biomechanical properties. Translational Relevance: Agreeing with the Corvis ST regarding the assessment of corneal biomechanical properties, the CID can be a novel clinical tool for biomechanical evaluation of the cornea.

Stronger secondary pollution processes despite decrease in gaseous precursors: A comparative analysis of summer 2020 and 2019 in Beijing.

To control the spread of COVID-19, China implemented a series of lockdowns, limiting various offline interactions. This provided an opportunity to study the response of air quality to emissions control. By comparing the characteristics of pollution in the summers of 2019 and 2020, we found a significant decrease in gaseous pollutants in 2020. However, particle pollution in the summer of 2020 was more severe; PM2.5 levels increased from 35.8 to 44.7 µg m-3, and PM10 increased from 51.4 to 69.0 µg m-3 from 2019 to 2020. The higher PM10 was caused by two sandstorm events on May 11 and June 3, 2020, while the higher PM2.5 was the result of enhanced secondary formation processes indicated by the higher sulfate oxidation rate (SOR) and nitrate oxidation rate (NOR) in 2020. Higher SOR and NOR were attributed mainly to higher relative humidity and stronger oxidizing capacity. Analysis of PMx distribution showed that severe haze occurred when particles within Bin2 (size ranging 1-2.5 µm) dominated. SO42-(1/2.5) and SO42-(2.5/10) remained stable under different periods at 0.5 and 0.8, respectively, indicating that SO42- existed mainly in smaller particles. Decreases in NO3-(1/2.5) and increases in NO3-(2.5/10) from clean to polluted conditions, similar to the variations in PMx distribution, suggest that NO3- played a role in the worsening of pollution. O3 concentrations were higher in 2020 (108.6 µg m-3) than in 2019 (96.8 µg m-3). Marked decreases in fresh NO alleviated the titration of O3. Furthermore, the oxidation reaction of NO2 that produces NO3- was dominant over the photochemical reaction of NO2 that produces O3, making NO2 less important for O3 pollution. In comparison, a lower VOC/NOx ratio (less than 10) meant that Beijing is a VOC-limited area; this indicates that in order to alleviate O3 pollution in Beijing, emissions of VOCs should be controlled.

Objective Assessment of the Effect of Optical Treatment on Magnocellular and Parvocellular-biased Visual Response in Anisometropic Amblyopia.

Purpose: Optical treatment can improve visual function in anisometropic amblyopia, but there is no electrophysiological evidence, and the underlying change in visual pathway remains unknown. Our aims were to characterize the functional loss in magnocellular and parvocellular visual pathways in anisometropic amblyopia at baseline and to investigate the effect of optical treatment on the 2 visual pathways. Methods: Using isolated-check visual-evoked potential, we measured the magnocellular- and parvocellular-biased contrast response functions in 15 normal controls (20.13 ± 3.93 years; mean ± standard deviation), 16 patients with anisometropic amblyopia (18.00 ± 6.04 years) who were fully refractive corrected before and 29 (19.41 ± 7.41 years) who had never been corrected. Twelve previously uncorrected amblyopes received optical treatment for more than 2 months and finished the follow-up measurement. Results: Both the magnocellular- and parvocellular-biased contrast response functions in the amblyopic eye exhibited significantly reduced response and weaker contrast gains. We also found that the uncorrected amblyopes showed a more severe response reduction in magnocellular-biased, but not parvocellular-biased condition when compared with those corrected, with a weaker initial contrast gain and lower maximal response. After optical treatment, 12 uncorrected amblyopes demonstrated improved visual acuity of the amblyopic eye and a significant response gain to magnocellular-biased but not parvocellular-biased stimuli. Conclusions: We demonstrated deficits to both magnocellular- and parvocellular-biased stimuli in subjects with anisometropic amblyopia. Optical treatment could produce neurophysiological changes in visual pathways even in older children and adults, which may be mediated through the magnocellular pathway.