Publications by authors named "Xun Xu"

763 Publications

Transcriptional Start Site Coverage Analysis in Plasma Cell-Free DNA Reveals Disease Severity and Tissue Specificity of COVID-19 Patients.

Front Genet 2021 28;12:663098. Epub 2021 May 28.

BGI-Shenzhen, Shenzhen, China.

Symptoms of coronavirus disease 2019 (COVID-19) range from asymptomatic to severe pneumonia and death. A deep understanding of the variation of biological characteristics in severe COVID-19 patients is crucial for the detection of individuals at high risk of critical condition for the clinical management of the disease. Herein, by profiling the gene expression spectrum deduced from DNA coverage in regions surrounding transcriptional start site in plasma cell-free DNA (cfDNA) of COVID-19 patients, we deciphered the altered biological processes in the severe cases and demonstrated the feasibility of cfDNA in measuring the COVID-19 progression. The up- and downregulated genes in the plasma of severe patient were found to be closely related to the biological processes and functions affected by COVID-19 progression. More importantly, with the analysis of transcriptome data of blood cells and lung cells from control group and cases with severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection, we revealed that the upregulated genes were predominantly involved in the viral and antiviral activity in blood cells, reflecting the intense viral replication and the active reaction of immune system in the severe patients. Pathway analysis of downregulated genes in plasma DNA and lung cells also demonstrated the diminished adenosine triphosphate synthesis function in lung cells, which was evidenced to correlate with the severe COVID-19 symptoms, such as a cytokine storm and acute respiratory distress. Overall, this study revealed tissue involvement, provided insights into the mechanism of COVID-19 progression, and highlighted the utility of cfDNA as a noninvasive biomarker for disease severity inspections.
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http://dx.doi.org/10.3389/fgene.2021.663098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194351PMC
May 2021

Life History Recorded in the Vagino-cervical Microbiome Along with Multi-omics.

Genomics Proteomics Bioinformatics 2021 Jun 9. Epub 2021 Jun 9.

BGI-Shenzhen, Shenzhen 518083, China.

The vagina contains at least a billion microbial cells, dominated by lactobacilli. Here we perform metagenomic shotgun sequencing on cervical and fecal samples from a cohort of 516 Chinese women of reproductive age, and cervical, fecal, and salivary samples from a second cohort of 632 women. Factors such as pregnancy, delivery histories, cesarean section, and breast-feeding were all more important than menstrual cycle in shaping the microbiome, and such information would be necessary before trying to interpret differences between vagino-cervical microbiome data. Greater proportion of Bifidobacterium breve was seen with older age at sexual debut. The relative abundance of lactobacilli especially Lactobacillus crispatus was negatively associated with pregnancy history. Potential markers for lack of menstrual regularity, heavy flow, dysmenorrhea, and contraceptives were also identified. Lactobacilli were rare during breast-feeding or post-menopause. Other features such as mood fluctuations and facial speckles could potentially be predicted from the vagino-cervical microbiome. Gut and salivary microbiome, plasma vitamins, metals, amino acids, and hormones showed associations with the vagino-cervical microbiome. Our results offer an unprecedented glimpse into the microbiota of the female reproductive tract and call for international collaborations to better understand its long-term health impact other than in the settings of infection or pre-term birth.
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http://dx.doi.org/10.1016/j.gpb.2021.01.005DOI Listing
June 2021

Prevalence, Causes, and Factors Associated with Visual Impairment in a Chinese Elderly Population: The Rugao Longevity and Aging Study.

Clin Interv Aging 2021 25;16:985-996. Epub 2021 May 25.

Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.

Purpose: This study aimed to explore the current prevalence, causes, and factors associated with visual impairment in a Chinese elderly population.

Methods: A random sample of 2164 candidates aged ≥70 years was selected. Among them, 1914 participants (response rate: 88.4%) underwent comprehensive eye examinations. The prevalence and causes of visual impairment were estimated, and the associated factors were identified.

Results: The standardized prevalence of mild visual impairment (<6/12 to ≥6/18), moderate to severe visual impairment (MSVI) (<6/18 to ≥3/60), and blindness (<3/60) in the better eye were 20.5%, 25.8%, and 3.4%, respectively. The leading cause of visual impairment was cataract (49.7%), followed by uncorrected refractive error (26.5%), myopic maculopathy (5.8%), and posterior capsular opacification (5.5%). Optical coherence tomography revealed that vitreoretinal interface abnormalities were the third most common cause of monocular mild visual impairment (2.2%) and MSVI (4.4%) in the elderly population. A large number of patients with visual impairment (81.7%) were amenable to undergo the interventions. Visual impairment was associated with advanced age (odds ratio [OR], 1.09 per year; <0.001), female sex (OR, 1.59; =0.003), self-reported visual impairment (OR, 1.91; <0.001), cognitive impairment (OR, 1.40, =0.005), and high educational level (OR, 0.75; primary, =0.045; and OR, 0.53, secondary or higher; <0.001).

Conclusion: Visual impairment was common in the Chinese elderly population and a severe health and social problem. Practicable policies are urgently needed to popularize eye health knowledge and promote treatments for visual impairment in elderly people in rural China.
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http://dx.doi.org/10.2147/CIA.S304730DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8164868PMC
June 2021

Dissecting the genome of star fruit (Averrhoa carambola L.).

Hortic Res 2020 Jun 1;7(1):94. Epub 2020 Jun 1.

State Key Laboratory of Agricultural Genomics, China National GeneBank, BGI-Shenzhen, 518120, Shenzhen, China.

Averrhoa carambola is commonly known as star fruit because of its peculiar shape, and its fruit is a rich source of minerals and vitamins. It is also used in traditional medicines in countries such as India, China, the Philippines, and Brazil for treating various ailments, including fever, diarrhea, vomiting, and skin disease. Here, we present the first draft genome of the Oxalidaceae family, with an assembled genome size of 470.51 Mb. In total, 24,726 protein-coding genes were identified, and 16,490 genes were annotated using various well-known databases. The phylogenomic analysis confirmed the evolutionary position of the Oxalidaceae family. Based on the gene functional annotations, we also identified enzymes that may be involved in important nutritional pathways in the star fruit genome. Overall, the data from this first sequenced genome in the Oxalidaceae family provide an essential resource for nutritional, medicinal, and cultivational studies of the economically important star-fruit plant.
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http://dx.doi.org/10.1038/s41438-020-0306-4DOI Listing
June 2020

Enhancing CRISPR-Cas9 gRNA efficiency prediction by data integration and deep learning.

Nat Commun 2021 05 28;12(1):3238. Epub 2021 May 28.

Lars Bolund Institute of Regenerative Medicine, Qingdao-Europe Advanced Institute for Life Sciences, BGI-Qingdao, Qingdao, China.

The design of CRISPR gRNAs requires accurate on-target efficiency predictions, which demand high-quality gRNA activity data and efficient modeling. To advance, we here report on the generation of on-target gRNA activity data for 10,592 SpCas9 gRNAs. Integrating these with complementary published data, we train a deep learning model, CRISPRon, on 23,902 gRNAs. Compared to existing tools, CRISPRon exhibits significantly higher prediction performances on four test datasets not overlapping with training data used for the development of these tools. Furthermore, we present an interactive gRNA design webserver based on the CRISPRon standalone software, both available via https://rth.dk/resources/crispr/ . CRISPRon advances CRISPR applications by providing more accurate gRNA efficiency predictions than the existing tools.
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http://dx.doi.org/10.1038/s41467-021-23576-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8163799PMC
May 2021

Intravitreal conbercept for diabetic macular oedema: 2-year results from a randomised controlled trial and open-label extension study.

Br J Ophthalmol 2021 May 17. Epub 2021 May 17.

Department of Ophthalmology (aka National Clinical Research Center for Eye Diseases), Shanghai General Hospital, Shanghai, China

Background: To demonstrate the efficacy and safety of intravitreal injections of conbercept versus laser photocoagulation in the treatment of diabetic macular oedema (DME).

Methods: A 12-month multicentre, randomised, double-masked, double-sham, parallel controlled, phase III trial (Sailing Study), followed by a 12-month open-label extension study. Patients with centre-involved DME were randomly assigned to receive either laser photocoagulation followed by pro re nata (PRN) sham intravitreal injections (laser/sham) or sham laser photocoagulation followed by PRN 0.5 mg conbercept intravitreal injections (sham/conbercept). Patients who entered the extension study received PRN conbercept treatment. The primary endpoint was the changes in best-corrected visual acuity (BCVA) from baseline.

Results: A total of 248 eyes were included in the full analysis set and 157 eyes continued in the extension study. Significant improvement in mean change in BCVA from baseline to month 12 was observed in the sham/conbercept group (8.2±9.5 letters), whereas no improvement was observed in the laser/sham group (0.3±12.0 letters). Patients in the laser/sham group showed a marked improvement in BCVA after the switch to conbercept in the extension study, and there was no difference in BCVA between the two groups at the end of the extension study.

Conclusion: The use of a conbercept PRN intravitreal injection regimen improved the BCVA of patients with DME, and its efficacy was better than that of laser photocoagulations, and the same efficacy was observed when the eyes treated with laser alone were switched to conbercept.

Trial Registration Number: NCT02194634.
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http://dx.doi.org/10.1136/bjophthalmol-2020-318690DOI Listing
May 2021

A Higher Serum Calcium Level is an Independent Risk Factor for Vision-Threatening Diabetic Retinopathy in Patients with Type 2 Diabetes: Cross-Sectional and Longitudinal Analyses.

Endocr Pract 2021 May 14. Epub 2021 May 14.

Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; National Clinical Research Center for Eye Diseases, Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai engineering center for precise diagnosis and treatment of eye diseases, Shanghai, China. Electronic address: https://orcid.org/0000-0001-8435-0240.

Objective: An elevated serum calcium level is associated with a higher risk of type 2 diabetes (T2D), but its role in microvascular complications remains unclear. This study was conducted to investigate the association between serum calcium levels and vision-threatening diabetic retinopathy (VTDR).

Methods: This study employed a cross-sectional and longitudinal design. The cross-sectional part included all patients treated for T2D at Shanghai General Hospital between 2007 and 2016, while the longitudinal part involved an overlapping cohort of diabetic patients without VTDR who were followed from their admission until December 2019. VTDR was defined as severe nonproliferative, proliferative diabetic retinopathy, or clinically significant macular edema. Multivariable logistic and Cox proportional hazard regression analyses were performed respectively.

Results: A total of 3269 patients were included in the cross-sectional analysis, and 649 patients were included in the longitudinal analysis. In the cross-sectional analysis, the following factors were independently associated with VTDR: higher corrected serum calcium (odds ratio 1.31 per 0.1 mmol/L, 95% confidence interval [CI] 1.16-1.49), younger age, longer diabetes duration, albuminuria, impaired renal function, and lower serum magnesium. In the longitudinal analysis, 95 subjects developed VTDR during follow-up (9.7 years, interquartile range 7.4-10.9 years). The following variables were identified as independent risk factors for VTDR: higher corrected serum calcium (hazard ratio 1.38 per 0.1 mmol/L, 95% CI 1.10-1.72), younger age, longer diabetes duration, sub-VTDR, albuminuria, lower serum magnesium, and higher HbA1c.

Conclusions: A higher serum calcium level may be an independent risk factor for VTDR in patients with T2D.
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http://dx.doi.org/10.1016/j.eprac.2021.05.003DOI Listing
May 2021

Imaging Features by Machine Learning for Quantification of Optic Disc Changes and Impact on Choroidal Thickness in Young Myopic Patients.

Front Med (Lausanne) 2021 29;8:657566. Epub 2021 Apr 29.

Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

To construct quantifiable models of imaging features by machine learning describing early changes of optic disc and peripapillary region, and to explore their performance as early indicators for choroidal thickness (ChT) in young myopic patients. Eight hundred and ninety six subjects were enrolled. Imaging features were extracted from fundus photographs. Macular ChT (mChT) and peripapillary ChT (pChT) were measured on swept-source optical coherence tomography scans. All participants were divided randomly into training (70%) and test (30%) sets. Imaging features correlated with ChT were selected by LASSO regression and combined into new indicators of optic disc (IODs) for mChT (IOD_mChT) and for pChT (IOD_pChT) by multivariate regression models in the training set. The performance of IODs was evaluated in the test set. A significant correlation between IOD_mChT and mChT ( = 0.650, = 0.423, < 0.001) was found in the test set. IOD_mChT was negatively associated with axial length (AL) ( = -0.562, < 0.001) and peripapillary atrophy (PPA) area ( = -0.738, < 0.001) and positively associated with ovality index ( = 0.503, < 0.001) and torsion angle ( = 0.242, < 0.001) in the test set. Every 1 × 10 μm decrease in IOD_mChT was associated with an 8.87 μm decrease in mChT. A significant correlation between IOD_pChT and pChT ( = 0.576, = 0.331, < 0.001) was found in the test set. IOD_pChT was negatively associated with AL ( = -0.478, < 0.001) and PPA area ( = -0.651, < 0.001) and positively associated with ovality index ( = 0.285, < 0.001) and torsion angle ( = 0.180, < 0.001) in the test set. Every 1 × 10 μm decrease in IOD_pChT was associated with a 9.64 μm decrease in pChT. The study introduced a machine learning approach to acquire imaging information of early changes of optic disc and peripapillary region and constructed quantitative models significantly correlated with choroidal thickness. The objective models from fundus photographs represented a new approach that offset limitations of human annotation and could be applied in other areas of fundus diseases.
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http://dx.doi.org/10.3389/fmed.2021.657566DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8116583PMC
April 2021

Multi-scale GCN-assisted two-stage network for joint segmentation of retinal layers and discs in peripapillary OCT images.

Biomed Opt Express 2021 Apr 22;12(4):2204-2220. Epub 2021 Mar 22.

State Key Lab of Advanced Optical Communication Systems and Networks, Department of Electronic Engineering, Shanghai Jiao Tong University, Shanghai 200240, China.

An accurate and automated tissue segmentation algorithm for retinal optical coherence tomography (OCT) images is crucial for the diagnosis of glaucoma. However, due to the presence of the optic disc, the anatomical structure of the peripapillary region of the retina is complicated and is challenging for segmentation. To address this issue, we develop a novel graph convolutional network (GCN)-assisted two-stage framework to simultaneously label the nine retinal layers and the optic disc. Specifically, a multi-scale global reasoning module is inserted between the encoder and decoder of a U-shape neural network to exploit anatomical prior knowledge and perform spatial reasoning. We conduct experiments on human peripapillary retinal OCT images. We also provide public access to the collected dataset, which might contribute to the research in the field of biomedical image processing. The Dice score of the proposed segmentation network is 0.820 ± 0.001 and the pixel accuracy is 0.830 ± 0.002, both of which outperform those from other state-of-the-art techniques.
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http://dx.doi.org/10.1364/BOE.417212DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8086482PMC
April 2021

Characteristics of Fundal Changes in Fundus Tessellation in Young Adults.

Front Med (Lausanne) 2021 26;8:616249. Epub 2021 Apr 26.

Shanghai Eye Disease Prevention and Treatment Center, Shanghai Eye Hospital, Shanghai, China.

To explore the characteristics and associated factors of fundus tessellation, especially the alternation of choroidal thickness among different degrees of tessellated fundus in young adults. Cross-sectional, population-based study. A total of 796 students were included in the study and underwent comprehensive ophthalmic examinations, including anterior segment examinations and swept-source optical coherence tomography (OCT) measurements. The degree of tessellated fundus was assessed by fundus photographs applying an early treatment of diabetic retinopathy study grid to evaluate the location of fundus tessellation and then divided into five groups. The topographic variation and factors, tilted disc ratio, parapapillary atrophy (PPA), retinal thickness (ReT), choroidal thickness (ChT), and subfoveal scleral thickness (SST) related to tessellated fundus were analyzed. Compared to normal fundus, tessellated fundus had a lower spherical equivalent (SE) ( < 0.0001), worse best-corrected visual acuity (BCVA)( = 0.043), longer axial length (AL) ( < 0.0001), thinner retina ( < 0.0001), thinner ( < 0.0001) choroid, and thinner sclera in center fovea ( = 0.0035). Among all subfields of macular and peripapillary regions, center fovea and macula-papillary region showed the most significant decrease in choroidal thickness. The proportion of fundus tessellation significantly increased with lower body weight index (BMI) ( = 0.0067), longer AL ( < 0.0001), larger PPA( = 0.0058), thinner choroid ( < 0.0001), and thinner sclera ( < 0.0001). Eyes showed more severe myopic morphological alternation with the increasement of proportion of fundus tessellation to the center fovea, including a significant decrease in both choroid and scleral thickness. Choroidal thinning may progress most rapidly in the macula-papillary region as fundus tessellation approaches to the center fovea.
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http://dx.doi.org/10.3389/fmed.2021.616249DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107222PMC
April 2021

Plasma homocysteine and macular thickness in older adults-the Rugao Longevity and Aging Study.

Eye (Lond) 2021 May 11. Epub 2021 May 11.

State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, China.

Objectives: To determine the association of plasma homocysteine levels with retinal layer thickness in a large community cohort of older adults.

Methods: The Rugao Longevity and Ageing Study is an observational, prospective and community-based cohort study. A total of 989 older adults who underwent spectral-domain optical coherence tomography (SD-OCT) were included and analyzed. Foveal, macular retinal nerve fibre layer (mRNFL) and ganglion cell layer plus inner plexiform layer (GC-IPL) thicknesses were measured by SD-OCT. Plasma homocysteine levels were measured using chemiluminescence immunoassay. Linear regression analyses were performed to evaluate the relationship between plasma homocysteine and retinal layer thickness while controlling for confounding factors.

Results: Of the 989 participants, 500 (50.56%) were men. The mean age was 78.26 (4.58) years, and the mean plasma homocysteine level was 16.38 (8.05) μmol/L. In multivariable analyses, each unit increase in plasma homocysteine was associated with an 8.84 × 10 (95% CI: -16.54 × 10 to -1.15 × 10, p = 0.032) μm decrease in the average inner thickness of the GC-IPL after controlling for confounding factors. The association remained significant even in participants without major cardiovascular disease or diabetes (β = -10.33 × 10, 95% CI: -18.49 × 10 to -2.18 × 10, p = 0.013). No significant associations of plasma homocysteine levels with macular thickness or mRNFL were found in primary and sensitivity analyses (p > 0.05).

Conclusions: Increased plasma homocysteine levels are associated with a thinner GC-IPL. Plasma homocysteine may be a risk factor for thinner retinas in older adults.
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http://dx.doi.org/10.1038/s41433-021-01549-3DOI Listing
May 2021

Correction to: Automatic identification of myopic maculopathy related imaging features in optic disc region via machine learning methods.

J Transl Med 2021 May 11;19(1):203. Epub 2021 May 11.

Department of Preventative Ophthalmology, Shanghai Eye Diseases Prevention and Treatment Center, Shanghai Eye Hospital, No. 380 Kangding Road, Shanghai, 200040, China.

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http://dx.doi.org/10.1186/s12967-021-02874-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8114694PMC
May 2021

Chromosome-level genome of Himalayan yew provides insights into the origin and evolution of the paclitaxel biosynthetic pathway.

Mol Plant 2021 May 2. Epub 2021 May 2.

Key Laboratory of Systems Microbial Biotechnology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin 300308, China; National Center of Technology Innovation for Synthetic Biology, Tianjin 300308, China.

Taxus, commonly known as yew, is a well-known gymnosperm with great ornamental and medicinal value. In this study, by assembling a chromosome-level genome of the Himalayan yew (Taxus wallichiana) with 10.9 Gb in 12 chromosomes, we revealed that tandem duplication acts as the driving force of gene family evolution in the yew genome, resulting in the main genes for paclitaxel biosynthesis, i.e. those encoding the taxadiene synthase, P450s, and transferases, being clustered on the same chromosome. The tandem duplication may also provide genetic resources for the nature to sculpt the core structure of taxoids at different positions and subsequently establish the complex pathway of paclitaxel by neofunctionalization. Furthermore, we confirmed that there are two genes in the cluster encoding isoenzymes of a known enzyme in the paclitaxel biosynthetic pathway. The reference genome of the Himalayan yew will serve as a platform for decoding the complete biosynthetic pathway of paclitaxel and understanding the chemodiversity of taxoids in gymnosperms.
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http://dx.doi.org/10.1016/j.molp.2021.04.015DOI Listing
May 2021

Eyes grow towards mild hyperopia rather than emmetropia in Chinese preschool children.

Acta Ophthalmol 2021 May 3. Epub 2021 May 3.

Department of Preventative Ophthalmology, Shanghai Eye Disease Prevention and Treatment Center, Shanghai Eye Hospital, Shanghai, China.

Purpose: To document one-year changes in refraction and refractive components in preschool children.

Methods: Children, 3-5 years old, in the Jiading District, Shanghai, were followed for one year. At each visit, axial length (AL), refraction under cycloplegia (1% cyclopentolate), spherical dioptres (DS), cylinder dioptres (DC), spherical equivalent refraction (SER) and corneal curvature radius (CR) were measured.

Results: The study included 458 right eyes of 458 children. The mean changes in DS, DC and SER were 0.02 ± 0.35 D, -0.02 ± 0.33 D and 0.01 ± 0.37 D, while the mean changes in AL, CR and lens power (LP) were 0.27 ± 0.10 mm, 0.00 ± 0.04 mm and - 0.93 ± 0.49 D. The change in the SER was linearly correlated with the baseline SER (coefficient = -0.147, p < 0.001). When the baseline SER was at 1.05 D (95% CI = 0.21 to 2.16), the change in SER was 0 D. The baseline SER was also linearly associated with the change in LP (coefficient = 0.104, p = 0.013), but not with the change in AL (p = 0.957) or with the change in CR (p = 0.263).

Conclusion: In eyes with a baseline SER less than +1.00 D, LP loss was higher compared to axial elongation, leading to hyperopic shifts in refraction, whereas for those with baseline SER over this range, loss of LP compared to axial elongation was reduced, leading to myopic shifts. This model indicated the homeostasis of human refraction and explained how refractive development leads to a preferred state of mild hyperopia.
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http://dx.doi.org/10.1111/aos.14810DOI Listing
May 2021

Automatic identification of myopic maculopathy related imaging features in optic disc region via machine learning methods.

J Transl Med 2021 04 26;19(1):167. Epub 2021 Apr 26.

Department of Preventative Ophthalmology, Shanghai Eye Diseases Prevention and Treatment Center, Shanghai Eye Hospital, No. 380 Kangding Road, Shanghai, 200040, China.

Background: Myopic maculopathy (MM) is the most serious and irreversible complication of pathologic myopia, which is a major cause of visual impairment and blindness. Clinic proposed limited number of factors related to MM. To explore additional features strongly related with MM from optic disc region, we employ a machine learning based radiomics analysis method, which could explore and quantify more hidden or imperceptible MM-related features to the naked eyes and contribute to a more comprehensive understanding of MM and therefore may assist to distinguish the high-risk population in an early stage.

Methods: A total of 457 eyes (313 patients) were enrolled and were divided into severe MM group and without severe MM group. Radiomics analysis was applied to depict features significantly correlated with severe MM from optic disc region. Receiver Operating Characteristic were used to evaluate these features' performance of classifying severe MM.

Results: Eight new MM-related image features were discovered from the optic disc region, which described the shapes, textural patterns and intensity distributions of optic disc region. Compared with clinically reported MM-related features, these newly discovered features exhibited better abilities on severe MM classification. And the mean values of most features were markedly changed between patients with peripapillary diffuse chorioretinal atrophy (PDCA) and macular diffuse chorioretinal atrophy (MDCA).

Conclusions: Machine learning and radiomics method are useful tools for mining more MM-related features from the optic disc region, by which complex or even hidden MM-related features can be discovered and decoded. In this paper, eight new MM-related image features were found, which would be useful for further quantitative study of MM-progression. As a nontrivial byproduct, marked changes between PDCA and MDCA was discovered by both new image features and clinic features.
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http://dx.doi.org/10.1186/s12967-021-02818-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8074495PMC
April 2021

Adipose Tissue-derived Microvascular Fragments as Vascularization Units for Dental Pulp Regeneration.

J Endod 2021 Apr 19. Epub 2021 Apr 19.

National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, China; State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China; Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, China. Electronic address:

Introduction: The transplantation of dental pulp stem cells (DPSCs) has emerged as a novel strategy for the regeneration of lost dental pulp after pulpitis and trauma. Dental pulp regeneration of the young permanent tooth with a wide tooth apical foramen has achieved significant progress in the clinical trials. However, because of the narrow apical foramen, dental pulp regeneration in adult teeth using stem cells remains difficult in the clinic. Finding out how to promote vascular reconstitution is essential for the survival of stem cells and the regeneration of dental pulp after transplantation into the adult tooth.

Methods: Adipose tissue-derived microvascular fragments (ad-MVFs) were isolated from human adipose tissues. The apoptosis and senescence of DPSCs cultured in conditioned media were evaluated to explore the effects of ad-MVFs on DPSCs. DPSCs combined with ad-MVFs were inserted into the human tooth root segments and implanted subcutaneously into immunodeficient mice. Regenerated pulplike tissues were analyzed by hematoxylin and eosin and immunohistochemistry. The vessels in regenerated tissues were analyzed by Micro-CT and immunofluorescence.

Results: The isolated ad-MVFs contained endothelial cells and pericytes. ad-MVFs effectively prevented the apoptosis and senescence of the transplanted DPSCs both in vivo and in vitro. Combined with DPSCs, ad-MVFs obviously facilitated the formation of vascular networks in the transplants. DPSCs combined with ad-MVFs formed dental pulp-like tissues with abundant cells and matrix after 4 weeks of implantation. The supplementation of ad-MVFs led to more odontoblastlike cells and increased the formation of mineralized substance around the root canal.

Conclusions: Cotransplantation with ad-MVFs promotes the angiogenesis and revascularization of transplanted DPSC aggregates, leading to robust regeneration of dental pulp.
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http://dx.doi.org/10.1016/j.joen.2021.04.012DOI Listing
April 2021

Novel Peptide NT/K-CFY Derived from Kringle Structure of Neurotrypsin Inhibits Neovascularization.

Curr Eye Res 2021 Apr 19:1-8. Epub 2021 Apr 19.

Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

: To assess the anti-neovascularization effect of a novel peptide NT/K-CFY derived from the kringle domain of neurotrypsin.: Cell migration, lumen formation and cell proliferation assays were performed to determine the anti-neovascularization effect of NT/K-CFY in primary human umbilical vein endothelial cells (HUVECs). Chick chorioallantoic membrane (CAM) and oxygen-induced retinopathy (OIR) models were established to assess the anti-angiogenic role of NT/K-CFY . The retinal expression of vascular endothelial growth factor (VEGF) and pigment epithelium-derived factor (PEDF) was examined by western blot and real-time PCR in OIR model.: The results showed that NT/K-CFY effectively and safely decreased VEGF-induced cell migration, cell proliferation and tube formation in HUVECs. In addition, NT/K-CFY showed certain efficacy in angiogenesis inhibition in chicken embryos and oxygen-treated mouse pups. Moreover, the CFY peptide also improved retinal blood perfusion and reversed the abnormal expression of VEGF and PEDF in OIR mouse model.: NT/K-CFY peptide strongly inhibits neovascularization . This novel peptide may become a promising therapeutic agent for ocular angiogenesis-related diseases.
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http://dx.doi.org/10.1080/02713683.2021.1907417DOI Listing
April 2021

Characterization of respiratory microbial dysbiosis in hospitalized COVID-19 patients.

Cell Discov 2021 Apr 13;7(1):23. Epub 2021 Apr 13.

BGI-Shenzhen, Shenzhen, 518083, China.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic of Coronavirus disease 2019 (COVID-19). However, the microbial composition of the respiratory tract and other infected tissues as well as their possible pathogenic contributions to varying degrees of disease severity in COVID-19 patients remain unclear. Between 27 January and 26 February 2020, serial clinical specimens (sputum, nasal and throat swab, anal swab and feces) were collected from a cohort of hospitalized COVID-19 patients, including 8 mildly and 15 severely ill patients in Guangdong province, China. Total RNA was extracted and ultra-deep metatranscriptomic sequencing was performed in combination with laboratory diagnostic assays. We identified distinct signatures of microbial dysbiosis among severely ill COVID-19 patients on broad spectrum antimicrobial therapy. Co-detection of other human respiratory viruses (including human alphaherpesvirus 1, rhinovirus B, and human orthopneumovirus) was demonstrated in 30.8% (4/13) of the severely ill patients, but not in any of the mildly affected patients. Notably, the predominant respiratory microbial taxa of severely ill patients were Burkholderia cepacia complex (BCC), Staphylococcus epidermidis, or Mycoplasma spp. (including M. hominis and M. orale). The presence of the former two bacterial taxa was also confirmed by clinical cultures of respiratory specimens (expectorated sputum or nasal secretions) in 23.1% (3/13) of the severe cases. Finally, a time-dependent, secondary infection of B. cenocepacia with expressions of multiple virulence genes was demonstrated in one severely ill patient, which might accelerate his disease deterioration and death occurring one month after ICU admission. Our findings point to SARS-CoV-2-related microbial dysbiosis and various antibiotic-resistant respiratory microbes/pathogens in hospitalized COVID-19 patients in relation to disease severity. Detection and tracking strategies are needed to prevent the spread of antimicrobial resistance, improve the treatment regimen and clinical outcomes of hospitalized, severely ill COVID-19 patients.
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http://dx.doi.org/10.1038/s41421-021-00257-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8043102PMC
April 2021

Whole-genome resequencing of 445 Lactuca accessions reveals the domestication history of cultivated lettuce.

Nat Genet 2021 05 12;53(5):752-760. Epub 2021 Apr 12.

State Key Laboratory of Agricultural Genomics, BGI-Shenzhen, Shenzhen, China.

Lettuce (Lactuca sativa) is an important vegetable crop worldwide. Cultivated lettuce is believed to be domesticated from L. serriola; however, its origins and domestication history remain to be elucidated. Here, we sequenced a total of 445 Lactuca accessions, including major lettuce crop types and wild relative species, and generated a comprehensive map of lettuce genome variations. In-depth analyses of population structure and demography revealed that lettuce was first domesticated near the Caucasus, which was marked by loss of seed shattering. We also identified the genetic architecture of other domestication traits and wild introgressions in major resistance clusters in the lettuce genome. This study provides valuable genomic resources for crop breeding and sheds light on the domestication history of cultivated lettuce.
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http://dx.doi.org/10.1038/s41588-021-00831-0DOI Listing
May 2021

Protective or Harmful: The Dual Roles of Autophagy in Diabetic Retinopathy.

Front Med (Lausanne) 2021 25;8:644121. Epub 2021 Mar 25.

Shanghai Key Laboratory of Ocular Fundus Diseases, Department of Ophthalmology, National Clinical Research Center for Eye Diseases, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai General Hospital, Shanghai, China.

Autophagy is a self-degradative pathway involving intracellular substance degradation and recycling. Recently, this process has attracted a great deal of attention for its fundamental effect on physiological processes in cells, tissues, and the maintenance of organismal homeostasis. Dysregulation of autophagy occurs in some diseases, including immune disease, cancer, and neurodegenerative conditions. Diabetic retinopathy (DR), as a serious microvascular complication of diabetes, is the main cause of visual loss in working-age adults worldwide. The pathogenic mechanisms of DR are thought to be associated with accumulation of oxidative stress, retinal cell apoptosis, inflammatory response, endoplasmic reticulum (ER) stress, and nutrient starvation. These factors are closely related to the regulation of autophagy under pathological conditions. Increasing evidence has demonstrated the potential role of autophagy in the progression of DR through different pathways. However, to date this role is not understood, and whether the altered level of autophagy flux protects DR, or instead aggravates the progression, needs to be explored. In this review, we explore the alterations and functions of autophagy in different retinal cells and tissues under DR conditions, and explain the mechanisms involved in DR progression. We aim to provide a basis on which DR associated stress-modulated autophagy may be understood, and to suggest novel targets for future therapeutic intervention in DR.
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http://dx.doi.org/10.3389/fmed.2021.644121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026897PMC
March 2021

stLFRsv: A Germline Structural Variant Analysis Pipeline Using Co-barcoded Reads.

Front Genet 2021 18;12:636239. Epub 2021 Mar 18.

BGI-Shenzhen, Shenzhen, China.

Co-barcoded reads originating from long DNA fragments (mean length >30 kbp) maintain both single base level accuracy and long-range genomic information. We propose a pipeline, stLFRsv, to detect structural variation using co-barcoded reads. stLFRsv identifies abnormal large gaps between co-barcoded reads to detect potential breakpoints and reconstruct complex structural variants (SVs). Haplotype phasing by co-barcoded reads increases the signal to noise ratio, and barcode sharing profiles are used to filter out false positives. We integrate the short read SV caller smoove for smaller variants with stLFRsv. The integrated pipeline was evaluated on the well-characterized genome HG002/NA24385, and 74.5% precision and a 22.4% recall rate were obtained for deletions. stLFRsv revealed some large variants not included in the benchmark set that were verified by long reads or assembly. For the HG001/NA12878 genome, stLFRsv also achieved the best performance for both resource usage and the detection of large variants. Our work indicates that co-barcoded read technology has the potential to improve genome completeness.
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http://dx.doi.org/10.3389/fgene.2021.636239DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8012683PMC
March 2021

The Prevalence of and the Occurrence of MRSA CC398 in Monkey Feces in a Zoo Park in Eastern China.

Animals (Basel) 2021 Mar 8;11(3). Epub 2021 Mar 8.

Key Laboratory of Prevention and Control of Biological Hazard Factors (Animal Origin) for Agri-Food Safety and Quality, Ministry of Agriculture of China, Yangzhou University, Wenhui East Road 48, Yangzhou 225009, China.

Methicillin-resistant (MRSA) is one of the important antibiotic resistant pathogens causing infections in humans and animals. The increasing observation of MRSA in wildlife species has raised the concern of its impact on animal health and the potential of zoonotic transmission. This study investigated the prevalence of in fecal samples from non-human primates in a zoo located in Jiangsu, China, in which 6 out of 31 (19.4%) fecal samples, and 2 out of 14 (14.3%) indoor room floor swab samples were -positive. The antibiotic susceptibility tests of the eight isolates showed that the two isolates were resistant to both penicillin and cefoxitin, the three isolates were resistant only to penicillin, while three isolates were susceptible to all detected antibiotics. The two isolates resistant to cefoxitin were further identified as MRSA by the presence of . Five different types were identified including t034 of two MRSA isolates from , t189 of two methicillin-susceptible (MSSA) isolates from , t377 of two MSSA isolates from , and two novel types t19488 and t19499 from . Whole genome sequencing analysis showed that MRSA t034 isolates belonged to ST398 clustered in clonal complex 398 (CC398) and carried the type B ΦSa3 prophage. The phylogenetic analysis showed that the two MRSA t034/ST398 isolates were closely related to the human-associated MSSA in China. Moreover, two MRSA isolates contained the virulence genes relating to the cell adherence, biofilm formation, toxins, and the human-associated immune evasion cluster, which indicated the potential of bidirectional transfer of MRSA between monkeys and humans. This study is the first to report MRSA CC398 from monkey feces in China, indicating that MRSA CC398 could colonize in monkey and have the risk of transmission between humans and monkeys.
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http://dx.doi.org/10.3390/ani11030732DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7998827PMC
March 2021

Versatile Functions of Somatostatin and Somatostatin Receptors in the Gastrointestinal System.

Front Endocrinol (Lausanne) 2021 16;12:652363. Epub 2021 Mar 16.

Department of Neurobiology, Department of Neurology of the Second Affiliated Hospital, School of Brain Science and Brain Medicine, Hangzhou, China.

Somatostatin (SST) and somatostatin receptors (SSTRs) play an important role in the brain and gastrointestinal (GI) system. SST is produced in various organs and cells, and the inhibitory function of somatostatin-containing cells is involved in a range of physiological functions and pathological modifications. The GI system is the largest endocrine organ for digestion and absorption, SST-endocrine cells and neurons in the GI system are a critical effecter to maintain homeostasis SSTRs 1-5 and co-receptors, while SST-SSTRs are involved in chemo-sensory, mucus, and hormone secretion, motility, inflammation response, itch, and pain the autocrine, paracrine, endocrine, and exoendocrine pathways. It is also a power inhibitor for tumor cell proliferation, severe inflammation, and post-operation complications, and is a first-line anti-cancer drug in clinical practice. This mini review focuses on the current function of producing SST endocrine cells and local neurons SST-SSTRs in the GI system, discusses new development prognostic markers, phosphate-specific antibodies, and molecular imaging emerging in diagnostics and therapy, and summarizes the mechanism of the SST family in basic research and clinical practice. Understanding of endocrines and neuroendocrines in SST-SSTRs in GI will provide an insight into advanced medicine in basic and clinical research.
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http://dx.doi.org/10.3389/fendo.2021.652363DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8009181PMC
March 2021

SLR-superscaffolder: a de novo scaffolding tool for synthetic long reads using a top-to-bottom scheme.

BMC Bioinformatics 2021 Mar 25;22(1):158. Epub 2021 Mar 25.

BGI-Qingdao, BGI-Shenzhen, Qingdao, 266555, China.

Background: Synthetic long reads (SLR) with long-range co-barcoding information are now widely applied in genomics research. Although several tools have been developed for each specific SLR technique, a robust standalone scaffolder with high efficiency is warranted for hybrid genome assembly.

Results: In this work, we developed a standalone scaffolding tool, SLR-superscaffolder, to link together contigs in draft assemblies using co-barcoding and paired-end read information. Our top-to-bottom scheme first builds a global scaffold graph based on Jaccard Similarity to determine the order and orientation of contigs, and then locally improves the scaffolds with the aid of paired-end information. We also exploited a screening algorithm to reduce the negative effect of misassembled contigs in the input assembly. We applied SLR-superscaffolder to a human single tube long fragment read sequencing dataset and increased the scaffold NG50 of its corresponding draft assembly 1349 fold. Moreover, benchmarking on different input contigs showed that this approach overall outperformed existing SLR scaffolders, providing longer contiguity and fewer misassemblies, especially for short contigs assembled by next-generation sequencing data. The open-source code of SLR-superscaffolder is available at https://github.com/BGI-Qingdao/SLR-superscaffolder .

Conclusions: SLR-superscaffolder can dramatically improve the contiguity of a draft assembly by integrating a hybrid assembly strategy.
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http://dx.doi.org/10.1186/s12859-021-04081-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7993450PMC
March 2021

Global Landscape of Clostridioides Difficile Phylogeography, Antibiotic Susceptibility, and Toxin Polymorphisms by Post-Hoc Whole-Genome Sequencing from the MODIFY I/II Studies.

Infect Dis Ther 2021 Jun 22;10(2):853-870. Epub 2021 Mar 22.

BGI-Shenzhen, Shenzhen, China.

Introduction: Clostridioides (Clostridium) difficile infection, the leading cause of healthcare-associated diarrhea, represents a significant burden on global healthcare systems. Despite being a global issue, information on C. difficile from a global perspective is lacking. The aim of this study is to model the global phylogeography of clinical C. difficile.

Methods: Using samples collected from the MODIFY I and II studies (NCT01241552, NCT01513239), we performed whole-genome sequencing of 1501 clinical isolates including 37 novel sequence types (STs), representing the largest worldwide collection to date.

Results: Our data showed ribotypes, multi-locus sequence typing clades, and whole-genome phylogeny were in good accordance. The clinical C. difficile genome was found to be more conserved than previously reported (61% core genes), and modest recombination rates of 1.4-5.0 were observed across clades. We observed a significant continent distribution preference among five C. difficile clades (Benjamini-Hochberg corrected Fisher's exact test P < 0.01); moreover, weak association between geographic and genetic distance among ribotypes suggested sources beyond healthcare-related transmission. Markedly different trends of antibiotic susceptibility among lineages and regions were identified, and three novel mutations (in pyridoxamine 5'-phosphate oxidase family protein: Tyr130Ser, Tyr130Cys, and a promoter SNP) associated with metronidazole-reduced susceptibility were discovered on a nim-related gene and its promotor by genome-wide association study. Toxin gene polymorphisms were shown to vary within and between prevalent ribotypes, and novel severe mutations were found on the tcdC toxin regulator protein.

Conclusion: Our systematic characterization of a global set of clinical trial C. difficile isolates from infected individuals demonstrated the complexity of the genetic makeup of this pathogenic organism. The geographic variability of clades, variability in toxin genes, and mutations associated with antibiotic susceptibility indicate a highly complex interaction of C. difficile between host and environment. This dataset will provide a useful resource for validation of findings and future research of C. difficile.
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http://dx.doi.org/10.1007/s40121-021-00426-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8116447PMC
June 2021

Dynamic versus static ultra-widefield fluorescein angiography in eyes with diabetic retinopathy: a pilot prospective cross-sectional study.

Int J Ophthalmol 2021 18;14(3):409-415. Epub 2021 Mar 18.

Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.

Aim: To analyze differences in ultra-widefield fluorescein angiography (UWFA) findings between dynamic and static images of eyes with diabetic retinopathy (DR).

Methods: This cross-sectional study included 28 eyes of 28 patients with DR undergoing UWFA. A series of UWFA images acquired from each patient were converted into a time-lapse video and used as a dynamic image. A single, clear, arteriovenous phase image was chosen as a static image. Non-perfusion index (NPI) and its correlation with vascular abnormalities in different zones were compared between dynamic and static UWFA imaging.

Results: NPI appeared to increase from the center to the far-periphery in both groups. Dynamic NPI was lower in the total retinal area (0.26 0.29, =0.009) and far-periphery (0.33 0.36, adjusted =0.042), which was contrary to the static NPI. Far-peripheral NPI was associated with intraretinal microvascular abnormality in the posterior area in both groups.

Conclusion: Time-lapse dynamic UWFA imaging is a useful modality to differentially diagnose hypofluorescence in the most peripheral region. This modality could provide a reliable method for NPI measurement.
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http://dx.doi.org/10.18240/ijo.2021.03.13DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930541PMC
March 2021

Protective effects of peptide FK18 against neuro-excitotoxicity in SH-SY5Y cells.

Exp Ther Med 2021 May 1;21(5):451. Epub 2021 Mar 1.

Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai 200080, P.R. China.

Excitotoxic neuronal injury is associated with numerous acute and chronic neurological disorders, such as Alzheimer's disease and glaucoma. Neuroprotection is a direct and effective therapeutic approach, with small-molecule bioactive peptides displaying certain advantages, including high membrane permeability, low immunogenicity and convenient synthesis and modification. FK18 is a novel peptide derived from basic fibroblast growth factor, which is a protein with neuroprotective effects. The present study aims to evaluate the neuroprotective effect of FK18 against excitotoxic injury. For this purpose, cell viability was determined by the MTS assay, cell apoptosis was assessed by flow cytometry and the TUNEL assay; expression of antiapoptotic proteins Bcl-2, proapoptotic protein Bax and caspase-3 as well as the phosphorylation of Akt and Erk was estimated by western blotting. The results of the present study demonstrated that FK18 effectively increased the viability of, and attenuated glutamate-induced apoptosis of SH-SY5Y cells. In addition, FK18 significantly increased Akt phosphorylation and decreased Erk phosphorylation in SH-SY5Y cells. FK18 also increased the Bcl-2/Bax ratio and decreased the level of cleaved-caspase-3 in SY5Y cells, which was reversed by the Akt pathway inhibitor LY294002, but not by the Erk pathway inhibitor U0126. The findings of the present study suggested that FK18 may be a promising therapeutic agent for the inhibition of neuronal cell death in multiple neurological diseases involving excitotoxicity.
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http://dx.doi.org/10.3892/etm.2021.9880DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7967878PMC
May 2021

Population Bottlenecks and Intra-host Evolution During Human-to-Human Transmission of SARS-CoV-2.

Front Med (Lausanne) 2021 15;8:585358. Epub 2021 Feb 15.

State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

The emergence of the novel human coronavirus, SARS-CoV-2, causes a global COVID-19 (coronavirus disease 2019) pandemic. Here, we have characterized and compared viral populations of SARS-CoV-2 among COVID-19 patients within and across households. Our work showed an active viral replication activity in the human respiratory tract and the co-existence of genetically distinct viruses within the same host. The inter-host comparison among viral populations further revealed a narrow transmission bottleneck between patients from the same households, suggesting a dominated role of stochastic dynamics in both inter-host and intra-host evolutions.
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http://dx.doi.org/10.3389/fmed.2021.585358DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917136PMC
February 2021

Integrated genetic analyses revealed novel human longevity loci and reduced risks of multiple diseases in a cohort study of 15,651 Chinese individuals.

Aging Cell 2021 03 3;20(3):e13323. Epub 2021 Mar 3.

Center for the Study of Aging and Human Development, Medical School of Duke University, Durham, USA.

There is growing interest in studying the genetic contributions to longevity, but limited relevant genes have been identified. In this study, we performed a genetic association study of longevity in a total of 15,651 Chinese individuals. Novel longevity loci, BMPER (rs17169634; p = 7.91 × 10 ) and TMEM43/XPC (rs1043943; p = 3.59 × 10 ), were identified in a case-control analysis of 11,045 individuals. BRAF (rs1267601; p = 8.33 × 10 ) and BMPER (rs17169634; p = 1.45 × 10 ) were significantly associated with life expectancy in 12,664 individuals who had survival status records. Additional sex-stratified analyses identified sex-specific longevity genes. Notably, sex-differential associations were identified in two linkage disequilibrium blocks in the TOMM40/APOE region, indicating potential differences during meiosis between males and females. Moreover, polygenic risk scores and Mendelian randomization analyses revealed that longevity was genetically causally correlated with reduced risks of multiple diseases, such as type 2 diabetes, cardiovascular diseases, and arthritis. Finally, we incorporated genetic markers, disease status, and lifestyles to classify longevity or not-longevity groups and predict life span. Our predictive models showed good performance (AUC = 0.86 for longevity classification and explained 19.8% variance of life span) and presented a greater predictive efficiency in females than in males. Taken together, our findings not only shed light on the genetic contributions to longevity but also elucidate correlations between diseases and longevity.
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http://dx.doi.org/10.1111/acel.13323DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7963337PMC
March 2021

Prevalence of fundus tessellation and its associated factors in Chinese children and adolescents with high myopia.

Acta Ophthalmol 2021 Feb 24. Epub 2021 Feb 24.

Shanghai Eye Disease Prevention and Treatment Center, Shanghai Eye Hospital, Shanghai Children and Adolescent Myopia Prevention and Treatment Technology Center, Shanghai, China.

Purpose: To investigate the prevalence and associated factors of fundus tessellation in highly myopic children and adolescents.

Methods: A total of 513 high myopes (spherical equivalent [SE] ≤ -5.0 D, 4-19 years of age) without any advanced pathological myopic lesions were enrolled. Fundus photographs and choroidal thickness (ChT) data were collected by SS-OCT. A novel grading approach was adopted to classify fundus tessellation into four categories on colour fundus photography, referring to the location of tessellation divided by an Early Treatment Diabetic Retinopathy Study grid centred on the fovea, through which closer to the fovea represents higher grades of fundus tessellation. Peripapillary atrophy (PPA) area and ovality index were also measured.

Results: Among the participants, with a mean age of 13.47 ± 3.13 years and mean SE of - 8.34 ± 1.91 D, there were 29 (5.7%), 95 (18.5%), 233 (45.4%) and 156 (30.4%) participants with grade 0 to grade 3 fundus tessellation, respectively. The ChT in both the macular and peripapillary area was negatively correlated with the fundus tessellation grade (R = -0.763 and -0.537, respectively, all p < 0.001). Higher grades of fundus tessellation were independently associated with thinner macular ChT (OR = 1.734, 95% CI: 1.621-1.856, p < 0.001), longer axial length (OR = 1.368, 95% CI: 1.105-1.695, p = 0.004), larger PPA area (OR = 1.391, 95% CI: 1.073-1.802, p = 0.013) and the female sex (OR = 1.605, 95% CI: 1.092-2.359, p = 0.016).

Conclusion: The fundus tessellation grade could reflect the ChT, representing the severity of myopic maculopathy among young high myopes who rarely had any advanced lesions of pathological myopia. Fundus tessellation grade might be a potential index for assessing early-stage myopic maculopathy in children and adolescents.
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http://dx.doi.org/10.1111/aos.14826DOI Listing
February 2021