Publications by authors named "Yumei Li"

305 Publications

Highly enriched exosomal lncRNA OIP5-AS1 regulates osteosarcoma tumor angiogenesis and autophagy through miR-153 and ATG5.

Am J Transl Res 2021 15;13(5):4211-4223. Epub 2021 May 15.

Department of Radiology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine 725 Wanping South Road, Xuhui District, Shanghai 200032, China.

Objective: This study aims to investigate the regulatory role of exosome lncRNA OIP5-AS1 in tumor progression and autophagy.

Methods: Seventy-three cases of osteosarcoma (OS) tissues and 56 cases of adjacent normal tissues were collected to culture human OS cell line HOS. The exosomes secreted by OS cell line were isolated and collected. Apoptosis and exosome markers were detected by flow cytometry. A nude mouse model of OS was established. The gene expression levels of lncRNA OIP5-AS1, miR-153 and autophagy-related protein 5 (ATG5) were quantified by real-time quantitative PCR (RT-PCR). The binding sites of lncRNA OIP5-AS1 and miR-153 were predicted by Starbase3.0, and the binding sites of miR-153 and ATG5 were predicted by Targetscan7.2. The gene binding sites were verified by luciferase reporter gene detection or RNA immunoprecipitation (RIP). The relative level of protein was tested by Western blot. Transwell was applied to test migration and invasion of OS cells. The angiogenesis of OS cells was tested by tubule formation test.

Results: The results of RT-PCR showed that lncRNA OIP5-AS1 levels were elevated in OS cells and exosomes secreted by cells. Cell function experiments revealed that the proliferation, migration, and invasion of OS cells were promoted by exosomal lncRNA OIP5-AS1. In exosomes, lncRNA OIP5-AS1 inhibited the expression of LC3-II and Beclin 1 proteins, indicating that exosomal lncRNA OIP5-AS1 inhibited autophagy. According to the results of bioinformatics tools and dual-luciferase reporter (DLR) assay or RNA immunoprecipitation (RIP), miR-153 targeted the 3'-UTR of lncRNA OIP5-AS1 and autophagy-related protein 5 (ATG5). The results of western blot (WB) assay showed that exosomal lncRNA OIP5-AS1 and down-regulated miR-153 led to the enhancement of ATG5 protein expression, while up-regulated miR-153 resulted in the decrease of ATG5 protein expression. ATG5 was negatively correlated with miR-153 and positively correlated with lncRNA OIP5-AS1. The results of tubule formation assay disclosed an increase in the angiogenesis level caused by the exosomal lncRNA OIP5-AS1, which was then reversed by the increase of miR-153 and decrease of ATG5.

Conclusion: Highly enriched exosomal lncRNA OIP5-AS1 can regulate OS tumor angiogenesis and autophagy through miR-153 and ATG5.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8205742PMC
May 2021

Transcript isoforms of Reep6 have distinct functions in the retina.

Hum Mol Genet 2021 Jun 8. Epub 2021 Jun 8.

Human Genome Sequencing Center, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, 77030, USA.

Much of the complexity of the eukaryotic cell transcriptome is due to the alternative splicing of mRNA. However, knowledge on how transcriptome complexity is translated into functional complexity remains limited. For example, although different isoforms of a gene may show distinct temporal and spatial expression patterns, it is largely unknown whether these isoforms encode proteins with distinct functions matching their expression pattern. In this report, we investigated the function and relationship of the two isoforms of Reep6, namely Reep6.1 and Reep6.2, in rod photoreceptor cells. These two isoforms result from the alternative splicing of exon 5 and show mutually exclusive expression patterns. Reep6.2 is the canonical isoform that is expressed in non-retinal tissues while Reep6.1 is the only expressed isoform in the adult retina. The Reep6.1 isoform-specific knockout mouse, Reep6E5/E5, is generated by deleting exon 5 and a homozygous deletion phenotypically displayed a rod degeneration phenotype comparable to a Reep6 full knockout mouse, indicating that the Reep6.1 isoform is essential for the rod photoreceptor cell survival. Consistent with the results obtained from a loss-of-function experiment, overexpression of Reep6.2 failed to rescue the rod degeneration phenotype of Reep6 knockout mice while overexpression of Reep6.1 does lead to rescue. These results demonstrate that, consistent with the expression pattern of the isoform, Reep6.1 has rod-specific functions that cannot be substituted by its canonical isoform. Our findings suggested that a strict regulation of splicing is required for the maintenance of photoreceptor cells.
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http://dx.doi.org/10.1093/hmg/ddab157DOI Listing
June 2021

Hyperlactatemia associated with diabetic ketoacidosis in pediatric intensive care unit.

BMC Endocr Disord 2021 May 27;21(1):110. Epub 2021 May 27.

Department of Pediatric Intensive Care Unit, The First Hospital of Jilin University, Xin Min Street, 130021, Changchun, China.

Background: Children with diabetic ketoacidosis often have elevated lactate. In this study, we investigated the clinical variables associated with hyperlactatemia in children with diabetic ketoacidosis.

Methods: We designed a single-center retrospective descriptive study of children with diabetic ketoacidosis in a pediatric intensive care unit.

Results: Of the 107 patients with diabetic ketoacidosis included in the analysis, 61 developed hyperlactatemia. Multivariate logistic regression analysis showed that heart rate (p = 0.003),diastolic blood pressure (p = 0.001) and stage of severity (p = 0.042) were independently associated with the development of hyperlactatemia in diabetic ketoacidosis. We found that lactate level was not significantly associated with length of hospital stay (p = 0.115) or the length of time to diabetic ketoacidosis resolution (p = 0.143).

Conclusions: Children with diabetic ketoacidosis presenting with severer stage, elevated heart rate and higher diastolic blood pressure may be prone to hyperlactatemia. Hyperlactatemia was not associated with length of time to DKA resolution and length of hospital stay.
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http://dx.doi.org/10.1186/s12902-021-00776-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8157405PMC
May 2021

Activation of palindromes on a degradable modular grafting probe enables ultrasensitive detection of microRNAs.

Chem Commun (Camb) 2021 Jun;57(48):5941-5944

College of Chemistry, Fuzhou University, Fuzhou 350002, China. and School of Pharmacy, Anhui Medical University, Hefei 230031, China.

This work describes a single-stranded degradable modular grafting probe for analyzing microRNA-21. In the system, the exonuclease activity of phi29 polymerase restrains the SYBR Green I/ssDNA induced background. The palindrome activation caused remarkable target fluorescence. The detection limit was achieved as 0.26 fM, showing potential in biochemical analysis.
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http://dx.doi.org/10.1039/d1cc01150bDOI Listing
June 2021

An atlas of alternative polyadenylation quantitative trait loci contributing to complex trait and disease heritability.

Nat Genet 2021 Jul 13;53(7):994-1005. Epub 2021 May 13.

Division of Computational Biomedicine, Department of Biological Chemistry, School of Medicine, University of California, Irvine, Irvine, CA, USA.

Genome-wide association studies have identified thousands of noncoding variants associated with human traits and diseases. However, the functional interpretation of these variants is a major challenge. Here, we constructed a multi-tissue atlas of human 3'UTR alternative polyadenylation (APA) quantitative trait loci (3'aQTLs), containing approximately 0.4 million common genetic variants associated with the APA of target genes, identified in 46 tissues isolated from 467 individuals (Genotype-Tissue Expression Project). Mechanistically, 3'aQTLs can alter poly(A) motifs, RNA secondary structure and RNA-binding protein-binding sites, leading to thousands of APA changes. Our CRISPR-based experiments indicate that such 3'aQTLs can alter APA regulation. Furthermore, we demonstrate that mapping 3'aQTLs can identify APA regulators, such as La-related protein 4. Finally, 3'aQTLs are colocalized with approximately 16.1% of trait-associated variants and are largely distinct from other QTLs, such as expression QTLs. Together, our findings show that 3'aQTLs contribute substantially to the molecular mechanisms underlying human complex traits and diseases.
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http://dx.doi.org/10.1038/s41588-021-00864-5DOI Listing
July 2021

Polyadenylation-related isoform switching in human evolution revealed by full-length transcript structure.

Brief Bioinform 2021 May 11. Epub 2021 May 11.

Laboratory of Bioinformatics and Genomic Medicine, Institute of Molecular Medicine, Peking University, Beijing, China.

Rhesus macaque is a unique nonhuman primate model for human evolutionary and translational study, but the error-prone gene models critically limit its applications. Here, we de novo defined full-length macaque gene models based on single molecule, long-read transcriptome sequencing in four macaque tissues (frontal cortex, cerebellum, heart and testis). Overall, 8 588 227 poly(A)-bearing complementary DNA reads with a mean length of 14 106 nt were generated to compile the backbone of macaque transcripts, with the fine-scale structures further refined by RNA sequencing and cap analysis gene expression sequencing data. In total, 51 605 macaque gene models were accurately defined, covering 89.7% of macaque or 75.7% of human orthologous genes. Based on the full-length gene models, we performed a human-macaque comparative analysis on polyadenylation (PA) regulation. Using macaque and mouse as outgroup species, we identified 79 distal PA events newly originated in humans and found that the strengthening of the distal PA sites, rather than the weakening of the proximal sites, predominantly contributes to the origination of these human-specific isoforms. Notably, these isoforms are selectively constrained in general and contribute to the temporospatially specific reduction of gene expression, through the tinkering of previously existed mechanisms of nuclear retention and microRNA (miRNA) regulation. Overall, the protocol and resource highlight the application of bioinformatics in integrating multilayer genomics data to provide an intact reference for model animal studies, and the isoform switching detected may constitute a hitherto underestimated regulatory layer in shaping the human-specific transcriptome and phenotypic changes.
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http://dx.doi.org/10.1093/bib/bbab157DOI Listing
May 2021

Circulating extracellular vesicles are effective biomarkers for predicting response to cancer therapy.

EBioMedicine 2021 May 7;67:103365. Epub 2021 May 7.

Department of Respiratory and Critical Care Medicine, NHC Key Laboratory of Pulmonary Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, Hubei 430022, P.R. China. Electronic address:

Cancer remains one of the most challenging diseases, as many patients show limited therapeutic response to treatment. Liquid biopsy is a minimally invasive method that has the advantage of providing real-time disease information with the least damage to cancer patients. Extracellular vesicles (EVs) released by the parental cells and protected by lipid bilayer membrane structure represent an emerging liquid biopsy modality. Apart from promoting cell growth, proliferation, and migration, EVs and their cargos (mainly miRNAs and proteins) are also biomarkers for cancer diagnosis and prognosis. Furthermore, their alterations pre- and post-therapy can guide therapeutic strategy determinations for better-stratified therapy. In this review, we summarize the potential clinical significance of EVs and their cargos in therapeutic response monitoring and prediction in several cancers (mainly lung cancer, prostate cancer, breast cancer, melanoma, lymphoma, glioblastoma, and head and neck squamous cell carcinoma) and discuss the questions that require future investigation.
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http://dx.doi.org/10.1016/j.ebiom.2021.103365DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8121992PMC
May 2021

Melittin inhibits lung metastasis of human osteosarcoma: Evidence of wnt/β-catenin signaling pathway participation.

Toxicon 2021 Jul 28;198:132-142. Epub 2021 Apr 28.

Department of Orthopaedics, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200071, China. Electronic address:

Melittin is a major active peptide component of bee venom that has been demonstrated to show anti-tumor effects. Osteosarcoma is a type of bone tumor with a high degree of malignancy, and metastasis is the main challenge of osteosarcoma therapy. This study aimed to investigate the role of melittin in the lung metastasis of osteosarcoma. 143 B cells were treated with different concentrations of melittin in vitro. Wound-healing and transwell assays were performed to determine the cell migration and invasion potential. Quantitative real-time PCR and Western blot experiments were performed to evaluate the expression levels of Wnt/β-catenin signaling pathway-related factors after treatment with melittin. The orthotopic implantation model and hematoxylin-eosin staining were used to investigate the effect of melittin treatment on tumor formation and lung metastasis. Immunohistochemical staining and Western blot experiments were performed to indicate the melittin-mediated expression changes in Wnt/β-catenin signaling pathway-related factors. The cell migration and invasion potential were observed to be inhibited in a dose-dependent manner upon treatment with melittin. Treatment with medium and high concentrations of melittin attenuated the mRNA and protein expression of LRP5, β-catenin, MMP-2, cyclin D, c-Myc, survivin, MMP-9, and VEGF genes in vitro. Melittin significantly inhibited the growth of tibia xenografts in nude mice and decreased the number of lung metastatic nodules. Consistent with the results observed in vitro, treatment with melittin at medium and high concentrations attenuated the expression of Wnt/β-catenin signaling pathway-related factors in vivo. In vitro, Wnt/β-catenin signaling pathway was involved in Melittin-mediated -migration and invasion potential of 143 B cells. Similarly, as observed in the in vivo experiments, Wnt/β-catenin signaling pathway was also associated with the role of melittin on lung metastasis of osteosarcomas.
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http://dx.doi.org/10.1016/j.toxicon.2021.04.024DOI Listing
July 2021

Noncoding mutation in contributes to inherited retinal degenerations.

Mol Vis 2021 18;27:95-106. Epub 2021 Mar 18.

Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas.

Purpose: Despite the extensive use of next-generation sequencing (NGS) technology to identify disease-causing genomic variations, a major gap in our understanding of Mendelian diseases is the unidentified molecular lesion in a significant portion of patients. For inherited retinal degenerations (IRDs), although currently close to 300 disease-associated genes have been identified, the mutations in approximately one-third of patients remain unknown. With mounting evidence that noncoding mutations might contribute significantly to disease burden, we aimed to systematically investigate the contributions of noncoding regions in the genome to IRDs.

Methods: In this study, we focused on , which has been linked to various IRD phenotypes, including Leber congenital amaurosis (LCA), retinitis pigmentosa (RP), and macular dystrophy (MD). As several noncoding mutant alleles have been reported in and we observed that the mutation carrier frequency of is higher in patient cohorts with unsolved IRDs, we hypothesized that mutations in the noncoding regions of might be a significant contributor to pathogenicity. To test this hypothesis, we performed whole-genome sequencing (WGS) for 25 patients with unassigned IRD who carry a single mutation in .

Results: Three noncoding variants in , including a 2,890 bp deletion and two deep-intronic variants (c.2710+233G>A and c.1468-263G>C), were identified as putative second hits of in three patients with LCA. The mutant alleles were validated with direct sequencing or in vitro assays.

Conclusions: The results highlight the significance of the contribution of noncoding pathogenic variants to unsolved IRD cases.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056464PMC
March 2021

Blood supply of the male breast nipple-areola complex evaluated by CTA.

J Plast Reconstr Aesthet Surg 2021 Mar 10. Epub 2021 Mar 10.

Department of Radiology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Shuai Fu Yuan 1#, Dongcheng Dist., Beijing 100730, China. Electronic address:

Purpose: In addition to women, men also undergo breast surgeries, and early studies on the blood supply of breasts are nearly all conducted in female subjects. The vasculature of the male breast is seldom studied. Understanding the male-specific blood supply of the breast is important for pre-operative planning and reducing complications. The purpose of this retrospective study is to fill the gap in the literature by describing the main blood supply and its orientation in the male breast.

Methods: We retrospectively evaluated thoracic computed tomographic angiography (CTA) data from January 1, 2017 to July 30, 2019. Single or multiple dominant arteries and their origins were traced, and the artery route and orientation related to the nipple-areola complex (NAC) were revealed through data analysis of the images.

Results: Totally, 284 breasts were included. Most breasts were supplied by a single dominant artery (196, 69%), among which the lateral thoracic artery (LTA; 119, 41.9%; type I) and internal thoracic artery (ITA; 63, 22.2%; type II) were the most common arteries. A minority of breasts were supplied by vascular anastomoses formed by dual arteries (17, 6.0%; type III), and in 25.0% of breasts, no specific dominant artery was found (type IV). The predominant artery distribution was evaluated.

Conclusion: This study cohort of male thoracic CTA provided and analysed the elaborate vascular anatomy of the NAC region. Our results favour inferior periareolar incision in regard to diminished vascular-related complications in male surgeries without pre-operative vascular evaluation. This study also suggests that super-lateral or lower-lateral-based pedicles can reserve more vasculature.
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http://dx.doi.org/10.1016/j.bjps.2021.02.006DOI Listing
March 2021

Sputum microbiota as a potential diagnostic marker for multidrug-resistant tuberculosis.

Int J Med Sci 2021 3;18(9):1935-1945. Epub 2021 Mar 3.

Dongguan Key Laboratory of Medical Bioactive Molecular Developmental and Translational Research, Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Guangdong Medical University, Dongguan, China.

The prevalence of drug-resistant (Mtb) strains makes disease control more complicated, which is the main cause of death in tuberculosis (TB) patients. Early detection and timely standard treatment are the key to current prevention and control of drug-resistant TB. In recent years, despite the continuous advancement in drug-resistant TB diagnostic technology, the needs for clinical rapid and accurate diagnosis are still not fully met. With the development of sequencing technology, the research of human microecology has been intensified. This study aims to use 16 rRNA sequencing technology to detect and analyze upper respiratory flora of TB patients with anti-TB drug sensitivity (DS, n = 55), monoresistance isoniazide (MR-INH, n = 33), monoresistance rifampin (MR-RFP, n = 12), multidrug resistance (MDR, n = 26) and polyresistance (PR, n = 39) in southern China. Potential microbial diagnostic markers for different types of TB drug resistance are searched by screening differential flora, which provides certain guiding significance for drug resistance diagnosis and clinical drug use of TB. The results showed that the pulmonary microenvironment of TB patients was more susceptible to infection by external pathogens, and the infection of different drug-resistant Mtb leads to changes in different flora. Importantly, seven novel microorganisms (Leptotrichia, Granulicatella, Campylobacter, Delfitia, Kingella, Chlamydophila, Bordetella) were identified by 16S rRNA sequencing as diagnostic markers for different drug resistance types of TB. Leptotrichia, Granulicatella, Campylobacter were potential diagnostic marker for TB patients with INH single-resistance. Delftia was a potential diagnostic marker for TB patients with RFP single drug-resistance. Kingella and Chlamydophila can be used as diagnostic markers for TB patients with PR. Bordetella can be used as a potential diagnostic marker for identification of TB patients with MDR.
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http://dx.doi.org/10.7150/ijms.53492DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040397PMC
March 2021

Inflammatory profiles and clinical features of COVID-19 survivors three months after discharge in Wuhan, China.

J Infect Dis 2021 Apr 4. Epub 2021 Apr 4.

Department of Respiratory and Critical Care Medicine, NHC Key Laboratory of Pulmonary Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.

Background: Post-discharge immunity and its correlation with clinical features among patients recovered from COVID-19 are poorly described. This prospective cross-sectional study explored the inflammatory profiles and clinical recovery of COVID-19 patients at 3 months post-discharge.

Methods: COVID-19 patients discharged from four hospitals in Wuhan, recovered asymptomatic patients (APs) from an isolation hotel, and uninfected healthy controls (HCs) were recruited. Viral nucleic acid and antibody detection, laboratory examination, computed tomography, pulmonary function assessment, multiplex cytokine assay, and flow cytometry were performed.

Results: The 72 age-, sex- and body mass index-matched participants included 19 severe/critical patients (SPs), 20 mild/moderate patients (MPs), 16 APs, and 17 HCs. At 3 months after discharge, levels of pro-inflammatory cytokines and factors related to vascular injury/repair in recovered COVID-19 patients had not returned to those of the HCs, especially among recovered SPs compared to recovered MPs and APs. These cytokines were significantly correlated with impaired pulmonary function and chest CT abnormalities. However, levels of immune cells had returned to nearly normal levels and were not significantly correlated with abnormal clinical features.

Conclusion: Vascular injury, inflammation, and chemotaxis persisted in COVID-19 patients and were correlated with abnormal clinical features 3 months after discharge, especially in recovered SPs.
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http://dx.doi.org/10.1093/infdis/jiab181DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8083630PMC
April 2021

The gut microbial composition in polycystic ovary syndrome with insulin resistance: findings from a normal-weight population.

J Ovarian Res 2021 Mar 27;14(1):50. Epub 2021 Mar 27.

Department of Assisted Reproduction, Xiangya Hospital, Central South University, 410008, Changsha, People's Republic of China.

Background: Limited studies have reported the relationship between intestinal flora dysbiosis and clinical characteristics in polycystic ovary syndrome (PCOS). However, the structure and characteristics of gut microbiota in PCOS have not been fully elucidated.

Objective: To analyze the composition of the Intestinal flora population in normal-weight women with PCOS and insulin resistance(IR) compared to PCOS alone and healthy women.

Methods: A total of 14 PCOS patients with insulin resistant(PCOS-IR) and 12 PCOS alone (PCOS-NIR), and 10 age- and body mass index-matched healthy control women (HC). BMI: 18.5-23.9 kg/m. The bacterial 16 S rDNA V3-V4 fragment was amplified and sequenced. Then, the sequencing data were analyzed for species annotation, community diversity, and inter-group differences, to explore gut microbial characteristics of the subjects and their correlation with clinical parameters.

Results: No significant difference in diversity was observed between PCOA and sample cluster analysis among the three groups (Beta-diversity) and Alpha-diversity. The relative abundance of Rothia, Ruminococcus, and Enterococcus was significantly higher in the PCOS-IR group than in the other two groups (P < 0.05), while that of Prevotella was dramatically decreased (P < 0.05). The abundance of Enterococcus was positively correlated with waist circumference, hip circumference, diastolic blood pressure, and insulin resistance index. Meanwhile, Rothia abundance is positively associated with waist circumference and free fatty acids.

Conclusions: The gut microbial composition of PCOS patients with insulin resistance is different from that of PCOS alone and healthy women. The difference is correlated with the clinical characteristics of PCOS, with regards to insulin resistance, abdominal obesity, free fatty acids, and other indicators. PCOS-IR patients have an increased abundance of Enterococcus which potentially the intestinal environment of the host by enriching the metabolic pathways related to insulin resistance, causing the occurrence and development of PCOS.
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http://dx.doi.org/10.1186/s13048-021-00799-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005233PMC
March 2021

Identification of Deep-Intronic Splice Mutations in a Large Cohort of Patients With Inherited Retinal Diseases.

Front Genet 2021 2;12:647400. Epub 2021 Mar 2.

Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, United States.

High throughput sequencing technologies have revolutionized the identification of mutations responsible for a diverse set of Mendelian disorders, including inherited retinal disorders (IRDs). However, the causal mutations remain elusive for a significant proportion of patients. This may be partially due to pathogenic mutations located in non-coding regions, which are largely missed by capture sequencing targeting the coding regions. The advent of whole-genome sequencing (WGS) allows us to systematically detect non-coding variations. However, the interpretation of these variations remains a significant bottleneck. In this study, we investigated the contribution of deep-intronic splice variants to IRDs. WGS was performed for a cohort of 571 IRD patients who lack a confident molecular diagnosis, and potential deep intronic variants that affect proper splicing were identified using SpliceAI. A total of six deleterious deep intronic variants were identified in eight patients. An minigene system was applied to further validate the effect of these variants on the splicing pattern of the associated genes. The prediction scores assigned to splice-site disruption positively correlated with the impact of mutations on splicing, as those with lower prediction scores demonstrated partial splicing. Through this study, we estimated the contribution of deep-intronic splice mutations to unassigned IRD patients and leveraged and methods to establish a framework for prioritizing deep intronic variant candidates for mechanistic and functional analyses.
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http://dx.doi.org/10.3389/fgene.2021.647400DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7960924PMC
March 2021

Attenuation of Inflammation by DJ-1 May Be a Drug Target for Cerebral Ischemia-Reperfusion Injury.

Neurochem Res 2021 Jun 8;46(6):1470-1479. Epub 2021 Mar 8.

Department of Pathology, Basic Medical College, Chongqing Medical University, Yixueyuan Road 1, Chongqing, 400016, People's Republic of China.

The pathophysiological process of cerebral apoplexy is complex, and there are currently no specific drugs for this condition. The study of effective drug targets has become a hot topic in neuroscience. Currently, adeno-associated viruses (AAVs) and polypeptides are commonly used in drug research. DJ-1 has been widely considered a neuroprotective target in recent times, but the mechanism of its neuroprotective effects is unclear. In this study, we simulated ischemic injury by establishing a middle cerebral artery occlusion reperfusion (MCAO/R) model to compare the protective effect of DJ-1 overexpression induced by DJ-1 AAV and ND-13 on cerebral ischemia-reperfusion (I/R) injury. We found that DJ-1 overexpression and ND-13 significantly reduced the neurological function scores and infarct volume and alleviated pathological damage to brain tissue. In addition, Western blotting, ELISA and immunofluorescence labeling revealed that DJ-1 overexpression and ND-13 increased the expression of the anti-inflammatory cytokines IL-10 and IL-4, and decreased the levels of the pro-inflammatory cytokines IL-1β and TNF-α. In summary, our study shows that DJ-1 overexpression and ND-13 can regulate the expression of inflammatory factors and alleviate cerebral I/R injury. Thus, DJ-1 is a possible drug target for cerebral I/R injury.
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http://dx.doi.org/10.1007/s11064-021-03288-zDOI Listing
June 2021

Outer membrane protein A inhibits the degradation of caspase-1 to regulate NLRP3 inflammasome activation and exacerbate the Acinetobacter baumannii pulmonary inflammation.

Microb Pathog 2021 Apr 8;153:104788. Epub 2021 Feb 8.

Department of Anatomy, School of Basic Medical Sciences, Guizhou Medical University/ Department of Respiratory and Critical Medicine, Guizhou Provincial People's Hospital, Guiyang, Guizhou, 550025, China. Electronic address:

Acinetobacter baumannii (A. baumannii), one of the major pathogens that causes severe nosocomial infections, is characterised by a high prevalence of drug resistance. It has been reported that A. baumannii triggers the NOD-like receptor 3 (NLRP3) inflammasome, but the role of its virulence-related outer membrane protein A (ompA) remains unclear. Therefore, this study aimed to explore the effects of ompA on the NLRP3 inflammasome and its underlying molecular mechanisms. Results showed that ompA enhanced inflammatory damage, which was reduced as a result of knockout of the ompA gene. Additionally, ompA-stimulated expression of NLRP3 inflammasome was significantly blocked by silencing caspase-1, but activation of NLRP3 inflammasome was not altered after silencing ASC; this indicated that ompA was dependent on the caspase-1 pathway to activate the inflammatory response. Simultaneously, the wild-type (WT) strains triggered NLRP3 inflammasome after inhibition of caspase-1 degradation by proteasome inhibitor MG-132, aggravating tissue damage. These findings indicated that ompA may be dependent on the caspase-1 pathway to enhance inflammation and exacerbate tissue damage. Taken together, these results confirmed a novel capsase-1-modulated mechanism underpinning ompA activity, which further reveals the NLRP3 inflammasome pathway as a potential immunomodulatory target against A. baumannii infections.
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http://dx.doi.org/10.1016/j.micpath.2021.104788DOI Listing
April 2021

The Nomogram of MRI-based Radiomics with Complementary Visual Features by Machine Learning Improves Stratification of Glioblastoma Patients: A Multicenter Study.

J Magn Reson Imaging 2021 08 8;54(2):571-583. Epub 2021 Feb 8.

Department of Radiology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital of Hangzhou Medical College, Hangzhou, China.

Background: Glioblastomas (GBMs) represent both the most common and the most highly malignant primary brain tumors. The subjective visual imaging features from MRI make it challenging to predict the overall survival (OS) of GBM. Radiomics can quantify image features objectively as an emerging technique. A pragmatic and objective method in the clinic to assess OS is strongly in need.

Purpose: To construct a radiomics nomogram to stratify GBM patients into long- vs. short-term survival.

Study Type: Retrospective.

Population: One-hundred and fifty-eight GBM patients from Brain Tumor Segmentation Challenge 2018 (BRATS2018) were for model construction and 32 GBM patients from the local hospital for external validation.

Field Strength/sequence: 1.5 T and 3.0 T MRI Scanners, T WI, T WI, T FLAIR, and contrast-enhanced T WI sequences ASSESSMENT: All patients were divided into long-term or short-term based on a survival of greater or fewer than 12 months. All BRATS2018 subjects were divided into training and test sets, and images were assessed for ependymal and pia mater involvement (EPI) and multifocality by three experienced neuroradiologists. All tumor tissues from multiparametric MRI were fully automatically segmented into three subregions to calculate the radiomic features. Based on the training set, the most powerful radiomic features were selected to constitute radiomic signature.

Statistical Tests: Receiver operating characteristic (ROC) curve, sensitivity, specificity, and the Hosmer-Lemeshow test.

Results: The nomogram had a survival prediction accuracy of 0.878 and 0.875, a specificity of 0.875 and 0.583, and a sensitivity of 0.704 and 0.833, respectively, in the training and test set. The ROC curve showed the accuracy of the nomogram, radiomic signature, age, and EPI for external validation set were 0.858, 0.826, 0.664, and 0.66 in the validate set, respectively.

Data Conclusion: Radiomics nomogram integrated with radiomic signature, EPI, and age was found to be robust for the stratification of GBM patients into long- vs. short-term survival.

Level Of Evidence: 3 TECHNICAL EFFICACY STAGE: 2.
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http://dx.doi.org/10.1002/jmri.27536DOI Listing
August 2021

General and mild modification of food-derived extracellular vesicles for enhanced cell targeting.

Nanoscale 2021 Feb;13(5):3061-3069

Department of Chemical Biology, MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, Key Laboratory for Chemical Biology of Fujian Province, Collaborative Innovation Center of Chemistry for Energy Materials, College of Chemistry and Chemical Engineering, Xiamen University, 361005, Xiamen, China.

Food-derived extracellular vesicles (FDEVs) have attracted increasing attention as potential delivery vehicles for therapeutic agents due to their desirable features such as excellent biocompatibility, easy accessibility and cost effectiveness. However, the intrinsic targeting capability of FDEVs is unsatisfactory compared to artificial nanoparticles or other source-derived EVs, which calls for efficient surface engineering strategies to equip them with specific ligands. Here we report a general and mild modification method via reduction of disulfide groups to maleimide reactive thiols. Taking milk-derived EVs (mEVs) as a model system, we demonstrated the feasibility for tethering various ligands on the surface without compromising the vesicular structures. Building an ultra-sensitive nano-flow cytometer (nFCM), the heterogeneous nature of the functionalized samples was revealed, and a magnetic separation approach was proposed accordingly to remove the as-observed non-EV particles. The cellular uptake and cytotoxicity experiments provided direct evidence showing an enhanced cell targeting and cargo delivery capability of the ligand conjugated mEVs. In addition, the in vivo imaging further proved the applicability of transferrin conjugation for increased tumor enrichment of mEVs. Collectively, this general and mild ligand conjugation method enables an efficient surface functionalization of FDEVs, which is of vital importance for enhanced targeting delivery.
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http://dx.doi.org/10.1039/d0nr06309fDOI Listing
February 2021

Cerebral venous sinus thrombosis in a young child with acute lymphoblastic leukemia: a case report and literature review.

J Int Med Res 2021 Jan;49(1):300060520986291

Department of Pediatrics Intensive Care Unit, The First Hospital of Jilin University, Changchun, China.

Acute lymphoblastic leukemia (ALL) is a hematological malignancy. There are many risk factors for thrombus development in patients with ALL, and thrombi may develop in different parts of the body. Cerebral venous sinus thrombosis (CVST) is a rare complication of ALL that usually appears during treatment. We present a patient who developed CVST twice, once before diagnosis and once after treatment for ALL. We also reviewed the literature describing ALL and CVST.
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http://dx.doi.org/10.1177/0300060520986291DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7871092PMC
January 2021

Early prediction of live birth for assisted reproductive technology patients: a convenient and practical prediction model.

Sci Rep 2021 01 11;11(1):331. Epub 2021 Jan 11.

Department of Epidemiology and Health Statistics, XiangYa School of Public Health, Central South University, Changsha, 410008, Hunan, China.

Live birth is the most important concern for assisted reproductive technology (ART) patients. Therefore, in the medical reproductive centre, obstetricians often need to answer the following question: "What are the chances that I will have a healthy baby after ART treatment?" To date, our obstetricians have no reference on which to base the answer to this question. Our research aimed to solve this problem by establishing prediction models of live birth for ART patients. Between January 1, 2010, and May 1, 2017, we conducted a retrospective cohort study of women undergoing ART treatment at the Reproductive Medicine Centre, Xiangya Hospital of Central South University, Hunan, China. The birth of at least one live-born baby per initiated cycle or embryo transfer procedure was defined as a live birth, and all other pregnancy outcomes were classified as no live birth. A live birth prediction model was established by stepwise multivariate logistic regression. All eligible subjects were randomly allocated to two groups: group 1 (80% of subjects) for the establishment of the prediction models and group 2 (20% of subjects) for the validation of the established prediction models. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of each prediction model at different cut-off values were calculated. The prediction model of live birth included nine variables. The area under the ROC curve was 0.743 in the validation group. The sensitivity, specificity, PPV, and NPV of the established model ranged from 97.9-24.8%, 7.2-96.3%, 44.8-83.8% and 81.7-62.5%, respectively, at different cut-off values. A stable, reliable, convenient, and satisfactory prediction model for live birth by ART patients was established and validated, and this model could be a useful tool for obstetricians to predict the live rate of ART patients. Meanwhile, it is also a reference for obstetricians to create good conditions for infertility patients in preparation for pregnancy.
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http://dx.doi.org/10.1038/s41598-020-79308-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7801433PMC
January 2021

Efficacy and safety of OM-85 in paediatric recurrent respiratory tract infections which could have a possible protective effect on COVID-19 pandemic: A meta-analysis.

Int J Clin Pract 2021 May 22;75(5):e13981. Epub 2021 Jan 22.

Hospital Infection Management Office, The Hospital of Xinjiang Production and Construction Corps, Wulumuqi, P.R. China.

Introduction: The OM-85 (Broncho-Vaxom) consumption has drawn considerable attention in the prevention of recurrent respiratory tract infections. However, it has been reported that the relationship between OM-85 consumption and recurrent respiratory tract infections is variable. This meta-analysis was performed to evaluate this relationship.

Methods: A systematic literature search up-to May 2020 was performed and 14 studies were detected with 1859 paediatric subjects, of them 890 consumed OM-85. They were reporting relationships between OM-85 consumption and recurrent respiratory tract infections. Odds ratio (OR) or mean differences (MD) with 95% confidence intervals (CIs) was calculated to evaluate the prognostic role of OM-85 consumption and recurrent respiratory tract infections using the dichotomous or continuous method with a random or fixed-effect model.

Results: OM-85 consumption was significantly related to lower frequency of respiratory tract infections (MD, -1.16; 95% CI, -1.66 to -0.65, P < .001); lower total duration of respiratory tract infections (MD, -19.51; 95% CI, -23.00 to -16.01, P < .001); lower incidence of respiratory tract infections (OR, 0.40; 95% CI, 0.21-0.77, P = .006); lower number of antibiotic courses (MD, -1.40; 95% CI, -2.63 to 0.17, P = .03); and lower antibiotic use (OR, 0.38; 95% CI, 0.29-0.52, P < .001). However, OM-85 consumption was not significantly related to adverse event rate (OR, 1.02; 95% CI, 0.52-2.03, P = .94); or to wheezing attacks frequency (MD, -0.25; 95% CI, -0.59 to 0.08, P = .14).

Conclusions: The impact of OM-85 consumption on recurrent respiratory tract infections may have a great effect as a tool to improve subjects' immunity against recurrent respiratory tract infections, which could be helpful in crucial situations, eg, COVID-19 pandemic. OM-85 non-consumers had an independent risk relationship with recurrent respiratory tract infections. This relationship forces us to recommend OM-85 consumption with those with a high risk of recurrent respiratory tract infections to avoid any possible complications.
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http://dx.doi.org/10.1111/ijcp.13981DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7883224PMC
May 2021

Effects of Edaravone on Functional Recovery of a Rat Model with Spinal Cord Injury Through Induced Differentiation of Bone Marrow Mesenchymal Stem Cells into Neuron-Like Cells.

Cell Reprogram 2021 Feb 5;23(1):47-56. Epub 2021 Jan 5.

Department of Anatomy, School of Basic Medical Sciences, Guizhou Medical University, Guiyang, China.

Edaravone can induce differentiation of bone marrow mesenchymal stem cells (BMSCs) into neuron-like cells and replace lost cells by transplanting neuron-like cells to repair spinal cord injury (SCI). In this study, BMSCs were derived from the bone marrow of male Wistar rats (4 weeks old) through density gradient centrifugation (1.073 /mL), and the cell purity of BMSCs was up to 95%. The combined injection of basic fibroblast growth factor and edaravone was conducted to differentiate BMSCs into neuron-like cells. In this study, 120 male Wistar rats were used to establish the model of semitransverse SCI; on the seventh day, neuron-like cells were labeled by BrdU and then injected into the epicenter of the injury of rats. On the 14th day after cell transplantation, the biotin dextran amine (BDA) fluorescent agent was used to track the repair of nerve damage. At 7, 14, 21, and 30 days after SCI, the Basso, Beattie, and Bresnahan (BBB) locomotor scale method was used to measure the functional recovery of hind limbs in rats. Additionally, hematoxylin and eosin (H&E) staining, Nissl staining, immunohistochemistry, transmission electron microscopy (TEM), Western blotting, and Real-time quantitative reverse transcripion PCR (qRT-PCR) were used to observe the regeneration of nerve cells. In the edaravone+BMSC group, behavioral analysis of locomotor function showed that functional recovery was significantly enhanced after transplantation of the cells, BrdU-positive cells could be observed scattered in the injured area and extended to both the head and tail, and the BDA tracer shows that the edaravone+BMSC group emits more fluorescent signals. Additionally, H&E staining, Nissl staining, and immunohistochemistry revealed that the space of spinal cord tissue was attenuated and the neurons were increased. Western blotting and qRT-PCR showed that the expression levels of neuron-specific enolase (NSE), Nestin, and neurofilament 200 (NF) were increased, while the expression of glial fibrillary acidic protein (GFAP) was decreased. TEM showed that cytoplasmic edema was reduced, mitochondrial vacuoles were attenuated, and nuclear chromatin concentration was declined after transplantation of neuron-like cells. Moreover, with the extension of time of edaravone+BMSC transplantation, the structures of mitochondria and endoplasmic reticulum tended to be normal. In summary, the induced differentiation of BMSC transplantation can significantly promote the functional repair of SCI.
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http://dx.doi.org/10.1089/cell.2020.0055DOI Listing
February 2021

DJ-1 Regulates Microglial Polarization Through P62-Mediated TRAF6/IRF5 Signaling in Cerebral Ischemia-Reperfusion.

Front Cell Dev Biol 2020 17;8:593890. Epub 2020 Dec 17.

Department of Pathology, Chongqing Medical University, Chongqing, China.

The polarization of microglia/macrophage, the resident immune cells in the brain, plays an important role in the injury and repair associated with ischemia-reperfusion (I/R). Previous studies have shown that DJ-1 has a protective effect in cerebral I/R. We found that DJ-1 regulates the polarization of microglial cells/macrophages after cerebral I/R and explored the mechanism by which DJ-1 mediates microglial/macrophage polarization in cerebral I/R. Middle cerebral artery occlusion/reperfusion (MCAO/R) and oxygen and glucose deprivation/reoxygenation (OGD/R) models were used to simulate cerebral I/R and , respectively. DJ-1 siRNA and the DJ-1-based polypeptide ND13 were used to produce an effect on DJ-1, and the P62-specific inhibitor XRK3F2 was used to block the effect of P62. Enhancing the expression of DJ-1 induced anti-inflammatory (M2) polarization of microglia/macrophage, and the expression of the anti-inflammatory factors IL-10 and IL-4 increased. Interference with DJ-1 expression induced pro-inflammatory (M1) polarization of microglia/macrophage, and the expression of the proinflammatory factors TNF-α and IL-1β increased. DJ-1 inhibited the expression of P62, impeded the interaction between P62 and TRAF6, and blocked nuclear entry of IRF5. In subsequent experiments, XRK3F2 synergistically promoted the effect of DJ-1 on microglial/macrophage polarization, further attenuating the interaction between P62 and TRAF6.
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http://dx.doi.org/10.3389/fcell.2020.593890DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7773790PMC
December 2020

Outer membrane protein a in Acinetobacter baumannii induces autophagy through mTOR signalling pathways in the lung of SD rats.

Biomed Pharmacother 2021 Mar 31;135:111034. Epub 2020 Dec 31.

College of Life Sciences, Guizhou University, Guiyang 550025, PR China; Institute of Biological Engineering, Guizhou University, Guiyang 550025, PR China. Electronic address:

Outer membrane protein A (OmpA) of Acinetobacter baumannii (A. baumannii) is associated with autophagy, which plays an important role in its pathogenicity. However, its exact pathophysiological role in the process of lung tissue cell autophagy remains unclear. In this study, animal and cell infection models were established by wild A. baumannii strain and An OmpA knockout mutant (OmpA-/- A. baumannii) strain. The expression levels of markers autophagy, histological change, cell viability and protein expression levels of inflammatory cytokines were examined. OmpA-/-A. baumannii was successfully constructed. The capacities of bacterial adhesion and invasion to host cells increased more obviously in the AB group and the AB + Rapa group than in the OmpA-/- AB group and AB + CQ group. The AB group and AB + Rapa group could produce double membrane vacuoles, endoplasmic reticulum dilation, mitochondrial ridge rupture, and mitochondrial vacuoles. OmpA could lead to increased LC3, AMPK, and PAMPK protein release, and decreased levels of P62, mTOR and pmTOR proteins in vivo and in vitro. OmpA caused lung pathology and the release of inflammatory cytokines. A. baumannii OmpA promotes autophagy in lung cells through the mTOR signalling pathway, which increases the bacterial colonization ability in the double-layer membrane autophagosome formed by the autophagy reaction to escape the clearance of bacteria by the host, promote the release of inflammatory mediators and aggravate the damage to the host.
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http://dx.doi.org/10.1016/j.biopha.2020.111034DOI Listing
March 2021

Single-cell transcriptomics identifies limbal stem cell population and cell types mapping its differentiation trajectory in limbal basal epithelium of human cornea.

Ocul Surf 2021 04 1;20:20-32. Epub 2021 Jan 1.

HGSC, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA. Electronic address:

Purpose: This study aimed to uncover novel cell types in heterogenous basal limbus of human cornea for identifying LSC at single cell resolution.

Methods: Single cells of human limbal basal epithelium were isolated from young donor corneas. Single-cell RNA-Sequencing was performed using 10x Genomics platform, followed by clustering cell types through the graph-based visualization method UMAP and unbiased computational informatic analysis. Tissue RNA in situ hybridization with RNAscope, immunofluorescent staining and multiple functional assays were performed using human corneas and limbal epithelial culture models.

Results: Single-cell transcriptomics of 16,360 limbal basal cells revealed 12 cell clusters belonging to three lineages. A smallest cluster (0.4% of total cells) was identified as LSCs based on their quiescent and undifferentiated states with enriched marker genes for putative epithelial stem cells. TSPAN7 and SOX17 are discovered and validated as new LSC markers based on their exclusive expression pattern and spatial localization in limbal basal epithelium by RNAscope and immunostaining, and functional role in cell growth and tissue regeneration models with RNA interference in cultures. Interestingly, five cell types/states mapping a developmental trajectory of LSC from quiescence to proliferation and differentiation are uncovered by Monocle3 and CytoTRACE pseudotime analysis. The transcription factor networks linking novel signaling pathways are revealed to maintain LSC stemness.

Conclusions: This human corneal scRNA-Seq identifies the LSC population and uncovers novel cell types mapping the differentiation trajectory in heterogenous limbal basal epithelium. The findings provide insight into LSC concept and lay the foundation for understanding the corneal homeostasis and diseases.
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http://dx.doi.org/10.1016/j.jtos.2020.12.004DOI Listing
April 2021

Identifying rare variants for quantitative traits in extreme samples of population via Kullback-Leibler distance.

BMC Genet 2020 11 24;21(1):130. Epub 2020 Nov 24.

School of Mathematics and Computational Science, Huaihua University, Huaihua, Hunan, 418008, People's Republic of China.

Background: The rapid development of sequencing technology and simultaneously the availability of large quantities of sequence data has facilitated the identification of rare variant associated with quantitative traits. However, existing statistical methods depend on certain assumptions and thus lacking uniform power. The present study focuses on mapping rare variant associated with quantitative traits.

Results: In the present study, we proposed a two-stage strategy to identify rare variant of quantitative traits using phenotype extreme selection design and Kullback-Leibler distance, where the first stage was association analysis and the second stage was fine mapping. We presented a statistic and a linkage disequilibrium measure for the first stage and the second stage, respectively. Theory analysis and simulation study showed that (1) the power of the proposed statistic for association analysis increased with the stringency of the sample selection and was affected slightly by non-causal variants and opposite effect variants, (2) the statistic here achieved higher power than three commonly used methods, and (3) the linkage disequilibrium measure for fine mapping was independent of the frequencies of non-causal variants and simply dependent on the frequencies of causal variants.

Conclusions: We conclude that the two-stage strategy here can be used effectively to mapping rare variant associated with quantitative traits.
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http://dx.doi.org/10.1186/s12863-020-00951-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7687851PMC
November 2020

The Use of Continuous Blood Purification for the Treatment of Malignant Hyperthermia in an Infant.

J Cardiothorac Vasc Anesth 2020 Nov 2. Epub 2020 Nov 2.

Department of Pediatric Intensive Care Unit, First Hospital of Jilin University, Jilin, China. Electronic address:

Background: Malignant hyperthermia (MH) is a rare and potentially life-threatening pharmacogenetic disorder encountered during general anesthesia, with the incidence higher in children than in adults. Dantrolene is the specific antagonist of MH, but it is not readily available in China, thus developing alternative treatment protocols is of great practical importance.

Case Presentation: Herein, the authors report a two-month-old infant who underwent holmium laser epiglottis retrofitting through a bronchoscope, but developed limb muscular stiffness, tachypnea, tachycardia, and hyperthermia after sevoflurane exposure. After the diagnosis of MH, corresponding supportive treatment was implemented. Because there was no dantrolene available, continuous blood purification and mechanical ventilation were performed. A few days later, the boy recovered without any complications.

Conclusion: Based on the authors' successful clinical practice, the authors consider continuous blood purification as a reliable treatment for MH. But its feasibility still needs to be clarified after multicenter clinical observations.
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http://dx.doi.org/10.1053/j.jvca.2020.10.055DOI Listing
November 2020

Aberrant expression of miR-16, B12 and CD272 in peripheral blood mononuclear cells from patients with active tuberculosis.

Am J Transl Res 2020 15;12(10):6076-6091. Epub 2020 Oct 15.

Dongguan Key Laboratory of Medical Bioactive Molecular Developmental and Translational Research, Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Guangdong Medical University Dongguan 523808, Guangdong, China.

Tuberculosis (TB) immunity is affected by complex immune regulation processes, which involve various immune cells, immune molecules, and cytokines. Here, we evaluated the expression of B12, CD272 and miR-16 in peripheral blood mononuclear cells (PBMC) of patients with active pulmonary tuberculosis. The results showed that monocytes expressing CD272 or B12 were down-regulated in patients with tuberculosis. The expression of B12 and CD272 in T cells and monocytes is related to tuberculosis. In TB patients, the up-regulation of miR-16 was negatively correlated with B12 mRNA expression, miR-16 was mainly expressed in CD14 monocytes, and CD272 mRNA was mainly expressed in CD19 B cells. It is worth noting that the overexpression of miR-16 inhibits the expression of CD272 and B12 in monocytes of TB patients. After BCG stimulation, miR-16 expression of CD14 monocytes was up-regulated and B12 mRNA and CD272 mRNA expressions were down-regulated in TB patients. Finally, we found that miR-16 may participate in the TB immunization process through targeted regulation of B12 expression. These studies indicate that the expression of B12, CD272 and miR-16 in PBMC may be related to tuberculosis.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7653578PMC
October 2020

Adsorption and photocatalytic activity of Cu-doped cellulose nanofibers/nano-titanium dioxide for different types of dyes.

Water Sci Technol 2020 Oct;82(8):1665-1675

College of Textiles and Clothing, Qingdao University, Qingdao 266071, China E-mail: Center of Shandong province for eco-textile collaborative innovation, Qingdao 266071, China.

Cu-doped cellulose nanofibers/nano-titanium dioxide (Cu-TOCN/TiO) photocatalysts were prepared by the hydrolysis-precipitation method using TiCl as the source of titanium and cellulose nanofibers suspension as a reaction medium. The prepared photocatalysts were used to decolorize organic dyes (reactive brilliant red K-2BP and cationic red X-GRL) efficiently under the synergistic effect of simultaneous adsorption and photocatalysis. The combination of TOCN inhibited the growth of TiO crystals, reduced agglomeration and increased the specific surface area. When compared with TiO, TOCN/TiO improved the decolorization efficiency of the two dyes by 14.82% and 22.87%, respectively, under UV-light irradiation. The absorption edge exhibited red-shift from 380 to 410 nm after Cu doping. An excellent photocatalytic activity was recorded by 0.5 mol % Cu-TOCN/TiO and the decolorization efficiency of the two dyes was further improved by 34.76% and 10.44% respectively, compared with no Cu doping. After 2 hours of irradiation, the decolorization efficiency reached 96.57% and 99.73% respectively, while under dark conditions, it was 47.64% and 91.56% for the two dyes. The degradation mechanism of the dyes was verified as the destruction of the azo chromophore and benzene ring. This work provides a potential method for the development of a novel adsorptive photocatalyst with excellent recyclability.
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http://dx.doi.org/10.2166/wst.2020.434DOI Listing
October 2020

Single-Cell Transcriptome Analysis Reveals Dynamic Cell Populations and Differential Gene Expression Patterns in Control and Aneurysmal Human Aortic Tissue.

Circulation 2020 Oct 5;142(14):1374-1388. Epub 2020 Oct 5.

Division of Cardiothoracic Surgery, Michael E. DeBakey Department of Surgery (Yanming Li, P.R., A. Dawson, H.G.V., W.A., C.Z., W.L., J.S.C., Y.H.S., S.A.L.), Baylor College of Medicine, Houston, TX.

Background: Ascending thoracic aortic aneurysm (ATAA) is caused by the progressive weakening and dilatation of the aortic wall and can lead to aortic dissection, rupture, and other life-threatening complications. To improve our understanding of ATAA pathogenesis, we aimed to comprehensively characterize the cellular composition of the ascending aortic wall and to identify molecular alterations in each cell population of human ATAA tissues.

Methods: We performed single-cell RNA sequencing analysis of ascending aortic tissues from 11 study participants, including 8 patients with ATAA (4 women and 4 men) and 3 control subjects (2 women and 1 man). Cells extracted from aortic tissue were analyzed and categorized with single-cell RNA sequencing data to perform cluster identification. ATAA-related changes were then examined by comparing the proportions of each cell type and the gene expression profiles between ATAA and control tissues. We also examined which genes may be critical for ATAA by performing the integrative analysis of our single-cell RNA sequencing data with publicly available data from genome-wide association studies.

Results: We identified 11 major cell types in human ascending aortic tissue; the high-resolution reclustering of these cells further divided them into 40 subtypes. Multiple subtypes were observed for smooth muscle cells, macrophages, and T lymphocytes, suggesting that these cells have multiple functional populations in the aortic wall. In general, ATAA tissues had fewer nonimmune cells and more immune cells, especially T lymphocytes, than control tissues did. Differential gene expression data suggested the presence of extensive mitochondrial dysfunction in ATAA tissues. In addition, integrative analysis of our single-cell RNA sequencing data with public genome-wide association study data and promoter capture Hi-C data suggested that the erythroblast transformation-specific related gene() exerts an important role in maintaining normal aortic wall function.

Conclusions: Our study provides a comprehensive evaluation of the cellular composition of the ascending aortic wall and reveals how the gene expression landscape is altered in human ATAA tissue. The information from this study makes important contributions to our understanding of ATAA formation and progression.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.120.046528DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7539140PMC
October 2020
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