Publications by authors named "Haoyu Wang"

209 Publications

neoDL: a novel neoantigen intrinsic feature-based deep learning model identifies IDH wild-type glioblastomas with the longest survival.

BMC Bioinformatics 2021 Jul 23;22(1):382. Epub 2021 Jul 23.

Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, Beijing Advanced Innovation Centre for Biomedical Engineering, School of Engineering Medicine, School of Biological Science and Medical Engineering, Beihang University, No.37 Xueyuan Road, Haidian District, Beijing, 100083, People's Republic of China.

Background: Neoantigen based personalized immune therapies achieve promising results in melanoma and lung cancer, but few neoantigen based models perform well in IDH wild-type GBM, and the association between neoantigen intrinsic features and prognosis remain unclear in IDH wild-type GBM. We presented a novel neoantigen intrinsic feature-based deep learning model (neoDL) to stratify IDH wild-type GBMs into subgroups with different survivals.

Results: We first derived intrinsic features for each neoantigen associated with survival, followed by applying neoDL in TCGA data cohort(AUC = 0.988, p value < 0.0001). Leave one out cross validation (LOOCV) in TCGA demonstrated that neoDL successfully classified IDH wild-type GBMs into different prognostic subgroups, which was further validated in an independent data cohort from Asian population. Long-term survival IDH wild-type GBMs identified by neoDL were found characterized by 12 protective neoantigen intrinsic features and enriched in development and cell cycle.

Conclusions: The model can be therapeutically exploited to identify IDH wild-type GBM with good prognosis who will most likely benefit from neoantigen based personalized immunetherapy. Furthermore, the prognostic intrinsic features of the neoantigens inferred from this study can be used for identifying neoantigens with high potentials of immunogenicity.
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http://dx.doi.org/10.1186/s12859-021-04301-6DOI Listing
July 2021

Tribo-Induced Color Tuner toward Smart Lighting and Self-Powered Wireless Sensing.

Adv Sci (Weinh) 2021 Jun 2;8(12):2004970. Epub 2021 May 2.

Department of Mechanical and Automation Engineering The Chinese University of Hong Kong Shatin, N.T. Hong Kong China.

The color-tuning capability of solid-state lighting (SSL) systems are highly demanded for smart lighting according to the environmental conditions, as well as wireless sensing of the environmental information. In the meanwhile, state-of-the-art triboelectric nanogenerator (TENG)-based sensing systems rely on bulky and expensive devices, which require cable connections and additional power consumptions. This work aims at solving these challenges, through developing a tribo-induced color tuner that can be integrated into the vastly distributed commercial SSL system. This tribo-induced color tuner includes a concentric color conversion plate consisting of (Sr,Ca)AlSiN:Eu phosphor and TiO, a tribo-induced liquid lens, and a rotary freestanding sliding TENG. The color oscillation between purple and pink is achieved upon the tribo-charging by the TENG, which reveals the input mechanical motion signals. The signal can be conveniently sent by everywhere-existed lamps and processed by everyone-owned smartphone cameras or closed-circuit televisions. Through this approach, the function of wireless sensing is achieved without the need of preamplification, with no additional power supply required, as demonstrated for wireless sensing of the rotation speed. The smart lighting for underwater photographing is also demonstrated by the color-tunable SSL system with the best imaging quality achieved.
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http://dx.doi.org/10.1002/advs.202004970DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8224429PMC
June 2021

Effects of continuous nursing based on WeChat platform on the functional recovery and quality of life in elderly patients after total hip arthroplasty.

Am J Transl Res 2021 15;13(5):5623-5628. Epub 2021 May 15.

The First Department of Orthopedics, The Second Affiliated Hospital of Xi'an Jiaotong University Xi'an, Shaanxi Province, China.

Objective: To investigate the effects of continuous nursing (CN) based on WeChat platform on the functional recovery and quality of life (QOL) in elderly patients after total hip arthroplasty (THA).

Methods: A prospective study was performed on selected 124 patients undergoing THA in Orthopedics and Traumatology Department. According to the random number method, the patients were divided into control group (CN, n=62) and observation group (CN based on WeChat platform, n=62). Hip joint function before and after intervention, postoperative complications and QOL were observed.

Results: Harris hip scores and QOL scores 3 and 6 months after intervention were higher in both groups than those before intervention, and the improvement was better in the observation group (all P<0.05). The excellent-effective rate of hip joint function improvement 6 months after intervention in the observation group was higher than that in the control group (P<0.05). The incidence of complications and readmission rate in the observation group were significantly lower than those in the control group (both P<0.05).

Conclusion: CN based on WeChat platform can improve the hip joint function, reduce complications and postoperative readmission rate, and ameliorate QOL of patients after THA.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8205822PMC
May 2021

The effect of continuing care on postoperative life quality and long-term functional recovery in elderly patients with hip fracture.

Am J Transl Res 2021 15;13(5):5512-5518. Epub 2021 May 15.

The First Department of Orthopedics, The Second Affiliated Hospital of Xi'an Jiaotong University Xi'an, Shaanxi Province, China.

Objective: To apply continuing care to elderly patients with hip fracture undergoing surgery, and to explore its impact on life quality and long-term functional recovery.

Methods: This prospective study was performed in 136 elderly hip fracture patients, who were admitted to the department of orthopedics of our hospital for surgical treatment. According to the random number table, these patients were assigned to the control group and the experimental group (68 patients in each group). Patients in the control group received routine care and guidance for discharge, while those in the experimental group received routine care and continuing care for discharge. The hip joint function (Harris hip score), quality of life (MOS 36-item short form health survey score), compliance to functional exercise, anxiety (self-rating anxiety scale score), depression (self-rating depression scale score), postoperative complications (infection, joint stiffness, and deep vein thrombosis), and satisfaction in care after discharge were compared between the two groups.

Results: Compared with the control group, the compliance to functional exercise (rates of compliance to exercise time, exercise action, and exercise site), Harris hip score at 3 months after discharge, MOS 36-item short form health survey scores in physical functioning, general health, social functioning, role-emotional, and mental health, and satisfaction in care outside the hospital in the experimental group were all increased (p<0.05). Meanwhile, self-rating anxiety scale score, self-rating depression scale score, and the incidence of complications like lung infection, joint stiffness, and deep vein thrombosis in the experimental group were lower than those in the control group (p<0.05).

Conclusion: The effect of continuous care on life quality and long-term functional recovery of elderly patients with hip fractures is significant. Significant reduction of anxiety, depression, and complications is beneficial to improve satisfaction of care.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8205694PMC
May 2021

Beyond the virus: a first look at coronavirus-themed Android malware.

Empir Softw Eng 2021 12;26(4):82. Epub 2021 Jun 12.

Beijing University of Posts and Telecommunications, Beijing, China.

As the COVID-19 pandemic emerged in early 2020, a number of malicious actors have started capitalizing the topic. Although a few media reports mentioned the existence of coronavirus-themed mobile malware, the research community lacks the understanding of the landscape of the coronavirus-themed mobile malware. In this paper, we present the first systematic study of coronavirus-themed Android malware. We first make efforts to create a daily growing COVID-19 themed mobile app dataset, which contains 4,322 COVID-19 themed apk samples (2,500 unique apps) and 611 potential malware samples (370 unique malicious apps) by the time of mid-November, 2020. We then present an analysis of them from multiple perspectives including trends and statistics, installation methods, malicious behaviors and malicious actors behind them. We observe that the COVID-19 themed apps as well as malicious ones began to flourish almost as soon as the pandemic broke out worldwide. Most malicious apps are camouflaged as benign apps using the same app identifiers (e.g., app name, package name and app icon). Their main purposes are either stealing users' private information or making profit by using tricks like phishing and extortion. Furthermore, only a quarter of the COVID-19 malware creators are habitual developers who have been active for a long time, while 75% of them are newcomers in this pandemic. The malicious developers are mainly located in the US, mostly targeting countries including English-speaking countries, China, Arabic countries and Europe. To facilitate future research, we have publicly released all the well-labelled COVID-19 themed apps (and malware) to the research community. Till now, over 30 research institutes around the world have requested our dataset for COVID-19 themed research.
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http://dx.doi.org/10.1007/s10664-021-09974-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8196937PMC
June 2021

A high-resolution cell atlas of the domestic pig lung and an online platform for exploring lung single-cell data.

J Genet Genomics 2021 Apr 30. Epub 2021 Apr 30.

Institute of Pediatrics, Department of Pediatric Surgery, Shenzhen Children's Hospital, Shenzhen 518038, China; Department of Pediatrics, The Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China. Electronic address:

The genetically engineered pig is regarded as an optimal source of human organs for transplantation and an excellent model for human disease research, given its comparable physiology to human beings. A myriad of single-cell RNA sequencing (scRNA-seq) data on humans has been reported, but such data on pigs are scarce. Here, we apply scRNA-seq technology to study the cellular heterogeneity of 3-month-old pig lungs, generating the single-cell atlas of 13,580 cells covering 16 major cell types. Based on these data, we systematically characterize the similarities and differences in the cellular cross-talk and expression patterns of respiratory virus receptors in each cell type of pig lungs compared with human lungs. Furthermore, we analyze pig lung xenotransplantation barriers and reported the cell-type expression patterns of 10 genes associated with pig-to-human immunobiological incompatibility and coagulation dysregulation. We also investigate the conserved transcription factors (TFs) and their candidate target genes and constructed five conserved TF regulatory networks in the main cell types shared by pig and human lungs. Finally, we present a comprehensive and openly accessible online platform, ScdbLung. Our scRNA-seq atlas of the domestic pig lung and ScdbLung database can guide pig lung research and clinical applicability.
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http://dx.doi.org/10.1016/j.jgg.2021.03.012DOI Listing
April 2021

Reference Intervals for Serum Thyroid-Stimulating Hormone Based on a Recent Nationwide Cross-Sectional Study and Meta-Analysis.

Front Endocrinol (Lausanne) 2021 1;12:660277. Epub 2021 Jun 1.

Department of Endocrinology and Metabolism and the institute of Endocrinology, The NHC Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, The First Hospital of China Medical University, Shenyang, China.

Objective: The aim of our study was to compare the reference intervals (RIs) [median (2.5-97.5 percentiles)] for thyroid-stimulating hormone (TSH) between subgroups stratified by ethnicity and iodine status in a global context.

Design And Methods: Primary data were derived from a recently published cross-sectional study in mainland China. Secondary data were obtained from online databases. The RIs for TSH were calculated in the reference population according to the National Academy of Clinical Biochemistry (NACB) standard and in the disease-free population. A meta-analysis of ethnicity- and iodine status-specific TSH RIs was performed.

Results: The primary data showed that the TSH RI (mU/L) in the disease-free population was 2.33 (0.67, 7.87), which is wider than the published RI [2.28 (0.74, 7.04)] in the reference population. The meta-analysis showed that whether in the reference or disease-free population, the RIs in Yellows were much higher than those in Caucasians. In the reference population, the median and 2.5 percentile in the iodine-sufficient subgroup were both lower than the iodine-deficient or more-than-adequate subgroup, while the 97.5 percentile showed a positive trend with increasing sufficiency of iodine. However, in the disease-free population, the iodine-sufficient subgroup had a lower median and 97.5 percentile but higher 2.5 percentile than the iodine-deficient subgroup.

Conclusion: Yellows have a higher TSH RI than Caucasians. In the reference population, both the median and 2.5 percentile TSH in the iodine-sufficient population were the lowest among the different iodine status subgroups, while the 97.5 percentile of TSH showed an upward trend with increasing iodine sufficiency.
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http://dx.doi.org/10.3389/fendo.2021.660277DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8204855PMC
June 2021

Mechanism of Lentinan Intestinal Absorption: Clathrin-Mediated Endocytosis and Macropinocytosis.

J Agric Food Chem 2021 Jul 16;69(26):7344-7352. Epub 2021 Jun 16.

Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030 Wuhan, China.

Lentinan (LNT), a typical triple helix β-glucan extracted from , has been widely used as a functional food and an orally administered drug. However, its oral pharmacokinetics has been rarely reported. The aim of this work is to systematically study the pharmacokinetics and intestinal absorption mechanism of LNT after oral administration. Radioactive 99m-technetium (Tc) was introduced to label LNT to determine the plasma concentration, tissue distribution, and excretion of the β-glucan in rats after oral administration. The results confirmed the absorption of LNT, with the maximal plasma concentration reached at 1 h. 5-([4,6-Dichlorotriazin-2-yl]amino)fluorescein (DTAF) was used to label LNT to explore the absorption mechanism of LNT, utilizing both a Ussing chamber and a monolayer of Caco-2 cells. These transport assays showed that LNT could penetrate through the intestine and epithelial monolayer, which was mediated by macropinocytosis and clathrin-mediated endocytosis. These findings provide a pharmacokinetic reference for LNT and help provide a greater understanding of the absorption of β-glucans in general.
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http://dx.doi.org/10.1021/acs.jafc.1c00349DOI Listing
July 2021

Identification of Histone Modifications Reveals a Role of H2b Monoubiquitination in Transcriptional Regulation of in .

Int J Biol Sci 2021 11;17(8):2009-2020. Epub 2021 May 11.

Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan 430072, China.

Gonadal trans-differentiation from ovary to testis occurs in a same individual, suggesting a role of epigenetic regulation. However, histone modifications concerning the sex reversal process remain elusive. We analyzed histone modifications using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Chromatin immunoprecipitation followed by sequencing (ChIP-seq) technology was used to test chromatin immunoprecipitation of gonads. Western blot analysis was performed to analyze protein expression. Immunofluorescence analysis was conducted to localize proteins in gonadal tissues. Here, we report a developmental atlas of histone modifications in the gonadal differentiation, including acetylation, methylation, and ubiquitination. We provided a detail distribution map of these modification sites including novel histone modifications along histones H2a, H2b, H3, and H4, and revealed their relationship with types of gonadal differentiation. We then determined a testis-enriched histone modification site, H2b monoubiquitination at K120, and its association with spermatogenesis. ChIP-seq demonstrated that the modification was highly enriched in the male sex-determining gene (doublesex and mab-3 related transcription factor 1), in particular, in its exon regions, suggesting its role in transcriptional regulation of in testis. Together, these data not only provide a new resource for epigenetic study in gonadal development, but also define an association of histone modifications with gonadal differentiation from ovary to testis.
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http://dx.doi.org/10.7150/ijbs.59347DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8193266PMC
May 2021

Acute effects of 2.856 GHz and 1.5 GHz microwaves on spatial memory abilities and CREB-related pathways.

Sci Rep 2021 Jun 11;11(1):12348. Epub 2021 Jun 11.

Department of Experimental Pathology, Beijing Institute of Radiation Medicine, Beijing, People's Republic of China.

This study aimed to evaluate the acute effects of 2.856 GHz and 1.5 GHz microwaves on spatial memory and cAMP response element binding (CREB)-related pathways. A total of 120 male Wistar rats were divided into four groups: a control group (C); 2.856 GHz microwave exposure group (S group); 1.5 GHz microwave exposure group (L group); and 2.856 and 1.5 GHz cumulative exposure group (SL group). Decreases in spatial memory abilities, changes in EEG, structural injuries, and the downregulation of phosphorylated-Ak strain transforming (p-AKT), phosphorylated-calcium/calmodulin-dependent protein kinase II (p-CaMKII), phosphorylated extracellular signal regulated kinase (p-ERK) and p-CREB was observed 6 h after microwave exposure. Significant differences in the expression of p-CaMKII were found between the S and L groups. The power amplitudes of the EEG waves (θ, δ), levels of structural injuries and the expression of p-AKT, p-CaMK II, p-CREB, and p-ERK1/2 were significantly different in the S and L groups compared to the SL group. Interaction effects between the 2.856 and 1.5 GHz microwaves were found in the EEG and p-CREB changes. Our findings indicated that 2.856 GHz and 1.5 GHz microwave exposure induced a decline in spatial memory, which might be related to p-AKT, p-CaMK II, p-CREB and p-ERK1/2.
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http://dx.doi.org/10.1038/s41598-021-91622-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8196025PMC
June 2021

Enzymatically synthesized α-galactooligosaccharides attenuate metabolic syndrome in high-fat diet induced mice in association with the modulation of gut microbiota.

Food Funct 2021 Jun;12(11):4960-4971

College of Basic Medicine, Qingdao University, Qingdao, Shandong, China.

The composition and structure of gut microbiota plays an important role in obesity induced by a high-fat diet (HFD) and related metabolic syndrome (MetS). Previous studies have shown that galacto-oligosaccharides (GOSs) have an effective anti-obesity effect. In this study, we aimed to investigate the effect of enzymatically synthesized α-galacto-oligosaccharides (ES-α-GOSs) on MetS and gut microbiota dysbiosis in HFD-fed mice, and to further investigate whether the attenuation of MetS is associated with the modulation of gut microbiota. Our results indicated that ES-α-GOS could notably ameliorate obesity-related MetS, including hyperlipidemia, insulin resistance and mild inflammation. The subsequent analysis of gut microbiota further showed that ES-α-GOS supplements can significantly modulate the overall composition of the gut microbiota and reverse the gut microbiota disorder caused by HFD feeding. Moreover, Spearman correlation analysis showed that 40 key bacteria reversed by ES-α-GOS were highly associated with metabolic parameters. These results suggested that ES-α-GOSs could serve as a potential candidate for preventing obesity-induced MetS in association with the modulation of gut microbiota.
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http://dx.doi.org/10.1039/d0fo03113eDOI Listing
June 2021

A targeted ancestry informative InDels panel on capillary electrophoresis for ancestry inference in Asian populations.

Electrophoresis 2021 Jun 3. Epub 2021 Jun 3.

West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, P. R. China.

CE is the primary methodology used in forensic DNA typing. Alleles of commonly used types of genetic markers could be separated and detected via CE based on dye color and migration time. Insertion/deletion (InDel) is an ideal genetic marker for forensic DNA analysis due to their abundance in the human genome, low mutation rate, availability of their allele types via CE, and elimination of stutter peaks. Moreover, InDels could be used as ancestry informative markers since allele frequencies of InDels is different among geographically separated populations. Several ancestry informative insertion/deletion panels have been established based on CE platform to achieve the intercontinental populations distinction. However, improvements to differentiate intracontinental populations is few. In this study, 21 InDels with fixation index (F ) > 0.15 were selected and assembled into one ancestry informative insertion/deletion panel. Using well-designed primers, those 21 InDels could be amplified successfully and genotyped on the CE platform accurately and completely. The panel showed a large F distance distinction among the ten Asian populations. Using clustering analysis, ten Asian populations were classified into three subgroups: East Asian, Southeast Asian, and South Asian subgroups. To evaluate the panel's capability in ancestry inference, a validation experiment was undertaken with 319 individuals from four geographically separated populations in China. Four Chinese populations were classified into different ancestry subgroups and 81.8% test individuals' ancestry could be inferred correctly. Our result showed that development of high ancestry informative InDels panel based on CE platform is a potential for individual ancestry inference among intracontinental populations.
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http://dx.doi.org/10.1002/elps.202100016DOI Listing
June 2021

Large-scale 3D imaging of mouse cochlea using serial block-face scanning electron microscopy.

STAR Protoc 2021 Jun 4;2(2):100515. Epub 2021 May 4.

Shanghai Institute of Precision Medicine, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

This protocol describes how to prepare intact mouse cochleae for serial block-face scanning electron microscopy (SBEM). The detailed workflow includes cochlea fixation, staining, resin embedding, X-ray microscopy-guided trimming and SBEM data acquisition. This protocol allows large-scale, nanometer-resolution three-dimensional imaging of subcellular structures in a targeted tonotopic range of the cochlea and enables fast volumetric scan at submicron resolution using a compact X-ray microscope. For complete details on the use and execution of this protocol, please refer to Hua et al. (2021).
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http://dx.doi.org/10.1016/j.xpro.2021.100515DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8121772PMC
June 2021

A new mechanism of obeticholic acid on NASH treatment by inhibiting NLRP3 inflammasome activation in macrophage.

Metabolism 2021 Jul 10;120:154797. Epub 2021 May 10.

Laboratory of Anti-inflammation, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, PR China. Electronic address:

Objective: Obeticholic acid (OCA) has been proved to play potential therapeutic effect on nonalcoholic steatohepatitis (NASH). Up to now, the study of OCA on NLRP3 inflammasome activation in macrophage is still blank and merits great attention. Here, we aimed to better characterize the role and mechanism of OCA on NASH treatment focusing on NLRP3 inflammasome activation in macrophages.

Methods: The effects of OCA on inflammasome activation were investigated in BMDM, Kupffer cell, BMDC and LX2 cell. Preconditioned media from BMDM culture was used to treat primary hepatocytes to explore the effects of macrophage NLRP3 inflammasome activation on the function of hepatocytes. In vivo, high fat diet plus CCl (DIO + CCl) induced murine NASH model and choline-deficient and amino acid-defined (CDA) diet-induced NASH mice were used to verify the inhibitory effect of OCA on inflammasome activation in liver macrophages and recapitulate its protective role on NASH progressing. To clear up the effect of OCA on macrophage is FXR dependent or not, FXR siRNA was introduced into BMDMs.

Results: OCA blockaded NLRP3 inflammasome in BMDMs by impacting on the activation stage and disrupting ASC oligomerization. Preconditioned supernatant from LPS + ATP treated BMDMs increased mRNA expression of lipogenic enzymes and lipid content, whereas preconditioned supernatant from OCA treated BMDM blocked these effects in both normal and the FXR knockdown hepatocytes. In DIO + CCl mice, the population of inflammatory myeloid lineage cells in livers was decreased upon OCA treatment. Accordingly, the level of IL-1β and IL-18 in liver, the hepatic expression of ASC, pro-caspase-1 and active caspase-1, the expression of caspase 1 p20 in liver macrophages were also reduced. Similar results were obtained in CDA diet-fed mice. Furthermore, OCA maintained the inhibition on NLRP3 inflammasome activation in FXR knockdown BMDMs, suggesting FXR could be dispensable in this effect.

Conclusions: This finding brings up a new mechanism of OCA on NASH treatment, suggested by direct inhibition on NLRP3 inflammasome activation in macrophage, further suppression on inflammasome activation-elicited hepatic lipid accumulation, and contributing to the amelioration of NASH.
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http://dx.doi.org/10.1016/j.metabol.2021.154797DOI Listing
July 2021

Effects of 1.5 and 4.3 GHz microwave radiation on cognitive function and hippocampal tissue structure in Wistar rats.

Sci Rep 2021 May 12;11(1):10061. Epub 2021 May 12.

Department of Experimental Pathology, Beijing Institute of Radiation Medicine, Beijing, 100850, China.

Previous studies have shown that single-frequency microwave radiation can lead to cognitive decline in rats. However, few studies have focused on the combined effects of irradiation with different frequencies of microwaves. Our research aimed to investigate the effects of 1.5 GHz and 4.3 GHz microwave radiation, singly and in combination, on cognitive function and hippocampal tissue structure in rats. A total of 140 male Wistar rats were randomly divided into 4 groups: the S group (sham radiation group), L10 group (10 mW/cm 1.5 GHz group), C10 group (10 mW/cm 4.3 GHz band group) and LC10 group (10 mW/cm 1.5 and 4.3 GHz multi-frequency radiation group). For 1-28 days after microwave radiation, we analyzed the average escape latency for the Morris water maze task, electroencephalograms, change in hippocampal tissue structure and ultrastructure, content of the Nissl body in the hippocampus, and activities of lactate dehydrogenase and succinate dehydrogenase. Compared to the S group, all exposure groups showed varying degrees of learning and memory decline and hippocampal structural damage. The results showed that 1.5 GHz and 4.3 GHz microwave radiation was able to induce cognitive impairment and hippocampal tissue damage in rats and combined radiation with both frequencies caused more serious injuries, but none of these damaging effects varied with microwave frequency.
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http://dx.doi.org/10.1038/s41598-021-89348-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8115682PMC
May 2021

A single-cell atlas of mouse olfactory bulb chromatin accessibility.

J Genet Genomics 2021 Feb 17;48(2):147-162. Epub 2021 Mar 17.

Shenzhen Children's Hospital, Shenzhen 518083, China; Zunyi Medical University, Zunyi, Guizhou 563099, China; China Medical University, Shenyang, Liaoning 110122, China. Electronic address:

Olfaction, the sense of smell, is a fundamental trait crucial to many species. The olfactory bulb (OB) plays pivotal roles in processing and transmitting odor information from the environment to the brain. The cellular heterogeneity of the mouse OB has been studied using single-cell RNA sequencing. However, the epigenetic landscape of the mOB remains mostly unexplored. Herein, we apply single-cell assay for transposase-accessible chromatin sequencing to profile the genome-wide chromatin accessibility of 9,549 single cells from the mOB. Based on single-cell epigenetic signatures, mOB cells are classified into 21 clusters corresponding to 11 cell types. We identify distinct sets of putative regulatory elements specific to each cell cluster from which putative target genes and enriched potential functions are inferred. In addition, the transcription factor motifs enriched in each cell cluster are determined to indicate the developmental fate of each cell lineage. Our study provides a valuable epigenetic data set for the mOB at single-cell resolution, and the results can enhance our understanding of regulatory circuits and the therapeutic capacity of the OB at the single-cell level.
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http://dx.doi.org/10.1016/j.jgg.2021.02.007DOI Listing
February 2021

Systemic acitretin in the management of periocular squamous cell carcinoma.

BMJ Case Rep 2021 Apr 21;14(4). Epub 2021 Apr 21.

Ophthalmology Department, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK.

We report a case of periocular squamous cell carcinoma invading the anterior orbit that significantly reduced in size and regressed from invasive to in situ following treatment with oral acitretin, a second-generation retinoid. The residual in situ disease was then successfully treated with cryotherapy and the patient remains in remission 12 months following cessation of systemic acitretin.
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http://dx.doi.org/10.1136/bcr-2020-241167DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8061867PMC
April 2021

Contrasting ecological niches lead to great postzygotic ecological isolation: a case of hybridization between carnivorous and herbivorous cyprinid fishes.

Front Zool 2021 Apr 21;18(1):18. Epub 2021 Apr 21.

Key Laboratory of Freshwater Fish Reproduction and Development (Ministry of Education), Key Laboratory of Aquatic Science of Chongqing, School of Life Sciences, Southwest University, Chongqing, 400715, China.

Background: Postzygote isolation is an important part of species isolation, especially for fish, and it can be divided into two aspects: genetic isolation and ecological isolation. With the increase in parental genetic distance, the intensity of genetic isolation between them also increases. Will the increase in parental ecological niche differences also lead to the increase in ecological isolation intensity between them? This question is difficult to answer based on the current literature due to the lack of hybridization cases of contrasting ecological niche parents.

Results: Cyprinid fish parents (Schizothorax wangchiachii and Percocypris pingi) with contrasting ecological niches (herbivorous and carnivorous) and their F1 hybrids were used as research objects. Fish and periphytic algae were selected as food corresponding to different parental resources. The foraging-related traits of these hybrids are generally the same between parents; however, the intermediate foraging traits of hybrids did not result in intermediate foraging performance for parental resources, and these hybrids could hardly forage for parental resources. The poor foraging performance of these hybrids for parental resources was caused not only by the decline in the foraging ability of these hybrids but, more importantly, by the decrease in foraging activity. Interestingly, these hybrids initially showed a high interest in foraging small fishes; however, after the first successful capture, these hybrids had difficulty ingesting fish and spit them out, which led to the subsequent decrease in foraging activity. We designed a series of experiments to explore the mechanism of the fish spitting of these hybrids, excluding the taste and the size of prey, and found that the decrease in their pharyngeal tooth puncture ability may be the reason.

Conclusions: This study was the first to demonstrate that these parents with contrasting ecological niches will produce great postzygotic ecological isolation for parental resources. The poor foraging performance of these hybrids for parental resources is mainly due to the decrease in foraging activity. Interestingly, these hybrids have obvious fish-spitting behaviour, which is a typical example of the incompatibility between intermediate traits and genetic behaviors.
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http://dx.doi.org/10.1186/s12983-021-00401-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8059018PMC
April 2021

Practice of immediate sequential bilateral cataract surgery (ISBCS) since COVID-19: a patient and surgeon survey.

Eye (Lond) 2021 Apr 6. Epub 2021 Apr 6.

Ophthalmology Department, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK.

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http://dx.doi.org/10.1038/s41433-021-01521-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8023778PMC
April 2021

Correction to: Mettl14-mediated m6A modification modulates neuron apoptosis during the repair of spinal cord injury by regulating the transformation from pri-mir-375 to miR-375.

Cell Biosci 2021 Apr 2;11(1):67. Epub 2021 Apr 2.

Key Laboratory of Shanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, 98 XiWu Road, Xi'an, 710004, Shaanxi, China.

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http://dx.doi.org/10.1186/s13578-021-00573-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019178PMC
April 2021

Cytoarchitecture and innervation of the mouse cochlear amplifier revealed by large-scale volume electron microscopy.

J Comp Neurol 2021 Aug 18;529(11):2958-2969. Epub 2021 Mar 18.

Department of Otolaryngology-Head and Neck Surgery, Shanghai Ninth People's Hospital, Shanghai, China.

In mammalian cochlea, sound-induced vibration is amplified by a three-row lattice of Y-shaped microstructures consisting of electromotile outer hair cell and supporting Deiters cell. This highly organized structure is thought to be essential for hearing of low-level sounds. Prior studies reported differences in geometry and synaptic innervation of the outer hair cells between rows, but how these fine features are achieved at subcellular level still remains unclear. Using serial block-face electron microscopy, we acquired few-hundred-micron-sized cytoarchitecture of mouse organ of Corti at nanometer resolution. Structural quantifications were performed on the Y-shapes as well as afferent and efferent projections to outer hair cells (OHCs). Several new features, which support the previously observed inter-row heterogeneity, are described. Our result provides structural bases for the gradient of mechanical properties and diverse centrifugal regulation of OHC rows.
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http://dx.doi.org/10.1002/cne.25137DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8252425PMC
August 2021

Mettl14-mediated m6A modification modulates neuron apoptosis during the repair of spinal cord injury by regulating the transformation from pri-mir-375 to miR-375.

Cell Biosci 2021 Mar 11;11(1):52. Epub 2021 Mar 11.

Key Laboratory of Shanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, 98 XiWu Road, Xi'an, 710004, Shaanxi, China.

Background: Spinal cord injury (SCI) is a disabling disorder, resulting in neurological impairments. This study investigated the mechanism of methyltransferase-like 14 (Mettl14) on apoptosis of spinal cord neurons during SCI repair by mediating pri-microRNA (miR) dependent N6-methyladenosine (m6A) methylation.

Methods: The m6A content in total RNA and Mettl14 levels in spinal cord tissues of SCI rats were detected. Mettl14 expression was intervened in SCI rats to examine motor function, neuron apoptosis, and recovery of neurites. The cell model of SCI was established and intervened with Mettl14. miR-375, related to SCI and positively related to Mettl14, was screened out. The expression of miR-375 and pri-miR-375 after Mettl14 intervention was detected. The expression of pri-miR-375 combined with DiGeorge critical region 8 (DGCR8) and that modified by m6A was detected. Furthermore, the possible downstream gene and pathway of miR-375 were analysed. SCI cell model with Mettl14 intervention was combined with Ras-related dexamethasone-induced 1 (RASD1)/miR-375 intervention to observe the apoptosis.

Results: Mettl14 level and m6A content in spinal cord tissue were significantly increased. After Mettl14 knockdown, the injured motor function was restored and neuron apoptosis was reduced. In vitro, Mettl14 silencing reduced the apoptosis of SCI cells; miR-375 was reduced and pri-miR-375 was increased; miR-375 targeted RASD1. Silencing Mettl14 inactivated the mTOR pathway. The apoptosis in cells treated with silencing Mettl14 + RASD1/miR-375 was inhibited.

Conclusions: Mettl14-mediated m6A modification inhibited RASD1 and induced the apoptosis of spinal cord neurons in SCI by promoting the transformation of pri-miR-375 to mature miR-375.
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http://dx.doi.org/10.1186/s13578-020-00526-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7953660PMC
March 2021

Heme supplementation ameliorates lupus nephritis through rectifying the disorder of splenocytes and alleviating renal inflammation and oxidative damage.

Int Immunopharmacol 2021 May 24;94:107482. Epub 2021 Feb 24.

Laboratory of Anti-inflammation, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China; School of Pharmacy, University of Chinese Academy of Sciences, Beijing, China. Electronic address:

Heme is an important iron-containing porphyrin molecule expressed ubiquitously in organisms. Recently, this endogenous molecule has been widely reported to be involved in the pathogenesis of numerous diseases such as sepsis, atherosclerosis and inflammatory bowel disease. However, the role of heme during systemic lupus erythematosus (SLE) pathogenesis has not been previously evaluated. Herein, we have measured the levels of heme in lupus-prone mice and explored the influence of heme on the pathogenesis of lupus. We revealed that heme levels in serum, kidney and spleen lymphocytes are all negatively associated with the levels of proteinuria in lupus-prone mice. Heme supplementation at 15 mg/kg could significantly ameliorate the syndromes of lupus in MRL/lpr mice, extending lifespan, reducing the level of proteinuria and alleviating splenomegaly and lymphadenopathy. Further study demonstrated that heme replenishment corrected the abnormal compartment of T cell subsets, plasma cells and macrophages in the spleen and alleviates inflammation and oxidative damage in kidney of MRL/lpr mice. Our study well defined heme as a relevant endogenous molecule in the etiology of SLE, as well as a potential therapeutic target for treating this autoimmune disease. Meanwhile, heme replenishment might be a new choice to therapeutically modulate immune homeostasis and prevent SLE.
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http://dx.doi.org/10.1016/j.intimp.2021.107482DOI Listing
May 2021

Green Thermoplastic Vulcanizates Based on Silicone Rubber and Poly(butylene succinate) via In Situ Interfacial Compatibilization.

ACS Omega 2021 Feb 2;6(6):4461-4469. Epub 2021 Feb 2.

Key Laboratory for Rubber Elastomer of Liaoning Province, Shenyang University of Chemical Technology, Shenyang 110142, China.

Presenting a combination of sustainability and environmental friendliness, a new class of green and non-petroleum-based thermoplastic vulcanizates (TPVs) was successfully developed from silica-filled silicone rubber (FSR) and poly(butylene succinate) (PBS) via dynamic vulcanization. The phase morphology, interfacial compatibilization, and microstructural properties of FSR/PBS TPVs were investigated. Notably, a large number of FSR microparticles were observed and were dispersed in the continuous PBS phase, indicating complete phase inversion during the dynamic vulcanization. The fine phase morphology of FSR/PBS TPVs was achieved by a fine phase morphology of the SR/PBS premix, the good interfacial compatibility between the PBS phase and the cross-linked FSR phase, and complete phase inversion. The as-prepared TPVs possessed high tensile strength, good elastic behavior, easy processability, and reprocessability. These novel non-petroleum-based TPVs have potential applications in packagings, biomedical devices, and three-dimensional (3D) printing materials.
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http://dx.doi.org/10.1021/acsomega.0c06036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893803PMC
February 2021

MicroRNA-140-5p is Downregulated in Osteosarcoma and Overexpression of MicroRNA-140-5p Inhibits Cancer Cell Proliferation by Downregulating GLUT-1.

Onco Targets Ther 2021 11;14:995-1002. Epub 2021 Feb 11.

Department of Orthopedics, Dalian Municipal Central Hospital Affiliated of Dalian Medical University, Dalian, 116000, People's Republic of China.

Background: MicroRNA-140-5p plays pivotal role in different types of human malignancies, while its involvement in osteosarcoma is unknown.

Objective: Our study aimed to investigate the functionality of microRNA-140-5p in osteosarcoma.

Methods: Plasma levels of microRNA-140-5p and glucose transporter 1 (GLUT-1) in both osteosarcoma and healthy controls were measured by qRT-PCR and ELISA, respectively. Correlation between plasma levels of microRNA-140-5p and GLUT-1 was analyzed by Pearson correlation coefficient. Correlation between plasma levels of microRNA-140-5p and clinical data of patients with osteosarcoma was analyzed by Chi-square test. MicroRNA-140-5p mimic and GLUT-1 expression vector were transfected into cells of human osteosarcoma cell lines, and the effects on microRNA-140-5p expression, GLUT-1 expression and cell proliferation were analyzed by qRT-PCR, Western-blot and CCK-8 assay, respectively.

Results: Plasma levels of microRNA-140-5p were significantly lower and plasma levels of GLUT-1 were significantly higher in osteosarcoma patients than that in healthy controls. Levels of plasma microRNA-140-5p and GLUT-1 were reversely correlated in osteosarcoma patients. Plasma levels of microRNA-140-5p were correlated with tumor size but not with other clinical data of patients. MicroRNA-140-5p mimic significantly inhibited cancer cell proliferation, while GLUT-1 overexpression significantly promoted cancer cell proliferation. MicroRNA-140-5p mimic significantly downregulated GLUT-1 expression.

Conclusion: GLUT-1 overexpression showed no significant effect on microRNA-140-5p expression but attenuated the inhibitory effects of microRNA-140-5p mimic on cell proliferation. We therefore conclude that microRNA-140-5p is downregulated in osteosarcoma and overexpression of microRNA-140-5p may inhibit cancer cell proliferation by downregulating GLUT-1.
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http://dx.doi.org/10.2147/OTT.S289229DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884943PMC
February 2021

Kallmann Syndrome Due to Heterozygous Mutation in Coexisting With Waardenburg Syndrome Type II: Case Report and Review of Literature.

Front Endocrinol (Lausanne) 2020 1;11:592831. Epub 2021 Feb 1.

Liaoning Provincial Key Laboratory of Endocrine Diseases, Department of Endocrinology and Metabolism, Institute of Endocrinology, The First Hospital, China Medical University, Shenyang, China.

Introduction: Kallmann syndrome (KS) is idiopathic hypogonadotropic hypogonadism with olfactory loss or decline. Waardenburg syndrome type II (WS2) is a clinically and genetically heterogeneous disease, characterized by congenital sensorineural deafness and abnormal pigmentation of the iris, hair, and skin. Recently, mutations in the well-known WS pathogenic gene have been found in some KS patients with deafness, but whether is a co-pathogenic gene of KS and WS remains uncertain. Here, we report a rare case of KS and WS2 co-occurrence due to mutations.

Methods: Detailed histories were collected through questionnaires and physical examination. Blood samples of the patient and his family members were collected after obtaining informed consents. Suspected mutations were amplified and verified by Sanger sequencing after the next generation sequencing of related genes. The raw sequence data were compared to the known gene sequence data in publicly available sequence data bases using Burrows-Wheeler Aligner software (BWA, 0.7.12-r1039).

Results: A 28-year-old male patient sought treatment for hypogonadism and the absence of secondary sexual characteristics. In addition, he showed signs of obesity, hyposmia, sensorineural hearing loss, and blue iris. Magnetic resonance imaging (MRI) of the olfactory bulb showed small bilateral olfactory bulbs and tracts and diaphragma cerebri. MRI of the pituitary gland revealed a flat pituitary gland in the sella. Laboratory examination demonstrated hypogonadotropic hypogonadism, pituitary hypothyroidism, subclinical hypothyroidism, and the presence of insulin resistance with normal blood glucose levels. Sequencing of the SOX10 gene showed a 20 bp insertion in between coding bases 1,179 and 1,180 (c.1179_1180insACTATGGCTCAGCCTTCCCC). This results in a frame-shifting mutation of the 394th amino acid serine in exon4 with the resulting the amino acid sequence of the protein predicted to be TMAQPSP PSPAPSLTTL TISPQDPIMA TRARPLASTR PSPIWGPRSG PSTRPSLTPA PQGPSPTAPH TGSSQYIRHC PGPKGGPVAT TPRPAPAPSL CALFLAHLRP GGGSGGG*.

Conclusion: plays an important role in some critical stages of neural crest cell development and mutation may be a common pathogenic factor for both KS and WS. Therefore, mutation analysis should be considered for KS patients with combined WS clinical manifestations, especially deafness.
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http://dx.doi.org/10.3389/fendo.2020.592831DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7883637PMC
May 2021

A General Supramolecular Approach to Regulate Protein Functions by Cucurbit[7]uril and Unnatural Amino Acid Recognition.

Angew Chem Int Ed Engl 2021 05 12;60(20):11196-11200. Epub 2021 Apr 12.

State Key Laboratory of Natural and Biomimetic Drugs, Department of Molecular and Cellular Pharmacology, Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Haidian District, Beijing, 100191, China.

Regulation of specific protein function is of great importance for both research and therapeutic development. Many small or large molecules have been developed to control specific protein function, but there is a lack of a universal approach to regulate the function of any given protein. We report a general host-guest molecular recognition approach involving modification of the protein functional surfaces with genetically encoded unnatural amino acids bearing guest side chains that can be specifically recognized by cucurbit[7]uril. Using two enzymes and a cytokine as models, we showed that the activity of proteins bearing unnatural amino acid could be turned off by host molecule binding, which blocked its functional binding surface. Protein activity can be switched back by treatment with a competitive guest molecule. Our approach provides a general tool for reversibly regulating protein function through molecular recognition and can be expected to be valuable for studying protein functions.
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http://dx.doi.org/10.1002/anie.202100916DOI Listing
May 2021

Resistance of Soda Residue-Fly Ash Based Geopolymer Mortar to Acid and Sulfate Environments.

Materials (Basel) 2021 Feb 7;14(4). Epub 2021 Feb 7.

School of Civil and Transportation Engineering, Hebei University of Technology, Tianjin 300401, China.

The early mechanical performances of low-calcium fly ash (FFA)-based geopolymer (FFA-GEO) mortar can be enhanced by soda residue (SR). However, the resistance of SR-FFA-GEO mortar to acid or sulfate environments is unclear, owing to the various inorganic calcium salts in SR. The aim of this study was to investigate the long-term mechanical strengths of up to 360 d and evaluate the resistance of SR-FFA-GEO mortar to 5% HCl and 5% NaSO environments through the losses in compressive strength and mass. Scanning Electron Microscopy (SEM), Energy-Dispersive Spectroscopy (EDS) and Fourier Transform Infrared Spectrometer (FTIR) experiments were conducted for the SR-FFA-GEO mortars, both before and after chemical attack, to clarify the attack mechanism. The results show that the resistances of the SR-FFA-GEO mortar with 20% SR (namely M10) to 5% HCl and 5% NaSO environments are superior to those of cement mortar. The environmental HCl reacts with the calcites in SR to produce CaCl, CO and HO to form more pores under HCl attack, and the environmental Na cations from NaSO go into Si-O-Al network structure, to further enhance the strength of mortar under NaSO attack. These results provide the experimental basis for the durability optimization of SR-FFA-GEO mortars.
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http://dx.doi.org/10.3390/ma14040785DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7915557PMC
February 2021

Impact of COVID-19 pandemic on eye cancer care in United Kingdom.

Br J Cancer 2021 04 9;124(8):1357-1360. Epub 2021 Feb 9.

Sheffield Ocular Oncology Service, Royal Hallamshire Hospital, Sheffield, UK.

The COVID-19 pandemic has had an unprecedented impact on the National Health Service in United Kingdom. The UK Ocular Oncology Services evaluated the impact on the adult eye cancer care in the UK. All four adult Ocular Oncology centres participated in a multicentre retrospective review comparing uveal melanoma referral patterns and treatments in a 4-month period during the national lockdown and first wave of the COVID-19 pandemic in 2020 with corresponding periods in previous 2 years. During the national lockdown, referral numbers and confirmed uveal melanoma cases reduced considerably, equalling to ~120 fewer diagnosed uveal melanoma cases compared to previous 2 years. Contrary to the recent trend, increased caseloads of enucleation and stereotactic radiosurgery (p > 0.05), in comparison to fewer proton beam therapy (p < 0.05), were performed. In the 4-month period following lockdown, there was a surge in clinical activities with more advanced diseases (p < 0.05) presenting to the services. As the COVID-19 pandemic continues to mount pressure and reveal its hidden impact on the eye cancer care, it is imperative for the Ocular Oncology Services to plan recovery strategies and innovative ways of working.
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http://dx.doi.org/10.1038/s41416-021-01274-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039025PMC
April 2021

High-throughput screening in postimplantation haploid epiblast stem cells reveals Hs3st3b1 as a modulator for reprogramming.

Stem Cells Transl Med 2021 May 29;10(5):743-755. Epub 2021 Jan 29.

State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin, People's Republic of China.

Epiblast stem cells (EpiSCs) derived from postimplantation epiblast are pluripotent stem cells, epigenetically distinct from embryonic stem cells (ESCs), which are widely used in reprogramming studies. Recent achieved haploid cell lines in mammalian species open a new era for high-throughput genetic screening, due to their homozygous phenotypes. Here, we report the generation of mouse haploid EpiSCs (haEpiSCs) from postimplantation chimeric embryos at embryonic day 6.5 (E6.5). These cells maintain one set of chromosomes, express EpiSC-specific genes, and have potentials to differentiate into three germ layers. We also develop a massive mutagenesis protocol with haEpiSCs, and subsequently perform reprogramming selection using this genome-wide mutation library. Multiple modules related to various pathways are implicated. The validation experiments prove that knockout of Hst3st3b1 (one of the candidates) can promote reprogramming of EpiSCs to the ground state efficiently. Our results open the feasibility of utilizing haEpiSCs to elucidate fundamental biological processes including cell fate alternations.
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http://dx.doi.org/10.1002/sctm.20-0468DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8046116PMC
May 2021
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