Publications by authors named "Lan Feng"

193 Publications

Efficient Correction of a Hypertrophic Cardiomyopathy Mutation by ABEmax-NG.

Circ Res 2021 Sep 16. Epub 2021 Sep 16.

Anzhen Hospital, Capital Medical University, CHINA.

Genetic editing has shown great potential for the treatment of human hereditary disorders via the elimination of mutations in embryos. However, the efficiency and safety of germline gene editing are not well understood. We aimed to examine the preclinical efficacy/safety of embryonic base editing in a mouse model of hypertrophic cardiomyopathy (HCM) using a novel adenine base editor (ABE) platform. Here, we described the use of an ABEmax-NG to directly correct the pathogenic R404Q/+ mutation (Myh6 c.1211C>T) in embryos for a mouse model of HCM, increasing the number of wild-type embryos for in vitro fertilization. Delivery of the ABEmax-NG mRNA to embryos from R404Q/+ HCM mice resulted in 62.5-70.8% correction of the Myh6 c.1211C>T, reducing the level of mutant RNA and eliminating HCM in the post-natal mice as well as their offspring. In addition, the same sgRNA was also used to target an intronic locus (TGG PAM) with an overall editing rate of 86.7%, thus confirming that ABEmax-NG can efficiently edit target loci with different PAMs (NG) and genomic distribution in vivo. Compared with CRISPR/ssODN-mediated correction, ABEmax-NG displayed a much higher correction rate without introducing indels. DNA and RNA off-target analysis did not detect off-target editing in treated embryos and founder mice. In utero injection of adeno-associated virus 9 (AAV9) encoding the ABEmax-NG also resulted in around 25.3% correction of the pathogenic mutation and reduced of mutant RNA, thereby indicating ABEmax-NG has the potential to correct the HCM mutation in vivo. We developed an ABEmax-NG system, which efficiently corrected a pathogenic Myh6 HCM mutation in mouse embryos without off target lesions, thus safely eliminating HCM in derived mice and their progeny.
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http://dx.doi.org/10.1161/CIRCRESAHA.120.318674DOI Listing
September 2021

Prevalence, Characterization, and Pathogenicity of Subspecies Serovar Derby from Yaks in the Aba Tibetan Autonomous Prefecture, China.

Animals (Basel) 2021 Aug 13;11(8). Epub 2021 Aug 13.

Key Laboratory of Bio-Resources and Eco-Environment, Ministry of Education, College of Life Science, Sichuan University, Chengdu 610064, China.

subsp. serovar Derby ( Derby) is one of the numerous non-typhoidal serovars and has been recognized as a food-borne pathogen. In 2019, outbreaks of salmonellosis were reported in 13 yak farms in the Aba Tibetan Autonomous Prefecture, China. A total of 32 salmonella strains were isolated from 162 fecal samples of yaks with diarrhea as well as from drinking water samples. The isolates were subjected to serovar identification, animal experiments, and whole-genome sequencing (WGS) analyses. The serovar of all the isolates was Derby, and the sequence types (STs) were ST40. The analysis of the differences of single-nucleotide polymorphisms (SNPs) showed that the salmonella strains isolated from 13 farms were clonally related. Animal experiments showed that the lethal dose (LD) was 4.57 × 10 CFU (colony-forming units); the shedding time of Derby in mice was 24 days; the bacterial loads in spleen were higher than those in other organs (ileum, liver, and cecum). Pathological analyses by hematoxylin and eosin (H&E) staining revealed obvious damage in the spleen, liver, and intestine. These results indicate that the Derby from yaks can cause infection in mice.
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http://dx.doi.org/10.3390/ani11082397DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8388676PMC
August 2021

Dynamic genetic diversity and population structure of .

Zookeys 2021 11;1055:135-148. Epub 2021 Aug 11.

Sichuan Province Key Laboratory of Characteristic Biological Resources of Dry and Hot River Valley, Panzhihua University, Panzhihua, 617000, China Panzhihua University Panzhihua China.

To investigate the genetic effects on the population of of dam constructions in the upper reaches of the Yangtze River, we analyzed the genetic diversity and population structure of 12 populations collected in 2009 and 2019 using mitochondrial DNA (mtDNA) control regions. There was no significant difference in genetic diversity between 2009 and 2019 ( > 0.05), but the population structure tended to become stronger. Genetic differentiation (FST) among five populations (LX, BB, YB, SF and JA) collected in 2009 was not significant ( > 0.05). However, some populations collected in 2019 were significantly differentiated ( < 0.05), indicating that the population structure has undergone change. A correlation analysis showed that the genetic diversity of the seven populations collected in 2019 was significantly negatively correlated with geographical height ( = -0.808, = 0.028), indicating that the populations at high elevations were more vulnerable than those at low elevations. In order to prevent the further decrease of genetic diversity and population resources, some conservation and restoration suggestions, such as fish passage and artificial breeding, are put forward.
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http://dx.doi.org/10.3897/zookeys.1055.70117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8376836PMC
August 2021

Corrigendum to "Changing of haemostatic system in a pig model during different types of hypothermic circulatory arrest" [95, 2021, 102817].

J Therm Biol 2021 Jul 13;99:102974. Epub 2021 May 13.

Department of Cardiac Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing, China; Beijing Aortic Disease Center, Cardiovascular Surgery Center, Beijing, China; Beijing Engineering Research Center for Vascular Prostheses, Beijing, China. Electronic address:

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http://dx.doi.org/10.1016/j.jtherbio.2021.102974DOI Listing
July 2021

ICAM-1-carrying targeted nano contrast agent for evaluating inflammatory injury in rabbits with atherosclerosis.

Sci Rep 2021 Aug 13;11(1):16508. Epub 2021 Aug 13.

Department of Pathology, Jiading District Central Hospital Affiliated Shanghai University of Medicine and Health Sciences, Shanghai, 201800, China.

To investigate the feasibility of using ICAM-1-targeted nano ultrasonic contrast to evaluate the degree of inflammatory injury at different stages in the abdominal aorta of rabbits with atherosclerosis (AS). Twenty-five experimental rabbits were assigned to five groups: the control group (A); the week-4 after modeling group (B); the week-8 after modeling group (C); the week-12 after modeling group (D); the week-16 after modeling group (E). All groups were given 2D ultrasonography, conventional ultrasonic contrast (SonoVue), and ICAM-1-targeted nano ultrasonic contrast, respectively. Signal intensity of vascular perfusion was evaluated. Signal intensity of ICAM-1-targeted nano ultrasonic contrast was substantially enhanced and prolonged in the vascular wall of the abdominal bubble aorta increased in B, C, D, and E groups (all P < 0.05). A positive linear correlation between intensity and the expression of ICAM-1 (r = 0.895, P < 0.001). The intensity of outer membrane was enhanced from week 4 to week 12, and both the intima-media membrane and outer membrane were enhanced with double-layer parallel echo at week 16, which was in line with the progression of atherosclerotic plaque inflammatory injury. ICAM-1-targeted nano contrast agent would be possibly a novel non-invasive molecular imaging method for plaque inflammatory injury and site high expression of specific adhesion molecules in early atherosclerotic lesions.
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http://dx.doi.org/10.1038/s41598-021-96042-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8363608PMC
August 2021

The effect of immunotherapy on cross-reactivity between house dust mite and other allergens in house dust mite -sensitized patients with allergic rhinitis.

Expert Rev Clin Immunol 2021 Sep 18;17(9):969-975. Epub 2021 Aug 18.

Department of Otolaryngology Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, Beijing, China.

Introduction: House dust mite (HDM) is a main perennial allergen causing allergic rhinitis (AR). It has been shown that HDM cross-reacts with a variety of other allergens. Presently, allergen-specific immunotherapy (AIT) is an effective way for management of mono-sensitized HDM AR patients. However, management approaches to polysensitized HDM-sensitized AR patients are not standardized yet.

Area Covered: This article reviews the data available in the literature for cross-reactivity between HDM and inhalant or food allergens, the diagnosis of cross-reactivity in HDM-sensitized AR patients, and the effect of immunotherapy on cross-reactivity in HDM-sensitized AR patients; which may help to develop effective therapeutic strategies for management of polysensitized HDM-sensitized AR patients in the future.

Expert Opinion: Pan-allergen proteins such as tropomyosin, arginine kinase (AK), glutathione S-transferase (GST), and hemocyanin are responsible for cross-reactivity between HDM and other allergens. To distinguish genuine or cross-reactive sensitization, molecular- or component-resolved diagnosis is suggested to apply in HDM-sensitized AR patients. The effect of HDM immunotherapy to treat the associated cross-reactivity in HDM-sensitized AR patients is still contradictory, and might be dependent on the degree of homology between two allergens. Furthermore, targeting tropomyosin might be a promising way to treat HDM patients with allergen cross-reactivity.

Abbreviations: AIT: allergen-specific immunotherapy; AK: arginine kinase; AR: allergic rhinitis; CRD: component-resolved diagnostics; Der f: Dermatophagoides farina; Der p: Dermatophagoides pteronyssinus; EAACI: European Academy of Allergy and Clinical Immunology; GST: glutathione S-transferase; GWAS: genome-wide association study; HDM: house dust mite; IgE: immunoglobulin E; RAST: radioallergosorbent test; sIgE: specific IgE; SIT: specific immunotherapy; SCIT: subcutaneous immunotherapy; SLIT: sublingual immunotherapy; SPT: skin prick test.
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http://dx.doi.org/10.1080/1744666X.2021.1968834DOI Listing
September 2021

Advances and highlights in allergic rhinitis.

Allergy 2021 Aug 11. Epub 2021 Aug 11.

Department of Allergy, Beijing TongRen Hospital, Capital Medical University, Beijing, China.

Allergic rhinitis (AR) is a growing public health, medical and economic problem worldwide. The current review describes the major discoveries related to AR during the past 2 years, including risk factors for the prevalence of AR, the corresponding diagnostic strategy, precise underlying immunological mechanisms, and efficient therapies for AR during the ongoing global "coronavirus disease 2019" (COVID-19) pandemic. The review further attempts to highlight future research perspectives. Increasing evidence suggests that environmental exposures, climate changes, and lifestyle are important risk factors for AR. Consequently, detailed investigation of the exposome and the connection between environmental exposures and health in the future should provide better risk profiles instead of single predictors, and also help mitigate adverse health outcomes in allergic diseases. Although patients with dual AR, a newly defined AR phenotype, display perennial and seasonal allergens-related nasal symptoms, they are only allergic to seasonal allergens, indicating the importance of measuring inflammation at the local sites. Herein, we suggest that a combination of precise diagnosis in local sites and traditional diagnostic methods may enhance the precision medicine-based approach for management of AR; however, this awaits further investigations. Apart from traditional treatments, social distancing, washing hands, and disinfection are also required to better manage AR patients in the ongoing global COVID-19 pandemic. Despite recent advances in understanding the immune mechanisms underlying the effects of allergen immunotherapy (AIT), further understanding changes of cell profiles after AIT and accurately evaluate the efficacy of AIT are required.
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http://dx.doi.org/10.1111/all.15044DOI Listing
August 2021

Facile and green approach towards biomass-derived hydrogel powders with hierarchical micro-nanostructures for ultrafast hemostasis.

J Mater Chem B 2021 Sep 11;9(33):6678-6690. Epub 2021 Aug 11.

College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu, 610065, China.

Although a series of biomass-derived hemostats has been developed, the desire for green-prepared hemostatic materials with biosafety has not decreased. Herein, we constructed porous carboxymethyl chitosan/sodium alginate/Ca(OH) powders (PCSCPs) with suitable adaptability for instant control of irregular hemorrhage via a facile and green approach. By one-pot chemical crosslinking of carboxymethyl chitosan and sodium alginate, hydrogels were formed and immediately ionically cross-linked along with the generation of Ca(OH) to prepare PCSCPs. As hydrogel powders, PCSCPs with abundant hydrophilic carboxymethyl groups and porous hierarchically micro-nanostructures displayed a high water absorption ratio of over 1600%. The PCSCPs were confirmed with favorable hemocompatibility, non-cytotoxic effects and excellent degradability. Hemostasis assays in vitro showed that PCSCPs possessed an outstanding property of platelet activation and red blood cell aggregation. The PCSCPs effectively shortened the hemostatic time and blood loss to ca. 50% in rodent bleeding models compared with medical gauze and commercial chitosan-based hemostats. Furthermore, a mouse subcutaneous implantation model demonstrated an ignorable inflammation response and potential tissue repair capability of PCSCPs. It's believed that green-prepared and biomass-derived PCSCPs are feasible biomedical hemostatic materials in view of engineering and provide a promising platform to design hemostats in prehospital management and clinical settings.
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http://dx.doi.org/10.1039/d1tb01477cDOI Listing
September 2021

Explainable deep learning predictions for illness risk of mental disorders in Nanjing, China.

Environ Res 2021 Jul 28;202:111740. Epub 2021 Jul 28.

School of Architecture and Urban Planning, Nanjing University, No. 22 Hankoulu Road, Nanjing, 210093, PR China. Electronic address:

Epidemiological studies have revealed the associations of air pollutants and meteorological factors with a range of mental health conditions. However, little is known about local explanations and global understanding on the importance and effect of input features in the complex system of environmental stressors - mental disorders (MDs), especially for exposure to air pollution mixture. In this study, we combined deep learning neural networks (DLNNs) with SHapley Additive exPlanation (SHAP) to predict the illness risk of MDs on the population level, and then provided explanations for risk factors. The modeling system, which was trained on day-by-day hospital outpatient visits of two major hospitals in Nanjing, China from 2013/07/01 through 2019/02/28, visualized the time-varying prediction, contributing factors, and interaction effects of informative features. Our results suggested that NO, SO, and CO made outstanding contributions in magnitude of feature attributions under circumstances of mixed air pollutants. In particular, NO at high concentration level was associated with an increase in illness risk of MDs, and the maximum and mean absolute SHAP value were approximated to 10 and 2 as a local and global measure of feature importance, respectively. It presented a marginally antagonistic effect for two pairs of gaseous pollutants, i.e., NO vs. SO and CO vs. NO. In contrast, CO and SO displayed the opposite direction of feature effects to the rise of observed concentrations, but an apparent synergistic effect was obviously captured. The primary risk factors driving a sharp increase in acute attack or exacerbation of MDs were also identified by depicting prediction paths of time-series samples. We believe that the significance of coupling accurate predictions from DLNNs with interpretable explanations of why a prediction is completed has broad applicability throughout the field of environmental health.
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http://dx.doi.org/10.1016/j.envres.2021.111740DOI Listing
July 2021

Synergetic toxicity of sliver nanoparticle and glyphosate on wheat (Triticum aestivum L.).

Sci Total Environ 2021 Jul 21;797:149200. Epub 2021 Jul 21.

College of Environment, Zhejiang University of Technology, Hangzhou 310032, PR China. Electronic address:

Silver nanoparticles (AgNPs) are one of the most commonly used nanomaterials in industrial and agricultural production. Glyphosate is a broad-spectrum systemic herbicide, which mainly acts in the phloem of weeds that compete with crop growth and is widely used in agriculture. This study investigated the interactive effects of AgNPs and glyphosate on the physiological morphology, gene transcription, and rhizosphere microorganisms of wheat. Our results demonstrated that wheat growth, and the structure and diversity of rhizosphere microorganisms were slightly influenced by AgNPs and glyphosate single treatment at the test concentration. However, AgNPs and glyphosate (Gly) combined treatment (AgNPs + Gly) strongly inhibited wheat growth and influenced gene transcription. In total, 955, 601, and 1336 genes were determined to be differentially expressed in AgNPs, glyphosate, and combined treatment, respectively. According to KEGG analysis, the combined groups induced an antioxidant response by upregulating the transcription of phenylpropanoid biosynthesis-related genes. In addition, more energy was needed, and disrupted cell membrane was shown in the combined treatment, which displayed in the upregulation of sucrose, starch, and lipid synthesis. Moreover, the relative abundance of Bradyrhizobium, Devosia, Kribbella, Sphingopyxis (nitrogen-fixing bacteria), and Streptomyces (plant growth-promoting bacteria) in soil microbiota were decreased, implicated that nitrogen fixation and some beneficial substance secretions were inhibited by the combined treatment. This study emphasized that the synergetic effects of AgNPs and glyphosate exerted a negative impact on wheat growth.
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http://dx.doi.org/10.1016/j.scitotenv.2021.149200DOI Listing
July 2021

Accuracy and error cause analysis, and recommendations for usage of Himawari-8 aerosol products over Asia and Oceania.

Sci Total Environ 2021 Nov 16;796:148958. Epub 2021 Jul 16.

National Marine Environmental Monitoring Center, Dalian 116023, China.

The Himawari-8 aerosol algorithm was updated to version 3 (V30). However, no study has evaluated its performance. The purpose of this study is to verify and to compare version 2.1 (V21) and V30 aerosol products, to explain which factor dominates the aerosol optical depth (AOD) error, and to provide recommendations for aerosol product usage. The AOD accuracy of V30 was better than that of V21, with a higher correlation coefficient (R) and a higher expected error (EE_DT). The V30 AOD metrics (including R, EE_DT, and the root mean square error) exceeded those of V21 on more than 69% of the AERONET sites and its bias from MODIS AOD was smaller than that of V21 AOD. However, the V30 AOD does not meet the metric of EE_DT > 0.66. The analysis results suggest that aerosol type parameters (primarily the Ångström exponent (AE)) may be the dominant factor determining the AOD error. This reveals the direction of H8 algorithm improvement. More than 59% of the H8 AE value meets the expected error but they do not capture the variety (R < 0.3). The FMF and SSA retrieved by H8 performed poorly. The V30 AOD performs best in Japan and South Korea (83.3% of AERONET sites meet the EE_DT > 0.66 requirement) and has better data accuracy in the morning. Therefore, we recommend V30 AOD morning data to users in Japan and South Korea regions.
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http://dx.doi.org/10.1016/j.scitotenv.2021.148958DOI Listing
November 2021

Spatiotemporal distributions of pan evaporation and the influencing factors in China from 1961 to 2017.

Environ Sci Pollut Res Int 2021 Jul 16. Epub 2021 Jul 16.

Key Laboratory of Regional Ecology and Environmental Change, School of Geography and Information Engineering, China University of Geosciences, Wuhan, China.

Pan evaporation (EVP) is an important element of the hydrological cycle and exhibits a close relationship with climate change. In this study, the generalized regression neural network (GRNN) model and extreme gradient boosting (Xgboost) model were applied to estimate the monthly EVP. The spatiotemporal distributions of EVP and influencing factors in China and eight subregions from 1961 to 2017 were analyzed. The root mean square error (RMSE) of all GRNN models was approximately 10%, and the Nash-Sutcliffe efficiency (NSE) coefficient was larger than 0.94 in different subregions. The annual mean EVP in all subregions and throughout China showed decreasing trends before 1993, while EVP increasing trends occurred in East China (EC), South China (SC), Southwest China (SWC), west of Northwest China (WNC), and throughout China after 1994. Subsequently, the variable importance in projection (VIP) between EVP and climatic factors obtained by partial least squares (PLS) regression and the relative contribution calculated by Xgboost stepwise regression analysis (SRA) were used to investigate the climatic parameter sensitivity to EVP. The results indicated that the combined effects of the vapor pressure deficit (VPD), sunshine duration (SSD), and wind speed (WIN) were the main reasons for the variations in EVP across China. At the seasonal scale, SSD, WIN, relative humidity (RHU), and VPD were the most sensitive climatic factors to EVP in different seasons. In addition, the Pacific decadal oscillation (PDO) index showed a significant negative correlation with EVP, and the El Niño 3.4 (N3.4) and East Atlantic/Western Russia (EA/WR) indices revealed positive correlations in most regions from 1961 to 1993, while the North Atlantic oscillation (NAO) was negatively correlated with EVP. Moreover, N3.4 and Atlantic multidecadal oscillation (AMO) were positively correlated with EVP from 1994 to 2017. Finally, the yearly number of heatwave events (HWN) was highly correlated with EVP because of the high VPD and SSD levels during the heatwave event periods.
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http://dx.doi.org/10.1007/s11356-021-15386-0DOI Listing
July 2021

Stanniocalcin-1 Protected Astrocytes from Hypoxic Damage Through the AMPK Pathway.

Neurochem Res 2021 Jul 15. Epub 2021 Jul 15.

Institute of Medicine and Equipment for High Altitude Region, College of High Altitude Military Medicine, Army Medical University, Chongqing, China.

Our previous studies revealed that the expression of stanniocalcin-1 (STC1) in astrocytes increased under hypoxic conditions. However, the role of STC1 in hypoxic astrocytes is not well understood. In this work, we first showed the increased expression of STC1 in astrocyte cell line and astrocytes in the brain tissues of mice after exposure to hypoxia. Then, we found that knockdown of STC1 inhibited cell viability and increased apoptosis. These effects were mediated by decreasing the levels of SIRT3, UCP2, and glycolytic genes and increasing the levels of ROS. Further studies suggested that STC1 silencing promoted oxidative stress and suppressed glycolysis by downregulating AMPKα1. Moreover, HIF-1α knockdown in hypoxic astrocytes led to decreased expression of STC1 and AMPKα1, indicating that the expression of STC1 was regulated by HIF-1α. In conclusion, our study showed that HIF-1α-induced STC1 could protect astrocytes from hypoxic damage by regulating glycolysis and redox homeostasis in an AMPKα1-dependent manner.
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http://dx.doi.org/10.1007/s11064-021-03393-zDOI Listing
July 2021

Leaf metabolic influence of glyphosate and nanotubes on the Arabidopsis thaliana phyllosphere.

J Environ Sci (China) 2021 Aug 27;106:66-75. Epub 2021 Jan 27.

College of Environment, Zhejiang University of Technology, Hangzhou 310032, China. Electronic address:

Chemical exposure can indirectly affect leaf microbiota communities, but the mechanism driving this phenomenon remains largely unknown. Results revealed that the co-exposure of glyphosate and multi-carbon nanotubes (CNTs) caused a synergistic inhibitory effect on the growth and metabolism of Arabidopsis thaliana shoots. However, only a slight inhibitory effect was induced by nanotubes or glyphosate alone at the tested concentrations. Several intermediate metabolites of nitrogen metabolism and fatty acid synthesis pathways were upregulated under the combined treatment, which increased the amount of energy required to alleviate the disruption caused by the combined treatment. Additionally, compared with the two individual treatments, the glyphosate/nanotube combination treatment induced greater fluctuations in the phyllosphere bacterial community members with low abundance (relative abundance (RA) <1%) at both the family and genus levels, and among these bacteria some plant growth promotion and nutrient supplement related bacteria were markable increased. Strikingly, strong correlations between phyllosphere bacterial diversity and metabolites suggested a potential role of leaf metabolism, particularly nitrogen and carbohydrate metabolism, in restricting the range of leaf microbial taxa. These correlations between phyllosphere bacterial diversity and leaf metabolism will improve our understanding of plant-microbe interactions and the extent of their drivers of variation and the underlying causes of variability in bacterial community composition.
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http://dx.doi.org/10.1016/j.jes.2021.01.002DOI Listing
August 2021

PEDOT-Coated Red Phosphorus Nanosphere Anodes for Pseudocapacitive Potassium-Ion Storage.

Nanomaterials (Basel) 2021 Jun 30;11(7). Epub 2021 Jun 30.

Center of Nanomaterials for Renewable Energy, State Key Laboratory of Electrical Insulation and Power Equipment, School of Electrical Engineering, Xi'an Jiaotong University, Xi'an 710054, China.

Potassium-ion batteries (KIBs) have come up as a potential alternative to lithium-ion batteries due to abundant potassium storage in the crust. Red phosphorus is a promising anode material for KIBs with abundant resources and high theoretical capacity. Nevertheless, large volume expansion, low electronic conductivity, and limited K charging speed in red phosphorus upon cycling have severely hindered the development of red phosphorus-based anodes. To obtain improved conductivity and structural stability, surface engineering of red phosphorus is required. Poly(3,4-ethylenedioxythiophene) (PEDOT)-coated red phosphorus nanospheres ([email protected]) with an average diameter of 60 nm were synthesized via a facile solution-phase approach. PEDOT can relieve the volume change of red phosphorus and promote electron/ion transportation during charge-discharge cycles, which is partially corroborated by our DFT calculations. A specific capacity of 402 mAh g at 0.1 A g after 40 cycles, and a specific capacity of 302 mAh g at 0.5 A g after 275 cycles, were achieved by [email protected] anode with a high pseudocapacitive contribution of 62%. The surface-interface engineering for the organic-inorganic composite of [email protected] provides a novel perspective for broad applications of red phosphorus-based KIBs in fast charging occasions.
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http://dx.doi.org/10.3390/nano11071732DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8308171PMC
June 2021

Evaluation and Future Projection of Extreme Climate Events in the Yellow River Basin and Yangtze River Basin in China Using Ensembled CMIP5 Models Data.

Int J Environ Res Public Health 2021 06 3;18(11). Epub 2021 Jun 3.

Hubei Key Laboratory of Critical Zone Evolution, School of Geography and Information Engineering, China University of Geosciences, Wuhan 430074, China.

The Yellow River Basin (YLRB) and Yangtze River Basin (YZRB) are heavily populated, important grain-producing areas in China, and they are sensitive to climate change. In order to study the temporal and spatial distribution of extreme climate events in the two river basins, seven extreme temperature indices and seven extreme precipitation indices were projected for the periods of 2010-2039, 2040-2069, and 2070-2099 using data from 16 Coupled Model Intercomparison Project Phase 5 (CMIP5) models, and the delta change and reliability ensemble averaging (REA) methods were applied to obtain more robust ensemble values. First, the present evaluation indicated that the simulations satisfactorily reproduced the spatial distribution of temperature extremes, and the spatial distribution of precipitation extremes was generally suitably captured. Next, the REA values were adopted to conduct projections under different representative concentration pathway (RCP) scenarios (i.e., RCP4.5, and RCP8.5) in the 21st century. Warming extremes were projected to increase while cold events were projected to decrease, particularly on the eastern Tibetan Plateau, the Loess Plateau, and the lower reaches of the YZRB. In addition, the number of wet days (CWD) was projected to decrease in most regions of the two basins, but the highest five-day precipitation (Rx5day) and precipitation intensity (SDII) index values were projected to increase in the YZRB. The number of consecutive dry days (CDD) was projected to decrease in the northern and western regions of the two basins. Specifically, the warming trends in the two basins were correlated with altitude and atmospheric circulation patterns, and the wetting trends were related to the atmospheric water vapor content increases in summer and the strength of external radiative forcing. Notably, the magnitude of the changes in the extreme climate events was projected to increase with increasing warming targets, especially under the RCP8.5 scenario.
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http://dx.doi.org/10.3390/ijerph18116029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8199935PMC
June 2021

Smart Asymmetric Hydrogel with Integrated Multi-Functions of NIR-Triggered Tunable Adhesion, Self-Deformation, and Bacterial Eradication.

Adv Healthc Mater 2021 May 29:e2100784. Epub 2021 May 29.

College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering, Med-X Center for Materials, Sichuan University, Chengdu, 610065, China.

Multifunctional hydrogels acting as wound dressing have received extensive attention in soft tissue repair; however, it is still a challenge to develop a non-antibiotic-dependent antibacterial hydrogel that has tunable adhesion and deformation to achieve on-demand removal. Herein, an asymmetric adhesive hydrogel with near-infrared (NIR)-triggered tunable adhesion, self-deformation, and bacterial eradication is designed. The hydrogel is prepared by the crosslinking polymerization of N-isopropylacrylamide and acrylic acid, during the sedimentation of conductive PPy-PDA nanoparticles based on the polymerization of pyrrole (Py) and dopamine (DA). Due to the conversion capacity from NIR light into heat for PPy-PDA NPs, the formed temperature-sensitive hydrogel exhibits tissue adhesive as well as NIR-triggered tunable adhesion and self-deformation property, which can achieve an on-demand dressing refreshing. Systematically in vitro/in vivo antibacterial experiments indicate that the hydrogel shows excellent disinfection capability to both Gram-negative and Gram-positive bacteria. The in vivo experiments in a full-layer cutaneous wound model demonstrate that the hydrogel has a good treatment effect to promote wound healing. Overall, the asymmetric hydrogel with tunable adhesion, self-deformation, conductive, and photothermal antibacterial activity may be a promising candidate to fulfill the functions of adhesion on skin tissue, easy removing on-demand, and accelerating the wound healing process.
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http://dx.doi.org/10.1002/adhm.202100784DOI Listing
May 2021

hERG-deficient human embryonic stem cell-derived cardiomyocytes for modelling QT prolongation.

Stem Cell Res Ther 2021 05 7;12(1):278. Epub 2021 May 7.

Beijing Laboratory for Cardiovascular Precision Medicine, The Key Laboratory of Biomedical Engineering for Cardiovascular Disease Research, The Key Laboratory of Remodeling-Related Cardiovascular Disease, Ministry of Education, Beijing Anzhen Hospital, Capital Medical University, Research Institute Building, Room 323, 2 Anzhen Road, Chaoyang District, Beijing, 100029, China.

Background: Long-QT syndrome type 2 (LQT2) is a common malignant hereditary arrhythmia. Due to the lack of suitable animal and human models, the pathogenesis of LQT2 caused by human ether-a-go-go-related gene (hERG) deficiency is still unclear. In this study, we generated an hERG-deficient human cardiomyocyte (CM) model that simulates 'human homozygous hERG mutations' to explore the underlying impact of hERG dysfunction and the genotype-phenotype relationship of hERG deficiency.

Methods: The KCNH2 was knocked out in the human embryonic stem cell (hESC) H9 line using the CRISPR/Cas9 system. Using a chemically defined differentiation protocol, we obtained and verified hERG-deficient CMs. Subsequently, high-throughput microelectrode array (MEA) assays and drug interventions were performed to characterise the electrophysiological signatures of hERG-deficient cell lines.

Results: Our results showed that KCNH2 knockout did not affect the pluripotency or differentiation efficiency of H9 cells. Using high-throughput MEA assays, we found that the electric field potential duration and action potential duration of hERG-deficient CMs were significantly longer than those of normal CMs. The hERG-deficient lines also exhibited irregular rhythm and some early afterdepolarisations. Moreover, we used the hERG-deficient human CM model to evaluate the potency of agents (nifedipine and magnesium chloride) that may ameliorate the phenotype.

Conclusions: We established an hERG-deficient human CM model that exhibited QT prolongation, irregular rhythm and sensitivity to other ion channel blockers. This model serves as an important tool that can aid in understanding the fundamental impact of hERG dysfunction, elucidate the genotype-phenotype relationship of hERG deficiency and facilitate drug development.
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http://dx.doi.org/10.1186/s13287-021-02346-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8103639PMC
May 2021

Tropomyosin in mugwort cross-reacts to house dust mite, eliciting non-Th2 response in allergic rhinitis patients sensitized to house dust mite.

Clin Mol Allergy 2021 Apr 2;19(1). Epub 2021 Apr 2.

Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology, Beijing, China.

Background: Mugwort and house dust mite (HDM) are two of the most common inhalant allergens in Asia, however, whether mugwort affects polysensitized HDM allergic rhinitis (AR) patients has not been elucidated.

Methods: Overall, 15,884 AR outpatients were assessed for clinical status. Amino acid sequences of mugwort were determined by mass spectrometry. Afterward, cross-reactivity between mugwort tropomyosin and Dermatophagoides pteronyssinus 10 (Der p10) was analysed by ELISA inhibition and basophil activation experiments. To compare immunologic responses eliciting by two different tropomyosins, peripheral blood mononuclear cells (PBMCs) of HDM-monosensitized patients were stimulated by mugwort, HDM, Der p10 and synthetic peptides representing mugwort tropomyosin respectively.

Results: Polysensitized HDMAR patients were mainly sensitized to cat and mugwort, and the positive rate of monosensitized HDMAR out-clinic patients was increased during the mugwort pollen season. Tropomyosin protein was able to find in mugwort. Synthetic tropomyosin peptide of mugwort activated basophils which were primed by HDM-specific IgE; ELISA inhibition experiment showed synthetic tropomyosin peptide of mugwort inhibited IgE binding to HDM tropomyosin, Der p10. Unlike HDM and Derp 10, mugwort and mugwort tropomyosin mainly induced IFN-γ and IL-17 release in PBMCs of monosensitized HDMAR patients, but not IL-5.

Conclusions: Pan-allergen tropomyosin accounts for the cross-reactivity between mugwort and HDM, which reminds HDM patients to reduce mugwort exposure in mugwort pollen season in virtue of the tropomyosin induced mild inflammation.
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http://dx.doi.org/10.1186/s12948-021-00142-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017758PMC
April 2021

A Potential Role of Group 2 Innate Lymphoid Cells in Eosinophilic Chronic Rhinosinusitis With Nasal Polyps.

Allergy Asthma Immunol Res 2021 May;13(3):363-374

Department of Otorhinolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing Institute of Otorhinolaryngology, Key Laboratory of Otorhinolaryngology Head and Neck Surgery, Ministry of Education, Beijing Key Laboratory of Nasal Diseases, Beijing, China.

Chronic rhinosinusitis with nasal polyps (CRSwNP), a type 2-based upper airway disease, is mainly characterized by high asthma comorbidity and recurrence after surgery. It has been shown that type 2 cytokines, including interleukin (IL)-4, IL-5, and IL-13 released from T helper 2 (Th2) cells as well as group 2 innate lymphoid cells (ILC2s), contribute to chronic inflammation of CRSwNP. This review summarizes recent progresses made in our understanding of ILC2 activity, particularly ILC2 accumulation at airway inflammation sites, cooperation with Th2 cells in aggravating the CRSwNP inflammatory process and interactions with regulatory T cells (Tregs) in resisting Tregs-mediated suppressive function in allergic inflammation. A better understanding of the biology of ILC2s should lay a good foundation in elucidating the pathogenesis of CRSwNP, and subsequently may lead to the development of new therapeutic strategies for the management of CRSwNP.
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http://dx.doi.org/10.4168/aair.2021.13.3.363DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7984954PMC
May 2021

Cell sheet formation enhances the therapeutic effects of human umbilical cord mesenchymal stem cells on myocardial infarction as a bioactive material.

Bioact Mater 2021 Sep 5;6(9):2999-3012. Epub 2021 Mar 5.

Department of Cardiac Surgery, Peking University Third Hospital, Beijing, 100191, China.

Stem cell-based therapy has been used to treat ischaemic heart diseases for two decades. However, optimal cell types and transplantation methods remain unclear. This study evaluated the therapeutic effects of human umbilical cord mesenchymal stem cell (hUCMSC) sheet on myocardial infarction (MI).

Methods: hUCMSCs expressing luciferase were generated by lentiviral transduction for bio-luminescent imaging tracking of cells. We applied a temperature-responsive cell culture surface-based method to form the hUCMSC sheet. Cell retention was evaluated using an bio-luminescent imaging tracking system. Unbiased transcriptional profiling of infarcted hearts and further immunohistochemical assessment of monocyte and macrophage subtypes were used to determine the mechanisms underlying the therapeutic effects of the hUCMSC sheet. Echocardiography and pathological analyses of heart sections were performed to evaluate cardiac function, angiogenesis and left ventricular remodelling.

Results: When transplanted to the infarcted mouse hearts, hUCMSC sheet significantly improved the retention and survival compared with cell suspension. At the early stage of MI, hUCMSC sheet modulated inflammation by decreasing Mcp1-positive monocytes and CD68-positive macrophages and increasing Cx3cr1-positive non-classical macrophages, preserving the cardiomyocytes from acute injury. Moreover, the extracellular matrix produced by hUCMSC sheet then served as bioactive scaffold for the host cells to graft and generate new epicardial tissue, providing mechanical support and routes for revascularsation. These effects of hUCMSC sheet treatment significantly improved the cardiac function at days 7 and 28 post-MI.

Conclusions: hUCMSC sheet formation dramatically improved the biological functions of hUCMSCs, mitigating adverse post-MI remodelling by modulating the inflammatory response and providing bioactive scaffold upon transplantation into the heart.

Translational Perspective: Due to its excellent availability as well as superior local cellular retention and survival, allogenic transplantation of hUCMSC sheets can more effectively acquire the biological functions of hUCMSCs, such as modulating inflammation and enhancing angiogenesis. Moreover, the hUCMSC sheet method allows the transfer of an intact extracellular matrix without introducing exogenous or synthetic biomaterial, further improving its clinical applicability.
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http://dx.doi.org/10.1016/j.bioactmat.2021.01.036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7941025PMC
September 2021

Discovery and engineering of small SlugCas9 with broad targeting range and high specificity and activity.

Nucleic Acids Res 2021 04;49(7):4008-4019

State Key Laboratory of Genetic Engineering, School of Life Sciences, Zhongshan Hospital, Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200438, China.

The compact CRISPR/Cas9 system, which can be delivered with their gRNA and a full-length promoter for expression by a single adeno-associated virus (AAV), is a promising platform for therapeutic applications. We previously identified a compact SauriCas9 that displays high activity and requires a simple NNGG PAM, but the specificity is moderate. Here, we identified three compact Cas9 orthologs, Staphylococcus lugdunensis Cas9 (SlugCas9), Staphylococcus lutrae Cas9 (SlutrCas9) and Staphylococcus haemolyticus Cas9 (ShaCas9), for mammalian genome editing. Of these three Cas9 orthologs, SlugCas9 recognizes a simple NNGG PAM and displays comparable activity to SaCas9. Importantly, we generated a SlugCas9-SaCas9 chimeric nuclease, which has both high specificity and high activity. We finally engineered SlugCas9 with mutations to generate a high-fidelity variant that maintains high specificity without compromising on-target editing efficiency. Our study offers important minimal Cas9 tools that are ideal for both basic research and clinical applications.
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http://dx.doi.org/10.1093/nar/gkab148DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8053104PMC
April 2021

Microscale grooves regulate maturation development of hPSC-CMs by the transient receptor potential channels (TRP channels).

J Cell Mol Med 2021 04 10;25(7):3469-3483. Epub 2021 Mar 10.

Beijing Lab for Cardiovascular Precision Medicine, Anzhen Hospital, Capital Medical University, Beijing, China.

The use of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) is limited in drug discovery and cardiac disease mechanism studies due to cell immaturity. Micro-scaled grooves can promote the maturation of cardiomyocytes by aligning them in order, but the mechanism of cardiomyocytes alignment has not been studied. From the level of calcium activity, gene expression and cell morphology, we verified that the W20H5 grooves can effectively promote the maturation of cardiomyocytes. The transient receptor potential channels (TRP channels) also play an important role in the maturation and development of cardiomyocytes. These findings support the engineered hPSC-CMs as a powerful model to study cardiac disease mechanism and partly mimic the myocardial morphological development. The important role of the TRP channels in the maturation and development of myocardium is first revealed.
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http://dx.doi.org/10.1111/jcmm.16429DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034460PMC
April 2021

Mussel-inspired ultra-stretchable, universally sticky, and highly conductive nanocomposite hydrogels.

J Mater Chem B 2021 03;9(9):2221-2232

College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu, 610065, China. and College of Biomedical Engineering, Sichuan University, Chengdu, 610064, China and College of Chemical Engineering, Sichuan University, Chengdu, 610065, China.

Developing ultra-stretchable, universally sticky, and highly conductive nanocomposite hydrogels without doping agents and nanoparticle-aggregation is still a challenge. Herein, doping-free and nanoparticle-aggregation-inhibited hydrogels composed of Fe3+, dopamine (DA), pyrrole (Py) and polyacrylic acid (PAA) were prepared. Polypyrrole-polydopamine (PPy-PDA)/PAA hydrogels were quickly formed due to the abundant ionic bonds and physical cross-linking under the addition of Fe3+. Moreover, the H+ ions of the carboxylic acid groups on the PAA polymer chain helped to improve the conductivity of the hydrogels. Surprisingly, the multi-functional hydrogels received a high stretchability of 1900%, a tissue-like elastic modulus of 22 kPa, an adhesive strength of 2125.9 J m-2, and a high conductivity of 0.39 S m-1. Besides, the PPy-PDA/PAA hydrogels showed good antioxidant activity, biocompatibility and tissue repairing behavior. In short, the prepared multi-functional hydrogels have potential to address the human clinical problem of tissue repair and regeneration.
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http://dx.doi.org/10.1039/d1tb00019eDOI Listing
March 2021

Novel roles of an intragenic G-quadruplex in controlling microRNA expression and cardiac function.

Nucleic Acids Res 2021 03;49(5):2522-2536

Department of Cardiology, Institute of Vascular Medicine, NHC Key Laboratory of Cardiovascular Molecular Biology and RegulatoryPeptides, Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Peking University Third Hospital, Beijing 100191, China.

Simultaneous dysregulation of multiple microRNAs (miRs) affects various pathological pathways related to cardiac failure. In addition to being potential cardiac disease-specific markers, miR-23b/27b/24-1 were reported to be responsible for conferring cardiac pathophysiological processes. In this study, we identified a conserved guanine-rich RNA motif within the miR-23b/27b/24-1 cluster that can form an RNA G-quadruplex (rG4) in vitro and in cells. Disruption of this intragenic rG4 significantly increased the production of all three miRs. Conversely, a G4-binding ligand tetrandrine (TET) stabilized the rG4 and suppressed miRs production in human and rodent cardiomyocytes. Our further study showed that the rG4 prevented Drosha-DGCR8 binding and processing of the pri-miR, suppressing the biogenesis of all three miRs. Moreover, CRISPR/Cas9-mediated G4 deletion in the rat genome aberrantly elevated all three miRs in the heart in vivo, leading to cardiac contractile dysfunction. Importantly, loss of the G4 resulted in reduced targets for the aforementioned miRs critical for normal heart function and defects in the L-type Ca2+ channel-ryanodine receptor (LCC-RyR) coupling in cardiomyocytes. Our results reveal a novel mechanism for G4-dependent regulation of miR biogenesis, which is essential for maintaining normal heart function.
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http://dx.doi.org/10.1093/nar/gkab055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969000PMC
March 2021

Changing of haemostatic system in a pig model during different types of hypothermic circulatory arrest.

J Therm Biol 2021 Jan 4;95:102817. Epub 2021 Jan 4.

Department of Cardiac Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing, China; Beijing Aortic Disease Center, Cardiovascular Surgery Center, Beijing, China; Beijing Engineering Research Center for Vascular Prostheses, Beijing, China. Electronic address:

Background: Hypothermic circulatory arrest is usually used in aortic surgery, congenital heart defect repairs and other complex surgeries. It is frequently associated with excessive postoperative bleeding and the transfusion of allogeneic blood products. The physiopathology of hypothermic circulatory arrest-induced coagulopathy has never been systematically studied. The aim of the study was to investigate this phenomenon in a pig model.

Methods: Ten pigs were randomly assigned to 30 min of hypothermic circulatory arrest at either 15 °C (n = 5) or 25 °C (n = 5). Detection of apoptosis and haemostatic system assays were performed in this experiment. Enzyme-linked immunosorbent assays were performed at ten time points in each group to study the changes in the coagulation system in hypothermic circulatory arrest. All of the statistical analyses were performed in SPSS software, version 18.0, and as bilateral tests, and p < 0.05 was considered statistically significant.

Results: There was no significant difference in the effect of different types of hypothermic circulatory arrest on routine laboratory tests and tissue sample analysis (p > 0.05, for all). Our results demonstrated that more severe systemic activation of the coagulation system (TAT and F1+2) was applied in the deep hypothermic circulatory arrest group but not in the moderate hypothermic circulatory arrest group (TAT/p = 0.01, F1+2/p = 0.03). However, this activation of the coagulation system (AT III and PC) was not associated with changes in the anticoagulation pathway (AT III/p = 0.24, PC/p = 0.33). In addition, analysis of biomarkers of the haemostatic system revealed that the consumption of coagulation is more concentrated on extrinsic coagulation factors (FVII/p = 0.01).

Conclusions: Moderate hypothermic circulatory arrest is more suitable for patients with coagulation dysfunction. We believe the application of deep hypothermic circulatory arrest should pay more attention to changes in coagulation rather than the anticoagulation pathway. Extrinsic coagulation factor supplementation is more effective after deep hypothermic circulatory arrest.
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http://dx.doi.org/10.1016/j.jtherbio.2020.102817DOI Listing
January 2021

Knockout of MYOM1 in human cardiomyocytes leads to myocardial atrophy via impairing calcium homeostasis.

J Cell Mol Med 2021 02 15;25(3):1661-1676. Epub 2021 Jan 15.

Department of Cardiology, Peking University Third Hospital, Beijing, China.

Myomesin-1 (encoded by MYOM1 gene) is expressed in almost all cross-striated muscles, whose family (together with myomesin-2 and myomesin-3) helps to cross-link adjacent myosin to form the M-line in myofibrils. However, little is known about its biological function, causal relationship and mechanisms underlying the MYOM1-related myopathies (especially in the heart). Regrettably, there is no MYMO1 knockout model for its study so far. A better and further understanding of MYOM1 biology is urgently needed. Here, we used CRISPR/Cas9 gene-editing technology to establish an MYOM1 knockout human embryonic stem cell line (MYOM1 hESC), which was then differentiated into myomesin-1 deficient cardiomyocytes (MYOM1 hESC-CMs) in vitro. We found that myomesin-1 plays an important role in sarcomere assembly, contractility regulation and cardiomyocytes development. Moreover, myomesin-1-deficient hESC-CMs can recapitulate myocardial atrophy phenotype in vitro. Based on this model, not only the biological function of MYOM1, but also the aetiology, pathogenesis, and potential treatments of myocardial atrophy caused by myomesin-1 deficiency can be studied.
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http://dx.doi.org/10.1111/jcmm.16268DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7875908PMC
February 2021

Associations between C-reactive protein and white blood cell count, occurrence of delayed cerebral ischemia and poor outcome following aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis.

Acta Neurol Belg 2021 Oct 9;121(5):1311-1324. Epub 2021 Jan 9.

Department of Neurosurgery, Yuquan Hospital, Tsinghua University, No. 5 Shijingshan Road, Shijingshan District, Beijing, 100049, China.

This review and meta-analysis investigated associations of systemic inflammatory marker C-reactive protein (CRP) and white blood cell count (WBC) with occurrence of delayed cerebral ischemia (DCI) and poor functional outcome after aneurysmal subarachnoid hemorrhage (aSAH). Pubmed, EMBASE, and CENTRAL databases were searched until November 30, 2019, selecting prospective and retrospective studies of patients with spontaneous SAH due to ruptured aneurysm. Outcome measures were occurrence of DCI, defined as new focal neurological deficit or a deterioration of consciousness; and/or a new infarct on computed tomography or magnetic resonance imaging that was not visible initially. Occurrence of poor functional outcome at follow-up were measured by modified Rankin Scale or Glasgow outcomes scale. Fifteen studies analyzing data of 3268 patients with aSAH were included. Meta-analysis revealed early increase in CRP was significantly associated with higher risk of occurrence of DCI (pooled OR 1.30, 95% CI 1.10-1.54; P = 0.002), whereas not with poor functional outcome (pooled OR 1.02, 95% CI 1.00-1.04, P = 0.052). No significant associations between early increase in WBC and DCI (pooled OR 1.13, 95% CI 0.95-1.34; P = 0.179) were observed, whereas increase in WBC was significantly associated with increased risk of poor functional outcome (pooled OR 1.17, 95% CI 1.07-1.28, P = 0.001). Early increase in blood CRP appears to correlate with DCI after SAH, while increase in WBC correlates with poor functional outcome. However, strong conclusion cannot be made due to the small study number, between-study heterogeneity and suspicion of uncontrolled factors. Whether early phase CRP and WBC may serve as prognostic markers for aSAH needs more investigation.
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http://dx.doi.org/10.1007/s13760-020-01496-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7796813PMC
October 2021

Ascorbic acid can promote the generation and expansion of neuroepithelial-like stem cells derived from hiPS/ES cells under chemically defined conditions through promoting collagen synthesis.

Stem Cell Res Ther 2021 01 9;12(1):48. Epub 2021 Jan 9.

Beijing Laboratory for Cardiovascular Precision Medicine, MOE Key Laboratory of Medical Engineering for Cardiovascular Diseases, MOE Key Laboratory of Remodeling-Related Cardiovascular Disease, Beijing Collaborative Innovation Center for Cardiovascular Disorders, Anzhen Hospital, Capital Medical University, Beijing, 100029, China.

Introduction: Spinal cord injury (SCI) is a neurological, medically incurable disorder. Human pluripotent stem cells (hPSCs) have the potential to generate neural stem/progenitor cells (NS/PCs), which hold promise in the treatment of SCI by transplantation. In our study, we aimed to establish a chemically defined culture system using serum-free medium and ascorbic acid (AA) to generate and expand long-term self-renewing neuroepithelial-like stem cells (lt-NES cells) differentiated from hPSCs effectively and stably.

Methods: We induced human embryonic stem cells (hESCs)/induced PSCs (iPSCs) to neurospheres using a newly established in vitro induction system. Moreover, lt-NES cells were derived from hESC/iPSC-neurospheres using two induction systems, i.e., conventional N2 medium with gelatin-coated plates (coated) and N2+AA medium without pre-coated plates (AA), and were characterized by reverse transcription polymerase chain reaction (RT-PCR) analysis and immunocytochemistry staining. Subsequently, lt-NES cells were induced to neurons. A microelectrode array (MEA) recording system was used to evaluate the functionality of the neurons differentiated from lt-NES cells. Finally, the mechanism underlying the induction of lt-NES cells by AA was explored through RNA-seq and the use of inhibitors.

Results: HESCs/iPSCs were efficiently induced to neurospheres using a newly established induction system in vitro. lt-NES cells derived from hESC/iPSC-neurospheres using the two induction systems (coated vs. AA) both expressed the neural pluripotency-associated genes PAX6, NESTIN, SOX1, and SOX2. After long-term cultivation, we found that they both exhibited long-term expansion for more than a dozen generations while maintaining neuropluripotency. Moreover, the lt-NES cells retained the ability to differentiate into general functional neurons that express β-tubulin at high levels. We also demonstrated that AA promotes the generation and long-term expansion of lt-NES cells by promoting collagen synthesis via the MEK-ERK1/2 pathway.

Conclusions: This new chemically defined culture system was stable and effective regarding the generation and culture of lt-NES cells induced from hESCs/iPSCs using serum-free medium combined with AA. The lt-NES cells induced under this culture system maintained their long-term expansion and neural pluripotency, with the potential to differentiate into functional neurons.
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http://dx.doi.org/10.1186/s13287-020-02115-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7796386PMC
January 2021

Establishing a deeper understanding of the osteogenic differentiation of monolayer cultured human pluripotent stem cells using novel and detailed analyses.

Stem Cell Res Ther 2021 01 7;12(1):41. Epub 2021 Jan 7.

National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, People's Republic of China.

Background: Derivation of osteoblast-like cells from human pluripotent stem cells (hPSCs) is a popular topic in bone tissue engineering. Although many improvements have been achieved, the low induction efficiency because of spontaneous differentiation hampers their applications. To solve this problem, a detailed understanding of the osteogenic differentiation process of hPSCs is urgently needed.

Methods: Monolayer cultured human embryonic stem cells and human-induced pluripotent stem cells were differentiated in commonly applied serum-containing osteogenic medium for 35 days. In addition to traditional assays such as cell viability detection, reverse transcription-polymerase chain reaction, immunofluorescence, and alizarin red staining, we also applied studies of cell counting, cell telomerase activity, and flow cytometry as essential indicators to analyse the cell type changes in each week.

Results: The population of differentiated cells was quite heterogeneous throughout the 35 days of induction. Then, cell telomerase activity and cell cycle analyses have value in evaluating the cell type and tumourigenicity of the obtained cells. Finally, a dynamic map was made to integrate the analysis of these results during osteogenic differentiation of hPSCs, and the cell types at defined stages were concluded.

Conclusions: Our results lay the foundation to improve the in vitro osteogenic differentiation efficiency of hPSCs by supplementing with functional compounds at the desired stage, and then establishing a stepwise induction system in the future.
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http://dx.doi.org/10.1186/s13287-020-02085-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7792045PMC
January 2021
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