Publications by authors named "Dan Zhu"

712 Publications

Independent variations in genome-wide expression, alternative splicing, and DNA methylation in brain tissues among castes of the buff-tailed bumblebee, Bombus terrestris.

J Genet Genomics 2021 May 25. Epub 2021 May 25.

State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing 100080, PR China; CAS Centre for Excellence in Biotic Interactions, University of Chinese Academy of Sciences, Beijing 100049, PR China. Electronic address:

Caste differentiation in social hymenopterans is an intriguing example of phenotypic plasticity. However, the co-ordination among gene regulatory factors to mediate caste differentiation remains inconclusive. In this study, we determined the role of gene regulation and related epigenetic processes in pre-imaginal caste differentiation in the primitively eusocial bumblebee Bombus terrestris. By combining RNA-seq data from Illumina and PacBio and accurately quantifying methylation at whole-genomic base pair resolution, we found that queens, workers, and drones mainly differentiate in gene expression but not in alternative splicing and DNA methylation. Gynes are the most distinct with the lowest global level of whole-genomic methylation and with the largest number of caste-specific transcripts and alternative splicing events. By contrast, workers exhibit few uniquely expressed or alternatively spliced genes. Moreover, several genes involved in hormone and neurotransmitter metabolism are related to caste differentiation, whereas several neuropeptides are linked with sex differentiation. Despite little genome-wide association among differential gene expression, splicing, and differential DNA methylation, the overlapped gene ontology (GO) terms point to nutrition-related activity. Therefore, variations in gene regulation correlate with the behavioral differences among castes and highlight the specialization of toolkit genes in bumblebee gynes at the beginning of the adult stage.
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http://dx.doi.org/10.1016/j.jgg.2021.04.008DOI Listing
May 2021

The effect of human mobility restrictions on the COVID-19 transmission network in China.

PLoS One 2021 19;16(7):e0254403. Epub 2021 Jul 19.

Department of Econometrics and Business Statistics, Monash University, Caulfield, Victoria, Australia.

Background: COVID-19 poses a severe threat worldwide. This study analyzes its propagation and evaluates statistically the effect of mobility restriction policies on the spread of the disease.

Methods: We apply a variation of the stochastic Susceptible-Infectious-Recovered model to describe the temporal-spatial evolution of the disease across 33 provincial regions in China, where the disease was first identified. We employ Bayesian Markov Chain Monte-Carlo methods to estimate the model and to characterize a dynamic transmission network, which enables us to evaluate the effectiveness of various local and national policies.

Results: The spread of the disease in China was predominantly driven by community transmission within regions, which dropped substantially after local governments imposed various lockdown policies. Further, Hubei was only the epicenter of the early epidemic stage. Secondary epicenters, such as Beijing and Guangdong, had already become established by late January 2020. The transmission from these epicenters substantially declined following the introduction of mobility restrictions across regions.

Conclusions: The spatial transmission network is able to differentiate the effect of the local lockdown policies and the cross-region mobility restrictions. We conclude that both are important policy tools for curbing the disease transmission. The coordination between central and local governments is important in suppressing the spread of infectious diseases.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0254403PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8289089PMC
July 2021

Health risk assessment of rural older population.

Work 2021 Jul 14. Epub 2021 Jul 14.

Economic management Department, DePauw University, Greencastle, USA.

Background: With the accelerated development of aging, the health problems of rural elderly are becoming increasingly severe.

Objective: The study aims to understand the mental health issues of the rural older population.

Methods: The risk factor analysis and the disease risk assessment are utilized to analyze the impacts of depression on older adults. First, the prevalence of depression in China's rural older population is counted and analyzed. Next, both single and multi-factor analyses are employed to analyze the degree of depression among rural older adults quantitatively, and the existing risk factors are determined. The multiple risk factors and multi-source logistic regression algorithm establish the risk assessment model of depression in the rural older population. Finally, the risk factors of depression in older adults are calculated by analyzing and processing the above statistical data. A risk assessment model of depression is built, whose sensitivity and specificity are tested.

Results: Single-factor analysis and multi-factor analysis reveal 20 vital influencing factors of depression in older adults, such as cognitive ability, emotional state, and memory. The sensitivity and specificity of the risk assessment model based on multi-factor logistic regression are 87.3%80.2%, respectively, capable of effectively assessing and screening the potential population of depression among older adults.

Conclusions: This model provides a scientific basis for screening out and preventing older adults' mental health issues with depression and improving older adults' quality of life.
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http://dx.doi.org/10.3233/WOR-205350DOI Listing
July 2021

A MnO-coated multivariate porphyrinic metal-organic framework for oxygen self-sufficient chemo-photodynamic synergistic therapy.

Nanomedicine 2021 Jul 10:102440. Epub 2021 Jul 10.

Key Laboratory of Molecular Biophysics, Hebei Province, Institute of Biophysics, School of Sciences, Hebei University of Technology, Tianjin, China; State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China. Electronic address:

Lately, chemotherapy and photodynamic therapy (PDT) synergistic therapy has become a promising anti-cancer treatment mean. However, the hypoxia in tumor leads to huge impediments to the oxygen-dependent PDT effects. In this work, a multifunctional nanoplatform (TUDMP) based on a multivariable porphyrin-nMOFs core and a manganese dioxide (MnO) shell was prepared for relieving tumor hypoxia and enhancing chemo-photodynamic synergistic therapy performance. The obtained TUDMP nanoplatform could effectively catalyze the hydrolysis of hydrogen peroxide to generate oxygen and also lead to consumption of antioxidant GSH, thereby facilitating the production of cytotoxic reactive oxygen species (ROS) by photosensitizer under laser irradiation. More importantly, the decomposition of the MnO shell would further promote the release of the loaded doxorubicin (DOX), and thus an efficient chemo-PDT synergistic therapy was realized. Both in vitro and in vivo experimental results demonstrated the oxygen self-sufficient multifunctional nanoplatform could exhibit significantly enhanced anticancer efficiencies compared with chemotherapy or PDT alone.
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http://dx.doi.org/10.1016/j.nano.2021.102440DOI Listing
July 2021

Modulation of CD47-SIRPα innate immune checkpoint axis with Fc-function detuned anti-CD47 therapeutic antibody.

Cancer Immunol Immunother 2021 Jul 10. Epub 2021 Jul 10.

Bristol Myers Squibb, 10300 Campus Point Drive, Suite 100, San Diego, CA, 92121, USA.

Cluster of differentiation 47 (CD47) is a transmembrane protein ubiquitously expressed on human cells but overexpressed on many different tumor cells. The interaction of CD47 with signal-regulatory protein alpha (SIRPα) triggers a "don't eat me" signal to the macrophage, inhibiting phagocytosis. Thus, overexpression of CD47 enables tumor cells to escape from immune surveillance via the blockade of phagocytic mechanisms. We report here the development and characterization of CC-90002, a humanized anti-CD47 antibody. CC-90002 is unique among previously reported anti-CD47 bivalent antibodies that it does not promote hemagglutination while maintaining high-affinity binding to CD47 and inhibition of the CD47-SIRPα interaction. Studies in a panel of hematological cancer cell lines showed concentration-dependent CC-90002-mediated phagocytosis in acute lymphoblastic leukemia, acute myeloid leukemia (AML), lenalidomide-resistant multiple myeloma (MM) cell lines and AML cells from patients. In vivo studies with MM cell line-derived xenograft models established in immunodeficient mice demonstrated significant dose-dependent antitumor activity of CC-90002. Treatment with CC-90002 significantly prolonged survival in an HL-60-disseminated AML model. Mechanistic studies confirmed the binding of CC-90002 to tumor cells and concomitant recruitment of F4-80 positive macrophages into the tumor and an increase in expression of select chemokines and cytokines of murine origin. Furthermore, the role of macrophages in the CC-90002-mediated antitumor activity was demonstrated by transient depletion of macrophages with liposome-clodronate treatment. In non-human primates, CC-90002 displayed acceptable pharmacokinetic properties and a favorable toxicity profile. These data demonstrate the potential activity of CC-90002 across hematological malignancies and provided basis for clinical studies CC-90002-ST-001 (NCT02367196) and CC-90002-AML-001 (NCT02641002).
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http://dx.doi.org/10.1007/s00262-021-03010-6DOI Listing
July 2021

[Induction of mouse T lymphocyte differentiation in vitro by thymic organoids].

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2021 Aug;37(8):679-686

Center for Clinical Molecular Medicine, Children's Hospital, Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders (Chongqing), China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Engineering Research Center for Stem Cell Therapy, Chongqing 400014, China. *Corresponding author, E-mail:

Objective To induce the differentiation of hematopoietic stem progenitor cells (HSPCs) into T cell by creating thymic organoids and simulating the three-dimensional structure of thymus tissue in vitro. Methods The retroviral vector expressing the DLL1 and Green fluorescent protein (GFP) was constructed, and the OP9-DLL1 cell line was established in OP9 cells with the aid of retroviral infection. The mRNA and protein level of DLL1 in OP9-DLL1 cells was detected by quantitative real-time PCR and Western blot respectively. Immunofluorescence assay was used to detect the DLL1 protein expression and distribution in OP9-DLL1 cells. HSPCs were extracted from E13.5 fetal liver and bone marrow of C57BL/6 mouse, and mixed with OP9-DLL1 cells in an appropriate ratio respectively, then compacted by centrifuging and cultured at the air-liquid interface in medium. Fluorescence microscope was used to observe the growth of thymic organoids. Flow cytometry was used to detect the expression of T cell surface markers, including CD3, CD4, CD8, CD25, CD44, CD45, CD117 and TCRβ. Immunofluorescence cytochemical staining was used to observe the distribution of hematopoietic cells in thymic organoids. Results The retroviral vector expressing DLL1 and GFP was successfully constructed. The OP9 cells were infected with the retrovirus constructed, and OP9-DLL1 cells were obtained by GFP screening. The mRNA and protein level of DLL1 in OP9-DLL1 cells significantly increased, and DLL1 was expressed in the membrane OP9-DLL1 cells. During the 40 days of culture, the thymic organoids remained in good condition and increased gradually in volume. The thymic organoids induced programmed differentiation of T cells, and differentiation of HSPCs into CD3 T cells. Conclusion OP9-DLL1 cells can be used to construct thymic organoids and to induce differentiation of HSPCs into T cells in vitro.
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August 2021

Association Between the Concentration and Rangeability of Cystatin C and Mortality of COVID-19 Patients With or Without Type 2 Diabetes Mellitus: A Retrospective Analysis.

Front Endocrinol (Lausanne) 2021 21;12:642452. Epub 2021 Jun 21.

School of Software Engineering, Xi'an Jiaotong University, Xi'an, China.

Background: We investigated if the concentration and "rangeability" of cystatin C (CysC) influenced the prognosis of coronavirus disease 2019 (COVID-19) in patients suffering from, or not suffering from, type 2 diabetes mellitus (T2DM).

Methods: A total of 675 T2DM patients and 572 non-T2DM patients were divided into "low" and "high" CysC groups and low and high CysC-rangeability groups according to serum CysC level and range of change of CysC level, respectively. Demographic characteristics, clinical data, and laboratory results of the four groups were analyzed.

Results: COVID-19 patients with a high level and rangeability of CysC had more organ damage and a higher risk of death compared with those with a low level or low rangeability of CysC. Patients with a higher level and rangeability of CysC had more blood lymphocytes and higher levels of C-reactive protein, alanine aminotransferase, and aspartate aminotransferase. After adjustment for possible confounders, multivariate analysis revealed that CysC >0.93 mg/dL was significantly associated with the risk of heart failure (OR = 2.231, 95% CI: 1.125-5.312) and all-cause death (2.694, 1.161-6.252). CysC rangeability >0 was significantly associated with all-cause death (OR = 4.217, 95% CI: 1.953-9.106). These associations were stronger in patients suffering from T2DM than in those not suffering from T2DM.

Conclusions: The level and rangeability of CysC may influence the prognosis of COVID-19. Special care and appropriate intervention should be undertaken in COVID-19 patients with an increased CysC level during hospitalization and follow-up, especially for those with T2DM.
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http://dx.doi.org/10.3389/fendo.2021.642452DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8256889PMC
July 2021

Longitudinal characterization of phenotypic profile of T cells in chronic hepatitis B identifies immune markers associated with HBsAg loss.

EBioMedicine 2021 Jul 4;69:103464. Epub 2021 Jul 4.

Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Joint International Laboratory of Infection and Immunity, Huazhong University of Science and Technology, Wuhan 430022, China. Electronic address:

Background: The current desirable endpoint of treatment against chronic hepatitis B virus infection (cHBV) is to achieve a functional cure, which is defined as HBsAg loss (sAg-L) with or without anti-HBs seroconversion. However, the immunological features that are associated with functional cure have not been studied in detail.

Methods: 172 cHBV patients (67 HBeAg+ and 105 HBeAg-), including 141 HBsAg retained (sAg-R) patients (115 chronic hepatitis and 26 asymptomatic carriers), 31 sAg-L patients, and 24 healthy individuals (vaccinated but not infected with HBV) were examined for their T cell phenotypic profile and HBV-specific T cell responses by flow cytometry. 18 cHBV patients with low serum HBsAg levels were also longitudinally followed for their T cell phenotypic profile and HBV-specific T cell responses up to 60 weeks.

Findings: sAg-L patients showed distinct CD4 and CD8 T cell phenotype fingerprints compared to those of sAg-R patients, as mainly indicated by the upregulation of HLA-DR on both CD4 and CD8 T cells, and a potent HBcAg-specific CD8 T cell response. The changes in the T cell phenotype in cHBV patients were even more profound during rapid HBsAg decrease and was associated with interferon α treatment. The expression of HLA-DR (r = 0·3269, p = 0·0037), CD95 (r = 0·2796, p = 0·0151), CD40L (r = 0·2747, p = 0·0156), CTLA-4 (r = 0·2786, p = 0·0148), TIM-3 (r = 0·3082, p = 0·0068), CD107a (r = 0·3597, p = 0·0013) on CD4 T cells, and HLA-DR (r = 0·3542, p = 0·0016), CD69 (r = 0·2507, p = 0·0279), CD107a (r = 0·2875, p = 0·0112) on CD8 T cells were positively correlated with the rate of HBsAg decrease. The expression of HLA-DR (r = 0·2846, p = 0·0009) and CD95 (r = 0·2442, p = 0·0049) on CD8 T cells were positively correlated with the magnitude of the HBcAg-specific T cell responses in cHBV patients. Importantly, CTLA-4, CD95 and CD107a expression on CD4 T cells, as well as HLA-DR and TIM-3 expression on CD8 T cells in combination with HBsAg quantification were identified as potential predictive factors for sAg-L within 48 weeks in cHBV patients.

Interpretation: The onset of HBsAg decrease and subsequent loss in cHBV patients on treatment is associated with significant alterations of both CD4 and CD8 T cell phenotypes. Characterization of the T cell phenotype in cHBV patients may present predicative value for sAg-L.

Funding: National Natural Science Foundation of China, National Scientific and Technological Major Project of China, Integrated Innovative Team for Major Human Diseases Program of Tongji Medical College, "Double-First Class" Project for the International Cooperation Center on Infection and Immunity, HUST.
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http://dx.doi.org/10.1016/j.ebiom.2021.103464DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8261015PMC
July 2021

Proteomics of Homeobox7 Enhanced Salt Tolerance in .

Int J Mol Sci 2021 Jun 15;22(12). Epub 2021 Jun 15.

Department of Biology, Genetics Institute, University of Florida, Gainesville, FL 32610, USA.

(common ice plant) is a halophyte species that has adapted to extreme conditions. In this study, we cloned a transcription factor gene from the ice plant. The expression of was significantly induced by 500 mM NaCl and it reached the peak under salt treatment for 7 days. The protein was targeted to the nucleus. -overexpressing in ice plant leaves through -mediated transformation led to 25 times more transcripts than the non-transformed wild type (WT). After 500 mM NaCl treatment for 7 days, the activities of superoxide dismutase (SOD) and peroxidase (POD) and water content of the transgenic plants were higher than the WT, while malondialdehyde (MDA) was decreased in the transgenic plants. A total of 1082 and 1072 proteins were profiled by proteomics under control and salt treatment, respectively, with 22 and 11 proteins uniquely identified under control and salt stress, respectively. Among the 11 proteins, 7 were increased and 4 were decreased after salt treatment. Most of the proteins whose expression increased in the overexpression (OE) ice plants under high salinity were involved in transport regulation, catalytic activities, biosynthesis of secondary metabolites, and response to stimulus. The results demonstrate that the transcription factor plays a positive role in improving plant salt tolerance.
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http://dx.doi.org/10.3390/ijms22126390DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8232686PMC
June 2021

Brain Mechanisms of COVID-19-Sleep Disorders.

Int J Mol Sci 2021 Jun 28;22(13). Epub 2021 Jun 28.

Institute of Physics, Humboldt University, Newtonstrasse 15, 12489 Berlin, Germany.

2020 and 2021 have been unprecedented years due to the rapid spread of the modified severe acute respiratory syndrome coronavirus around the world. The coronavirus disease 2019 (COVID-19) causes atypical infiltrated pneumonia with many neurological symptoms, and major sleep changes. The exposure of people to stress, such as social confinement and changes in daily routines, is accompanied by various sleep disturbances, known as 'coronasomnia' phenomenon. Sleep disorders induce neuroinflammation, which promotes the blood-brain barrier (BBB) disruption and entry of antigens and inflammatory factors into the brain. Here, we review findings and trends in sleep research in 2020-2021, demonstrating how COVID-19 and sleep disorders can induce BBB leakage via neuroinflammation, which might contribute to the 'coronasomnia' phenomenon. The new studies suggest that the control of sleep hygiene and quality should be incorporated into the rehabilitation of COVID-19 patients. We also discuss perspective strategies for the prevention of COVID-19-related BBB disorders. We demonstrate that sleep might be a novel biomarker of BBB leakage, and the analysis of sleep EEG patterns can be a breakthrough non-invasive technology for diagnosis of the COVID-19-caused BBB disruption.
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http://dx.doi.org/10.3390/ijms22136917DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8268116PMC
June 2021

Differentiation of breast tissue types for surgical margin assessment using machine learning and polarization-sensitive optical coherence tomography.

Biomed Opt Express 2021 May 29;12(5):3021-3036. Epub 2021 Apr 29.

Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.

We report an automated differentiation model for classifying malignant tumor, fibro-adipose, and stroma in human breast tissues based on polarization-sensitive optical coherence tomography (PS-OCT). A total of 720 PS-OCT images from 72 sites of 41 patients with H&E histology-confirmed diagnoses as the gold standard were employed in this study. The differentiation model is trained by the features extracted from both one standard OCT-based metric (i.e., intensity) and four PS-OCT-based metrics (i.e., phase difference between two channels (), phase retardation (), local phase retardation (), and degree of polarization uniformity ()). Further optimized by forward searching and validated by leave-one-site-out-cross-validation (LOSOCV) method, the best feature subset was acquired with the highest overall accuracy of 93.5% for the model. Furthermore, to show the superiority of our differentiation model based on PS-OCT images over standard OCT images, the best model trained by intensity-only features (usually obtained by standard OCT systems) was also obtained with an overall accuracy of 82.9%, demonstrating the significance of the polarization information in breast tissue differentiation. The high performance of our differentiation model suggests the potential of using PS-OCT for intraoperative human breast tissue differentiation during the surgical resection of breast cancer.
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http://dx.doi.org/10.1364/BOE.423026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194620PMC
May 2021

Nucleoprotein (P40) Binding to 5HT2C Receptors (5HT2CR) is the Key Point in the Pathogenesis of BoDV-1-Infected Hosts.

Neurochem Res 2021 Sep 24;46(9):2427-2438. Epub 2021 Jun 24.

NHC Key Laboratory of Diagnosis and Treatment On Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, 1 Yixueyuan Road, Yuzhong, Chongqing, 400016, China.

Nucleoprotein (P40) is one of the most important proteins of Borna disease virus 1 (BoDV-1), but which proteins it would bind to in the pathogenesis of BoDV-1-infected hosts is unknown. We used lentivirus LV5-P40 overexpressing P40 to infect primary hippocampal neurons and characterized the interactome of P40 with co-immunoprecipitation (Co-IP) followed by mass spectrometry (MS) analysis. These interacting protein partners revealed the pathogenesis of BoDV-1-infected hosts. We also show for the first time that P40 interacts with 5HT2CR in rat neurons, which may be the molecular basis leading to neuropsychiatric diseases such as anxiety disorders and behavioral abnormalities after BoDV-1 infection of hosts.
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http://dx.doi.org/10.1007/s11064-021-03385-zDOI Listing
September 2021

Near work, screen time, outdoor time and myopia in schoolchildren in the Sunflower Myopia AEEC Consortium.

Acta Ophthalmol 2021 Jun 17. Epub 2021 Jun 17.

Singapore Eye Research Institute, Singapore, Singapore.

Purpose: To examine the association between near work, screen time including TV and outdoor time with myopia in children from the Sunflower Myopia Asian Eye Epidemiology Consortium (AEEC).

Methods: We analysed AEEC cross-sectional data (12 241 children) on risk factors (near work, screen time including TV and outdoor time) and myopia of six population-based studies (China, Hong Kong and Singapore). Cycloplegic refraction and axial length (AL) measurements were included. Risk factors were determined using questionnaires. Data were pooled from each study, and multivariable regression analysis was performed to evaluate the associations between risks factors and myopia, spherical equivalent (SE) and AL.

Results: Among the included children, 52.1% were boys, 98.1% were Chinese and 69.7% lived in urban areas. Mean±standard deviation (SD) for age was 8.8 ± 2.9 years, for SE was -0.14 ± 1.8 D and for AL was 23.3 ± 1.1 mm. Myopia prevalence was 30.6%. In multivariate analysis, more reading and writing (OR = 1.17; 95% CI, 1.11-1.24), more total near work (OR = 1.05; 95% CI, 1.02-1.09) and less outdoor time (OR = 0.82, 95% CI, 0.75-0.88) were associated with myopia (p's < 0.05). These factors were similarly associated with SE and AL (p's < 0.05), except for total near work and AL (p = 0.15). Screen time including TV was not significantly associated with myopia (p = 0.49), SE (p = 0.49) or AL (p = 0.83).

Conclusion: In this study, increased reading and writing and decreased outdoor time were associated with myopia. Screen time may be a surrogate factor of near work or outdoor time, but further research is needed to assess its role as an independent risk factor for myopia.
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http://dx.doi.org/10.1111/aos.14942DOI Listing
June 2021

Bacillus amyloliquefaciens FH-1 significantly affects cucumber seedlings and the rhizosphere bacterial community but not soil.

Sci Rep 2021 Jun 8;11(1):12055. Epub 2021 Jun 8.

Tianjin Key Laboratory for Industrial Biological Systems and Bioprocessing Engineering, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, 300308, People's Republic of China.

Plant growth-promoting bacteria (PGPB) inoculants have been applied worldwide. However, the ecological roles of PGPB under different soil conditions are still not well understood. The present study aimed to explore the ecological roles of Bacillus amyloliquefaciens FH-1 (FH) on cucumber seedlings, rhizosphere soil properties, and the bacterial community in pot experiments. The results showed that FH had significant effects on cucumber seedlings and the rhizosphere bacterial community but not on soil properties. The FH promoted cucumber seedlings growth, reduced the rhizosphere bacterial diversity, increased Proteobacteria, and decreased Acidobacteria. Linear discriminant analysis (LDA) effect size (LEfSe) revealed that FH enriched two taxa (GKS2_174 and Nannocystaceae) and inhibited 18 taxa (mainly Acidobacteria, Actinobacteria, BRC1, Chloroflexi, Plantctomycetes, and Verrucomicrobia). Co-occurrence network analysis demonstrated that FH increased bacteria-bacteria interactions and that Bacillus (genus of FH) had few interactions with the enriched and inhibited taxa. This might indicate that FH does not directly affect the enriched and inhibited taxa. Correlation analysis results displayed that cucumber seedlings' weight and height/length (except root length) were significantly correlated with the 18 inhibited taxa and the enriched taxa Nannocystaceae. It was speculated that FH might promote cucumber seedling growth by indirectly enriching Nannocystaceae and inhibiting some taxa from Acidobacteria, Actinobacteria, BRC1, Chloroflexi, Plantctomycetes, and Verrucomicrobia.
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http://dx.doi.org/10.1038/s41598-021-91399-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187646PMC
June 2021

Large historical carbon emissions from cultivated northern peatlands.

Sci Adv 2021 Jun 4;7(23). Epub 2021 Jun 4.

Department of Geography, University of Utah, Salt Lake City, UT, USA.

When a peatland is drained and cultivated, it behaves as a notable source of CO However, we lack temporally and spatially explicit estimates of carbon losses from cultivated peatlands. Using a process-based land surface model that explicitly includes representation of peatland processes, we estimate that northern peatlands converted to croplands emitted 72 Pg C over 850-2010, with 45% of this source having occurred before 1750. This source surpassed the carbon accumulation by high-latitude undisturbed peatlands (36 to 47 Pg C). Carbon losses from the cultivation of northern peatlands are omitted in previous land-use emission assessments. Adding this ignored historical land-use emission implies an 18% larger terrestrial carbon storage since 1750 to close the historical global carbon budget. We also show that carbon emission per unit area decrease with time since drainage, suggesting that time since drainage should be accounted for in inventories to refine land-use emissions from cultivated peatlands.
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http://dx.doi.org/10.1126/sciadv.abf1332DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8177697PMC
June 2021

Effect of liquid volume and microflora source on degradation rate and microbial community in corn stover degradation.

AMB Express 2021 Jun 1;11(1):80. Epub 2021 Jun 1.

Tianjin Key Laboratory for Industrial Biological Systems and Bioprocessing Engineering, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, No. 32, West 7th Avenue, Tianjin Airport Economic Area, Tianjin, 300308, P R China.

Degradation is the bottleneck in the utilization of crop straw. In this paper, we screened the microbial consortia degrading corn stover from straw degrading consortia MC1 (M), sheep feces (Y), and mixtures (Q) of M, Y, and cattle feces. The effects of microflora source and liquid volume (representing dissolved oxygen) on the microbial community and degradation rate of corn stover were investigated. The results showed that the degradation rate and cellulase activity of a 200 mL liquid volume (L2) were significantly higher than that of 100 mL (L1). Microflora source had a significant effect on bacterial and fungal diversity, composition and taxa. Q and Y had higher bacterial and fungal α-diversity than that of M. The degradation rate was significantly correlated with cellulase activity but not with microbial diversity. This indicated that liquid volume had a significant effect on degradation rate while microflora source had a significant effect on microbial community in corn stover degradation.
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http://dx.doi.org/10.1186/s13568-021-01233-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8169732PMC
June 2021

Individualized Nomogram for Predicting Survival in Patients with Brain Metastases After Stereotactic Radiosurgery Utilizing Driver Gene Mutations and Volumetric Surrogates.

Front Oncol 2021 13;11:659538. Epub 2021 May 13.

Department of Oncology, Guangdong Sanjiu Brain Hospital, Guangzhou, China.

It is well-known that genomic mutational analysis plays a significant role in patients with NSCLC for personalized treatment. Given the increasing use of stereotactic radiosurgery (SRS) for brain metastases (BM), there is an emerging need for more precise assessment of survival outcomes after SRS. Patients with BM and treated by SRS were eligible in this study. The primary endpoint was overall survival (OS). Cox regression models were used to identify independent prognostic factors. A survival predictive nomogram was developed and evaluated by Concordance-index (C-index), area under the curve (AUC), and calibration curve. From January 2016 to December 2019, a total of 356 BM patients were eligible. The median OS was 17.7 months [95% confidence interval (CI) 15.5-19.9] and the actual OS at 1- and 2-years measured 63.2 and 37.6%, respectively. A nomogram for OS was developed by incorporating four independent prognostic factors: Karnofsky Performance Score, cumulative tumor volume, gene mutation status, and serum lactate dehydrogenase. The nomogram was validated in a separate cohort and demonstrated good calibration and good discriminative ability (C-index = 0.780, AUC = 0.784). The prognostic accuracy of the nomogram (0.792) was considerably enhanced when compared with classical prognostic indices, including the Graded Prognostic Assessment (0.708), recursive partitioning analysis (0.587), and the SRS (0.536). Kaplan-Meier curves showed significant differences in OS among the stratified low-, median- and high-risk groups ( < 0.001). In conclusion, we developed and validated an individualized prognostic nomogram by integrating physiological, volumetric, clinical chemistry, and molecular biological surrogates. Although this nomogram should be validated by independent external study, it has a potential to facilitate more precise risk-stratifications to guide personalized treatment for BM.
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http://dx.doi.org/10.3389/fonc.2021.659538DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8158152PMC
May 2021

Single sample scoring of hepatocellular carcinoma: A study based on data mining.

Int J Immunopathol Pharmacol 2021 Jan-Dec;35:20587384211018389

Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.

Hepatocellular carcinoma (HCC) is a high mortality malignancy and the second leading cause of cancer-related deaths. Because the immune system plays a dual role by assisting the host barrier and tumor progression, there are complex interactions with considerable prognostic significance. Herein, we performed single-sample gene set enrichment (ssGSEA) to explore the tumor microenvironment (TME) and quantify the tumor-infiltrating immune cell (TIIC) subgroups of immune responses based on the HCC cohort of The Cancer Genome Atlas (TCGA) database. We evaluate molecular subpopulations, survival, function, and expression differential associations, as well as reveal potential targets, and biomarkers for immunotherapy. We combined the TME score and the 29 immune cell types in the low, medium, and high immunity groups. The stromal score, immune score, and ESTIMATE score were positively correlated with immune activity but negatively correlated with the tumor purity. There were 23 human leukocyte antigen (HLA)-related genes that were significantly different. However, KIAA1429 was not significant among the different immunity groups. Besides, programmed death-ligand 1 (PD-L1) and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) expression increased with the increase of immune activity. This may provide valuable information for HCC immunotherapy. We also found that there was no significant difference in naïve B cells, macrophages M1, activated mast cells, resting natural killer (NK) cells, and T cells gamma delta among the different immunity groups. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that the differential proteins were mainly enriched in alpha-linolenic acid (ALA) metabolism, cytokine-cytokine receptor interaction, glycosaminoglycan biosynthesis-heparan sulfate/heparin, glycosphingolipid biosynthesis-ganglio series and proteasome. Our findings provide a deeper understanding of the immune scene, uncovering remarkable immune infiltration patterns of various subtypes of HCC using ssGSEA. This study advances the understanding of immune response and provides a basis for research to enhance immunotherapy.
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http://dx.doi.org/10.1177/20587384211018389DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8168165PMC
May 2021

Tissue Optical Clearing for Biomedical Imaging: From In Vitro to In Vivo.

Adv Exp Med Biol 2021 ;3233:217-255

Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Wuhan, Hubei, China.

Tissue optical clearing technique provides a prospective solution for the application of advanced optical methods in life sciences. This chapter firstly gives a brief introduction to mechanisms of tissue optical clearing techniques, from the physical mechanism to chemical mechanism, which is the most important foundation to develop tissue optical clearing methods. During the past years, in vitro and in vivo tissue optical clearing methods were developed. In vitro tissue optical clearing techniques, including the solvent-based clearing methods and the hydrophilic reagents-based clearing methods, combined with labeling technique and advanced microscopy, can be applied to image 3D microstructure of tissue blocks or whole organs such as brain and spinal cord with high resolution. In vivo skin or skull optical clearing, promise various optical imaging techniques to detect cutaneous or cortical cell and vascular structure and function without surgical window.
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http://dx.doi.org/10.1007/978-981-15-7627-0_11DOI Listing
June 2021

The rosette-forming glioneuronal tumor mimicked cerebral cysticercosis: a case report.

Neurol Sci 2021 May 20. Epub 2021 May 20.

Department of Radiology, Shanghai East Hospital, Tongji University, No. 150 Jimo Road, Pudong New Area, Shanghai, 200120, China.

Introduction: Rosette-forming glioneuronal tumor (RGNT) is a rare variety of slow growing mixed glioneuronal tumor involving primarily fourth ventricular region. This is a comprehensive analysis of a 22-year-old woman with RGNT composed of mainly cystic components. In addition, the case showed multiple lesions located in brain parenchyma which mimicked cerebral cysticercosis. Here, we analyzed this case and listed some characteristics of RGNTs in reported literature which occurring in atypical locations for further understanding it.

Case Report: A 22-year-old woman presented with a history of transient dizziness, nausea, and vomiting. Magnetic resonance imaging (MRI) showed multiple cystic lesions in brain parenchyma and then the patient was diagnosed with cerebral cysticercosis possibility. Empirical anti-infective therapy in addition to a follow-up post 2 weeks of MRI examination showed the lesions unchanged. Finally, a biopsy of the right cerebellar hemisphere lesions verified RGNT.

Conclusion: RGNT is an uncommon tumor classified as grade I glioma by World Health Organization (WHO) with slightly longer course. The imaging findings of RGNT are not specific especially in atypical areas. RGNT is rare, but we should also consider the possibility in diagnosis and differential diagnosis.
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http://dx.doi.org/10.1007/s10072-021-05199-xDOI Listing
May 2021

Radiation-Induced Soft Tissue Injuries in Patients With Advanced Mandibular Osteoradionecrosis: A Preliminary Evaluation and Management of Various Soft Tissue Problems Around Radiation-Induced Osteonecrosis Lesions.

Front Oncol 2021 28;11:641061. Epub 2021 Apr 28.

Department of Oral Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Objectives: Radiation-induced soft-tissue injuries (STIs) in mandibular osteoradionecrosis (ORN) are not well studied regarding their correlations with nearby bone lesions. The aim of this study is to investigate the severity of radiation-induced STIs in advanced mandibular ORN and its relationship with hard-tissue damage and postoperative outcomes.

Methods: A retrospective study was performed in our institution from January 2017 to December 2019. Aside from demographic factors, the associations between the triad ORN variables (irradiation doses, ORN stages, ORN sizes) and radiation-related STI factors, vascular characteristics, and postoperative functional recovery were assessed. In addition, the severity of STI was also compared with treatment outcomes. Such correlations were established both univariate and multivariable analyses.

Results: A total number of 47 patients were included. The median follow-up reached 27 months. Nasopharyngeal cancer was the histology type among most patients (n = 21, 44.7%). The median irradiation doses reached 62 Gy (range, 40-110 Gy). For STI, the symptom scoring equaled an average of 5.4 (range from 1 to 12), indicative of the severity of STI problems. During preoperative MRI examinations, signs of hypertrophy or edema (n = 41, 87.2%) were frequently discerned. Most patients (n = 23, 48.9%) also had extensive muscular fibrosis and infection, which required further debridement and scar release. Surprisingly, most STI factors, except cervical fibrosis (p = 0.02), were not in parallel with the ORN levels. Even the intraoperative soft-tissue defect changes could not be extrapolated by the extent of ORN damage (p = 0.096). Regarding the outcomes, a low recurrence rate (n = 3, 6.9%) was reported. In terms of soft tissue-related factors, we found a strong correlation (p = 0.004) between symptom scores and recurrence. In addition, when taking trismus into consideration, both improvements in mouth-opening distance (p < 0.001) and facial contour changes (p = 0.004) were adversely affected. Correlations were also observed between the intraoperative soft-tissue defect changes and complications (p = 0.024), indicative of the importance of STI evaluation and management.

Conclusions: The coexistence of hard- and soft-tissue damage in radiation-induced advanced mandibular ORN patients reminds surgeons of the significance in assessing both aspects. It is necessary to take the same active measures to evaluate and repair both severe STIs and ORN bone lesions.
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http://dx.doi.org/10.3389/fonc.2021.641061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113699PMC
April 2021

IL-18 promotes erythrophagocytosis and erythrocyte degradation by M1 macrophages in a calcific microenvironment: IL-18 promotes erythrophagocytosis and degradation.

Can J Cardiol 2021 May 10. Epub 2021 May 10.

Department of Cardiovascular Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China. Shanghai Chest Hospital, Huaihai Road, Shanghai, China, 200000.. Electronic address:

Background: Calcific aortic valve disease (CAVD) is the most common cause of aortic valve replacement in developed countries. Intraleaflet haemorrhage has been found to be positively correlated with the progression of CAVD. Although most research has focused on erythrocyte degradation products, which promote CAVD progression, the process of erythrophagocytosis and erythrocyte degradation by macrophages in intraleaflet haemorrhage areas has remained unexplored.

Methods: The erythrocyte degradation products of aortic valve specimens were detected by Perls' staining and quantified. The gene and protein expression levels of IL-18 in THP-1-polarized macrophages cultured in osteogenic medium (OM) were tested. We also quantified the iron and heme degraded by macrophages and analyzed the expression of ferroportin (FPN) and heme oxygenase-1 (HO-1) in the osteogenic medium. Furthermore, we tested the mRNA and protein levels of osteoblast markers in VICs after co-culture with M1 macrophages treated with IL-18 and erythrocytes.

Results: Our experiments demonstrated that IL-18 activates HO-1 and FPN to promote erythrophagocytosis and erythrocyte degradation by macrophages in a calcific microenvironment via p38 and Erk1/2. We also found that the calcific microenvironment promotes IL-18 mRNA and protein expression in THP-1-polarized macrophages.

Conclusion: In conclusion, IL-18 promotes M1 macrophage-mediated erythrophagocytosis and erythrocyte degradation by regulating the activation of HO-1 and FPN via p38 and Erk1/2 in a calcific microenvironment.
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http://dx.doi.org/10.1016/j.cjca.2021.04.007DOI Listing
May 2021

Phase contrast coronary blood velocity mapping with both high temporal and spatial resolution using triggered Golden Angle rotated Spiral k-t Sparse Parallel imaging (GASSP) with shifted binning.

Magn Reson Med 2021 10 12;86(4):1929-1943. Epub 2021 May 12.

Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Purpose: High temporal and spatial resolutions are required for coronary blood flow measures. Current spiral breath-hold phase contrast (PC) MRI at 3T focus on either high spatial or high temporal resolution. We propose a golden angle (GA) rotated Spiral k-t Sparse Parallel imaging (GASSP) sequence for both high spatial (0.8 mm) and high temporal (<21 ms) resolutions.

Methods: GASSP PC data are acquired in left anterior descending and right coronary arteries of eight healthy subjects. Binning of GA rotated spiral data into cardiac frames may lead to large k-space gaps. To reduce those gaps, the binning window is shifted and a triggered GA scheme that resets the rotation angle every heartbeat is proposed. The gap reductions are evaluated in simulations and all subjects. Peak systolic velocity (PSV), peak diastolic velocity (PDV), coronary blood flow rate, and vessel area are validated against two reference scans, and repeatability/reproducibility are determined.

Results: Shifted binning reduced the mean k-space gaps of the triggered GA scheme by 14°-22° in simulations and about 20° in vivo. The k-space gap across three cardiac frames was reduced with the triggered GA scheme compared to the standard GA scheme (35.3°± 3.6° vs. 43°± 13.7°, t-test P = .04). PSV, PDV, flow rate, and area had high intra-scan repeatability (0.92 ≤ intraclass correlation coefficient [ICC] ≤ 0.99), and inter-scan (0.78 ≤ ICC ≤ 0.91) and intra-observer (0.91 ≤ ICC ≤ 0.98) reproducibility.

Conclusion: GASSP enables single breath-hold coronary PC MRI with high temporal and spatial resolutions. Shifted binning and a triggered GA scheme reduce k-space gaps. Quantitative coronary flow metrics are highly reproducible, especially within the same scanning session.
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http://dx.doi.org/10.1002/mrm.28837DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8295217PMC
October 2021

High glucose protects cardiomyocytes against ischaemia/reperfusion injury by suppressing myocardiocyte apoptosis via circHIPK3/miR-29b/AKT3 signalling.

J Cell Mol Med 2021 May 5. Epub 2021 May 5.

Department of Thoracic Cardiovascular Surgery, General Hospital of Central Theater Command of the People's Liberation Army, Wuhan, China.

High glucose promoted expression of AKT3, a direct target gene of miR-29b, by regulating circHIPK3 that functioned as ceRNA to sponge and down-regulate miR-29b. As a potential target gene of miR-29b, AKT3 plays a crucial role in the pathogenesis of myocardial ischaemia/reperfusion (I/R) injury, and this study aimed to investigate the potential role of high glucose in the outcome of I/R injury. qPCR and luciferase assay were carried out to investigate the relationship between the expression of circHIPK3, miR-29b and ATK3 mRNA. Immunohistochemistry and TUNEL were performed to analyse the relationship between AKT3 expression and apoptosis of myocardiocytes in vivo. No obvious difference in myocardial functions was observed between I/R and control rats under hyperglycaemia (HG) and normal glucose (NG) conditions, except that the infarct size/area at risk (IS/AR) ratio and the amount of h-FABP expression were different under HG and NG conditions. The expression of circHIPK3 and ATK3 was significantly elevated in the rats preconditioned by NG, whereas the expression of miR-29a was remarkably decreased. Meanwhile, the apoptosis of myocardial tissue was reduced in the rats preconditioned by NG. Luciferase assay confirmed that miR-29a played a repressive role in the expression of circHIPK3 and ATK3. And subsequent study indicated that the over-expressed AKT3 could rescue the increased cell apoptosis rate induced by the knockdown of circHIPK3. In this study, we demonstrated that high glucose protects cardiomyocytes against I/R associated injury by suppressing apoptosis and high glucose promoted the expression of AKT3 by regulating the expression of circHIPK3/miR-29b.
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http://dx.doi.org/10.1111/jcmm.16527DOI Listing
May 2021

Circ_0017956 promotes the proliferation and metastasis of non-small cell lung cancer through regulating miR-515-5p/ITGB8 axis.

Authors:
Na Li Dan Zhu

Cell Cycle 2021 May 4:1-13. Epub 2021 May 4.

Department of Respiratory, The Second Affiliated Hospital of Dalian Medical University, Dalian, China.

Circular RNAs (circRNAs) have been reported to exert vital roles in the tumorigenesis of non-small cell lung cancer (NSCLC). The study aimed to probe the function of circ_0017956 in NSCLC development. The expression of circ_0017956, microRNA (miR)-515-5p and integrin subunit beta 8 (ITGB8) was gauged by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot. The proliferation detection was conducted employing Cell Counting Kit-8 (CCK-8) and colony formation assays. Transwell assay was performed to determine cell migratory and invasive abilities. Western blot was implemented for the measurement of related proteins. The targeted interactions among circ_0017956, miR-515-5p and ITGB8 were affirmed by dual-luciferase reporter assay, RNA immunoprecipitation (RIP) assay and RNA pull-down assay. The role of circ_0017956 in NSCLC tumor growth was studied by xenograft mice model. Circ_0017956 and ITGB8 abundances were overtly raised whereas miR-515-5p was low expressed in NSCLC tissues and cells. Circ_0017956 knockdown caused inhibitory effects on the proliferative and metastasizing capacities of NSCLC cells. Mechanistically, circ_0017956 could sponge miR-515-5p, and circ_0017956 depletion blocked NSCLC cell malignant behaviors by increasing miR-515-5p expression. Furthermore, miR-515-5p targeted ITGB8 and ITGB8 overexpression also neutralized the miR-515-5p-triggered inhibition effects on NSCLC cell progression. Moreover, circ_0017956 could regulate ITGB8 expression through sponging miR-515-5p. In addition, circ_0017956 knockdown repressed NSCLC tumorigenesis by targeting miR-515-5p/ITGB8 axis . Circ_0017956 could promote NSCLC carcinogenesis at least partly through sponging miR-515-5p and upregulating ITGB8 level, providing a novel theoretical basis for NSCLC treatment.
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http://dx.doi.org/10.1080/15384101.2021.1919829DOI Listing
May 2021

Chemical profiling and multicomponents quantitative analysis of Panzerina lanata by ultra-fast liquid chromatography with tandem mass spectrometry.

J Sep Sci 2021 Jul 25;44(13):2524-2535. Epub 2021 May 25.

School of Pharmacy, Key Laboratory of Ethnomedicine of Ministry of Education, Minzu University of China, Beijing, P. R. China.

Panzerina lanata is a Chinese medicine with the bioactivity of detumescence and detoxification. In this study, novel qualitative and quantitative methods were established by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry and ultra-high-performance liquid chromatography-triple quadrupole linear ion trap mass spectrometry, respectively. As a result, 20 compounds were identified or tentatively characterized including flavonoids, organic acids, alkaloids, and lignans, five of which were identified for the first time based on the reference standards. The quantitative approach exhibited good linearity (R  > 0.995), precision (RSDs < 4.97%), stability (RSDs < 4.77%), and recovery (96.04-104.14%). Afterward, this method was implemented to determine 11 flavonoids in four batches of P. lanata. Among them, seven compounds were quantified for the first time. Narcissin was abundant in each batch of P. lanata (average of 10.890-14.230 mg/g) with the highest quantities. The results provide valuable information for quality evaluation.
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http://dx.doi.org/10.1002/jssc.202000944DOI Listing
July 2021

MicroRNA-223 Suppresses IL-1β and TNF-α Production in Gouty Inflammation by Targeting the NLRP3 Inflammasome.

Front Pharmacol 2021 16;12:637415. Epub 2021 Apr 16.

Research Center of Hyperuricemia and Gout, Affiliated Hospital of North Sichuan Medical College, North Sichuan Medical College, Nanchong, China.

MicroRNA-223 (MiR-223) serves as an important regulator of inflammatory and immune responses and is implicated in several auto-inflammatory disorders. Here, we measured miR-223 expression in acute and intercritical gout patients, after which we used RAW264.7 macrophages transfected with a miR-223 mimic/inhibitor to determine the function of miR-223 in monosodium urate (MSU)-induced gouty inflammation. MiR-223 was detected among 122 acute gout patients (AG), 118 intercritical gout patients (IG), and 125 healthy subjects (HC). RAW264.7 macrophages were cultured and treated with MSU. Over-expression or under-expression of miR-223 was inducted in RAW264.7 macrophages to investigate the function of miR-223. Real-time quantitative PCR, ELISA and western blotting were used to determine the expression levels of miR-223, cytokines and the NLRP3 inflammasome (NLRP3, ASC, and caspase-1). MiR-223 expression was significantly decreased in the AG group in comparison with the IG and HC groups ( < 0.001, respectively). Up-regulated expression of miR-223 was observed after acute gout remission in comparison with that observed during gout flares in 30 paired cases ( < 0.001). The abundance of the NLRP3 inflammasome and cytokines was significantly increased after RAW264.7 macrophages were treated with MSU ( < 0.01, respectively), while that of miR-223 was significantly reduced ( < 0.01). Up-regulation of miR-223 decreased the concentrations of IL-1β and TNF-α, as well as the NLRP3 inflammasome expression (p < 0.01, respectively), while IL-37 and TGF-β1 levels were unchanged ( > 0.05, respectively). Under-expression of miR-223 increased the concentrations of IL-1β and TNF-α, as well as NLRP3 inflammasome expression ( < 0.01, respectively), while IL-37 and TGF-β1 levels were not influenced ( > 0.05, respectively). These findings suggest that miR-223 provides negative feedback regulation of the development of gouty inflammation by suppressing production of IL-1β and TNF-α, but not by regulating IL-37 and TGF-β1. Moreover, miR-223 regulates cytokine production by targeting the NLRP3 inflammasome.
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http://dx.doi.org/10.3389/fphar.2021.637415DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085756PMC
April 2021

Magnetic resonance angiography and perfusion mapping by arterial spin labeling using Fourier transform-based velocity-selective pulse trains: Examination on a commercial perfusion phantom.

Magn Reson Med 2021 09 2;86(3):1360-1368. Epub 2021 May 2.

The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, Maryland, USA.

Purpose: Benchmarking of flow and perfusion MR techniques on standardized phantoms can facilitate the use of advanced angiography and perfusion-mapping techniques across multiple sites, field strength, and vendors. Here, MRA and perfusion mapping by arterial spin labeling (ASL) using Fourier transform (FT)-based velocity-selective saturation and inversion pulse trains were evaluated on a commercial perfusion phantom.

Methods: The FT velocity-selective saturation-based MRA and FT velocity-selective inversion-based ASL perfusion imaging were compared with time-of-flight and pseudo-continuous ASL at 3 T on the perfusion phantom at two controlled flow rates, 175 mL/min and 350 mL/min. Velocity-selective MRA (VSMRA) and velocity-selective ASL (VSASL) were each performed with three velocity-encoding directions: foot-head, left-right, and oblique 45°. The contrast-to-noise ratio for MRA scans and perfusion-weighted signal, as well as labeling efficiency for ASL methods, were quantified.

Results: On this phantom with feeding tubes having only vertical and transverse flow directions, VSMRA and VSASL exhibited the dependence of velocity-encoding directions. The foot-head-encoded VSMRA and VSASL generated similar signal contrasts as time of flight and pseudo-continuous ASL for the two flow rates, respectively. The oblique 45°-encoded VSMRA yielded more uniform contrast-to-noise ratio across slices than foot-head and left-right-encoded VSMRA scans. The oblique 45°-encoded VSASL elevated labeling efficiency from 0.22-0.68 to 0.82-0.90 through more uniform labeling of the entire feeding tubes.

Conclusion: Both FT velocity-selective saturation-based VSMRA and FT velocity-selective inversion-based VSASL were characterized on a commercial perfusion phantom. Careful selection of velocity-encoding directions along the major vessels is recommended for their applications in various organs.
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http://dx.doi.org/10.1002/mrm.28805DOI Listing
September 2021

Ten-eleven translocation protein 1 modulates medulloblastoma progression.

Genome Biol 2021 Apr 29;22(1):125. Epub 2021 Apr 29.

Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, 30322, USA.

Background: Medulloblastoma (MB) is the most common malignant pediatric brain tumor that originates in the cerebellum and brainstem. Frequent somatic mutations and deregulated expression of epigenetic regulators in MB highlight the substantial role of epigenetic alterations. 5-hydroxymethylcytosine (5hmC) is a highly abundant cytosine modification in the developing cerebellum and is regulated by ten-eleven translocation (TET) enzymes.

Results: We investigate the alterations of 5hmC and TET enzymes in MB and their significance to cerebellar cancer formation. We show total abundance of 5hmC is reduced in MB, but identify significant enrichment of MB-specific 5hmC marks at regulatory regions of genes implicated in stem-like properties and Nanog-binding motifs. While TET1 and TET2 levels are high in MBs, only knockout of Tet1 in the smoothened (SmoA1) mouse model attenuates uncontrolled proliferation, leading to a favorable prognosis. The pharmacological Tet1 inhibition reduces cell viability and platelet-derived growth factor signaling pathway-associated genes.

Conclusions: These results together suggest a potential key role of 5hmC and indicate an oncogenic nature for TET1 in MB tumorigenesis, suggesting it as a potential therapeutic target for MBs.
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http://dx.doi.org/10.1186/s13059-021-02352-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082834PMC
April 2021

The correlation between maternal age, parity, cardiac diastolic function and occurrence rate of pre-eclampsia.

Sci Rep 2021 Apr 23;11(1):8842. Epub 2021 Apr 23.

Department of Cardiology, NHFPC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Peking University Third Hospital, 49 Huayuan North Road, Haidian District, Beijing, 100191, China.

To evaluate the effect of age and parity on maternal cardiac diastolic function in second trimester among pregnant women with normal left ventricular ejection fraction. To analyze the correlation between impaired diastolic function and pre-eclampsia. It had been suggested that maternal cardiac adaptations during pregnancy differed between nulliparous and primiparous women and also varied according to age. Impaired cardiac function may precede pre-eclampsia. Therefore, we examined the effects of parity and age on cardiac diastolic function during pregnancy and whether impaired diastolic function during the second trimester correlates with pre-eclampsia. Women with singleton pregnancies at 13 + 0 to 27 + 6 weeks' gestation and left ventricular ejection fraction (LVEF) ≥ 50% were retrospectively identified. Diastolic function parameters were assessed using transthoracic echocardiography. Pre-eclampsia was identified from medical records. The effect of age and parity on maternal cardiac diastolic function as well as the correlation between impaired diastolic function and occurrence rate of pre-eclampsia were examined. 376 pregnant women were included (median age: 30 years; median gestational age: 14 weeks; 171 primiparous women). LVEF was 66%. Impaired cardiac diastolic function was seen in 7.8% of pregnant women < 35 years compared with 28.6% of those ≥ 35 years (p = 0.000). ROC curve showed women with maternal age over 32 began to have a higher rate of impaired cardiac diastolic function (AUC = 0.704, p = 0.000, sensitivity = 54.5%, specificity = 75.3%). There was no difference in diastolic function indices between maternal women grouped by parity. Higher maternal age was an independent risk factor of declining Em (p < 0.05). Em < 13 cm/s was significantly associated with pre-eclampsia occurrence (HR 8.56; 95% CI 3.40-21.57) after being adjusted for confounders. Maternal age is an independent risk factor for diastolic function decline. There is no difference in cardiac diastolic function between nulliparous women and primiparous women. Pre-eclampsia occurrence is significantly higher in patients with impaired diastolic function at mid-gestation. The application of risk grading using diastolic function at mid-gestation may improve the survival outcomes of pregnant women.
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http://dx.doi.org/10.1038/s41598-021-87953-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8065037PMC
April 2021
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