Publications by authors named "Yue Qi"

481 Publications

Inhibitory Effect of Dihydroartemisinin on the Proliferation and Migration of Melanoma Cells and Experimental Lung Metastasis From Melanoma in Mice.

Front Pharmacol 2021 2;12:727275. Epub 2021 Sep 2.

Department of Immunology and Pathogenic Biology, Yanbian University Medical College, Yanji, China.

Melanoma is aggressive and can metastasize in the early stage of tumor. It has been proved that dihydroartemisinin (DHA) positively affects the treatment of tumors and has no apparent toxic and side effects. Our previous research has shown that DHA can suppress the formation of melanoma. However, it remains poorly established how DHA impacts the invasion and metastasis of melanoma. In this study, B16F10 and A375 cell lines and metastatic tumor models will be used to investigate the effects of DHA. The present results demonstrated that DHA inhibited the proliferative capacity in A375 and B16F10 cells. As expected, the migration capacity of A375 and B16F10 cells was also reduced after DHA administration. DHA alleviated the severity and histopathological changes of melanoma in mice. DHA induced expansion of CD8CTL in the tumor microenvironment. By contrast, DHA inhibited Treg cells infiltration into the tumor microenvironment. DHA enhanced apoptosis of melanoma by regulating FasL expression and Granzyme B secretion in CD8CTLs. Moreover, DHA impacts STAT3-induced EMT and MMP in tumor tissue. Furthermore, Metabolomics analysis indicated that PGD2 and EPA significantly increased after DHA administration. In conclusion, DHA inhibited the proliferation, migration and metastasis of melanoma and . These results have important implications for the potential use of DHA in the treatment of melanoma in humans.
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http://dx.doi.org/10.3389/fphar.2021.727275DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8443781PMC
September 2021

Deletion of Causes Hearing Loss and Abnormal Auditory Nerve Fibers in the Mouse Cochlea.

Front Cell Neurosci 2021 25;15:713651. Epub 2021 Aug 25.

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

Complement C1q Like 1 (C1QL1), a secreted component of C1Q-related protein, is known to play an important role in synaptic maturation, regulation, and maintenance in the central nervous system. is expressed in adult cochlear inner and outer hair cells (IHCs and OHCs) with preferential expression in OHCs. We generated null mice to examine the role of C1QL1 in the auditory periphery. -null mice exhibited progressive hearing loss with elevated thresholds of auditory brainstem response and distortion product otoacoustic emission. Confocal microscopy showed that the number of nerve fibers innervating both IHCs and OHCs was significantly reduced. However, spiral ganglion neurons appeared to be normal under electron microscopy. IHC development and survival were not affected by deletion of Voltage-clamp recording and immunocytochmistry combined with confocal microscopy showed -null IHCs showed no significant reduction of pre-synaptic proteins and synaptic vesicle release. This is in contrast to significant OHC loss in the KO mice. Our study suggests that is essential for development of hair cell innervation and OHC survival. But maturation of presynaptic machinery in IHCs does not depend on C1QL1.
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http://dx.doi.org/10.3389/fncel.2021.713651DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8424102PMC
August 2021

Association of Serum Potassium Levels with Mortality and Cardiovascular Events: Findings from the Chinese Multi-provincial Cohort Study.

J Gen Intern Med 2021 Sep 10. Epub 2021 Sep 10.

Department of Epidemiology, Beijing An Zhen Hospital, Capital Medical University, Beijing, China.

Background: Dyskalemia involves critical electrolyte abnormalities and increases mortality risk in patients with acute clinical conditions. However, the association between dyskalemia and adverse outcomes in the general population is less well established.

Objective: To investigate the association of serum potassium levels with mortality and cardiovascular events in the general population and to explore the characteristics of individuals at high risk.

Design: A prospective cohort study.

Participants: A total of 5220 participants aged 50-79 years in the Chinese Multi-provincial Cohort Study.

Main Measures: Serum potassium levels were measured by the ion-selective electrode method. The outcomes were incident cardiovascular disease (CVD), CVD death, non-CVD death, and total death.

Key Results: Of the 5220 participants, 48.2% were men, and the mean age was 62.3 (SD 7.6) years. Hyperkalemia was found in 8.7% of the participants and was significantly associated with total death (hazard ratio [HR], 1.62; 95% confidence interval [CI], 1.18-2.23) and CVD death (HR, 2.12; 95% CI, 1.25-3.61) after adjustment. Furthermore, the HRs (95% CIs) of hyperkalemia combined with 2 and ≥ 3 risk factors were 2.37 (1.50-3.74) and 4.06 (2.37-6.95) for total death and 3.26 (1.56-6.80) and 8.42 (4.06-17.50) for CVD death, respectively. The 10-year cumulative incidence of total death was 17.4% for participants with 2 or more risk factors.

Conclusion: Hyperkalemia is associated with an increased risk of all-cause and CVD death, and this risk is more pronounced in patients with multiple risk factors. Our findings suggest that early identification and management of hyperkalemia in the general population are warranted.
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http://dx.doi.org/10.1007/s11606-021-07111-xDOI Listing
September 2021

TRIF Participates in the Innate Immune Response by Inducing NF-κB and IFN Activation and Promoting Apoptosis.

Front Immunol 2021 24;12:725150. Epub 2021 Aug 24.

Shandong Provincial Key Laboratory of Animal Resistance Biology, College of Life Sciences, Shandong Normal University, Jinan, China.

TRIF, an important adaptor downstream of Toll-like receptor signaling, plays a critical role in the innate immune response. In this study, the full-length coding sequence of TRIF from common carp ( L.) was cloned and characterized. Bioinformatics analysis showed that common carp TRIF exhibited a conserved TIR domain and had the closest relationship with grass carp TRIF. Expression analysis revealed that TRIF was constitutively expressed in the examined tissues of common carp, with the highest expression in the spleen and the lowest expression in the head kidney, and could be upregulated under and poly(I:C) stimulation and under poly(I:C), LPS, PGN, flagellin, and Pam3CSK4 stimulation . Laser confocal microscopy showed that common carp TRIF colocalized with the Golgi apparatus. A luciferase reporter assay showed that carp TRIF elicited the activity of ifn-1 and nf-κb through the C-terminal domain. Additionally, crystal violet staining and qPCR assays revealed that carp TRIF inhibited the replication of SVCV in epithelioma papulosum cyprini (EPC) cells. Then, the signaling downstream of carp TRIF was investigated. Coimmunoprecipitation and Western blotting analysis demonstrated that carp TRIF interacted with TBK1 and augmented the expression of TRAF6 and phosphorylation of TBK1. Overexpression of carp TRIF significantly enhanced the expression of interferon-stimulated genes and inflammatory cytokines. Furthermore, flow cytometric (FCM) analysis suggested that carp TRIF induced apoptosis through the activation of caspase-8. In summary, our study indicated that TRIF plays an essential role in the innate immune responses of common carp against bacterial and viral infection.
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http://dx.doi.org/10.3389/fimmu.2021.725150DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8421551PMC
August 2021

Therapeutic effects of different polar fractions of hawthorn extract on blood stasis model rats revealed by liquid chromatography-mass spectrometry metabolomics.

J Sep Sci 2021 Sep 7. Epub 2021 Sep 7.

College of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou, P. R. China.

Hawthorn, a commonly used traditional Chinese medicine, has been suggested to have therapeutic effects on cardiovascular disease. However, effective fractions of hawthorn extract in the treatment of cardiovascular disease, together with possible therapeutic mechanisms, remain unclear. This study aimed to investigate the effects of four different polar fractions of hawthorn extract on blood stasis model rats, and explore the possible metabolic mechanisms by using a liquid chromatography-mass spectrometry metabolomics approach. Evaluation of hemorheology and fibrinogen showed that n-butanol and ethyl acetate fractions of hawthorn extract had significant therapeutic effects on blood stasis model rats. Furthermore, metabolomics analysis showed that n-butanol and ethyl acetate fractions of hawthorn extract could reverse imbalanced biomarkers in plasma and urine of blood stasis model rats. Additionally, metabolic pathway analysis revealed that plasma biomarkers were responsible for several important pathways, including d-glutamine and d-glutamate metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, alanine, aspartate, and glutamate metabolism, sphingolipid metabolism, and arginine biosynthesis. Meanwhile, urine biomarkers were responsible for some important pathways, including phenylalanine metabolism, tyrosine metabolism, and lysine degradation. This study demonstrated that n-butanol and ethyl acetate fractions of hawthorn extract had significant therapeutic effects on blood stasis model rats, and the underlying mechanisms involved multiple metabolic pathways.
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http://dx.doi.org/10.1002/jssc.202100569DOI Listing
September 2021

The Association in Myopic Tractional Maculopathy With Myopic Atrophy Maculopathy.

Front Med (Lausanne) 2021 20;8:679192. Epub 2021 Aug 20.

Beijing Tongren Eye Center, Beijing Institute of Ophthalmology, Beijing Ophthalmology and Visual Sciences Key Laboratory, Beijing Tongren Hospital, Capital Medical University, Beijing, China.

To investigate the relationship between myopic tractional maculopathy (MTM) and myopic atrophy maculopathy (MAM). Two hundred and six eyes with definitive myopic retinoschisis were assessed in the retrospective observational case series study and the atrophic and tractional features were further evaluated. Atrophic changes were analyzed according to the atrophic component in the ATN classification and the occurrence of gamma zones and delta zones. Tractional changes were evaluated based on different retinoschisis layers, the location and range of outer retinoschisis, retinal detachment, inner lamellar macular hole (ILMH), outer lamellar MH (OLMH), full-thickness MH (FTMH), and paravascular abnormalities. Of all the eyes, 29.6, 42.7, 19.4, and 8.3% presented MAM grades with A1, A2, A3, and A4, respectively. The three layers of retinoschisis and the entire macular retinoschisis had the highest incidences in A2 (38.6%; 54.5%). The numbers of retinoschisis layers and the grades of outer retinoschisis had a weak negative correlation with MAM ( = -0.138, = 0.048; = -0.139, = 0.047). All the eyes had gamma zones, and 82.52% of eyes also had delta zones. The incidence of retinal detachment and OLMH reached the peak in A2 and then decreased gradually. With MAM aggravation, the prevalence of ILMH decreased. Eyes with A1 and A2 were more likely to have OLMH, and those with A3 and A4 were more likely to have FTMH ( = 0.028; OR, 3.423; 95% CI, 1.144-10.236; = 0.004; OR, 7.752; 95% CI, 1.951-30.803). With the MAM grades growing, the types of paravascular abnormalities increased ( = 0.165, = 0.018). Diffuse chorioretinal atrophy was the dominant MAM grade in eyes with MTM. In the study, 72.3% of eyes with MTM presented with diffuse chorioretinal atrophy and a tessellated fundus. Over 80% of eyes with MTM had both gamma zones and delta zones. Diffuse chorioretinal atrophy might be a complicated stage for MTM with the highest rate of three layers of retinoschisis, the entire macular retinoschisis, RD, and OLMH. Atrophic progression might involve the development of MH. When MTM combines with well-defined atrophy, the occurrence of FTMH should be noted.
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http://dx.doi.org/10.3389/fmed.2021.679192DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8417530PMC
August 2021

EXPRESS: Perceiving the facial trustworthiness: facial age, emotional expression and attractiveness.

Q J Exp Psychol (Hove) 2021 Sep 3:17470218211047176. Epub 2021 Sep 3.

Institute of Psychology Chinese Academy of Sciences, Renmin University of China 12471.

People can make trustworthiness judgements based on facial characteristics. However, the previous findings regarding on whether facial age influences interpersonal trust are inconsistent. Using the trust game, the current study investigated the interactions of facial age with attractiveness and emotional expression in regarding to trustworthiness judgements. In experiments 1 & 2, younger participants were asked to invest in either younger or older faces that were shown for 2000 ms and 33 ms respectively. The results showed that people trust the faces of older people more than they do of younger people. There was also an interaction between facial age and attractiveness. The participants invested more money in older faces than in younger faces only when they perceived the faces to be less attractive. However, the interaction between facial age and emotional expression was inconsistent in the two experiments. The participants invested more money in older faces that were shown for 2000 ms when they perceived the happy and sad emotions, but they invested more money in older faces that were shown for 33 ms when they perceived the happy emotion. These results reveal that people make trustworthiness judgements based on multiple facial cues when they view strangers of different ages.
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http://dx.doi.org/10.1177/17470218211047176DOI Listing
September 2021

Overexpression of TMEFF1 in Endometrial Carcinoma and the Mechanism Underlying its Promotion of Malignant Behavior in Cancer Cells.

J Cancer 2021 31;12(19):5772-5788. Epub 2021 Jul 31.

Shengjing Hospital of China Medical University, Department of Obstetrics and Gynecology, Shenyang, China.

Although tomoregulin-1 (TMEFF1) is involved in embryonic development and central nervous system regulation and is a cancer suppressor gene in brain cancers, its role in endometrial carcinoma remains unclear. The expression and prognostic value of TMEFF1 were analyzed by bioinformatics methods and immunohistochemistry. An endometrial carcinoma cell line with low expression of TMEFF1 was constructed. Scratch and Transwell assays were used to determine the effect of TMEFF1 on cell invasion and migration. Changes in key proteins in the MAPK and PI3K/AKT signaling pathways and in epithelial-mesenchymal transition (EMT)-related proteins were analyzed using western blot. Chromatin immunoprecipitation assay (ChIP) was performed to identify whether the TMEFF1 promoter region binds to the transcription factor p53. TMEFF1 was significantly upregulated in endometrial carcinoma, was closely associated with FIGO stage (=0.021) and lymph node metastasis (=0.029), and was an independent risk factor for prognosis (=0.044). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses showed that TMEFF1 and its related genes are involved in the cell cycle, regulation of mitosis, epigenetics, neural development, cell biological signal transduction and some key signal pathways. We also identified kinases, microRNAs and a transcription factor network related to TMEFF1 and the effect of TMEFF1 mutation on prognosis. knockdown of TMEFF1 significantly inhibited cell invasion and migration. Knockdown of TMEFF1 inhibited Epithelial-mesenchymal transition (EMT) and activation of the MAPK and PI3K/AKT pathways. However, the transcription factor p53 was not found to regulate the TMEFF1 gene. TMEFF1 plays an important role in endometrial carcinoma and may thus be a potential anticancer therapeutic target for endometrial carcinoma.
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http://dx.doi.org/10.7150/jca.58524DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8408118PMC
July 2021

Control of Liquid Crystal Microarray Optical Signals Using a Microspectral Mode Based on Photonic Crystal Structures.

Anal Chem 2021 08 16;93(34):11887-11895. Epub 2021 Aug 16.

State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, People's Republic of China.

Herein, a novel liquid crystal microarray (LCM) film with optical regulation ability is first constructed by combining liquid crystals (LC) and the highly ordered microporous structure of inverse opal photonic crystals (IOPhCs). The LCM films are fabricated by infiltrating LC molecules into the LC polymer with the structure of IOPhCs, and their properties are very different from those without the LC. Interestingly, the optical property of LCM films can be controlled by changing the orientation of LC molecules, which varies with the interfacial force. In combination with polarization images, spectral reflection peak, circular dichroism spectra, potential difference, and fluorescence images of LCM films, the mechanism of this change is investigated. It is found that the exposed basic group of single-stranded DNA is the key to the change of the optical property of LC microarrays. Meanwhile, the optical signals of LC microarrays based on the PhCs provide a novel LC signal mode for an LC sensing system (microspectral signal mode), and it can be recorded by a fiber-optic spectrometer, which is a great improvement on LC sensing signals. Therefore, the LC microarray sensing signal can be used for accurate analysis of targets by the change of the reflection peak intensity of PhCs. When the LC molecules are induced by different aptamers, the LC microarray sensing interface can be further used for the determination of different targets, such as cocaine and Hg. The research on LCM films is of significant value for the development of LC sensing technology and also shows great application prospects in biochemical sensing fields.
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http://dx.doi.org/10.1021/acs.analchem.1c02920DOI Listing
August 2021

Proteogenomic Analysis Unveils the HLA Class I-Presented Immunopeptidome in Melanoma and EGFR-Mutant Lung Adenocarcinoma.

Mol Cell Proteomics 2021 Aug 13;20:100136. Epub 2021 Aug 13.

Thoracic and GI Malignancies Branch, Center for Cancer Research, NCI, NIH, Bethesda, Maryland, USA; Bristol-Myers Squibb, Lawrenceville, New Jersey, USA. Electronic address:

Immune checkpoint inhibitors and adoptive lymphocyte transfer-based therapies have shown great therapeutic potential in cancers with high tumor mutational burden (TMB), such as melanoma, but not in cancers with low TMB, such as mutant epidermal growth factor receptor (EGFR)-driven lung adenocarcinoma. Precision immunotherapy is an unmet need for most cancers, particularly for cancers that respond inadequately to immune checkpoint inhibitors. Here, we employed large-scale MS-based proteogenomic profiling to identify potential immunogenic human leukocyte antigen (HLA) class I-presented peptides in melanoma and EGFR-mutant lung adenocarcinoma. Similar numbers of peptides were identified from both tumor types. Cell line and patient-specific databases (DBs) were constructed using variants identified from whole-exome sequencing. A de novo search algorithm was used to interrogate the HLA class I immunopeptidome MS data. We identified 12 variant peptides and several classes of tumor-associated antigen-derived peptides. We constructed a cancer germ line (CG) antigen DB with 285 antigens. This allowed us to identify 40 class I-presented CG antigen-derived peptides. The class I immunopeptidome comprised more than 1000 post-translationally modified (PTM) peptides representing 58 different PTMs, underscoring the critical role PTMs may play in HLA binding. Finally, leveraging de novo search algorithm and an annotated long noncoding RNA (lncRNA) DB, we developed a novel lncRNA-encoded peptide discovery pipeline to identify 44 lncRNA-derived peptides that are presented by class I. We validated tandem MS spectra of select variant, CG antigen, and lncRNA-derived peptides using synthetic peptides and performed HLA class I-binding assays to demonstrate binding to class I proteins. In summary, we provide direct evidence of HLA class I presentation of a large number of variant and tumor-associated peptides in both low and high TMB cancer. These results can potentially be useful for precision immunotherapies, such as vaccine or adoptive cell therapies in melanoma and EGFR-mutant lung cancers.
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http://dx.doi.org/10.1016/j.mcpro.2021.100136DOI Listing
August 2021

Increased concentrations of myeloperoxidase in serum and serum extracellular vesicles are associated with type 2 diabetes mellitus.

Clin Chim Acta 2021 Aug 11;522:70-76. Epub 2021 Aug 11.

Key Laboratory of Upper Airway Dysfunction-related Cardiovascular Diseases, Beijing Institute of Heart, Lung and Blood Vessel Disease, Beijing Anzhen Hospital, Capital Medical University, Beijing, China. Electronic address:

Background: Inflammatory response plays a critical role in the initiation and progression of type 2 diabetes mellitus (T2DM). Myeloperoxidase (MPO), a leukocyte-derived protagonist, exerts its proinflammatory properties in many complications. We explored the associations between serum extracellular vesicle (EV)-derived MPO as well as serum MPO and T2DM.

Methods: We performed a cross-sectional study in 151 individuals, including 93 patients with T2DM and 58 non-T2DM controls. The concentrations of serum EV-derived MPO and serum MPO were measured by Luminex Assay.

Results: Our data showed that serum EV-derived MPO concentrations and serum MPO concentrations were significantly higher in T2DM patients compared with non-T2DM subjects. In addition, multivariate logistic regression analysis revealed that serum EV-derived MPO as well as serum MPO was independently associated with the presence of T2DM even after adjusting for confounding factors (OR = 1.836 /1 ng EV-derived MPO, 95% CI = 1.395-2.417, P < 0.001; OR = 4.135 /10 ng serum MPO, 95% CI = 2.285-7.483, P < 0.001). Furthermore, serum MPO showed marginally higher discriminatory accuracy than serum EV-derived MPO in screening T2DM (AUC = 0.858; AUC = 0.779).

Conclusion: Increased concentrations of the inflammatory marker MPO either in serum or in serum EVs were independently associated with T2DM.
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http://dx.doi.org/10.1016/j.cca.2021.08.010DOI Listing
August 2021

The Interactions Between Antibiotic Resistance Genes and Heavy Metal Pollution Under Co-Selective Pressure Influenced the Bio-Enzyme Activity.

Front Chem 2021 14;9:691565. Epub 2021 Jul 14.

Engineering Research Center for Medicine, Harbin University of Commerce, Harbin, China.

The spread of antibiotic resistance genes (ARGs) has brought potential risks to public health. However, the interactions between heavy metals and ARGs, as well as their potential effect on bio-enzyme activity under the pressure of co-selectivity in soil still remain poorly understood. In this work, the distribution characteristics and the co-selective relationship of 28 ARGs and eight heavy metals in soil in a dairy farm were visualized the geographic information system (GIS) technique. Eight kinds of heavy metals were detected by an atomic fluorescence spectrometer and atomic absorption spectrophotometer, which were further evaluated the single factor pollution index value. The GIS analysis showed that arsenic (As) was the key element responsible for soil pollution, which was found to be positively related to soil depths. The top three comprehensive scores of ARGs ranked the orders of > > , indicating the high potential of risk caused by these genes in the soil environment. In addition, the functional predications performed with the 16 SrDNA sequencing data based on the KEGG database indicated that the sulfonamides in soil involved multiple pathways, especially the metabolism, transport and catabolism, and membrane transport processes. This suggested that most bio-enzymes were found to be expressed in low activities in different pathways. Significant correlations were observed between the heavy metals and ARGs ( < 0.05), particularly between the ARGs and As, Cu, Ni, Pb, and Zn ( < 0.01). This study offers deep insights into the potential interactions between heavy metals and ARGs in soil and provides guidance for the fabrication of enzyme-based smart materials for soil remediation in dairy farms.
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http://dx.doi.org/10.3389/fchem.2021.691565DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8316601PMC
July 2021

CircRtn4 Acts as the Sponge of miR-24-3p to Promote Neurite Growth by Regulating CHD5.

Front Mol Neurosci 2021 7;14:660429. Epub 2021 Jul 7.

Shenzhen Key Laboratory for Neuronal Structural Biology, Biomedical Research Institute, Shenzhen Peking University - The Hong Kong University of Science and Technology Medical Center, Shenzhen, China.

Circular RNAs (circRNAs) are covalently closed single-stranded RNA molecules. After derived from precursor mRNA back-splicing, circRNAs play important roles in many biological processes. Recently, it was shown that several circRNAs were enriched in the mammalian brain with unclear functions. The expression of circRtn4 in the mouse brain was increased with the differentiation of primary neurons. In our study, knockdown of circRtn4 inhibited neurite growth, while overexpression of circRtn4 significantly increased neurite length. By dual-luciferase reporter assay and RNA antisense purification assay, circRtn4 was identified as a miRNA sponge for miR-24-3p. Moreover, knockdown of miR-24-3p increased neurite length, while overexpression of miR-24-3p significantly inhibited neurite growth. Furthermore, CHD5 was confirmed to be a downstream target gene of miR-24-3p. And CHD5 silence counteracted the positive effect of circRtn4 overexpression on neurite growth. In conclusion, circRtn4 may act as the sponge for miR-24-3p to promote neurite growth by regulating CHD5.
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http://dx.doi.org/10.3389/fnmol.2021.660429DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8294096PMC
July 2021

Characterizing the Metabolic and Immune Landscape of Non-small Cell Lung Cancer Reveals Prognostic Biomarkers Through Omics Data Integration.

Front Cell Dev Biol 2021 6;9:702112. Epub 2021 Jul 6.

College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.

Non-small cell lung cancer (NSCLC) is one of the most common malignancies worldwide. The development of high-throughput single-cell RNA-sequencing (RNA-seq) technology and the advent of multi-omics have provided a solid basis for a systematic understanding of the heterogeneity in cancers. Although numerous studies have revealed the molecular features of NSCLC, it is important to identify and validate the molecular biomarkers related to specific NSCLC phenotypes at single-cell resolution. In this study, we analyzed and validated single-cell RNA-seq data by integrating multi-level omics data to identify key metabolic features and prognostic biomarkers in NSCLC. High-throughput single-cell RNA-seq data, including 4887 cellular gene expression profiles from NSCLC tissues, were analyzed. After pre-processing, the cells were clustered into 12 clusters using the t-SNE clustering algorithm, and the cell types were defined according to the marker genes. Malignant epithelial cells exhibit individual differences in molecular features and intra-tissue metabolic heterogeneity. We found that oxidative phosphorylation (OXPHOS) and glycolytic pathway activity are major contributors to intra-tissue metabolic heterogeneity of malignant epithelial cells and T cells. Furthermore, we constructed T-cell differentiation trajectories and identified several key genes that regulate the cellular phenotype. By screening for genes associated with T-cell differentiation using the Lasso algorithm and Cox risk regression, we identified four prognostic marker genes for NSCLC. In summary, our study revealed metabolic features and prognostic markers of NSCLC at single-cell resolution, which provides novel findings on molecular biomarkers and signatures of cancers.
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http://dx.doi.org/10.3389/fcell.2021.702112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290418PMC
July 2021

Estimating long-term time-resolved indoor PM of outdoor and indoor origin using easily obtainable inputs.

Indoor Air 2021 Jul 12. Epub 2021 Jul 12.

Department of Mechanical and Automation Engineering, The Chinese University of Hong Kong, Hong Kong SAR, China.

To evaluate the separate impacts on human health and establish effective control strategies, it is crucial to estimate the contribution of outdoor infiltration and indoor emission to indoor PM in buildings. This study used an algorithm to automatically estimate the long-term time-resolved indoor PM of outdoor and indoor origin in real apartments with natural ventilation. The inputs for the algorithm were only the time-resolved indoor/outdoor PM concentrations and occupants' window actions, which were easily obtained from the low-cost sensors. This study first applied the algorithm in an apartment in Tianjin, China. The indoor/outdoor contribution to the gross indoor exposure and time-resolved infiltration factor were automatically estimated using the algorithm. The influence of outdoor PM data source and algorithm parameters on the estimated results was analyzed. The algorithm was then applied in four other apartments located in Chongqing, Shenyang, Xi'an, and Urumqi to further demonstrate its feasibility. The results provided indirect evidence, such as the plausible explanations for seasonal and spatial variation, to partially support the success of the algorithm used in real apartments. Through the analysis, this study also identified several further development directions to facilitate the practical applications of the algorithm, such as robust long-term outdoor PM  monitoring using low-cost light-scattering sensors.
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http://dx.doi.org/10.1111/ina.12905DOI Listing
July 2021

Parallel Structure from Motion for Sparse Point Cloud Generation in Large-Scale Scenes.

Sensors (Basel) 2021 Jun 7;21(11). Epub 2021 Jun 7.

MiningLamp Technology, Beijing 100102, China.

Scene reconstruction uses images or videos as input to reconstruct a 3D model of a real scene and has important applications in smart cities, surveying and mapping, military, and other fields. Structure from motion (SFM) is a key step in scene reconstruction, which recovers sparse point clouds from image sequences. However, large-scale scenes cannot be reconstructed using a single compute node. Image matching and geometric filtering take up a lot of time in the traditional SFM problem. In this paper, we propose a novel divide-and-conquer framework to solve the distributed SFM problem. First, we use the global navigation satellite system (GNSS) information from images to calculate the GNSS neighborhood. The number of images matched is greatly reduced by matching each image to only valid GNSS neighbors. This way, a robust matching relationship can be obtained. Second, the calculated matching relationship is used as the initial camera graph, which is divided into multiple subgraphs by the clustering algorithm. The local SFM is executed on several computing nodes to register the local cameras. Finally, all of the local camera poses are integrated and optimized to complete the global camera registration. Experiments show that our system can accurately and efficiently solve the structure from motion problem in large-scale scenes.
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http://dx.doi.org/10.3390/s21113939DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201245PMC
June 2021

Analysis on leading-fiber-induced Doppler noise in interferometric FBG sensor arrays using polarization switching and PGC hybrid processing method.

Opt Express 2021 May;29(11):16118-16134

The random disturbance in the leading fiber is considered as a vital noise source in the practical interferometric fiber Bragg grating (FBG) sensor array, which is usually interrogated by periodic laser pulse pair. As the two interrogation laser pluses propagate through the leading fiber in a time-sharing manner, the leading fiber disturbance could cause undesired demodulated phase noises to both the polarization state and the pulse-interval, which are summarized as the polarization fading induced noise and the Doppler noise, respectively. This paper focused on the Doppler noise under the demodulation scheme of polarization switching (PS) and phase generated carrier (PGC) hybrid processing method. A model describing the transformation from arbitrary leading fiber stretching to sensor phase background was presented. The complexity was that the Doppler noise was coupled with the birefringence states, as verified by both simulation and experiment. In response to this issue, a two-stage Doppler noise suppression method was proposed, which is based on the PS and PGC hybrid processing and a reference sensor. A processing procedure was presented where the polarization synthesis must be performed before and the reference sensor was considered. Otherwise, the suppression algorithm will be completely invalid due to the mutual coupling of the Doppler noise and the birefringence. Experimental results showed that only after the first stage of polarization synthesis, identical Doppler noise in the two TDM channels could be obtained, with an amplitude error of 0.02 dB. The second stage involved non-sensitive reference sensor subtraction, which achieved a maximum suppression of about 30 dB, which was the highest to be best of our knowledge. The two-stage Doppler noise suppression method was tested for sinusoidal and wideband leading fiber disturbances, providing a solution for practical interferometric FBG array applications.
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http://dx.doi.org/10.1364/OE.423895DOI Listing
May 2021

The c.824C>A and c.616dupA mutations in the SLC17a8 gene are associated with auditory neuropathy and lead to defective expression of VGluT3.

Neuroreport 2021 08;32(11):949-956

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

Auditory neuropathy is sensorineural deafness where sound signals cannot be transmitted synchronously from the cochlea to the auditory center. Abnormal expression of vesicle glutamate transporter 3 (VGluT3) encoded by the SLC17a8 gene is associated with the pathophysiology of auditory neuropathy. Although several suspected pathogenic mutations of the SLC17a8 gene have been identified in humans, few studies have confirmed their pathogenicity. Here, we describe the effects of two known suspected pathogenic mutations (c.824C>A and c.616dupA) in the SLC17a8 gene coding VGluT3 protein and analyzed the potential pathogenicity of these mutations. The p.M206Nfs4 and p.A275D changes are caused by c.824C>A and c.616dupA mutations in the cytoplasmic loop, an important structure of VGluT3. To explore the potential pathogenic effects of c.824C>A and c.616dupA mutations, we performed a series of experiments on mRNA levels and protein expression in cell culture. The c.616dupA mutation in the SLC17a8 gene resulted in a significant decrease in transcriptional activity of mRNA, and the expression of VGluT3 was also reduced. The c.824C>A mutation in the SLC17a8 gene resulted in abnormal VGluT3, although this mutation did not affect the transcriptional activity of mRNA. Our results demonstrate that c.824C>A and c.616dupA mutations in the SLC17a8 gene could lead to pathological protein expression of VGluT3 and supported the potential pathogenicity of these mutations.
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http://dx.doi.org/10.1097/WNR.0000000000001687DOI Listing
August 2021

Reprogramming the immunosuppressive microenvironment of IDH1 wild-type glioblastoma by blocking Wnt signaling between microglia and cancer cells.

Oncoimmunology 2021 06 6;10(1):1932061. Epub 2021 Jun 6.

Key Laboratory of Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University, Shanghai, China.

The vast majority (>90%) of glioblastoma (GBM) patients belong to the isocitrate dehydrogenase 1 wild type (IDH1) group which exhibits a poor prognosis with a median survival of less than 15 months. This study demonstrated numerous immunosuppressive genes as well as β-catenin gene, pivotal for Wnt/β-catenin signaling, were upregulated in 206 IDH1 glioma patients using the Chinese Glioma Genome Atlas (CGGA) database. The increase in microglia with an immunosuppressive phenotype and the overexpression of β-catenin protein were further verified in IDH1 GBM patients and IDH1 GL261 glioma allografts. Subsequently, we found that IDH1 GL261 cell-derived conditioned medium activated Wnt/β-catenin signaling in primary microglia and triggered their transition to an immunosuppressive phenotype. Blocking Wnt/β-catenin signaling not only attenuated microglial polarization to the immunosuppressive subtype but also reactivated immune responses in IDH1 GBM allografts by simultaneously enhancing cytotoxic CD8 T cell infiltration and downregulating regulatory T cells. Positron emission tomography imaging demonstrated enhanced proinflammatory activities in IDH1 GBM allografts after the blockade of Wnt signaling. Finally, gavage administration of a Wnt signaling inhibitor significantly restrained tumor proliferation and improved the survival of model mice bearing IDH1 GBM allografts. Depletion of CD8 T cells remarkably abrogated the therapeutic efficacy induced by the Wnt signaling inhibitor. Overall, the present work indicates that the crosstalk between IDH1 glioma cells and immunosuppressive microglia is important in maintaining the immunosuppressive glioma microenvironment. Blocking Wnt/β-catenin signaling is a promising complement for IDH1 GBM treatment by improving the hostile immunosuppressive microenvironment.
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http://dx.doi.org/10.1080/2162402X.2021.1932061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183516PMC
June 2021

TTSurv: Exploring the Multi-Gene Prognosis in Thousands of Tumors.

Front Oncol 2021 25;11:691310. Epub 2021 May 25.

Department of Gynecology, The First Affiliated Hospital of Harbin Medical University, Harbin, China.

Thoracic malignancies are a common type of cancer and area major global health problem. These complex diseases, including lung cancer, esophageal cancer, and breast cancer, etc. have attracted considerable attention from researchers. Potential gene-cancer associations can be explored by demonstrating the association between clinical data and gene expression data. Emerging evidence suggests that the transcriptome plays a particularly critical role as a diagnostic biomarker in pathology and histology studies. Thus, there is an urgent need to develop a platform that allows users to perform a comprehensive prognostic analysis of thoracic cancers. Here, we developed TTSurv, which aims to correlate coding and noncoding genes with cancers by combining high-throughput data with clinical prognosis. TTSurv focuses on the application of high-throughput data to detect ncRNAs, such as lncRNAs and microRNAs, as novel diagnostic and prognostic biomarkers. For a more comprehensive analysis, a large amount of public expression profile data with clinical follow-up information have been integrated into TTSurv. TTSurv also provides flexible methods such as a minimum p-value algorithm and unsupervised clustering methods that can classify thoracic cancer samples into different risk groups. TTSurv will expand our understanding of ncRNAs in thoracic malignancies and provide new insights into their application as potential prognostic/diagnostic biomarkers.
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http://dx.doi.org/10.3389/fonc.2021.691310DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8186665PMC
May 2021

Charge-transfer biexciton annihilation in a donor-acceptor co-crystal yields high-energy long-lived charge carriers.

Chem Sci 2020 Aug 13;11(35):9532-9541. Epub 2020 Aug 13.

Department of Chemistry and Institute for Sustainability and Energy at Northwestern, Northwestern University 2145 Sheridan Road Evanston Illinois 60208-3113 USA

Organic donor-acceptor (D-A) co-crystals have attracted much interest due to their important optical and electronic properties. Co-crystals having ⋯DADA⋯ π-stacked morphologies are especially interesting because photoexcitation produces a charge-transfer (CT) exciton, D˙-A˙, between adjacent D-A molecules. Although several studies have reported on the steady-state optical properties of this type of CT exciton, very few have measured the dynamics of its formation and decay in a single D-A co-crystal. We have co-crystallized a -xanthenoxanthene () donor with a ,-bis(3-pentyl)-2,5,8,11-tetraphenylperylene-3,4:9,10-bis(dicarboximide) () acceptor to give an orthorhombic - ⋯DADA⋯ π-stacked co-crystal with a CT transition dipole moment that is perpendicular to the transition moments for S ← S excitation of and . Using polarized, broadband, femtosecond pump-probe microscopy, we have determined that selective photoexcitation of in the single co-crystal results in CT exciton formation within the 300 fs instrument response time. At early times (0.3 ≤ ≤ 500 ps), the CT excitons decay with a dependence, which is attributed to CT biexciton annihilation within the one-dimensional ⋯DADA⋯ π-stacks producing high-energy, long-lived (>8 ns) electron-hole pairs in the crystal. These energetic charge carriers may prove useful in applications ranging from photovoltaics and opto-electronics to photocatalysis.
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http://dx.doi.org/10.1039/d0sc03301dDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8162030PMC
August 2020

Identification of Potential Genes Associated with Vemurafenib Efficacy and Melanoma Prognosis.

Authors:
Yue Qi GuiE Ma

Comb Chem High Throughput Screen 2021 Jun 3. Epub 2021 Jun 3.

15th Department, Plastic Surgery Hospital Chinese Academy of Medical Sciences, Beijing, 10083, China.

Objective: This work aimed to investigate the molecular mechanisms underlying the efficacy of vemurafenib as a treatment for melanoma.

Methods: The GSE52882 dataset, which includes A375 and A2058 melanoma cell lines treated with vemurafenib and dimethyl sulfoxide (DMSO), and clinical information associated with melanoma patients, were acquired from the Gene Expression Omnibus (GEO) database and University of California Santa Cruz (UCSC), respectively. Functional enrichment analysis, protein-protein interaction (PPI) network construction, sub-module analysis, and transcriptional regulation analysis were performed on overlapping differentially expressed genes (DEGs) identified in both cell lines. Finally, we performed a survival analysis based on the genes identified.

Results: A total of 447 consistently overlapping DEGs (176 up- and 271 down-regulated DEGs) were screened. Upregulated genes were enriched in pathways of neurotrophin signaling, estrogen signaling, and transcriptional misregulation in cancer. Downregulated DEGs played essential roles in melanogenesis, pathways of cancer, PI3K-Akt signaling pathway, and AMPK signaling pathway. Upregulated (MMP2, JUN, KAT28, and PIK3R3) and downregulated genes (CXCL8, CCND1, IGF1R, and ITGB3) were considered as hub genes in the PPI network. Additionally, PIK3R3 and LEF1 served as key genes in the regulatory network. The overexpression of MMP2 and CXCL8 was associated with a poor prognosis in melanoma patients.

Conclusion: MMP2, CXCL8, PIK3R3, ITGB3, and LEF1 may play roles in the efficacy of vemurafenib treatment in melanoma; for example, MMP2 and PIK3R3 are likely associated with vemurafenib resistance. These findings will contribute to the development of novel therapies for melanoma.
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http://dx.doi.org/10.2174/1386207324666210603152044DOI Listing
June 2021

Oncogenic Landscape of Somatic Mutations Perturbing Pan-Cancer lncRNA-ceRNA Regulation.

Front Cell Dev Biol 2021 17;9:658346. Epub 2021 May 17.

College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.

Competing endogenous RNAs (ceRNA) are transcripts that communicate with and co-regulate each other by competing for the binding of shared microRNAs (miRNAs). Long non-coding RNAs (lncRNAs) as a type of ceRNA constitute a competitive regulatory network determined by miRNA response elements (MREs). Mutations in lncRNA MREs destabilize their original regulatory pathways. Study of the effects of lncRNA somatic mutations on ceRNA mechanisms can clarify tumor mechanisms and contribute to the development of precision medicine. Here, we used somatic mutation profiles collected from TCGA to characterize the role of lncRNA somatic mutations in the ceRNA regulatory network in 33 cancers. The 31,560 mutation sites identified by TargetScan and miRanda affected the balance of 70,811 ceRNA regulatory pathways. Putative mutations were categorized as high or low based on mutation frequencies. Multivariate multiple regression revealed a significant effect of 162 high-frequency mutations in six cancer types on the expression levels of target mRNAs (ceMs) through the ceRNA mechanism. Low-frequency mutations in multiple cancers perturbing 1624 ceM have been verified by Student's -test, indicating a significant mechanism of changes in the expression level of oncogenic genes. Oncogenic signaling pathway studies involving ceMs indicated functional heterogeneity of multiple cancers. Furthermore, we identified that lncRNA, perturbing ceMs associated with patient survival, have potential as biomarkers. Our collective findings revealed individual differences in somatic mutations perturbing ceM expression and impacting tumor heterogeneity.
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http://dx.doi.org/10.3389/fcell.2021.658346DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166229PMC
May 2021

Mechanical Performance and Dimensional Stability of Bamboo Fiber-Based Composite.

Polymers (Basel) 2021 May 25;13(11). Epub 2021 May 25.

Research Institute of Forestry New Technology, Chinese Academy of Forestry, Beijing 100091, China.

The bamboo fiber-based composite (BFBC) has high-performce in terms of mechanical properties and dimensional stability. In this study, BFBCs were prepared with different hot-pressing temperatures (150 °C, 160 °C, 170 °C, 180 °C, 190 °C, and 200 °C) and designed with different densities (1.05 g/cm, 1.10 g/cm, 1.15 g/cm and 1.20 g/cm), and their selected properties were evaluated. Temperature affected BFBC performance, which, with a general increase in temperature, showed a decrement in mechanical properties and an improvement in dimensional stability. Holocellulose content significantly decreased, and the color of BFBC became darker with the increasing of the press temperature. As the density of BFBC increased, the modulus of elasticity (MOE) significantly increased from 23.09 GPa to 27.01 GPa with the increase in temperature. The thickness swelling ratio (TSR), width swelling ratio (WSR) and water absorption ratio (WAR) declined by more than 30% with the increase in density. Overall, the results of this study provide a theoretical basis and a source of technical support to promote the design, application, and popularization of BFBC in different fields.
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http://dx.doi.org/10.3390/polym13111732DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8199268PMC
May 2021

Investigation of Macular Choroidal Thickness and Blood Flow Change by Optical Coherence Tomography Angiography After Posterior Scleral Reinforcement.

Front Med (Lausanne) 2021 29;8:658259. Epub 2021 Apr 29.

Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology and Visual Sciences Key Laboratory, Beijing, China.

This work aimed to study the effect of posterior scleral reinforcement (PSR) on choroidal thickness (CT) and blood flow. This study included 25 eyes of 24 patients with high myopia ( ≤ -6.0 dioptres or axial length ≥ 26.0 mm) who underwent PSR surgery. All patients completed the 1-month follow-up visit. Myopic macular degeneration (MMD) was graded according to the International Meta-Analysis for Pathologic Myopia (META-PM) classification based on color fundus photographs. Swept-source optical coherence tomography angiography (SSOCTA) was performed to investigate CT, choroidal perfusion area (CPA), and choriocapillaris perfusion area (CCPA) change following PSR surgery. The distribution of MMD categories was 9 (36.0%) in category 1, 10 (40.0%) in category 2, and 6 (24.0%) in category 3 or 4. MMD severity was strongly correlated with CT (all < 0.01) and CPA (all < 0.04). Postoperative CT at each sector increased significantly at 1 week's follow-up, compared to preoperative measures (all < 0.05). Postoperative CPA at subfoveal, superior, inferior, and nasal sectors also increased significantly 1 week after PSR surgery (all < 0.05). Moreover, the increased CT, CPA, and CCPA remain after PSR surgery at 1 month's follow-up, but the difference was not statistically significant. We demonstrated that the CT and choroidal blood flow increased significantly in patients with high myopia who underwent PSR surgery in a short period of time. In addition, the CT and CPA were independently associated with MMD. However, whether the transient improvement of the choroidal circulation could prevent long-term progression of high myopia warrants further study in the future.
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http://dx.doi.org/10.3389/fmed.2021.658259DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8130341PMC
April 2021

sDR5-Fc inhibits macrophage M1 polarization by blocking the glycolysis.

J Geriatr Cardiol 2021 Apr;18(4):271-280

Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Disease, Beijing Key Laboratory of Precision Medicine of Coronary Atherosclerotic Disease, Clinical Center for Coronary Heart Disease, Capital Medical University, Beijing, China.

Background: M1 polarization of macrophages is an important pathological process in myocardial ischemia reperfusion injury, which is the major obstacle for the treatment of acute myocardial infarction. Currently, the strategies and mechanisms of inhibiting M1 polarization are poorly explored. This study aims to investigate the role of soluble death receptor 5-Fc (sDR5-Fc) in regulating M1 polarization of macrophages under extreme conditions and explore the mechanisms from the aspect of glycolysis.

Methods: Extreme conditions were induced in RAW264.7 cells. Real-time quantitative polymerase chain reaction and western blot were used to detect the expression of mRNA and proteins, respectively. Cell counting kit-8 was used to investigate the proliferation activity of cells. Expression levels of inflammatory cytokines were determined by enzyme-linked immunosorbent assay.

Results: We found that sDR5-Fc rescues the proliferation of macrophages under extreme conditions, including nutrition deficiency, excessive peroxide, and ultraviolet irradiation. In addition, administration of sDR5-Fc inhibits the M1 polarization of macrophages induced by lipopolysaccharide (LPS) and interferon-gamma (IFN-γ), as the expression of M1 polarization markers CD86, CXC motif chemokine ligand 10, matrix metalloproteinase 9, and tumor necrosis factor-α, as well as the secretion of inflammatory factors interleukin (IL)-1β and IL-6, were significantly decreased. By further investigation of the mechanisms, the results showed that sDR5-Fc can recover the LPS and IFN-γ induced pH reduction, lactic acid elevation, and increased expression of hexokinase 2 and glucose transporter 1, which were markers of glycolysis in macrophages.

Conclusions: sDR5-Fc inhibits the M1 polarization of macrophages by blocking the glycolysis, which provides a new direction for the development of strategies in the treatment of myocardial ischemia reperfusion injury.
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http://dx.doi.org/10.11909/j.issn.1671-5411.2021.04.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100429PMC
April 2021

Interfacial toughening with self-assembled monolayers enhances perovskite solar cell reliability.

Science 2021 05;372(6542):618-622

School of Engineering, Brown University, Providence, RI 02912, USA.

Iodine-terminated self-assembled monolayer (I-SAM) was used in perovskite solar cells (PSCs) to achieve a 50% increase of adhesion toughness at the interface between the electron transport layer (ETL) and the halide perovskite thin film to enhance mechanical reliability. Treatment with I-SAM also increased the power conversion efficiency from 20.2% to 21.4%, reduced hysteresis, and improved operational stability with a projected T80 (time to 80% initial efficiency retained) increasing from ~700 hours to 4000 hours under 1-sun illumination and with continuous maximum power point tracking. Operational stability-tested PSC without SAMs revealed extensive irreversible morphological degradation at the ETL/perovskite interface, including voids formation and delamination, whereas PSCs with I-SAM exhibited minimal damage accumulation. This difference was attributed to a combination of a decrease in hydroxyl groups at the interface and the higher interfacial toughness.
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http://dx.doi.org/10.1126/science.abf5602DOI Listing
May 2021

Treatment of Limb Ischemia with Conducted Effects of Catheter-Based Endovascular Ultrasound.

Ultrasound Med Biol 2021 08 29;47(8):2277-2285. Epub 2021 Apr 29.

Knight Cardiovascular Institute, Oregon Health & Science University, Portland, Oregon, USA; Oregon National Primate Research Center, Oregon Health & Science University, Portland, Oregon. Electronic address:

Ultrasound (US) is known to stimulate endogenous shear-dependent pathways, and can lower microvascular resistance through mediators that are conducted downstream from US exposure. We hypothesized that endovascular US, already in use for thrombolysis in humans, can improve tissue perfusion in the setting of acute limb ischemia through downstream-conducted effects. Models of severe peripheral arterial disease were developed in mice and in rhesus macaques. An endovascular US catheter (2.3 MHz, 0.5-1.1 MPa) was used to expose the limb adductor in mice for 10 min or the femoral artery distal to stenosis in macaques for 15 min. Quantitative contrast-enhanced ultrasound perfusion imaging was performed to assess flow augmentation in the adductor muscle of mice and the calf muscle of macaques. Microvascular blood flow in the ischemic limb relative to the contralateral control limb was reduced to 22 ± 8% in mice and 36 ± 20% in macaques. US produced immediate 2.3- and 3-fold increases (p < 0.05) in the murine and macaque ischemic limbs, respectively. In macaques, perfusion in the ischemic limb was increased to a normal level. We conclude that non-cavitating US produced by endovascular catheters that are used to enhance thrombolysis in humans can reduce vascular resistance and increase limb perfusion in the setting of acute ischemia.
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http://dx.doi.org/10.1016/j.ultrasmedbio.2021.03.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8243793PMC
August 2021

Alterations in the Global Proteome and Phosphoproteome in Third Generation EGFR TKI Resistance Reveal Drug Targets to Circumvent Resistance.

Cancer Res 2021 Jun 16;81(11):3051-3066. Epub 2021 Mar 16.

Thoracic and GI Malignancies Branch, Center for Cancer Research, NCI, NIH, Bethesda, Maryland.

Lung cancer is the leading cause of cancer mortality worldwide. The treatment of patients with lung cancer harboring mutant EGFR with orally administered EGFR tyrosine kinase inhibitors (TKI) has been a paradigm shift. Osimertinib and rociletinib are third-generation irreversible EGFR TKIs targeting the EGFR T790M mutation. Osimertinib is the current standard of care for patients with EGFR mutations due to increased efficacy, lower side effects, and enhanced brain penetrance. Unfortunately, all patients develop resistance. Genomic approaches have primarily been used to interrogate resistance mechanisms. Here we characterized the proteome and phosphoproteome of a series of isogenic EGFR-mutant lung adenocarcinoma cell lines that are either sensitive or resistant to these drugs, comprising the most comprehensive proteomic dataset resource to date to investigate third generation EGFR TKI resistance in lung adenocarcinoma. Unbiased global quantitative mass spectrometry uncovered alterations in signaling pathways, revealed a proteomic signature of epithelial-mesenchymal transition, and identified kinases and phosphatases with altered expression and phosphorylation in TKI-resistant cells. Decreased tyrosine phosphorylation of key sites in the phosphatase SHP2 suggests its inhibition, resulting in subsequent inhibition of RAS/MAPK and activation of PI3K/AKT pathways. Anticorrelation analyses of this phosphoproteomic dataset with published drug-induced P100 phosphoproteomic datasets from the Library of Integrated Network-Based Cellular Signatures program predicted drugs with the potential to overcome EGFR TKI resistance. The PI3K/MTOR inhibitor dactolisib in combination with osimertinib overcame resistance both and . Taken together, this study reveals global proteomic alterations upon third generation EGFR TKI resistance and highlights potential novel approaches to overcome resistance. SIGNIFICANCE: Global quantitative proteomics reveals changes in the proteome and phosphoproteome in lung cancer cells resistant to third generation EGFR TKIs, identifying the PI3K/mTOR inhibitor dactolisib as a potential approach to overcome resistance.
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http://dx.doi.org/10.1158/0008-5472.CAN-20-2435DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8182571PMC
June 2021

Upper Lip Reconstruction Utilizing a Two-Stage Approach with Nanofat Grafting After Hemangioma Treatment.

Facial Plast Surg Aesthet Med 2021 Jul-Aug;23(4):303-308. Epub 2021 Mar 11.

Chinese Academy of Medical Sciences and Peking Union Medical College, Plastic Surgery Hospital, Beijing, China.

Lip deformities that occur after treatment of vascular anomalies treatment are often followed by serious local cicatricial adhesion and mucosa atrophy that can complicate reconstruction methods involving simple fat grafting or local flap transfer. To develop a novel technique that combines flap transfer with nanofat grafting that can be used to reconstruct the upper lip after treatment of vascular anomalies. A retrospective study of a consecutive series of 24 patients with upper lip deformities (13 female and 11 male) aged between 7 and 24 years old was conducted. Of these, 15 patients were treated with nanofat grafting alone and 9 cases were treated with nanofat grafting combined with flap transfer (6 inferior- and 3 superior-based flaps). The appearance, symmetry, and smooth of upper lips with deformities before and after surgery were compared as the main outcome. Among the patients examined, 15 achieved satisfactory results after undergoing multiple nanofat grafting treatments. The remaining nine patients who had serious deformities of the upper lip were treated using a combination of nanofat grafting and flap transfer. For these nine patients, postoperative results showed that the final appearance of the lips was generally symmetrical and smooth. Functional problems such as whistling defects were effectively corrected and no significant complications occurred. The aesthetic symmetry was higher for inferior flaps than for superior flaps and the incision scar for superior flaps was more obvious than for inferior flaps. The technique combining nanofat autografting with local flap transfer for upper lip reconstruction was demonstrated to be effective, safe, and simple to perform. These findings suggest that this combined technique can be easily performed to achieve good results with only mild undercorrection.
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http://dx.doi.org/10.1089/fpsam.2020.0076DOI Listing
August 2021
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