Publications by authors named "Guojun Liu"

107 Publications

Remediation of Mucorales-contaminated Healthcare Linens at a Laundry Facility Following an Investigation of a Case Cluster of Hospital-acquired Mucormycosis.

Clin Infect Dis 2021 Jul 20. Epub 2021 Jul 20.

University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.

Background: In an investigation of hospital-acquired mucormycosis cases among transplant recipients, healthcare linens (HCLs) delivered to our center were found to be contaminated with Mucorales. We describe an investigation and remediation of Mucorales contamination at the laundry supplying our center.

Methods: We performed monthly RODAC cultures of HCLs upon hospital arrival, and conducted site inspections and surveillance cultures at the laundry facility. Remediation was designed and implemented by infection prevention and facility leadership teams.

Results: Prior to remediation, 20% of HCLs were culture-positive for Mucorales upon hospital arrival. Laundry facility layout and processes were consistent with industry standards. Significant step-ups in Mucorales and mould culture-positivity of HCLs were detected at the post-dryer step (0% to 12% (p=0.04) and 5% to 29% (p=0.01), respectively). Further increases to 17% and 40% culture-positivity, respectively, were noted during pre-transport holding. Site inspection revealed heavy Mucorales-positive lint accumulation in rooftop air intake and exhaust vents that cooled driers; intake and exhaust vents that were facing each other; rooftop and plant-wide lint accumulation, including in the pre-transport clean room; uncovered carts with freshly-laundered HCLs. Following environmental remediation, quality assurance measures and education directed toward these sources, Mucorales culture-positivity of newly-delivered HCLs was reduced to 0.3% (p=0.0001); area of lint-contaminated rooftop decreased from 918 m 2 to 0 m 2 on satellite images.

Conclusions: Targeted laundry facility interventions guided by site inspections and step-wise culturing significantly reduced Mucorales-contaminated HCLs delivered to our hospital. Collaboration between infection prevention and laundry facility teams was crucial to successful remediation.
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http://dx.doi.org/10.1093/cid/ciab638DOI Listing
July 2021

Epigenetic Marks and Variation of Sequence-Based Information Along Genomic Regions Are Predictive of Recombination Hot/Cold Spots in .

Front Genet 2021 29;12:705038. Epub 2021 Jun 29.

School of Life Sciences and Technology, Inner Mongolia University of Science and Technology, Baotou, China.

Characterization and identification of recombination hotspots provide important insights into the mechanism of recombination and genome evolution. In contrast with existing sequence-based models for predicting recombination hotspots which were defined in a ORF-based manner, here, we first defined recombination hot/cold spots based on public high-resolution Spo11-oligo-seq data, then characterized them in terms of DNA sequence and epigenetic marks, and finally presented classifiers to identify hotspots. We found that, in addition to some previously discovered DNA-based features like GC-skew, recombination hotspots in yeast can also be characterized by some remarkable features associated with DNA physical properties and shape. More importantly, by using DNA-based features and several epigenetic marks, we built several classifiers to discriminate hotspots from coldspots, and found that SVM classifier performs the best with an accuracy of ∼92%, which is also the highest among the models in comparison. Feature importance analysis combined with prediction results show that epigenetic marks and variation of sequence-based features along the hotspots contribute dominantly to hotspot identification. By using incremental feature selection method, an optimal feature subset that consists of much less features was obtained without sacrificing prediction accuracy.
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http://dx.doi.org/10.3389/fgene.2021.705038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8276760PMC
June 2021

A Cluster-Based Approach for the Discovery of Copy Number Variations From Next-Generation Sequencing Data.

Front Genet 2021 28;12:699510. Epub 2021 Jun 28.

School of Computer Science and Technology, Xidian University, Xi'an, China.

The next-generation sequencing technology offers a wealth of data resources for the detection of copy number variations (CNVs) at a high resolution. However, it is still challenging to correctly detect CNVs of different lengths. It is necessary to develop new CNV detection tools to meet this demand. In this work, we propose a new CNV detection method, called CBCNV, for the detection of CNVs of different lengths from whole genome sequencing data. CBCNV uses a clustering algorithm to divide the read depth segment profile, and assigns an abnormal score to each read depth segment. Based on the abnormal score profile, Tukey's fences method is adopted in CBCNV to forecast CNVs. The performance of the proposed method is evaluated on simulated data sets, and is compared with those of several existing methods. The experimental results prove that the performance of CBCNV is better than those of several existing methods. The proposed method is further tested and verified on real data sets, and the experimental results are found to be consistent with the simulation results. Therefore, the proposed method can be expected to become a routine tool in the analysis of CNVs from tumor-normal matched samples.
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http://dx.doi.org/10.3389/fgene.2021.699510DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8273656PMC
June 2021

Predicting the Most Deleterious Missense Nonsynonymous Single-Nucleotide Polymorphisms of Hennekam Syndrome-Causing CCBE1 Gene, In Silico Analysis.

ScientificWorldJournal 2021 10;2021:6642626. Epub 2021 Jun 10.

Department of Immunochemistry, Institute of Chemical Engineering, Ural Federal University, Yekaterinburg, Russia.

Hennekam lymphangiectasia-lymphedema syndrome has been linked to single-nucleotide polymorphisms in the CCBE1 (collagen and calcium-binding EGF domains 1) gene. Several bioinformatics methods were used to find the most dangerous nsSNPs that could affect CCBE1 structure and function. Using state-of-the-art in silico tools, this study examined the most pathogenic nonsynonymous single-nucleotide polymorphisms (nsSNPs) that disrupt the CCBE1 protein and extracellular matrix remodeling and migration. Our results indicate that seven nsSNPs, rs115982879, rs149792489, rs374941368, rs121908254, rs149531418, rs121908251, and rs372499913, are deleterious in the CCBE1 gene, four (G330E, C102S, C174R, and G107D) of which are the highly deleterious, two of them (G330E and G107D) have never been seen reported in the context of Hennekam syndrome. Twelve missense SNPs, rs199902030, rs267605221, rs37517418, rs80008675, rs116596858, rs116675104, rs121908252, rs147974432, rs147681552, rs192224843, rs139059968, and rs148498685, are found to revert into stop codons. Structural homology-based methods and sequence homology-based tools revealed that 8.8% of the nsSNPs are pathogenic. SIFT, PolyPhen2, M-CAP, CADD, FATHMM-MKL, DANN, PANTHER, Mutation Taster, LRT, and SNAP2 had a significant score for identifying deleterious nsSNPs. The importance of rs374941368 and rs200149541 in the prediction of post-translation changes was highlighted because it impacts a possible phosphorylation site. Gene-gene interactions revealed CCBE1's association with other genes, showing its role in a number of pathways and coexpressions. The top 16 deleterious nsSNPs found in this research should be investigated further in the future while researching diseases caused CCBE1 gene specifically HS. The FT web server predicted amino acid residues involved in the ligand-binding site of the CCBE1 protein, and two of the substitutions (R167W and T153N) were found to be involved. These highly deleterious nsSNPs can be used as marker pathogenic variants in the mutational diagnosis of the HS syndrome, and this research also offers potential insights that will aid in the development of precision medicines. CCBE1 proteins from Hennekam syndrome patients should be tested in animal models for this purpose.
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http://dx.doi.org/10.1155/2021/6642626DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8211529PMC
June 2021

Transcriptome-wide study revealed m6A regulation of embryonic muscle development in Dingan goose (Anser cygnoides orientalis).

BMC Genomics 2021 Apr 14;22(1):270. Epub 2021 Apr 14.

Tropical Crops Genetic Resources Institute, Chinese Academy of Tropical Agricultural Sciences, Haikou, 571101, People's Republic of China.

Background: The number of myofiber is determined during the embryonic stage and does not increase during the postnatal period for birds, including goose. Thus, muscle production of adult goose is pre-determined during embryogenesis. Previous studies show N-methyladenosine (m6A) is an important regulator for skeletal muscle development of birds and miRNAs play as a co-regulator for the skeletal muscle development in birds. Herein, we sequenced m6A and miRNA transcriptomes to investigate the profiles of m6A and their potential mechanism of regulating breast muscle development in Dingan Goose.

Results: We selected embryonic 21th day (E21) and embryonic 30th day (E30) to investigate the roles of transcriptome-wide m6A modification combining with mRNAs and miRNAs in goose breast muscle development. In this study, m6A peaks were mainly enriched in coding sequence (CDS) and start codon and397 genes were identified as differentially methylated genes (DMGs). GO and KEGG analysis showed that DMGs were highly related to cellular and metabolic process and that most DMGs were enriched in muscle-related pathways including Wnt signaling pathway, mTOR signaling and FoxO signaling pathway. Interestingly, a negative correlation between m6A methylation level and mRNA abundance was found through the analysis of m6A-RNA and RNA-seq data. Besides, we found 26 muscle-related genes in 397 DMGs. We also detected 228 differentially expressed miRNAs (DEMs), and further found 329 genes shared by the target genes of DEMs and DMGs (m6A-miRNA-genes), suggesting a tightly relationship between DEMs and DMGs. Among the m6A-miRNA-genes, we found 10 genes are related to breast muscle development. We further picked out an m6A-miRNA-gene, PDK3, from the 10 genes to visualize it and the result showed differentially methylated peaks on the mRNA transcript consistent with our m6A-seq results.

Conclusion: GO and KEGG of DMGs between E21 and E30 showed most DMGs were muscle-related. In total, 228 DEMs were found, and the majority of DMGs were overlapped with the targets of DEGs. The differentially methylated peaks along with an m6A-miRNA-gene, PDK3, showed the similar results with m6A-seq results. Taken together, the results presented here provide a reference for further investigation of embryonic skeletal muscle development mechanism in goose.
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http://dx.doi.org/10.1186/s12864-021-07556-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8048326PMC
April 2021

Hard yet Flexible Transparent Omniphobic GPOSS Coatings Modified with Perfluorinated Agents.

ACS Appl Mater Interfaces 2021 Mar 17;13(8):10467-10479. Epub 2021 Feb 17.

Department of Chemistry, Queen's University, 90 Bader Lane, Kingston, Ontario, Canada K7L 3N6.

Transparent materials with glasslike hardness and polymer-like flexibility are highly useful but rare. This paper reports the incorporation of the low-surface-tension pentafluoropropionic acid (FC-COOH) or tridecafluoroheptanoic acid (FC-COOH) into a 3-glycidyloxypropyl polyhedral oligomeric silsesquioxane (GPOSS) coating to yield hard/flexible omniphobic coatings. To avoid the macrophase separation of these additives from GPOSS and thus maintain the coating's high transparency, they are first reacted with excess GPOSS via the opening of the glycidyl rings with the carboxy groups to produce mixtures of GPOSS and GPOSS-FC or GPOSS-FC. The fluorinated GPOSS mixtures are then photochemically cured. This study investigates the influence of the type and amount of a fluorinated agent used on the wetting and mechanical properties of the coatings. The wetting properties studied include surface energies, liquid sliding behavior, and repellency against an artificial fingerprint liquid. Meanwhile, the mechanical properties include pencil hardness, Young's modulus, hardness, and resistance to abrasion by steel wool and cheesecloth. Aside from producing coatings that may serve as a viable alternative for the currently used hard/flexible coatings in foldable smartphones, this paper provides guidelines for producing coatings with further improved omniphobicity and wear resistance.
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http://dx.doi.org/10.1021/acsami.0c23151DOI Listing
March 2021

Defining muscle-invasive bladder cancer immunotypes by introducing tumor mutation burden, CD8+ T cells, and molecular subtypes.

Hereditas 2021 Jan 2;158(1). Epub 2021 Jan 2.

Department of Urology, Henan Provincial People's Hospital, Zhengzhou, 450003, China.

Immunotherapy, especially anti-PD-1, is becoming a pillar of modern muscle-invasive bladder cancer (MIBC) treatment. However, the objective response rates (ORR) are relatively low due to the lack of precise biomarkers to select patients. Herein, the molecular subtype, tumor mutation burden (TMB), and CD8+ T cells were calculated by the gene expression and mutation profiles of MIBC patients. MIBC immunotypes were constructed using clustering analysis based on tumor mutation burden, CD8+ T cells, and molecular subtypes. Mutated genes, enriched functional KEGG pathways and GO terms, and co-expressed network-specific hub genes have been identified. We demonstrated that ORR of immunotype A patients identified by molecular subtype, CD8+ T cells, and TMB is about 36% predictable. PIK3CA, RB1, FGFR3, KMT2C, MACF1, RYR2, and EP300 are differentially mutated among three immunotypes. Pathways such as ECM-receptor interaction, PI3K-Akt signaling pathway, and TGF-beta signaling pathway are top-ranked in enrichment analysis. Low expression of ACTA2 was associated with the MIBC survival benefit. The current study constructs a model that could identify suitable MIBC patients for immunotherapy, and it is an important step forward to the personalized treatment of bladder cancers.
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http://dx.doi.org/10.1186/s41065-020-00165-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7778803PMC
January 2021

Direct Measurement of Cerebrospinal Fluid Production in Mice.

Cell Rep 2020 12;33(12):108524

Center for Translational Neuromedicine, Department of Neurosurgery, University of Rochester Medical Center, Rochester, NY 14642, USA; Center for Translational Neuromedicine, Faculty of Health and Medical Sciences, University of Copenhagen, 2200, Copenhagen, Denmark. Electronic address:

The emerging interest in brain fluid transport has prompted a need for techniques that provide an understanding of what factors regulate cerebrospinal fluid (CSF) production. Here, we describe a methodology for direct quantification of CSF production in awake mice. We measure CSF production by placing a catheter in a lateral ventricle, while physically blocking outflow from the 4 ventricle. Using this methodology, we show that CSF production increases during isoflurane anesthesia, and to a lesser extent with ketamine/xylazine anesthesia, relative to the awake state. Aged mice have reduced CSF production, which is even lower in aged mice overexpressing amyloid-β. Unexpectedly, CSF production in young female mice is 30% higher than in age-matched males. Altogether, the present observations imply that a reduction in CSF production might contribute to the age-related risk of proteinopathies but that the rate of CSF production and glymphatic fluid transport are not directly linked.
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http://dx.doi.org/10.1016/j.celrep.2020.108524DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8186543PMC
December 2020

RKDOSCNV: A Local Kernel Density-Based Approach to the Detection of Copy Number Variations by Using Next-Generation Sequencing Data.

Front Genet 2020 4;11:569227. Epub 2020 Nov 4.

School of Computer Science and Technology, Xidian University, Xi'an, China.

Copy number variations (CNVs) are significant causes of many human cancers and genetic diseases. The detection of CNVs has become a common method by which to analyze human diseases using next-generation sequencing (NGS) data. However, effective detection of insignificant CNVs is still a challenging task. In this study, we propose a new detection method, RKDOSCNV, to meet the need. RKDOSCNV uses kernel density estimation method to evaluate the local kernel density distribution of each read depth segment (RDS) based on an expanded nearest neighbor (k-nearest neighbors, reverse nearest neighbors, and shared nearest neighbors of each RDS) data set, and assigns a relative kernel density outlier score (RKDOS) for each RDS. According to the RKDOS profile, RKDOSCNV predicts the candidate CNVs by choosing a reasonable threshold, which it uses split read approach to correct the boundaries of candidate CNVs. The performance of RKDOSCNV is assessed by comparing it with several current popular methods via experiments with simulated and real data at different tumor purity levels. The experimental results verify that the performance of RKDOSCNV is superior to that of several other methods. In summary, RKDOSCNV is a simple and effective method for the detection of CNVs from whole genome sequencing (WGS) data, especially for samples with low tumor purity.
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http://dx.doi.org/10.3389/fgene.2020.569227DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7673372PMC
November 2020

Genetic diversity of clinical and environmental Mucorales isolates obtained from an investigation of mucormycosis cases among solid organ transplant recipients.

Microb Genom 2020 12 27;6(12). Epub 2020 Nov 27.

J. Craig Venter Institute, La Jolla, CA, USA.

Mucormycoses are invasive infections by species and other Mucorales. Over 10 months, four solid organ transplant (SOT) recipients at our centre developed mucormycosis due to (=2), (=1) or (=1), at a median 31.5 days (range: 13-34) post-admission. We performed whole genome sequencing (WGS) on 72 Mucorales isolates (45 . , 19 . , six . , two species) from these patients, from five patients with community-acquired mucormycosis, and from hospital and regional environments. Isolates were compared by core protein phylogeny and global genomic features, including genome size, guanine-cytosine percentages, shared protein families and paralogue expansions. Patient isolates fell into six core phylogenetic lineages (clades). Phylogenetic and genomic similarities of isolates recovered 7 months apart from two SOT recipients in adjoining hospitals suggested a potential common source exposure. However, isolates from other patients and environmental sites had unique genomes. Many isolates that were indistinguishable by core phylogeny were distinct by one or more global genomic comparisons. Certain clades were recovered throughout the study period, whereas others were found at particular time points. In conclusion, mucormycosis cases could not be genetically linked to a definitive environmental source. Comprehensive genomic analyses eliminated false associations between Mucorales isolates that would have been assigned using core phylogenetic or less extensive genomic comparisons. The genomic diversity of Mucorales mandates that multiple isolates from individual patients and environmental sites undergo WGS during epidemiological investigations. However, exhaustive surveillance of fungal populations in a hospital and surrounding community is probably infeasible.
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http://dx.doi.org/10.1099/mgen.0.000473DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8116672PMC
December 2020

Transcriptomic Data Analyses Reveal a Reprogramed Lipid Metabolism in HCV-Derived Hepatocellular Cancer.

Front Cell Dev Biol 2020 27;8:581863. Epub 2020 Oct 27.

Cancer System Biology Center, The China-Japan Union Hospital of Jilin University, Changchun, China.

Reprograming lipid metabolism, one of the major metabolic alterations in cancer, is believed to play an essential role in cancer development, but the exact molecular mechanism remains elusive. Here, we present a computational study of transcriptomic data of HCC with HCV etiology to investigate how lipid metabolism alters during HCC progression. Our analyses reveal that: (1) cancer tissue cells tend to synthesize fatty acids and its phospholipid derivatives; (2) lipid catabolism and fatty acid oxidation are remarkably down-regulated in HCC; (3) the lipid metabolism in HCC is largely independent of lipids in blood circulation; (4) stage-specific co-expression networks for lipid metabolic genes were identified during HCC progression; and (5) the expression levels of several lipid metabolic genes that are differentially expressed or co-expressed specifically at the HCC stage have a strong correlation with cancer survival. Overall, the results provide detailed information about the reprogramed lipid metabolism in HCV-derived HCC.
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http://dx.doi.org/10.3389/fcell.2020.581863DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7652758PMC
October 2020

Study on the Mechanism of Targeted Poly(lactic-coglycolic acid) Nano-Delivery Carriers in the Treatment of Hemangiomas.

J Nanosci Nanotechnol 2021 02;21(2):1236-1243

Department of Vascular Surgery, Quzhou People's Hospital, Quzhou City, 324000, Zhejiang Province, China.

Hemangiomas, also called infantile hemangiomas (IH), are the most common congenital benign vascular tumors in infants and young children. At present, there are many treatment methods for proliferative hemangiomas, which have different effects and lack predictability. Propranolol has gradually replaced glucocorticoids as the first-line treatment for infants and young children with hemangiomas. However, premature discontinuation is prone to relapse, and the efficacy and safety of medication need to be further studied and determined. The exact pathogenesis of hemangiomas is still unclear. Therefore, in this study, poly(lactic-co-glycolic acid) (PLGA) nanoparticles were used as drug delivery carriers, propranolol was encapsulated, and PLGA-propranolol (PLGA-PP) nanodelivery preparations were prepared and targeted. Anisotropy and pharmacokinetics were preliminary studied. At the same time, after the treatment of HemECs cells with PLGA-PP in gradient concentration , CCK-8 method was used to detect the cell proliferation, and Anyixin-V/PI double staining method was used to detect the apoptosis rate of cells. The effect of PLGA-PP nano-delivery vector on hemangioma was studied by western blot method to detect the expression level of Id-1 protein in HemECs. The results showed that after PLGA-PP treated HemECs for 24 h, PLGA-PP significantly inhibited HeECs proliferation and promoted their apoptosis, and the intracellular Id-1 protein expression was also reduced. Therefore, this study believes that the mechanism of PLGA-PP nano-targeted delivery preparations in the treatment of hemangiomas is achieved by down-regulating the Id-1 gene, thereby inhibiting the colonization of HemECs and promoting its apoptosis effect.
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http://dx.doi.org/10.1166/jnn.2021.18689DOI Listing
February 2021

A targeted gene capture next-generation sequencing panel for genetic screening of newborns.

J Pak Med Assoc 2020 Oct;70(10):1789-1794

Department of Medical and Molecular Genetics, Dongguan Institute of Pediatrics, Dongguan, Guangdong, China.

Objective: The application of next-generation sequencing (NGS) will greatly promote the screening and diagnosis of genetic diseases. This study aimed to implement and validate a targeted NGS panel for genetic screening of over fifty types of genetic disorders in newborns.

Methods: A targeted gene panel consisting of 104 known genes related to genetic diseases with a target size of 347.8 kb was designed. Genes were selected through reference to databases including HGMD, OMIM, GeneReviews®, and Genetic Home Reference, and the latest peer-reviewed publications associated with the genetics of hereditary diseases.

Results: The average coverage for all targeted exons was 596X, and the mean targeted region coverage of 1X, 10X, 20X and 50X reads for each sample were 99.8%, 99.2%, 98.8%, and 95.3%, respectively. The panel showed 100% consistency in detecting 8 pathogenic insertion/deletion (indels) variants ranging from 1 to 16 bp in size and 20 pathogenic single-nucleotide variations (SNVs) across 32 samples previously confirmed by Sanger sequencing.

Conclusions: A dried blood spot (DBS)-based targeted NGS panel for efficient genetic screening of a wide variety of genetic diseases in newborns was developed and evaluated. Furthermore, our panel will contribute to providing accurate diagnosis for genetic disorders and will be helpful for gene therapy for specific diseases.
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http://dx.doi.org/10.5455/JPMA.28637DOI Listing
October 2020

A multifunctional anode with P-doped Si nanoparticles in a stress-buffering network of poly-γ-glutamate and graphene.

Chem Commun (Camb) 2020 Nov;56(92):14412-14415

Department of Chemistry, State University of New York at Binghamton, Binghamton, New York 13902, USA.

Here, a new strategy is reported for the preparation of a new class of nanocomposite anode materials consisting of ppm-level phosphorus-doped Si nanoparticles (P-Si) wrapped in a network of poly-γ-glutamate and graphene. The network produces not only a conductivity-enhanced conduit but also a mechanical stress buffer. The incorporation of poly-γ-glutamate in the nanocomposite enables self-healing capability and maintains the electrode structural integrity. This multifunctionality has significant implications for advancing the design of stable Si-based nanomaterials as high-performance anodes in Li-ion batteries.
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http://dx.doi.org/10.1039/d0cc06623kDOI Listing
November 2020

FPSC-DTI: drug-target interaction prediction based on feature projection fuzzy classification and super cluster fusion.

Mol Omics 2020 12 21;16(6):583-591. Epub 2020 Oct 21.

School of Computer Science and Technology, Harbin Institute of Technology, Harbin, 150001, China.

Identifying drug-target interactions (DTIs) is an important part of drug discovery and development. However, identifying DTIs is a complex process that is time consuming, costly, long, and often inefficient, with a low success rate, especially with wet-experimental methods. Computational methods based on drug repositioning and network pharmacology can effectively overcome these defects. In this paper, we develop a new fusion method, called FPSC-DTI, that fuses feature projection fuzzy classification (FP) and super cluster classification (SC) to predict DTI. As the experimental result, the mean percentile ranking (MPR) that was yielded by FPSC-DTI achieved 0.043, 0.084, 0.072, and 0.146 on enzyme, ion channel (IC), G-protein-coupled receptor (GPCR), and nuclear receptor (NR) datasets, respectively. And the AUC values exceeded 0.969 over all four datasets. Compared with other methods, FPSC-DTI obtained better predictive performance and became more robust.
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http://dx.doi.org/10.1039/d0mo00062kDOI Listing
December 2020

The Prevalence of Smartphones and WeChat Use Among Older Adults With Chronic Disease in a Western China.

Comput Inform Nurs 2020 Jul 8;39(1):42-47. Epub 2020 Jul 8.

Author Affiliations: School of Nursing, Youjiang Medical University for Nationalities, Baise (Dr Zhang and Ms Wei); Nursing Department, Taizhou Polytechnical College, Taizhou (Ms Xu); and Nursing Department (Ms Huang) and Neurology Department (Dr Liu), The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China.

Telemedicine is a promising way to deliver patient education and health services, but access to information technology among potential patients is a prerequisite. This study surveyed the prevalence of smartphone use and the use of the Chinese social networking platform WeChat and Wi-Fi access in the homes of older adults in a western area of China. A convenience sample of 225 older adults with chronic diseases in two tertiary hospitals was interviewed regarding smartphone ownership, WeChat use, and access to Wi-Fi at home. Participant ability in performing the activities of daily living was also assessed. Logistic regressions were used to analyze the independently associated factors of smartphone ownership, WeChat use, and Wi-Fi access at home. The results show that the prevalence of smartphone use was 19.6%, only 8.9% of those surveyed used WeChat, but 39.6% had access to Wi-Fi at home. Education level was the only factor significantly associated with the three dependent variables. Ability in performing activities of daily living was positively correlated with access to Wi-Fi at home (odds ratio, 2.549; P = .011). It will be difficult to implement telemedicine through smartphones in such relatively poor areas of China. Better-educated older adults who are less dependent in performing activities of daily living are potential users of telemedicine.
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http://dx.doi.org/10.1097/CIN.0000000000000638DOI Listing
July 2020

Surprising Lack of Influence on Water Droplet Motion by Hydrophilic Microdomains on Checkerboard-like Surfaces with Matched Contact Angle Hysteresis.

Langmuir 2020 Jul 3;36(27):7835-7843. Epub 2020 Jul 3.

National Institute of Advanced Industrial Science and Technology (AIST), 2266-98, Anagahora, Shimo-shidami, Moriyama-ku, Nagoya 463-8560, Japan.

Chemically and spatially micropatterned surfaces have been successfully prepared for a number of diverse applications, including water/fog harvesting, screen printing, microfluidics, and cell/protein assays. While there have been quite some reports on micropatterned surfaces, less is known about the factors that influence dynamic surface wettability. To that end, smooth checkerboard-like micropatterned hydrophobic/(super)hydrophilic surfaces (2, 5, 10, 20 μm pattern sizes) with regions of matching/mismatching contact angle hysteresis (CAH) were prepared on the basis of a simple chemisorption/photopatterning of monolayers. The effects of regional wettability/CAH and pattern size on the overall dynamic wettability were then examined by measuring the dynamic contact angles (CAs) and substrate tilt angles (θ) of water. It was found that the dynamic wettability on samples with matching regional CAH remained unchanged, even when using hydrophilic regions or changing the pattern size. In contrast, surfaces containing mismatching CAH regions pinned water droplets, leading to overall dynamic wetting properties markedly dependent on pattern size. In addition, the experimental data did not match values predicted by the Cassie equation because dynamic wetting behavior is dominated not by interfacial area but by the interactions of the liquid and solid at the three-phase contact line.
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http://dx.doi.org/10.1021/acs.langmuir.0c00808DOI Listing
July 2020

Clinical characteristics of acute respiratory syndrome with SARS-CoV-2 infection in children in South China.

Pediatr Pulmonol 2020 09 3;55(9):2419-2426. Epub 2020 Jul 3.

Pediatric Intensive Care Unit, Department of Pediatrics, Guangdong Provincial People's Hospital (GDPH), Guangdong Academy of Medical Sciences, Guangzhou, China.

Background: A retrospective study was conducted to summarize the clinical information of childhood infections during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic.

Methods: Children with SARS-CoV-2 infection in 11 hospitals from three provinces of South China were included in the study. Clinical information was collected and compared with children and adults infected by SARS-CoV-2 in Wuhan.

Results: In total, 52 children were enrolled, including 28 boys. The median age was 9 years (interquartile range [IQR], 4-12); 44.2% cases were of clustered occurrences, 40.4% patients had fever, 48.1% had cough, and 46.2% had a high lymphocyte count. No abnormalities were found in the liver and kidney function. Also, 82.7% of patients received antiviral therapy, but such therapy did not shorten the time to virus negativity or hospital stay (P = .082). The time to virus negativity was 12.0 days (IQR, 8.0-16.8) and hospital stay was 14.5 days (IQR, 10.3-17.9). Compared with reports in Wuhan, there were more acute upper respiratory tract infection (AURTI) and fewer pneumonia cases (P = .000). Compared with the non-ICU adult COVID-19 in Wuhan, these children's diseases were relatively mild, with fewer complications.

Conclusions: Children with SARS-CoV-2 infection had a mild fever, lymphocyte elevation was more common than reduction, and antiviral treatment had no obvious effect. The overall clinical manifestations were mild, and the prognosis was good.
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http://dx.doi.org/10.1002/ppul.24921DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7361845PMC
September 2020

MFCNV: A New Method to Detect Copy Number Variations From Next-Generation Sequencing Data.

Front Genet 2020 15;11:434. Epub 2020 May 15.

The School of Computer Science and Technology, Xidian University, Xi'an, China.

Copy number variation (CNV) is a very important phenomenon in tumor genomes and plays a significant role in tumor genesis. Accurate detection of CNVs has become a routine and necessary procedure for a deep investigation of tumor cells and diagnosis of tumor patients. Next-generation sequencing (NGS) technique has provided a wealth of data for the detection of CNVs at base-pair resolution. However, such task is usually influenced by a number of factors, including GC-content bias, sequencing errors, and correlations among adjacent positions within CNVs. Although many existing methods have dealt with some of these artifacts by designing their own strategies, there is still a lack of comprehensive consideration of all the factors. In this paper, we propose a new method, MFCNV, for an accurate detection of CNVs from NGS data. Compared with existing methods, the characteristics of the proposed method include the following: (1) it makes a full consideration of the intrinsic correlations among adjacent positions in the genome to be analyzed, (2) it calculates read depth, GC-content bias, base quality, and correlation value for each genome bin and combines them as multiple features for the evaluation of genome bins, and (3) it addresses the joint effect among the factors via training a neural network algorithm for the prediction of CNVs. We test the performance of the MFCNV method by using simulation and real sequencing data and make comparisons with several peer methods. The results demonstrate that our method is superior to other methods in terms of sensitivity, precision, and F1-score and can detect many CNVs that other methods have not discovered. MFCNV is expected to be a complementary tool in the analysis of mutations in tumor genomes and can be extended to be applied to the analysis of single-cell sequencing data.
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http://dx.doi.org/10.3389/fgene.2020.00434DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7243272PMC
May 2020

Fabrication of an Inverse Size-Selective Membrane Using an Electrospun Nanofiber Mat as a Template.

ACS Appl Mater Interfaces 2020 Apr 17;12(13):15686-15694. Epub 2020 Mar 17.

Department of Chemistry, Queen's University, 90 Bader Lane, Kingston, Ontario, Canada K7L 3N6.

Size-selective membranes have applications in water purification and other areas. Although many methods have been developed for the fabrication of nanoporous membranes, each method has its limitations. For example, thin films containing uniform nanochannels can be prepared from block copolymer precursors. However, block copolymers are expensive. The electrospinning of a polymer solution can yield long nanofibers that fold into mats and the diameters of these fibers can be tuned from nanometers to micrometers. Infusing another polymer into the voids between these fibers and subsequently removing the nanofiber template should yield an inverse porous membrane, complementary in pore structure to the original nanofiber mat membrane. In this paper, we report on the fabrication of these membranes. We discovered that the flux across such membranes increased by thermally annealing the nanofiber mats under pressure before the infusion of the second polymer and by etching the surfaces of the final membrane with plasma to expose the encapsulated nanochannels. We further discovered that the size of the pores formed at the junction of the fused nanofibers and, eventually, the nanotubes governed the size selectivity of the final membrane. The pore size at the junctions increased by increasing the thermal annealing temperature and, thus, the extent of fiber fusion. The developed methodology is general and should be useful for the fabrication of nanoporous membranes from different materials possessing pore diameters that are governed by the diameter of the templating nanofibers and the extent of their fusion.
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http://dx.doi.org/10.1021/acsami.0c00065DOI Listing
April 2020

Cerebrospinal fluid influx drives acute ischemic tissue swelling.

Science 2020 03 30;367(6483). Epub 2020 Jan 30.

Center for Translational Neuromedicine, Department of Neurosurgery, University of Rochester Medical Center, Rochester, NY 14642, USA.

Stroke affects millions each year. Poststroke brain edema predicts the severity of eventual stroke damage, yet our concept of how edema develops is incomplete and treatment options remain limited. In early stages, fluid accumulation occurs owing to a net gain of ions, widely thought to enter from the vascular compartment. Here, we used magnetic resonance imaging, radiolabeled tracers, and multiphoton imaging in rodents to show instead that cerebrospinal fluid surrounding the brain enters the tissue within minutes of an ischemic insult along perivascular flow channels. This process was initiated by ischemic spreading depolarizations along with subsequent vasoconstriction, which in turn enlarged the perivascular spaces and doubled glymphatic inflow speeds. Thus, our understanding of poststroke edema needs to be revised, and these findings could provide a conceptual basis for development of alternative treatment strategies.
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http://dx.doi.org/10.1126/science.aax7171DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7375109PMC
March 2020

Polarization-stabilized tunable VCSEL with internal-cavity sub-wavelength grating.

Opt Express 2019 Nov;27(24):35499-35511

In this paper, a tunable VCSEL with internal-cavity sub-wavelength grating structure at 850nm was demonstrated. Utilizing the birefringence and anti-reflection characteristics of the sub-wavelength grating, the tunable VCSEL with wide wavelength tuning range and stable TE polarization mode was achieved. The relationships between the parameters of sub-wavelength grating and the transmittance/effective index of two polarization modes were analyzed. The tuning efficiency, polarization mode and wavelength tuning range of the tunable VCSEL with internal-cavity sub-wavelength structure were studied. Simultaneously, the MEMS cantilever structure with 'bowknot' shape on the end of the cantilever was designed, which can effectively avoid the concentration of stress distribution and reduce the maximum stress. The results show that the wavelength tuning range is 22.7nm, the peak output power is 1.6mW at 20°C, and the polarization suppression ratio is more than 20dB.
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http://dx.doi.org/10.1364/OE.27.035499DOI Listing
November 2019

A Cancer Survival Prediction Method Based on Graph Convolutional Network.

IEEE Trans Nanobioscience 2020 01 21;19(1):117-126. Epub 2019 Aug 21.

Background And Objective: Cancer, as the most challenging part in the human disease history, has always been one of the main threats to human life and health. The high mortality of cancer is largely due to the complexity of cancer and the significant differences in clinical outcomes. Therefore, it will be significant to improve accuracy of cancer survival prediction, which has become one of the main fields of cancer research. Many calculation models for cancer survival prediction have been proposed at present, but most of them generate prediction models only by using single genomic data or clinical data. Multiple genomic data and clinical data have not been integrated yet to take a comprehensive consideration of cancers and predict their survival.

Method: In order to effectively integrate multiple genomic data (including genetic expression, copy number alteration, DNA methylation and exon expression) and clinical data and apply them to predictive studies on cancer survival, similar network fusion algorithm (SNF) was proposed in this paper to integrate multiple genomic data and clinical data so as to generate sample similarity matrix, min-redundancy and max-relevance algorithm (mRMR) was used to conduct feature selection of multiple genomic data and clinical data of cancer samples and generate sample feature matrix, and finally two matrixes were used for semi-supervised training through graph convolutional network (GCN) so as to obtain a cancer survival prediction method integrating multiple genomic data and clinical data based on graph convolutional network (GCGCN).

Result: Performance indexes of GCGCN model indicate that both multiple genomic data and clinical data play significant roles in the accurate survival time prediction of cancer patients. It is compared with existing survival prediction methods, and results show that cancer survival prediction method GCGCN which integrates multiple genomic data and clinical data has obviously superior prediction effect than existing survival prediction methods.

Conclusion: All study results in this paper have verified effectiveness and superiority of GCGCN in the aspect of cancer survival prediction.
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http://dx.doi.org/10.1109/TNB.2019.2936398DOI Listing
January 2020

In Vivo Imaging of Cerebrospinal Fluid Transport through the Intact Mouse Skull using Fluorescence Macroscopy.

J Vis Exp 2019 07 29(149). Epub 2019 Jul 29.

Center for Translational Neuromedicine, University of Rochester Medical Center; Center for Translational Neuromedicine, University of Copenhagen;

Cerebrospinal fluid (CSF) flow in rodents has largely been studied using ex vivo quantification of tracers. Techniques such as two-photon microscopy and magnetic resonance imaging (MRI) have enabled in vivo quantification of CSF flow but they are limited by reduced imaging volumes and low spatial resolution, respectively. Recent work has found that CSF enters the brain parenchyma through a network of perivascular spaces surrounding the pial and penetrating arteries of the rodent cortex. This perivascular entry of CSF is a primary driver of the glymphatic system, a pathway implicated in the clearance of toxic metabolic solutes (e.g., amyloid-β). Here, we illustrate a new macroscopic imaging technique that allows real-time, mesoscopic imaging of fluorescent CSF tracers through the intact skull of live mice. This minimally-invasive method facilitates a multitude of experimental designs and enables single or repeated testing of CSF dynamics. Macroscopes have high spatial and temporal resolution and their large gantry and working distance allow for imaging while performing tasks on behavioral devices. This imaging approach has been validated using two-photon imaging and fluorescence measurements obtained from this technique strongly correlate with ex vivo fluorescence and quantification of radio-labeled tracers. In this protocol, we describe how transcranial macroscopic imaging can be used to evaluate glymphatic transport in live mice, offering an accessible alternative to more costly imaging modalities.
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http://dx.doi.org/10.3791/59774DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7001880PMC
July 2019

A co-expression network for differentially expressed genes in bladder cancer and a risk score model for predicting survival.

Hereditas 2019 9;156:24. Epub 2019 Jul 9.

1Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515 China.

Background: Urothelial bladder cancer (BLCA) is one of the most common internal malignancies worldwide with poor prognosis. This study aims to explore effective prognostic biomarkers and construct a prognostic risk score model for patients with BLCA.

Methods: Weighted gene co-expression network analysis (WGCNA) was used for identifying the co-expression module related to the pathological stage of BLCA based on the RNA-Seq data retrieved from The Cancer Genome Atlas database. Prognostic biomarkers screened by Cox proportional hazard regression model and random forest were used to construct a risk score model that can predict the prognosis of patients with BLCA. The GSE13507 dataset was used as the independent testing dataset to test the performance of the risk score model in predicting the prognosis of patients with BLCA.

Results: WGCNA identified seven co-expression modules, in which the brown module consisted of 77 genes was most significantly correlated with the pathological stage of BLCA. Cox proportional hazard regression model and random forest identified TPST1 and P3H4 as prognostic biomarkers. Elevated TPST1 and P3H4 expressions were associated with the high pathological stage and worse survival. The risk score model based on the expression level of TPST1 and P3H4 outperformed pathological stage indicators and previously proposed prognostic models.

Conclusion: The gene co-expression network-based study could provide additional insight into the tumorigenesis and progression of BLCA, and our proposed risk score model may aid physicians in the assessment of the prognosis of patients with BLCA.
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http://dx.doi.org/10.1186/s41065-019-0100-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6617625PMC
February 2020

Transparent Omniphobic Coating with Glass-Like Wear Resistance and Polymer-Like Bendability.

Angew Chem Int Ed Engl 2019 Aug 26;58(35):12004-12009. Epub 2019 Jul 26.

Department of Chemistry, Queen's University, 90 Bader Lane, Kingston, Ontario, K7L 3N6, Canada.

Transparent omniphobic or anti-smudge coatings with glass-like wear resistance and polymer-like bendability have many potential applications but there are no reports of such materials. We Report herein a molecular composite possessing these properties. The composite is prepared via the photo-initiated ring-opening polymerization of the epoxide rings of glycidyloxypropyl polyhedral silsesquioxane (GPOSS). While the desired hardness is provided by the silica core, the flexibility is imparted by the glycidyloxypropyl network. Oil and water repellency is achieved without adversely affecting the other properties by incorporating a low-surface-tension liquid lubricant poly(dimethyl siloxane). On the final coating, various organic solvents and water readily and cleanly glide, while complex fluids, such as ink and paint facilely contract. These properties are retained after an initially flat coating sample is rolled into a U-shape 500 times or is abraded with steel wool.
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http://dx.doi.org/10.1002/anie.201904210DOI Listing
August 2019

Effects of two surface acoustic wave sorting chips on particles multi-level sorting.

Biomed Microdevices 2019 06 21;21(3):59. Epub 2019 Jun 21.

College of Mechanical and Aerospace Engineering, Jilin University, Changchun, 130025, China.

Particle/cell sorting has great potential in medical diagnosis and chemical analysis. Two kinds of microfluidic sorting chips (sequential sorting chip and direct sorting chip) are designed, which combine hydraulic force and acoustic radiation force to achieve continuous sorting of multiple particles. Firstly, the optimal values of the angle (α) between the interdigital transducer (IDT) and the main channel, the peak-to-peak voltage (Vpp), the main flow velocity (Vmax) and the flow ratio (A) are determined by simulation and experiments, the related optimal parameters were obtained that the α = 15°, Vpp = 25 V, Vmax = 4 mm/s, flow ratio A = 0.2, and A = 0.5, respectively. Then, the corresponding sorting experiments were carried out using two kinds of sorting chips to sort the polystyrene (PS) particles with diameters of 1 μm, 5 μm, and 10 μm, and the sorting rate and purity of particles were calculated and analyzed. Experimental results show that the two kinds of sorting chips can achieve continuous sorting of multiple particles, and the sorting effect of sequential sorting chip (control flow ratio) is better than that of direct sorting chip. In addition, the sorting chips in our research have the advantages of simple structure, high sorting efficiency, and the ability to sort multiple particles, which can be applied in medical and chemical research fields, such as cell sorting and chemical analysis.
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http://dx.doi.org/10.1007/s10544-019-0419-4DOI Listing
June 2019

[Effect of stromal cell-derived factor 1α/cysteine X cysteine receptor 4 signaling pathway on axial stress stimulation promoting bone regeneration].

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2019 Jun;33(6):689-697

Department of Orthopedics, the Affiliated Dongnan Hospital of Xiamen University, the 909th Hospital, Zhangzhou Fujian, 363099,

Objective: To observe the change of stromal cell-derived factor 1α/cysteine X cysteine receptor 4 (SDF-1α/CXCR4) signaling pathway during the process of axial stress stimulation promoting bone regeneration, and to further explore its mechanism.

Methods: A total of 72 male New Zealand white rabbits were selected to prepare the single cortical bone defect in diameter of 8 mm at the proximal end of the right tibia that repaired with deproteinized cancellous bone. All models were randomly divided into 3 groups ( =24). Group A was treated with intraperitoneally injection of PBS; Group B was treated with stress stimulation and intraperitoneally injection of PBS; Group C was treated with stress stimulation and intraperitoneally injection of AMD3100 solution. The X-ray films were taken and Lane-Sandhu scores of bone healing were scored at 2, 4, 8, and 12 weeks after operation, while specimens were harvested for HE staining, immunohistochemical staining of vascular endothelial growth factor (VEGF) and CXCR4, and Western blot (SDF-1α and CXCR4). The bone healing area was scanned by Micro-CT at 12 weeks after operation, and the volume and density of new bone were calculated.

Results: X-ray film showed that the Lane-Sandhu scores of bone healing in group B were significantly higher than those in groups A and C at 4, 8, and 12 weeks after operation ( <0.05). Micro-CT scan showed that the bone defect was repaired in group B and the pulp cavity was re-passed at 12 weeks after operation. The volume and density of new bone were higher in group B than in groups A and C ( <0.05). HE staining showed that the new bone growth in bone defect area and the degradation of scaffolds were faster in group B than in groups A and C after 4 weeks. The immunohistochemical staining showed that the expressions of VEGF and CXCR4 in 3 groups reached the peak at 4 weeks, and group B was higher than groups A and C ( <0.05). Western blot analysis showed that the expressions of SDF-1α and CXCR4 in group B were significantly higher than those in groups A and C at 4 and 8 weeks after operation ( <0.05).

Conclusion: Axial stress stimulation can promote the expression of SDF-1α in bone defect tissue, activate and regulate the CXCR4 signal collected by marrow mesenchymal stem cells, and accelerate bone regeneration in bone defect area.
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http://dx.doi.org/10.7507/1002-1892.201811031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8355772PMC
June 2019

Reactive Oxygen Species-Dependent Calpain Activation Contributes to Airway and Pulmonary Vascular Remodeling in Chronic Obstructive Pulmonary Disease.

Antioxid Redox Signal 2019 10 24;31(12):804-818. Epub 2019 Jun 24.

Department of Pharmacology & Toxicology, Medical College of Georgia, Augusta University, Augusta, Georgia.

Airway and pulmonary vascular remodeling is an important pathological feature in the pathogenesis of chronic obstructive pulmonary disease (COPD). Tobacco smoke (TS) induces the production of large amounts of reactive oxygen species (ROS) in COPD lungs. We investigated how ROS lead to airway and pulmonary vascular remodeling in COPD. We used bronchial and pulmonary artery smooth muscle cells (BSMCs and PASMCs), TS-induced COPD rodent models, and lung tissues of COPD patients. We found that HO and TS extract (TSE) induced calpain activation in BSMCs and PASMCs. Calpain activation was elevated in smooth muscle of bronchi and pulmonary arterioles in COPD patients and TS-induced COPD rodent models. Calpain inhibition attenuated HO- and TSE-induced collagen synthesis and proliferation of BSMCs and PASMCs. Exposure to TS causes increases in airway resistance, right ventricular systolic pressure (RVSP), and thickening of bronchi and pulmonary arteries. Calpain inhibition by smooth muscle-specific knockout of calpain and the calpain inhibitor MDL28170 attenuated increases in airway resistance, RVSP, and thickening of bronchi and pulmonary arteries. Moreover, smooth muscle-specific knockout of calpain did not reduce TS-induced emphysema in the mouse model, but MDL28170 did reduce TS-induced emphysema in the rat model. This study provides the first evidence that ROS-induced calpain activation contributes to airway and pulmonary vascular remodeling in TS-induced COPD. Calpain might be a novel therapeutic target for the treatment of COPD. These results indicate that ROS-induced calpain activation contributes to airway and pulmonary vascular remodeling and pulmonary hypertension in COPD.
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http://dx.doi.org/10.1089/ars.2018.7648DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7061305PMC
October 2019

Dexmedetomidine enhances glymphatic brain delivery of intrathecally administered drugs.

J Control Release 2019 06 5;304:29-38. Epub 2019 May 5.

Center for Translational Neuromedicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Center for Translational Neuromedicine, University of Rochester Medical Center, Rochester, NY, USA.

Drug delivery to the central nervous system remains a major problem due to biological barriers. The blood-brain-barrier can be bypassed by administering drugs intrathecally directly to the cerebrospinal fluid (CSF). The glymphatic system, a network of perivascular spaces promoting fluid exchange between CSF and interstitial space, could be utilized to enhance convective drug delivery from the CSF to the parenchyma. Glymphatic flow is highest during sleep and anesthesia regimens that induce a slow-wave sleep-like state. Here, using mass spectrometry and fluorescent imaging techniques, we show that the clinically used α-adrenergic agonist dexmedetomidine that enhances EEG slow-wave activity, increases brain and spinal cord drug exposure of intrathecally administered drugs in mice and rats. Using oxycodone, naloxone, and an IgG-sized antibody as relevant model drugs we demonstrate that modulation of glymphatic flow has a distinct impact on the distribution of intrathecally administered therapeutics. These findings can be exploited in the clinic to improve the efficacy and safety of intrathecally administered therapeutics.
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http://dx.doi.org/10.1016/j.jconrel.2019.05.005DOI Listing
June 2019
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