Publications by authors named "Ran Wang"

667 Publications

Antiviral effect of a bacteriophage on murine norovirus replication via modulation of the innate immune response.

Virus Res 2021 Sep 20:198572. Epub 2021 Sep 20.

Key Laboratory of Food Quality and Safety of Jiangsu Province-State Key Laboratory Breeding Base, Institute of Food Safety and Nutrition, Jiangsu Academy of Agricultural Sciences, Nanjing, 210014, P.R. China. Electronic address:

Bacteriophages (phages) are viruses of bacteria. Despite the growing progress in research on phage interactions with eukaryotic cells, our understanding of the roles of phages and their potential implications remains incomplete. The objective of this study was to investigate the effects of the Staphylococcus aureus phage vB_SauM_JS25 on murine norovirus (MNV) replication. Experiments were performed using the RAW 264.7 cell line. After phage treatment, MNV multiplication was significantly inhibited, as indicated by real-time quantitative polymerase chain reaction (RT-qPCR) analysis, western blotting, the 50% tissue culture infectious dose and immunofluorescence. Furthermore, we revealed transcriptional changes in phage/MNV co-incubated RAW 264.7 cells through RNA sequencing (RNA-seq) and bioinformatic analysis. Our subsequent analyses revealed that the innate immune response might play an important role in restriction of MNV replication, such as the cellular response to IFN-γ and response to IFN-γ. Additionally, gene expression of IL-10, Arg-1, Ccl22, GBP2, GBP3, GBP5, and GBP7 was increased significantly, which indicated a strong correlation between RT-qPCR and RNA-seq results. Furthermore, phage treatment activated guanylate binding proteins (GBPs), as revealed by RT-qPCR analysis, western blotting, and confocal microscopy. Taken together, these data suggest that the phage affects the innate response, such as the IFN-inducible GTPases and GBPs, and therefore exerts an antiviral effect in vitro. Collectively, our findings provide insights into the interactions of immune cells and phages, which establish phage-based antiviral effects.
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http://dx.doi.org/10.1016/j.virusres.2021.198572DOI Listing
September 2021

Functional Deficit of Sense Organs as a risk factor for Cognitive Functional Disorder in Chinese Community Elderly People.

Int J Clin Pract 2021 Sep 21:e14905. Epub 2021 Sep 21.

Mental Health Center, The First Hospital of Hebei Medical University, Shijiazhuang, China.

Objective: To explore the relationship between mild cognitive impairment (MCI) and sense organs functional deficit in community elderly people.

Methods: 3095 community elderly people above 60 years in Hebei Province were selected by cross-sectional random cluster sampling method, who were evaluated face-to-face for general demographic data, the condition of sense organs functional deficit (vision, hearing, gustation, olfactory sensation, taste) and cognitive function by Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA).

Results: A total of 3075 valid questionnaires were obtained. (1)1368 old people(44.49%) were defined with sense organs functional deficit(defined as one or more of glaucoma, fundus disease, hearing impairment, olfactory disorder, and taste disorder) in 3095 elderly people. According to questionnaires, MCI was diagnosed in 689 of 3075 participants (22.41%). The hearing disorder and glaucoma of MCI group were higher than that of the normal control group (X were 5.998 and 7.430, respectively, P were 0.014 and 0.006, respectively). (2) The MMSE score of the hearing disorder were significantly lower than those of non- hearing disorder group(t=2.046, P=0.041). (3) Multivariate Logistic regression analysis was applied by MCI as the dependent variable and the various sensory organs defects as independent variables. The hearing impairment (Wald=8.582, P=0.003, OR=1.485, 95% CI:1.140-1.934) and glaucoma (Wald=8.020, P=0.005, OR=1.847, 95% CI:1.208-2.824) were associated with MCI.

Conclusion: The sensory organs functional defects is associated with the mild cognitive impartment in Chinese elderly, especially in vision and hearing disorder.
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http://dx.doi.org/10.1111/ijcp.14905DOI Listing
September 2021

Analyzing the Properties of Murine Intestinal Mucins by Electrophoresis and Histology.

Bio Protoc 2017 Jul 20;7(14):e2394. Epub 2017 Jul 20.

Inflammatory Disease Biology and Therapeutics Group, Mater Research Institute-The University of Queensland, Translational Research Institute, Brisbane, Australia.

Specialized secretory cells known as goblet cells in the intestine and respiratory epithelium are responsible for the secretion of mucins. Mucins are large heavily glycosylated proteins and typically have a molecular mass higher than 10 Da. These large proteins are densely substituted with short glycan chains, which have many important functional roles including determining the hydration and viscoelastic properties of the mucus gel that lines and protects the intestinal epithelium. In this protocol, we comprehensively describe the method for extraction of murine mucus and its analysis by agarose gel electrophoresis. Additionally we describe the use of High Iron Diamine-Alcian Blue, Periodic Acid Schiff's-Alcian Blue and immune-staining methods to identify and differentiate between the different states of glycosylation on these mucin glycoproteins, in particular with a focus on sulphation and sialylation.
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http://dx.doi.org/10.21769/BioProtoc.2394DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8413512PMC
July 2017

Evaluation of testicular spermatogenic function by ultrasound elastography in patients with varicocele-associated infertility.

Am J Transl Res 2021 15;13(8):9136-9142. Epub 2021 Aug 15.

Emergency Department, Affiliated Hospital of Hebei Engineering University Handan, Hebei, China.

Objective: To investigate the application of ultrasound elastography and color Doppler ultrasound in the evaluation of testicular spermatogenic function in patients with varicocele (VC) associated infertility.

Methods: A total of 196 patients with VC-associated infertility treated in our hospital from January 2018 to January 2020 were included as the research subjects (VC group), and were classified into VC I group (66 cases), VC II group (60 cases), and VC III group (70 cases) according to the diameter of spermatic vein and the degree of reflux under ultrasound. 50 age-matched healthy subjects were included as the control group. Color ultrasound, ultrasound elastography and semen examination were performed on all patients.

Results: Compared with control group, a lower left testicular volume in VC group and a lower right testicular volume in VC III group were observed, and the left testicular volume was inversely proportional to VC grade (all P<0.05). Statistically significant differences in sperm viability, sperm density, peak systolic velocity (PSV), and MEAN values were determined among the 4 groups by one-way ANOVA, and between two groups by the independent-samples t test (all P<0.05). Pearson correlation analysis revealed that sperm viability and sperm density had no correlation with PSV, resistive index (RI) and pulsatility index (PI) of the left testicular artery in VC group, but were negatively correlated with the MEAN values of the testis.

Conclusion: Ultrasound elastography can predict the semen quality in patients with VC-associated infertility.

Clinical Trial Registration: This study was registered with the registration No. ChiCTR2010189 (URL: http://www.chictr.org.cn/showproj.aspx?proj=2018XE057-3).
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8430184PMC
August 2021

A Carbonate-Templated Decanuclear Mn Nanocage with Two Different Silsesquioxane Ligands.

Inorg Chem 2021 Sep 17. Epub 2021 Sep 17.

Key Laboratory of Colloid and Interface Chemistry, Ministry of Education, School of Chemistry and Chemical Engineering, State Key Laboratory of Crystal Materials, Shandong University, Ji'nan 250100, China.

The mild reaction of the preorganized silsesquioxane precursor with Mn(II) acetate under ambient conditions results in a mixed-valent {MnMn} nanocage () which is protected by both acyclic trimer [Si3] and cyclic tetramer [Si4]. Serendipitous capture of atmospheric CO as a μ-carbonate anion placed at the center supports the formation of the cluster. The magnetic analysis reveals the strong antiferromagnetic interactions between Mn ions. Moreover, the drop-casting film of shows photoelectric activity indicating its great potential as a semiconductor for photoelectric conversion applications.
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http://dx.doi.org/10.1021/acs.inorgchem.1c02190DOI Listing
September 2021

Integrated analysis of the molecular mechanisms in idiopathic pulmonary fibrosis.

Int J Med Sci 2021 2;18(15):3412-3424. Epub 2021 Aug 2.

Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China.

Idiopathic pulmonary fibrosis (IPF) is one of the most aggressive forms of idiopathic interstitial pneumonia. Some miRNAs may be associated with IPF and may affect the occurrence and development of IPF in various pathways. Many miRNAs and genes that may be involved in the development of IPF have been discovered using chip and high throughput technologies. We analyzed one miRNA and four mRNA databases. We identified hub genes and pathways related to IPF using GO, KEGG enrichment analysis, gene set variation analysis (GSVA), PPI network construction, and hub gene analysis. A comprehensive analysis of differentially expressed miRNAs (DEMs), predicted miRNA target genes, and differentially expressed genes (DEGs) led to the creation of a miRNA-mRNA regulatory network in IPF. We found 203 DEGs and 165 DEMs that were associated with IPF. The findings of enrichment analyses showed that these DEGs were mainly involved in antimicrobial humoral response, antimicrobial humoral immune response mediated by antimicrobial peptide, extracellular matrix organization, cell killing, and organ or tissue specific immune response. The VEGFA, CDH5, and WNT3A genes overlapped between hub genes and the miRNA-mRNA regulatory network. The miRNAs including miR-199b-5p, miR-140-5p, miR-199a-5p, miR-125A-5p, and miR-107 that we predicted would regulate the VEGFA, CDH5, and WNT3A genes, which were also associated with IPF or other fibrosis-related diseases. GSVA indicated that metabolic processes of UTP and IMP, immune response, regulation of Th2 cell cytokine production, and positive regulation of NK cell-mediated immunity are associated with the pathogenesis and treatment of IPF. These pathways also interact with VEGFA, CDH5, and WNT3A. These findings provide a new research direction for the diagnosis and treatment of IPF.
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http://dx.doi.org/10.7150/ijms.61309DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8436110PMC
August 2021

Is Identified and Validated as a Prognostic Biomarker Associated with Microsatellite Instability in Human Gastric Cancer.

DNA Cell Biol 2021 Sep 3. Epub 2021 Sep 3.

Department of Endocrinology, Renmin Hospital, Hubei University of Medicine, Shiyan, P.R. China.

Microsatellite instability (MSI) is emerging as a promising subtype related to immunotherapy in gastric cancer (GC). However, the underlying mechanism between MSI and microsatellite stability (MSS) remains unclear. In this study, we conducted a weighted gene co-expression network analysis and found that the expression of heterogeneous nuclear ribonucleoprotein L () was significantly increased in MSI GC compared with MSS GC. This finding was further validated in public GC cohorts and commercialized human GC tissue microarray. The significant negative correlation with the expression of mismatch repair protein mutL homolog 1 () may be one of the potential mechanisms for the upregulation of expression in MSI GC ( = -0.689,  = 8.59e-11). In addition, expression was markedly upregulated in GC tissues compared with adjacent normal tissues. High expression also predicted a poor prognosis in GC patients. Finally, gene set enrichment analysis revealed that high MSI GC samples were highly positive associated with the biological functions of inflammation and cell proliferation, such as interferon gamma response, MYC targets, E2F targets, and G2/M checkpoints. In conclusion, could be a new MSI-associated prognostic biomarker in GC and could be a new target for the MSI GC treatment.
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http://dx.doi.org/10.1089/dna.2021.0165DOI Listing
September 2021

High-Resolution Microstructure Analysis of Cork Spot Disordered Pear Fruit "Akizuki" ( Nakai) Using X-Ray CT.

Front Plant Sci 2021 16;12:715124. Epub 2021 Aug 16.

Department of Horticulture, Qingdao Agricultural University, Qingdao, China.

Cork spot is one of the most damaging physiological disorders in pear fruit, causing considerable economic loss every year. However, the mechanism of cork spot occurrence requires further examination. In this study, X-ray CT scanning was applied to analyze the microstructure of pear fruit "Akizuki" (), a cultivar susceptible to cork spot disorder, to elucidate the fruit texture alteration between healthy and cork spotted fruit. Results showed that cork spotted fruit had much higher porosity (9.37%) than healthy fruit (3.52%). Reconstructed three-dimensional (3D) network skeleton models showed highly branched pore channels in cork spotted fruit and a low degree of pore connectivity in healthy fruit. Even in areas of disordered fruit without cork spot, the pore throat diameter, pore length, and coordinated core number (i.e., 77, 160, and 16, respectively) were much higher than that of healthy fruit. The structure analysis of fruit core showed that core deformation only occurred in cork spotted fruit. A much more highly branched network was observed in cork spotted fruit cores compared with healthy fruit cores. High-resolution observation of flesh tissue directly demonstrated that pore size in cork spotted fruit (87 μm) was four times larger than that of healthy fruit (22 μm). Altered expression of genes related to Ca transport and the uneven distribution of intracellular Ca were also shown to associate with the development of cork spot disorder. Our results suggest that flesh tissue damage likely occurred prior to the initiation of cork spot. The dysfunction of long-distance and transmembrane Ca transport channels could be responsible for the imbalanced distribution of Ca inside the fruit, thus resulting in the development of cork spot.
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http://dx.doi.org/10.3389/fpls.2021.715124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8415714PMC
August 2021

Coupling spectral and resource-use complementarity in experimental grassland and forest communities.

Proc Biol Sci 2021 Sep 1;288(1958):20211290. Epub 2021 Sep 1.

Center for Advanced Land Management Information Technologies (CALMIT), School of Natural Resources, University of Nebraska-Lincoln, Lincoln, NE, USA.

Reflectance spectra provide integrative measures of plant phenotypes by capturing chemical, morphological, anatomical and architectural trait information. Here, we investigate the linkages between plant spectral variation, and spectral and resource-use complementarity that contribute to ecosystem productivity. In both a forest and prairie grassland diversity experiment, we delineated -dimensional hypervolumes using wavelength bands of reflectance spectra to test the association between the spectral space occupied by individual plants and their growth, as well as between the spectral space occupied by plant communities and ecosystem productivity. We show that the spectral space occupied by individuals increased with their growth, and the spectral space occupied by plant communities increased with ecosystem productivity. Furthermore, ecosystem productivity was better explained by inter-individual spectral complementarity than by the large spectral space occupied by productive individuals. Our results indicate that spectral hypervolumes of plants can reflect ecological strategies that shape community composition and ecosystem function, and that spectral complementarity can reveal resource-use complementarity.
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http://dx.doi.org/10.1098/rspb.2021.1290DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8437019PMC
September 2021

A Segmented Variable-Parameter ZNN for Dynamic Quadratic Minimization With Improved Convergence and Robustness.

IEEE Trans Neural Netw Learn Syst 2021 Aug 31;PP. Epub 2021 Aug 31.

As a category of the recurrent neural network (RNN), zeroing neural network (ZNN) can effectively handle time-variant optimization issues. Compared with the fixed-parameter ZNN that needs to be adjusted frequently to achieve good performance, the conventional variable-parameter ZNN (VPZNN) does not require frequent adjustment, but its variable parameter will tend to infinity as time grows. Besides, the existing noise-tolerant ZNN model is not good enough to deal with time-varying noise. Therefore, a new-type segmented VPZNN (SVPZNN) for handling the dynamic quadratic minimization issue (DQMI) is presented in this work. Unlike the previous ZNNs, the SVPZNN includes an integral term and a nonlinear activation function, in addition to two specially constructed time-varying piecewise parameters. This structure keeps the time-varying parameters stable and makes the model have strong noise tolerance capability. Besides, theoretical analysis on SVPZNN is proposed to determine the upper bound of convergence time in the absence or presence of noise interference. Numerical simulations verify that SVPZNN has shorter convergence time and better robustness than existing ZNN models when handling DQMI.
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http://dx.doi.org/10.1109/TNNLS.2021.3106640DOI Listing
August 2021

Distinct Compartmentalization of Microbial Community and Potential Metabolic Function in the Fruiting Body of .

J Fungi (Basel) 2021 Jul 22;7(8). Epub 2021 Jul 22.

The Germplasm Bank of Wild Species, Yunnan Key Laboratory for Fungal Diversity and Green Development, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China.

The uniquely compartmentalized fruiting body structure of the ectomycorrhizal fungus (EMF) , is a hotspot of microbial habitation and interaction. However, microbial diversity within this microniche structure of the EMF is rarely investigated. Furthermore, there is limited information concerning microbiomes associated with sporomes belonging to the ubiquitous fungal phylum Basidiomycota, particularly with respect to fungus-EMF interactions. In this study, we conducted high throughput sequencing, using ITS (fungal) and 16S rRNA (bacterial) marker genes to characterize and compare fruiting body microbiomes in the outer (pileipellis and stipitipellis) and inner layers (pileum context, stipe context, and lamellae) of the fruiting body of . Our results show the number of unique bacterial operational taxonomic units (OTUs) among the different compartments ranged from 410 to 499 and was more than double that of the shared/common OTUs (235). Micrococcales, Bacillales, , and were the primary significant bacterial taxa within the different compartments of the dissected fruiting body. Non-parametric multivariate analysis of variance showed significant compartmental differences for both the bacterial and the fungal community structure within the fruiting body. The metabolic profiling revealed putative metabolisms (of amino acids, carbohydrates, and nucleotides) and the biosynthesis of secondary metabolites to be highly enriched in outer layers; in the inner parts, the metabolisms of energy, cofactors, vitamins, and lipids were significantly higher. This study demonstrates for the first time the distinct compartmentalization of microbial communities and potential metabolic function profiles in the fruiting body of an economically important EMF .
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http://dx.doi.org/10.3390/jof7080586DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8397075PMC
July 2021

Association between serum uric acid and cardiovascular disease risk factors in adolescents in America: 2001-2018.

PLoS One 2021 23;16(8):e0254590. Epub 2021 Aug 23.

Department of Pediatric Cardiothoracic Surgery, Children's Hospital of Fudan University, Shanghai, China.

SUA is associated with cardiovascular disease and cardiovascular disease risk factors in adults, including chronic kidney disease, coronary artery disease, stroke, diabetes mellitus, preeclampsia, and hypertension. A cross-sectional study was carried out among 11219 adolescents 12 to 18 years of age examined in the 2001-2018 National health and Nutrition Examination Survey. We examined the association between SUA and CVD risk factors. The overall mean SUA level was 5.00±1.24mg/dl. Restricted cubic spline analysis results revealed SUA was inversely associated with HDL-C and SPISE and positively associated with TC, TG, LDL-C, nonHDL-C, insulin, SBP and DBP after full adjustment. Multiple logistic analyses showed SUA level was independently associated with high TC, high TG, high nonHDL-C and low HDL-C (all p<0.05). Furthermore, females in the highest quartile of SUA had significantly higher odds for elevated BP (OR = 2.38, 95%CI:1.02-5.54, P<0.05) and high TC (OR = 2.22, 95%CI: 1.49-3.30, P<0.001), which not observed in males. Increased levels of SUA were associated with increased odds of various cardiovascular risk factors in American adolescents, especially females.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0254590PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8382197PMC
August 2021

Nivolumab monotherapy or combination therapy with ipilimumab for lung cancer: a systemic review and meta-analysis.

Cancer Cell Int 2021 Aug 14;21(1):426. Epub 2021 Aug 14.

Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China.

Background: The high incidence and mortality of lung cancer have seriously affected human life and health. Nivolumab is a monoclonal antibody that can inhibit programmed death 1 (PD-1) and Ipilimumab is a monoclonal antibody against CTLA-4(cytotoxic T lymphocyte-associated antigen 4), both of which can prevent the immune escape of tumor cells. Our goal was to synthesize evidence from published randomized controlled trials involving the safety and efficacy of either Nivolumab alone or in combination for the treatment of unresectable lung cancer.

Methods: We searched the following electronic databases: PubMed, Embase, and Cochrane libraries, and screened the retrieved records for eligibility. We used the Stata16 software for the analyses. The results of the analysis are expressed as hazard ratios (HRs) or risk ratios (RRs) and their corresponding 95% confidence intervals (CI).

Results: The final analysis included seven trials involving 3817 patients. Among patients with advanced lung cancer, patients using immunotherapy had better overall survival (OS), progression-free survival (PFS), and an objective response rate (ORR) than patients receiving chemotherapy. The HR of Nivolumab monotherapy or combination therapy with OS was compared with that of chemotherapy (HR: 0.73, 95% CI 0.64-0.83; HR: 0.67, 95% CI 0.55-0.81), and the HR of PFS was (HR: 0.81, 95% CI 0.69-0.94; HR: 0.67, 95% CI 0.55-0.82).

Conclusions: Immunotherapy has been shown to have more clinically meaningful survival benefits for patients with lung cancer, whether monotherapy or combination immunotherapy. CRD42020213440.
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http://dx.doi.org/10.1186/s12935-021-02100-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8364020PMC
August 2021

[Analysis of FGD1 gene variant in a child with Aarskog-Scott syndrome].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2021 Aug;38(8):757-760

Department of Child Health Care, Wuxi Maternal and Child Health Care Hospital, Wuxi, Jiangsu 214000, China.

Objective: To detect pathogenic variant of the FGD1 gene in a boy with Aarskog-Scott syndrome.

Methods: Genetic variant was detected by high-throughput sequencing. Suspected variant was verified by Sanger sequencing. The nature and impact of the candidate variant were predicted by bioinformatic analysis.

Results: The child was found to harbor a novel c.1906C>T hemizygous variant of the FGD1 gene, which has led to conversion of Arginine to Tryptophane at codon 636(p.Arg636Trp). The same variant was found in his mother but not father. Based on the American College of Medical Genetics and Genomics guidelines, the c.1906C>T variant of FGD1 gene was predicted to be likely pathogenic(PM1+PM2+PM5+PP2+PP3+PP4).

Conclusion: The novel c.1906C>T variant of the FGD1 gene may underlay the Aarskog-Scott syndrome in this child. Above finding has enabled diagnosis for the boy.
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http://dx.doi.org/10.3760/cma.j.cn511374-20200605-00408DOI Listing
August 2021

Comparative Transcriptome Analysis of Different Fruit Parts Reveals Difference of Light Response during Fruit Coloration.

Biology (Basel) 2021 Jul 11;10(7). Epub 2021 Jul 11.

Zhengzhou Fruit Research Institute, Chinese Academy of Agricultural Sciences, Zhengzhou 450009, China.

Kiwifruit coloration is an important agronomic trait used to determine fruit quality, and light plays a vital role in the coloration process. The effect of light on fruit coloration has been studied in many species, but differences in the photoresponse of different fruit parts during fruit coloration is unclear in kiwifruit (). In this study, peel and core with bagging and non-bagging treatment at two stages were selected to perform high throughput RNA sequencing. A total of 100,417 unigenes (25,186 unigenes with length beyond 1000 bp) were obtained, of which 37,519 unigenes were annotated in functional databases. GO and KEGG enrichment results showed that 'plant hormone signal transduction' and 'carbon metabolism' were the key pathways in peel and core coloration, respectively. A total of 27 MYB-related TFs (transcription factors) were differentially expressed in peel and core. An R2R3-MYB typed TF, AaMYB308like, possibly served as a candidate objective, which played a vital role in light-inducible fruit coloration based on bioinformatics analysis. Transient overexpression of suggested overexpression of elevated transcription level of in leaves. Integration of all these results imply that AaMYB308like might be served as a light-responsive transcription factor to regulate anthocyanin biosynthesis in . Moreover, our study provided important insights into photoreponse mechanisms in coloration.
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http://dx.doi.org/10.3390/biology10070648DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8301191PMC
July 2021

Neuron navigator 2 is a novel mediator of rheumatoid arthritis.

Cell Mol Immunol 2021 Sep 28;18(9):2288-2289. Epub 2021 Jul 28.

State Key Laboratory of Quality Research in Chinese Medicine, School of Pharmacy, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macau, China.

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http://dx.doi.org/10.1038/s41423-021-00696-7DOI Listing
September 2021

Diagnosing Asthma With and Without Aerosol-Generating Procedures.

J Allergy Clin Immunol Pract 2021 Jul 21. Epub 2021 Jul 21.

Faculty of Biology, Medicine and Health, School of Biological Sciences, Division of Infection, Immunity & Respiratory Medicine, The University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom; NIHR Manchester Biomedical Research Unit and Manchester University NHS Foundation Trust, Manchester, United Kingdom. Electronic address:

Background: Asthma diagnostic guidelines require procedures with aerosol-generating potential (aerosol-generating procedures [AGPs]) to guide decision making. Restricted access to AGPs poses significant challenges in primary care and resource-poor countries, further amplified during the coronavirus disease 2019 pandemic.

Objective: To establish an approach to asthma diagnosis that does not require AGPs.

Method: Symptomatic yet untreated (beyond as-required bronchodilator use) adults with clinician-suspected asthma and maximum 10 pack year smoking history were recruited. Clinical history, physical examination, spirometry with bronchodilator reversibility, home peak flow monitoring, and bronchial challenges were performed, and fractional exhaled nitric oxide and serum eosinophils measured. Tests were then repeated following treatment with inhaled corticosteroids before an asthma diagnosis was confirmed or refuted by an expert panel.

Results: A total of 65 adults (mean age, 34.8 ± 12.2 years) were recruited. Five were excluded as "unclassifiable," because of borderline results or missing data. Of the remainder, 36 were diagnosed with asthma and 24 were not. Using data from non-AGPs only (wheeze on auscultation and blood eosinophilia) and home peak flow variability, a "rule-in" diagnostic model provided comparable discriminative ability to the application of established guidelines. Clinical suspicion of asthma together with at least 1 positive non-AGP test result provided a sensitivity of 55%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 60%. Application of this model reduced the need for spirometry-based tests by one-third.

Conclusions: The proposed diagnostic algorithm may be clinically useful in "ruling-in" asthma in adults when access to AGPs is limited. This algorithm is not suitable for those with low clinical probability, with a significant smoking history, or where alternative diagnoses are more likely. This pragmatic approach to asthma diagnosis merits prospective validation.
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http://dx.doi.org/10.1016/j.jaip.2021.07.006DOI Listing
July 2021

Pulmonary Sequelae at 4 Months After COVID-19 Infection: A Single-Centre Experience of a COVID Follow-Up Service.

Adv Ther 2021 08 18;38(8):4505-4519. Epub 2021 Jul 18.

Department of Respiratory Medicine, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester, UK.

Introduction: At the end of the first year of the COVID-19 pandemic, more than 78 million known survivors were recorded. The long-term pulmonary sequelae of COVID-19 remain unknown.

Methods: We performed a retrospective analysis of a post-COVID follow-up service to estimate the burden of persistent pulmonary morbidity in hospitalised COVID survivors.

Results: A total of 221 patients were followed-up: 44 intensive care unit (ICU) and 177 ward patients. Further investigations were planned as per British Thoracic Society Guidelines: For all ICU patients (n = 44) and for 38 of 177 (21%) ward-based patients who had persistent symptoms and/or persistent radiographic changes on CXR at their initial 8-week follow-up visit. In the ward-based cohort, statistically significant associations with persistent symptoms were being an ex- or current smoker, having pre-existing diabetes, and having a longer length of stay. In patients requiring further investigations, pulmonary function tests (PFTs; n = 67) at an average of 15 weeks post-discharge showed abnormalities in at least one PFT parameter in 79% (equating to 24% of the entire cohort). The most common abnormality was an abnormal diffusion capacity of carbon monoxide (TLCO), highest in the ICU cohort (64% ICU vs. 38% non-ICU). TLCO correlated negatively with length of stay and with maximum inspired FiO in the patient group as a whole. In ICU patients, TLCO correlated negatively with maximum inspired positive airway pressure. Computed tomography scans (n = 72) at an average of 18 weeks post-discharge showed evidence of persistent ground glass opacities in 44% and fibrosis in 21% (equating to 7% of the entire cohort).

Conclusion: Our data add to the growing evidence that there will be pulmonary sequelae in a proportion of COVID survivors, providing some insight into what may become a significant chronic global health problem.
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http://dx.doi.org/10.1007/s12325-021-01833-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8286847PMC
August 2021

Effectiveness and Safety of Adding Bevacizumab to Platinum-Based Chemotherapy as First-Line Treatment for Advanced Non-Small-Cell Lung Cancer: A Meta-Analysis.

Front Med (Lausanne) 2021 30;8:616380. Epub 2021 Jun 30.

Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, China.

Previous studies have evaluated the efficacy (OS, overall survival; PFS, progression-free survival; ORR, objective response rate) and adverse events of bevacizumab combined with platinum-based chemotherapy in first-line treatment of advanced non-small-cell lung cancer (NSCLC) compared with chemotherapy alone. However, the results were inconsistent. We conducted a comprehensive search of PubMed, EMBASE, and Cochrane Library for potentially eligible articles. The outcomes were evaluated in terms of risk ratio (RR) or hazard ratio (HR) and the associated 95% confidence intervals (CIs). Meta-analysis was performed using the Stata 12.0 software, and subgroup analyses were performed based on the treatment and bevacizumab dose. Six randomized controlled trials with 2,465 patients were included in this meta-analysis. The results demonstrated that bevacizumab significantly increased OS (HR = 0.87, 95% CI 0.79-0.96), extended PFS (HR = 0.65, 95% CI 0.54-0.77), and increased ORR (ES = 0.40, 95% CI 0.31-0.48) when added to first-line platinum-based chemotherapy in patients with advanced NSCLC. Subgroup analyses showed that only the higher dose (15 mg/kg) of bevacizumab plus carboplatin-paclitaxel significantly extended the OS and PFS, but both 7.5 mg/kg and 15 mg/kg of bevacizumab improved ORR. However, both 7.5 mg/kg and 15 mg/kg of bevacizumab could only increase PFS and ORR, but not extend OS, when added to cisplatin-gemcitabine. Bevacizumab significantly increased the risk of grade ≥3 events of febrile neutropenia, haemorrhagic events, hypertension, leukopenia, neutropenia, and proteinuria. Bevacizumab significantly increases OS, PFS, and ORR when added to first-line platinum-based chemotherapy in patients with advanced NSCLC, with no new safety signals found. Moreover, bevacizumab (15 mg/kg) plus carboplatin-paclitaxel is a better alternative in increasing OS to carboplatin-paclitaxel and bevacizumab (7.5 mg/kg and 15 mg/kg) plus cisplatin-gemcitabine.
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http://dx.doi.org/10.3389/fmed.2021.616380DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8277997PMC
June 2021

Facile synthesis of spherical covalent organic frameworks as stationary phases for short-column liquid chromatography.

Chem Commun (Camb) 2021 Jul;57(61):7501-7504

MOE Key Laboratory for Analytical Science of Food Safety and Biology, Fujian Provincial Key Laboratory of Analysis and Detection Technology for Food Safety, College of Chemistry, Fuzhou University, Fuzhou, Fujian 350116, China.

Micron-sized spherical covalent organic frameworks (SCOFs) with tunable sizes, narrow size distribution, and significant mono-dispersity were simply synthesized at room temperature. Thanks to their high specific surface areas, high chemical and mechanical stability, the SCOFs were used for the first time as stationary phases for high-efficiency separation of various small molecules and protein digests via short-column liquid chromatography.
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http://dx.doi.org/10.1039/d1cc03182aDOI Listing
July 2021

A retrospective cohort study in Chinese patients with adult polymyositis and dermatomyositis: risk of comorbidities and subclassification using machine learning.

Clin Exp Rheumatol 2021 Jun 26. Epub 2021 Jun 26.

Department of Internal Medicine of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China.

Objectives: To identify the risk factors in Chinese patients with adult polymyositis and dermatomyositis for their comorbidities and explore a subclassification system.

Methods: Clinical records of 397 patients with idiopathic inflammatory myopathies were retrospectively reviewed. Logistic regression was used to identify potential risk factors for interstitial lung disease (ILD), other rheumatic diseases, and malignancy after bivariate analysis. Hierarchical clustering and decisional tree were utilised to identify subgroups and explore a subclassification system.

Results: A total of 119 polymyositis and 191 dermatomyositis patients were included. Anti-PM/Scl, anti-Ro52, anti-aminoacyl-tRNA synthetase and anti-MDA5 (adjusted odds ratios (AOR)=4.779, 1.917, 5.092 and 7.714 respectively) antibodies were risks (p<0.05), whereas overlapping malignancy was protective (AOR=0.107; p=0.002) for ILD across polymyositis, dermatomyositis and the total group. In subgroup models, Raynaud's phenomenon, arthralgia and semi-quantitative anti-nuclear antibody (AOR=51.233, 4.261, 3.047 respectively) were risks for other overlapping rheumatic diseases (p<0.05). For overlapping malignancy, male and anti-TIF1γ antibodies (AOR=2.533, 16.949) were risks (p<0.05), whereas disease duration and combination of ILD (AOR=0.954, 0.106) were protective in the total group (p<0.05); while anti-NXP2 antibodies were identified as risk factors (AOR=73.152; p=0.038) in polymyositis. Hierarchical clustering suggested a subclassification with 6 subgroups: malignancy overlapping dermatomyositis, classical dermatomyositis, polymyositis with severe muscle involvement, dermatomyositis with ILD, polymyositis with ILD, and overlapping of myositis with other rheumatic diseases.

Conclusions: Accompanying ILD, other rheumatic diseases and malignancy are strongly associated with clinical manifestation and myositis-specific or myositis-associated autoantibodies among Chinese polymyositis and dermatomyositis patients. The subclassification system proposed a more precise phenotype defining toward stratified treatments.
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June 2021

Observation and measurement of applied anatomical features for thoracic intervertebral foramen puncture on computed tomography images.

World J Clin Cases 2021 Jun;9(18):4607-4616

Department of Pain Management, Nanjing Drum Tower Hospital, Clinical College of Xuzhou Medical University, Nanjing 210008, Jiangsu Province, China.

Background: Thoracic intervertebral foramen puncture is the key step for interventional therapy on the thoracic nerve roots or dorsal root ganglia. The anatomical features of the thoracic spine are complex, and puncture injury to the pleura, blood vessels, spinal cord, and other tissues may cause serious complications. The spatial anatomical characteristics and related parameters for thoracic intervertebral foramen puncture remain poorly understood.

Aim: To observe and summarize the spatially applied anatomical characteristics for intervertebral foramen puncture on different vertebral segments.

Methods: A total of 88 patients (41 males and 47 females) who underwent thoracic minimally invasive interventional treatment at Nanjing Drum Tower Hospital from January 2019 to June 2020 were included. Computed tomography images of 167 thoracic vertebral segments scanned in the prone position were collected. The width of the intertransverse space (D), the height of the rib neck/head above the lower transverse process (D), the width of the lateral border of the articular process/lamina (W), and the width of the posterior border of the vertebral body (W) were measured. At the upper 1/3 of the intervertebral foramina, the horizontal inclination angle (α) from the lateral border of the articular process/lamina to the posterolateral border of the vertebral body was measured. The ratios D/D and W/W were calculated. The intervertebral foramen parameters were compared between segments.

Results: No rib head/neck occlusion (D/D > 0) was found in the intertransverse spaces of T1-2 and T12-L1. The incidence of occlusion for the upper thoracic segments (T1-5, = 138), middle thoracic segments (T5-9, = 116), and lower thoracic segments (T9-L1, = 80) were 76.81%, 100%, and 82.50%, respectively. The incidence of occlusion for the middle thoracic segments was significantly higher than that for the upper and lower thoracic segments ( < 0.05). The incidence of > 1/2 occlusion (D/D > 1/2) for the upper, middle, and lower thoracic segments was 7.97%, 74.14%, and 32.50%, respectively. The incidence of > 1/2 occlusion for the middle thoracic segments was significantly higher than that for the upper and lower thoracic segments ( < 0.05). W was longer than W on T1-2 to T9-10 and shorter than W on T10-11 to T12-L1. The horizontal puncture angle (α) into the external opening of the intervertebral foramina was positively correlated with the segments of the thoracic vertebrae from the cephalic to caudal portion (left: = 0.772, < 0.01; right: = 0.771, < 0.01), and the horizontal inclination angle for T11-12 and T12-L1 was 90°.

Conclusion: It is necessary to identify the spatial impact of the rib head/neck on the puncture path of the intervertebral foramina and design appropriate puncture angles for different segments.
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http://dx.doi.org/10.12998/wjcc.v9.i18.4607DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8223838PMC
June 2021

Imidacloprid increases intestinal permeability by disrupting tight junctions.

Ecotoxicol Environ Saf 2021 Oct 30;222:112476. Epub 2021 Jun 30.

Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China; Key Laboratory of Precision Nutrition and Food Quality, Department of Nutrition and Health, China Agricultural University, Beijing 100083, China. Electronic address:

The neonicotinoid pesticide, imidacloprid (IMI), is frequently detected in the environment and in foods. It is absorbed and metabolized by the intestine; however, its effects on intestinal barrier integrity are not well studied. We investigated whether IMI disrupts the permeability of the intestinal epithelial barrier via in vivo tests on male Wistar rats, in vitro assays using the human intestinal epithelial cell line, Caco-2, and in silico analyses. A repeated oral dose 90-day toxicity study was performed (0.06 mg/kg body weight/day). IMI exposure significantly increased intestinal permeability, which led to significantly elevated serum levels of endotoxin and inflammatory biomarkers (tumor necrosis factor-alpha and interleukin-1 beta) without any variation in body weight. Decreased transepithelial electrical resistance with increased permeability was also observed in 100 nM and 100 μM IMI-treated Caco-2 cell monolayers. Amounts of tight junction proteins in IMI-treated colon tissues and between IMI-treated Caco-2 cells were significantly lower than those of controls. Increased levels of myosin light chain phosphorylation, myosin light chain kinase (MLCK), and p65 subunit of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB p65) phosphorylation were found in IMI-exposed cells compared with control cells. Furthermore, the barrier loss caused by IMI was rescued by the MLCK inhibitor, ML-7, and cycloheximide. Pregnane X receptor (PXR, NR1I2) was inhibited by low-dose IMI treatment. In silico analysis indicated potent binding sites between PXR and IMI. Together, these data illustrate that IMI induces intestinal epithelial barrier disruption and produces an inflammatory response, involving the down-regulation of tight junctions and disturbance of the PXR-NF-κB p65-MLCK signaling pathway. The intestinal barrier disruption caused by IMI deserves attention in assessing the safety of this neonicotinoid pesticide.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112476DOI Listing
October 2021

Construction of Multifunctional and Adjustable Langmuir-Blodgett Composite Films Containing Black Phosphorus with High Stability for Optically Electrical Applications.

Langmuir 2021 Jul 2;37(28):8616-8626. Epub 2021 Jul 2.

State Key Laboratory of Metastable Materials Science and Technology, Yanshan University, Qinhuangdao 066004, P. R. China.

Fabrication of composite thin-film materials based on black phosphorus (BP) will greatly broaden the applications of BP in various areas. However, it is still a challenge to prepare a BP-based composite film with good stability and controllable structure. In this work, a series of BP-based composite Langmuir-Blodgett (LB) films are prepared by the self-assembly of polyethyleneimine (PEI)-modified BP nanosheets (BPNSs) (BPNS-PEI) and dye molecules. The presence of PEI greatly improves the stability of BPNSs. As for BPNS-PEI and dye molecules, the electrostatic interactions or π-π stacking interactions ensure the formation of stable composite LB films. Due to the protonation and deprotonation of amino groups, the synthesized BPNS-PEI/dye composite films show a sensitive response to acid and alkali gases, which shows wide application prospects as a highly sensitive gas sensor. Furthermore, surface-enhanced Raman scattering (SERS) proves that the prepared LB films exhibit good reproducibility and obvious Raman enhancement effect on rhodamine 6G molecules. In addition, due to the high carrier transfer rate of the obtained composite films, they possess enhanced photocurrent generation performance than pure BPNS-PEI and pure dye films. The current work demonstrates an effective method for preparing the ordered self-assembled BP-based composite LB films with good SERS and photoelectric conversion performance.
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http://dx.doi.org/10.1021/acs.langmuir.1c01260DOI Listing
July 2021

Effects of Fermented Milk Containing Strain Shirota on Constipation in Patients with Depression: A Randomized, Double-Blind, Placebo-Controlled Trial.

Nutrients 2021 Jun 29;13(7). Epub 2021 Jun 29.

Department of Nutrition and Health, China Agricultural University, Beijing 100091, China.

Probiotics have been shown to benefit patients with constipation and depression, but whether they specifically alleviate constipation in patients with depression remains unclear. The aim of this study was to investigate the effect of strain Shirota (LcS), formerly strain Shirota, on constipation in patients with depression with specific etiology and gut microbiota and on depressive regimens. Eighty-two patients with constipation were recruited. The subjects consumed 100 mL of a LcS beverage (10 CFU/mL) or placebo every day for 9 weeks. After ingesting beverages for this period, we observed no significant differences in the total patient constipation-symptom (PAC-SYM) scores in the LcS group when compared with the placebo group. However, symptoms/scores in item 7 (rectal tearing or bleeding after a bowel movement) and items 8-12 (stool symptom subscale) were more alleviated in the LcS group than in the placebo group. The Beck Depression Index (BDI) and Hamilton Depression Rating Scale (HAMD) scores were all significantly decreased, and the degree of depression was significantly improved in both the placebo and LcS groups ( < 0.05), but there was no significant difference between the groups. The LcS intervention increased the beneficial , and levels and decreased the bacterial levels related to mental illness, such as , and Additionally, the interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α) levels were significantly decreased in both the placebo and LcS groups ( < 0.05). In particular, the IL-6 levels were significantly lower in the LcS group than the placebo group after the ingestion period ( < 0.05). In conclusion, the daily consumption of LcS for 9 weeks appeared to relieve constipation and improve the potentially depressive symptoms in patients with depression and significantly decrease the IL-6 levels. In addition, the LcS supplementation also appeared to regulate the intestinal microbiota related to mental illness.
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http://dx.doi.org/10.3390/nu13072238DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8308326PMC
June 2021

A Novel Photosensitizer for Lipid Droplet-Location Photodynamic Therapy.

Front Chem 2021 14;9:701771. Epub 2021 Jun 14.

State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian, China.

Lipid droplets (LDs), an extremely important cellular organelle, are responsible for the storage of neutral lipids in multiple biological processes, which could be a potential target site for photodynamic therapy (PDT) of cancer. Herein, a lipid droplet-targeted photosensitizer (BODSeI) is developed, allowing for fluorescence imaging-guided PDT. Owing to the location of lipid droplets, BODSeI demonstrates enhanced PDT efficiency with an extremely low IC50 value (around 125 nM). Besides, BODSeI shows good biocompatibility and high photostability. Therefore, BODSeI is promising for droplet-location PDT, which may trigger wide interest for exploring the pathway of lipid droplet-location PDT.
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http://dx.doi.org/10.3389/fchem.2021.701771DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8236597PMC
June 2021

A Novel Photosensitizer for Lipid Droplet-Location Photodynamic Therapy.

Front Chem 2021 14;9:701771. Epub 2021 Jun 14.

State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian, China.

Lipid droplets (LDs), an extremely important cellular organelle, are responsible for the storage of neutral lipids in multiple biological processes, which could be a potential target site for photodynamic therapy (PDT) of cancer. Herein, a lipid droplet-targeted photosensitizer (BODSeI) is developed, allowing for fluorescence imaging-guided PDT. Owing to the location of lipid droplets, BODSeI demonstrates enhanced PDT efficiency with an extremely low IC50 value (around 125 nM). Besides, BODSeI shows good biocompatibility and high photostability. Therefore, BODSeI is promising for droplet-location PDT, which may trigger wide interest for exploring the pathway of lipid droplet-location PDT.
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http://dx.doi.org/10.3389/fchem.2021.701771DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8236597PMC
June 2021

Unveiling sugarcane defense response to Mythimna separata herbivory by a combination of transcriptome and metabolic analyses.

Pest Manag Sci 2021 Oct 10;77(10):4799-4809. Epub 2021 Jul 10.

National Engineering Research Center of Sugarcane, Fujian Agricultural and Forestry University, Fuzhou, P. R. China.

Background: Sugarcane is the most important sugar crop in the world. Like other crops, sugarcane suffers from herbivorous insect attack. The oriental armyworm Mythimna separata is a devastating pest of various crops in northeast Asia and an outbreak of this pest can result in substantial yield loss for sugarcane. However, the plant defense response situation is widely acquisition in model crops, but there is little information about how sugarcane plants defend themselves against this herbivore at the molecular and biochemical levels.

Results: We combined transcriptome and metabolomic analysis to investigate the changes in gene expression and metabolic processes that occurred in sugarcane plants after continuous feeding by M. separata larvae for 12 and 24 h. We identified 13 662 genes and 55 metabolites that were differentially regulated in sugarcane plants fed on by M. separata. The genes involved in phytohormones, transcription factors, and kinase-related were activated and metabolism compounds such as carbohydrate, amino acid, ferulic substances and glutathione were detected regulated in sugarcane defense response. Comparable analyses showed a close correspondence relationship among pathways of phenylalanine metabolism, phenylpropanoid biosynthesis, and flavonoid biosynthesis in transcript and metabolite profiles. Furthermore, a bioassay experiment was conducted to test the influence of up-regulated metabolites on M. separata growth and found chlorogenic acid had a lethal effect.

Conclusion: The results of our study greatly enhanced the understanding of the sugarcane-induced defense response mechanism against herbivore infestation at the transcriptional and metabolic levels. Also make contributions to provide clues for development of green pest control method. © 2021 Society of Chemical Industry.
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http://dx.doi.org/10.1002/ps.6526DOI Listing
October 2021

Association between serum 25-hydroxyvitamin D concentrations and obesity in one-year-old Chinese infants.

Food Sci Nutr 2021 Jun 3;9(6):3191-3199. Epub 2021 May 3.

Department of Epidemiology and Biostatics Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases School of Public Health Medical College of Soochow University Suzhou China.

Recent studies suggested that vitamin D is linked with obesity, but evidence in infants is scarce. Therefore, we aimed to make an exploration in infants. A total of 414 infants at one year old who visited Maternity and Child Health Care Hospital of Wuxi in China were recruited. Finger-stick blood sampling was conducted in all the subjects, and serum 25-hydroxyvitamin D [25(OH)D] concentrations were measured. Maternal characteristics during pregnancy and infantile information were collected by questionnaires or extracting from medical records. Multivariable linear models were performed to assess the relationship between 25(OH)D and body mass index (BMI), while multivariable logistic regression models were used to examine the association between 25(OH)D and obesity. Among the 414 infants, 69 (16.67%) and 81 (19.57%) infants were defined as obesity and vitamin D deficiency [25(OH)D < 50 nmol/L], respectively. The mean () of 25(OH)D concentration was 68.05 (19.05) in infants without obesity, which was significantly higher than that of obese infants [60.36(18.49),  = .002]. Inverse linear relationships were observed between 25(OH)D level and BMI ( = -0.017,  = .004) as well as BMI -score ( = -0.010,  = .004). Furthermore, vitamin D deficiency was associated with an increased risk of obesity of infants (adjusted odds ratio = 2.74, 95% confidence interval = 1.20-6.25, with 25(OH)D ≥ 75 nmol/L as a reference). The results showed that serum 25(OH)D concentrations were significantly lower in infants with obesity, suggesting vitamin D deficiency may be an independent risk factor for obesity among one-year-old Chinese infants.
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http://dx.doi.org/10.1002/fsn3.2279DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194735PMC
June 2021

Individualized lncRNA differential expression profile reveals heterogeneity of breast cancer.

Oncogene 2021 Jul 15;40(27):4604-4614. Epub 2021 Jun 15.

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

Long non-coding RNAs (lncRNAs) play key regulatory roles in breast cancer. However, population-level differential expression analysis methods disregard the heterogeneous expression of lncRNAs in individual patients. Therefore, we individualized lncRNA expression profiles for breast invasive carcinoma (BRCA) using the method of LncRNA Individualization (LncRIndiv). After evaluating the robustness of LncRIndiv, we constructed an individualized differentially expressed lncRNA (IDElncRNA) profile for BRCA and investigated the subtype-specific IDElncRNAs. The breast cancer subtype-specific IDElncRNA showed frequent co-occurrence with alterations of protein-coding genes, including mutations, copy number variation and differential methylation. We performed hierarchical clustering to subdivide TNBC and revealed mesenchymal subtype and immune subtype for TNBC. The TNBC immune subtype showed a better prognosis than the TNBC mesenchymal subtype. LncRNA PTOV1-AS1 was the top differentially expressed lncRNA in the mesenchymal subtype. And biological experiments validated that the upregulation of PTOV1-AS1 could downregulate TJP1 (ZO-1) and E-Cadherin, and upregulate Vimentin, which suggests PTOV1-AS1 may promote epithelial-mesenchymal transition and lead to migration and invasion of TNBC cells. The mesenchymal subtype showed a higher fraction of M2 macrophages, whereas the immune subtype was more associated with CD4 + T cells. The immune subtype is characterized by genomic instability and upregulation of immune checkpoint genes, thereby suggesting a potential response to immunosuppressive drugs. Last, drug response analysis revealed lncRNA ENSG00000230082 (PRRT3-AS1) is a potential resistance biomarker for paclitaxel in BRCA treatment. Our analysis highlights that IDElncRNAs can characterize inter-tumor heterogeneity in BRCA and the new TNBC subtypes indicate novel insights into TNBC immunotherapy.
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http://dx.doi.org/10.1038/s41388-021-01883-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8266678PMC
July 2021
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