Publications by authors named "Hongyan Wu"

199 Publications

Graph Polish: A Novel Graph Generation Paradigm for Molecular Optimization.

IEEE Trans Neural Netw Learn Syst 2021 Sep 14;PP. Epub 2021 Sep 14.

Molecular optimization, which transforms a given input molecule X into another Y with desired properties, is essential in molecular drug discovery. The traditional approaches either suffer from sample-inefficient learning or ignore information that can be captured with the supervised learning of optimized molecule pairs. In this study, we present a novel molecular optimization paradigm, Graph Polish. In this paradigm, with the guidance of the source and target molecule pairs of the desired properties, a heuristic optimization solution can be derived: given an input molecule, we first predict which atom can be viewed as the optimization center, and then the nearby regions are optimized around this center. We then propose an effective and efficient learning framework, Teacher and Student polish, to capture the dependencies in the optimization steps. A teacher component automatically identifies and annotates the optimization centers and the preservation, removal, and addition of some parts of the molecules; a student component learns these knowledges and applies them to a new molecule. The proposed paradigm can offer an intuitive interpretation for the molecular optimization result. Experiments with multiple optimization tasks are conducted on several benchmark datasets. The proposed approach achieves a significant advantage over the six state-of-the-art baseline methods. Also, extensive studies are conducted to validate the effectiveness, explainability, and time savings of the novel optimization paradigm.
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http://dx.doi.org/10.1109/TNNLS.2021.3106392DOI Listing
September 2021

Smoothness Sensor: Adaptive Smoothness-Transition Graph Convolutions for Attributed Graph Clustering.

IEEE Trans Cybern 2021 Aug 16;PP. Epub 2021 Aug 16.

Clustering techniques attempt to group objects with similar properties into a cluster. Clustering the nodes of an attributed graph, in which each node is associated with a set of feature attributes, has attracted significant attention. Graph convolutional networks (GCNs) represent an effective approach for integrating the two complementary factors of node attributes and structural information for attributed graph clustering. Smoothness is an indicator for assessing the degree of similarity of feature representations among nearby nodes in a graph. Oversmoothing in GCNs, caused by unnecessarily high orders of graph convolution, produces indistinguishable representations of nodes, such that the nodes in a graph tend to be grouped into fewer clusters, and pose a challenge due to the resulting performance drop. In this study, we propose a smoothness sensor for attributed graph clustering based on adaptive smoothness-transition graph convolutions, which senses the smoothness of a graph and adaptively terminates the current convolution once the smoothness is saturated to prevent oversmoothing. Furthermore, as an alternative to graph-level smoothness, a novel fine-grained nodewise-level assessment of smoothness is proposed, in which smoothness is computed in accordance with the neighborhood conditions of a given node at a certain order of graph convolution. In addition, a self-supervision criterion is designed considering both the tightness within clusters and the separation between clusters to guide the entire neural network training process. The experiments show that the proposed methods significantly outperform 13 other state-of-the-art baselines in terms of different metrics across five benchmark datasets. In addition, an extensive study reveals the reasons for their effectiveness and efficiency.
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http://dx.doi.org/10.1109/TCYB.2021.3088880DOI Listing
August 2021

White rice ethanol extract is qualitatively, but not quantitatively, equivalent to that of brown rice as an antioxidant source.

Biosci Biotechnol Biochem 2021 Jul 19. Epub 2021 Jul 19.

Graduate School of Environmental and Life Science, Okayama University, Okayama 700-8530, Japan.

The purpose of this study is to compare the potentials to exhibit biologically-active antioxidant actions between white rice (WR) and brown rice (BR) in in vitro assays and a cellular model. The Trolox equivalent (TE) per 1 mg ethanol extract of WR for the 1,1-diphenyl-2-picrylhydrazyl assay was slightly higher than that of BR, whereas the TE per 1 g whole WR was much lower than that for BR. This tendency was very comparable to those for the oxygen radical absorbance capacity and total polyphenol content. Both of the ethanol extracts also similarly suppressed the hydrogen peroxide-induced cytotoxicity and enhanced the gene expression of drug-metabolizing enzymes. Based on the αT quantity, its contribution to the cytoprotective effect of the rice extracts is very limited. Taken together, the ethanol extract of WR might be a qualitatively, but not quantitatively, equivalent source of antioxidative phytochemicals to that of BR.
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http://dx.doi.org/10.1093/bbb/zbab133DOI Listing
July 2021

Expression of KLRG1 and CD127 defines distinct CD8 subsets that differentially impact patient outcome in follicular lymphoma.

J Immunother Cancer 2021 Jul;9(7)

Division of Hematology and Internal Medicine, Mayo Clinic, Rochester, MN, USA

Background: CD8 T-lymphocyte subsets defined by killer lectin-like receptor G1 (KLRG1) and CD127 expression have been reported to have an important role in infection, but their role in the setting of lymphoid malignancies, specifically follicular lymphoma (FL), has not been studied.

Methods: To characterize the phenotype of KLRG1/CD127-defined CD8 subsets, surface and intracellular markers were measured by flow cytometry and Cytometry by time of flight (CyTOF), and the transcriptional profile of these cells was determined by CITE-Seq (Cellular Indexing of Transcriptomes and Epitopes by Sequencing). The functional capacity of each subset was determined, as was their impact on overall survival (OS) and event-free survival (EFS) of patients with FL.

Results: We found that intratumoral CD8 cells in FL are skewed toward effector cell subsets, particularly KLRGCD127 and KLRG1CD127 cells over memory cell subsets, such as KLRG1CD127 and KLRG1CD127 cells. While effector subsets exhibited increased capacity to produce cytokines/granules when compared with memory subsets, their proliferative capacity and viability were found to be substantially inferior. Clinically, a skewed distribution of intratumoral CD8 T cells favoring effector subtypes was associated with an inferior outcome in patients with FL. Increased numbers of CD127KLRG1 and CD127KLRG1 were significantly associated with a favorable OS and EFS, while CD127KLRG1 correlated with a poor EFS and OS in patients with FL. Furthermore, we demonstrated that interleukin (IL)-15 promotes CD127KLRG1 cell development in the presence of dendritic cells via a phosphoinositide 3-kinase (PI3K)-dependent mechanism, and treatment of CD8 T cells with a PI3K inhibitor downregulated the transcription factors responsible for CD127KLRG1 differentiation.

Conclusions: Taken together, these results reveal not only a biological and prognostic role for KLRG1/CD127-defined CD8 subsets in FL but also a potential role for PI3K inhibitors to manipulate the differentiation of CD8 T cells, thereby promoting a more effective antitumor immune response.
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http://dx.doi.org/10.1136/jitc-2021-002662DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8258669PMC
July 2021

PM and water-soluble components induce airway fibrosis through TGF-β1/Smad3 signaling pathway in asthmatic rats.

Mol Immunol 2021 Sep 25;137:1-10. Epub 2021 Jun 25.

Department of Environmental Health, School of Public Health, Shanxi Medical University, 56 Xinjian South Road, Taiyuan, 030001, China. Electronic address:

Epidemiological studies have suggested that fine particulate matter (PM) and asthma have been independently associated with pulmonary fibrosis but rarely studied together. Furthermore, it is unknown whether airway fibrosis in asthma is more attributable to water-soluble ions of PM. Our current study was to explore the potential mechanism of PM and water-soluble components on airway fibrosis in ovalbumin (OVA)-sensitized asthmatic rats. Rats were intratracheally instilled with PM and water-soluble components every 3 days for 4 times or 8 times. Histopathological examination demonstrated that lung inflammatory and airway fibrosis were induced after PM and water-soluble components exposure. Meanwhile, PM, in particular water-soluble extracts, increased expression of collagen 1 (COL-1), connective tissue growth factor (CTGF), interleukin-6 (IL-6), transforming growth factor-β1 (TGF-β1), Smad family member 3 (Smad3), and p-Smad3, whereas decreased secretion of heme oxygenase-1 (HO-1). However, pretreating asthmatic rats with SB432542, the inhibitor of TGF-β1, and SIS3 HCl, the antagonist of Smad3, both reversed the activation of airway fibrosis induced by water-soluble extracts. Therefore, TGF-β1/Smad3 signaling pathway may be responsible for the pathological process of airway fibrosis in asthmatic rats following PM and water-soluble components exposure.
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http://dx.doi.org/10.1016/j.molimm.2021.06.005DOI Listing
September 2021

Bullatacin triggers immunogenic cell death of colon cancer cells by activating endoplasmic reticulum chaperones.

J Inflamm (Lond) 2021 Jun 10;18(1):23. Epub 2021 Jun 10.

Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, 210009, China.

Background: It is well accepted that the immune system efficiently contributes to positive outcomes of chemotherapeutic cancer treatment by activating immunogenic cell death (ICD). However, only a limited number of ICD-inducing compounds are well characterized at present; therefore, identification of novel ICD inducers is urgently needed for cancer drug discovery, and the need is becoming increasingly urgent.

Methods: Herein, we assessed the antitumour activity of bullatacin by MTS assay and apoptosis assay. ICD biomarkers, such as calreticulin (CRT), high-mobility group protein B1 (HMGB-1), heat shock protein (HSP)70, HSP90 and ATP, were assessed by Western blotting, ELISA and flow cytometry. Western blot and qPCR assays were performed to explore the underlying mechanisms of bullatacin-induced ICD. Flow cytometry was used to detect macrophage phagocytosis.

Results: First, bullatacin induced apoptosis in both SW480 cells and HT-29 cells in a time-dependent manner at 10 nM, as assessed by flow cytometry. Moreover, Western blot and flow cytometry assays showed that CRT and HSP90 (biomarkers of early ICD) significantly accumulated on the cell membrane surface after approximately 6 h of treatment with bullatacin. In addition, ELISAs and Western blot assays showed that the second set of hallmarks required for ICD (HMGB1, HSP70 and HSP90) were released in the conditioned media of both SW480 and HT-29 cells after 36 h of treatment. Furthermore, qPCR and Western blot assays indicated that bullatacin triggered ICD via activation of the endoplasmic reticulum stress (ERS) signalling pathway. Finally, bullatacin promoted macrophage phagocytosis.

Conclusion: This study documents that bullatacin, a novel ICD inducer, triggers immunogenic tumour cell death by activating ERS even at a relatively low concentration in vitro.
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http://dx.doi.org/10.1186/s12950-021-00289-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194247PMC
June 2021

Cinnamaldehyde Improves Metabolic Functions in Streptozotocin-Induced Diabetic Mice by Regulating Gut Microbiota.

Drug Des Devel Ther 2021 1;15:2339-2355. Epub 2021 Jun 1.

Fuwai Hospital, Chinese Academy of Medical Sciences, Shenzhen, People's Republic of China.

Purpose: The aim of the present study was to examine the protective effects of cinnamaldehyde (CA) on type 1 diabetes mellitus (T1DM) and explore the underlying molecular mechanisms by using multiple omics technology.

Methods: T1DM was induced by streptozotocin in the mice. Immunostaining was performed to evaluate glycogen synthesis in the liver and morphological changes in the heart. Gut microbiota was analyzed using 16S rRNA gene amplification sequencing. The serum metabolomics were determined by liquid chromatography-mass spectrometry. The relevant gene expression levels were determined by quantitative real-time PCR.

Results: CA treatment significantly improved the glucose metabolism and insulin sensitivity in T1DM mice. CA increased glycogen synthesis in the liver and protected myocardial injury in T1DM mice. CA affected the gut microbiota particularly by increasing the relative abundance of and decreasing the relative abundance of in T1DM mice. The glucose level was positively correlated with 88 functional pathways of gut microbiota and negatively correlated with 2 functional pathways of gut microbiota. Insulin resistance was positively correlated with 11 functional pathways. The analysis of serum metabolomics showed that CA treatment significantly increased the levels of taurochenodeoxycholic acid, tauroursodeoxycholic acid, tauro-α-muricholic acid and tauro-β-muricholic acid, taurodeoxycholic acid, taurocholic acid and taurohyodeoxycholic acid in T1DM mice. Taurohyodeoxycholic acid level was highly correlated with the blood glucose levels. Furthermore, the abundance of was positively correlated with AKT2, insulin like growth factor 1 receptor, E2F1 and insulin receptor substrate 1 mRNA expression levels, while taurohyodeoxycholic acid level was negatively correlated with IRS1 mRNA expression level.

Conclusion: Our results indicated that CA may interfere with gut microbiota to affect host metabolomics, especially the bile acids, so as to directly or indirectly modulate the expression levels of glucose metabolism-related genes, thus subsequently reducing the blood glucose level in the T1DM mice.
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http://dx.doi.org/10.2147/DDDT.S288011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8179756PMC
June 2021

Identification and construction of lncRNA-associated ceRNA network in diabetic kidney disease.

Medicine (Baltimore) 2021 Jun;100(22):e26062

Department of Science and Education, The First Affiliated Hospital of Yangtze University, Jingzhou First People's Hospital, Jingzhou, Hubei, China.

Abstract: Diabetic kidney disease (DKD) has become the major contributor to end-stage renal disease with high incidence and mortality. The functional roles and exact mechanisms of long noncoding RNA (lncRNA)-associated competing endogenous RNA (ceRNA) network in DKD are still largely unknown. This study sought to discover novel potential biomarkers and ceRNA network for DKD.The candidate differentially expressed genes (DEGs), lncRNAs and microRNAs (miRNAs) in human glomerular and tubular tissues derived from Gene Expression Omnibus database were systematically selected and analyzed. Functional enrichment analysis and protein-protein interaction network analysis were conducted to identify hub genes and reveal their regulatory mechanisms involved in DKD. Following this, the integrated ceRNA network was constructed by bioinformatics methods.A total of 164 DEGs, 6 lncRNAs and 18 miRNAs correlated with DKD were finally filtered and identified. It is noteworthy that the global lncRNA-associated ceRNA network related to DKD was constructed, among which lnc-HIST2H2AA4-1, VCAN-AS1 and MAGI2-AS1 were identified as the 3 key lncRNAs, and VCAN, FN1, CCL2, and KNG1 were identified as the predominant genes. Consistent with that observed in the training set, 3 of the key genes also showed significant differences in the 2 validation datasets. Integrating with functional enrichment analysis results, these key genes in the ceRNA network were mainly enriched in the immune and inflammation-related pathways.This study first identified key lncRNAs, miRNAs and their targets, and further revealed a global view of lncRNA-associated ceRNA network involved in DKD by using whole gene transcripts analysis.
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http://dx.doi.org/10.1097/MD.0000000000026062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183707PMC
June 2021

A critical role of PvFtsH2 in the degradation of photodamaged D1 protein in common bean.

Hortic Res 2021 Jun 1;8(1):126. Epub 2021 Jun 1.

Key Laboratory of Soybean Molecular Design Breeding, Northeast Institute of Geography and Agroecology, The Innovative Academy of Seed Design, Chinese Academy of Sciences, Haping Road 138, Nangang District, 150081, Harbin City, Heilongjiang Province, China.

Light is required for initiating chloroplast biogenesis and photosynthesis; however, the photosystem II reaction center (PSII RC) can be photodamaged. In this study, we characterized pvsl1, a seedling-lethal mutant of Phaseolus vulgaris. This mutant showed lethality when exposed to sunlight irradiation and a yellow-green leaf phenotype when grown in a growth chamber under low-light conditions. We developed 124 insertion/deletion (INDEL) markers based on resequencing data of Dalong1 and PI60234, two local Chinese common bean cultivars, for genetic mapping. We identified Phvul.002G190900, which encodes the PvFtsH2 protein, as the candidate gene for this pvsl1 mutation through fine-mapping and functional analysis. A single-base deletion occurred in the coding region of Phvul.002G190900 in the pvsl1 mutant, resulting in a frameshift mutation and a truncated protein lacking the Zn metalloprotease domain. Suppressed expression of Phvul.002G190900 at the transcriptional level was detected, while no change in the subcellular localization signal was observed. The seedlings of pvsl1 exhibited hypersensitivity to photoinhibition stress. In the pvsl1 mutant, abnormal accumulation of the D1 protein indicated a failure to rapidly degrade damaged D1 protein in the PSII RC. The results of this study demonstrated that PvFtsH2 is critically required for survival and maintaining photosynthetic activity by degrading photodamaged PSII RC D1 protein in common bean.
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http://dx.doi.org/10.1038/s41438-021-00554-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8167180PMC
June 2021

Restricting Glutamine Uptake Enhances NSCLC Sensitivity to Third-Generation EGFR-TKI Almonertinib.

Front Pharmacol 2021 14;12:671328. Epub 2021 May 14.

Faculty of Pharmacy, Bengbu Medical College, Bengbu, China.

The emergence of secondary resistance is the main failure cause of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) as a targeted therapy for non-small cell lung cancer (NSCLC). EGFR mutations of NSCLC cells can markedly increase glutamine transporter (SLC1A5) expression, thereby increasing glutamine metabolism. Glutamine metabolites can activate EGFR downstream signals, including mTOR, ERK1/2, STAT3, etc., which is an important cause for the decreased sensitivity of NSCLC to EGFR-TKIs. CCK8 and Annexin V/PI assays were conducted to detect the effects of Almonertinib and/or V9302 on the proliferation and apoptosis of NSCLC cells. Proteomics was used to determine the effect of Almonertinib on energy metabolism-related proteins in NSCLC. siRNA transfection was performed to study the effect of SLC1A5 down-regulation on cell proliferation. In addition, the effects of drugs on colony formation capacity were determined by colony formation assay. Immunofluorescence and Western blot were utilized to detect the apoptosis- and autophagy-related proteins expression. DAPI staining was utilized to detect the effect of drugs on the nucleus. Transmission electron microscope was used to observe the changes of submicroscopic structure such as autophagosomes and nucleus of cells. mCherry-GFP-LC3B tandem fluorescent protein was to used to detect the level of autophagy flux. Tumor-bearing nude mouse model was utilized to detect the effect of V9302 on the anti-tumor effect of Almonertinib . As a result, Almonertinib suppressed H1975 and A549 cell proliferation depended on its dosage and treatment duration, and it also induced apoptosis. A549 cells with wild-type EGFR had lower sensitivity to Almonertinib. The expression of SLC1A5 was up-regulated by stimulating with low concentration of Almonertinib in NSCLC cells. SLC1A5 was highly expressed in A549 cells with wild-type EGFR. Glutamine deletion or SLC1A5 inhibition/silencing inhibited the proliferation of NSCLC cells, and decreased cellular glutamine uptake. The combination of SLC1A5 inhibitor V9302 and Almonertinib had a synergistic inhibitory effect on the proliferation of NSCLC. V9302 enhanced the effect of Almonertinib in apoptosis-inducing in NSCLC cells. The combination of V9302 and Almonertinib might induce apoptosis by inhibiting autophagy.
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http://dx.doi.org/10.3389/fphar.2021.671328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8161200PMC
May 2021

Improving influenza surveillance based on multi-granularity deep spatiotemporal neural network.

Comput Biol Med 2021 07 13;134:104482. Epub 2021 May 13.

Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China. Electronic address:

Influenza is a common respiratory disease that can cause human illness and death. Timely and accurate prediction of disease risk is of great importance for public health management and prevention. The influenza data belong to typical spatiotemporal data in that influenza transmission is influenced by regional and temporal interactions. Many existing methods only use the historical time series information for prediction, which ignores the effect of spatial correlations of neighboring regions and temporal correlations of different time periods. Mining spatiotemporal information for risk prediction is a significant and challenging issue. In this paper, we propose a new end-to-end spatiotemporal deep neural network structure for influenza risk prediction. The proposed model mainly consists of two parts. The first stage is the spatiotemporal feature extraction stage where two-stream convolutional and recurrent neural networks are constructed to extract the different regions and time granularity information. Then, a dynamically parametric-based fusion method is adopted to integrate the two-stream features and making predictions. In our work, we demonstrate that our method, tested on two influenza-like illness (ILI) datasets (US-HHS and SZ-HIC), achieved the best performance across all evaluation metrics. The results imply that our method has outstanding performance for spatiotemporal feature extraction and enables accurate predictions compared to other well-known influenza forecasting models.
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http://dx.doi.org/10.1016/j.compbiomed.2021.104482DOI Listing
July 2021

MLH1/PMS2 Expression Could Tell Classical NTRK Fusion in Fluorescence Hybridization Positive Colorectal Carcinomas.

Front Oncol 2021 29;11:669197. Epub 2021 Apr 29.

Department of Pathology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.

To gain insight into the clinicopathologic profile of colorectal carcinomas harboring oncogenic NTRK fusions based on eastern populations as well as make the best testing algorithm for the screen, we use pan-Trk immunohistochemistry (IHC), fluorescence hybridization (FISH) respectively to screen NTRK fusions in a large, unselected cohort of 819 colon cancers; either IHC or FISH positive cases were further detected by next-generation sequencing (NGS). IHC staining was observed in ten (1.22%) cases. FISH positive was observed in 13 (1.59%) cases, and finally, a total of 18 cases were under both a DNA-based and an RNA-based NGS assay. RNA-based NGS was positive in 13 of 18 cases, whereas DNA-based NGS was only positive in three of 18 cases. In total 13 RNA-based NGS NTRK fusion-positive cases, only six cases were pan-TRK IHC positive 12 were FISH positive. More important, in 13 RNA-based NGS cases only five cases contain the full length of NTRK tyrosine kinase (TK) domain and form the classical fusion chimeras, other six cases only maintain parts of the TK domain and form the sub-classical fusion chimeras, two cases totally miss the TK domain and form the non-classical fusions. For clinicopathologic characteristics, besides the MMR (mismatch repair) status (p = 0.001), there is no difference between the NTRK fusion-positive and negative cases. Nevertheless, classical fusion cases prefer low differentiation (p = 0.001) and different patterns of growth (p < 0.001). Besides, we found all five classical NTRK fusion cases, and only one sub-classical case was harboring MLH1/PMS2 deficiency. When combining FISH and MMR (Mismatch Repair) status, besides one sub-classical case, all five classical fusions were detected, which means MLH1/PMS2 expression could further narrow the classical fusions in FISH NTRK fusion positive cases. Given the low sensitivity and specificity of the pan-Trk antibody, it would be useless to use IHC to screen NTRK fusion-positive CRCs. Combining FISH and MLH1/PMS2 IHC would be a good testing algorithm for the screen effective NTRK fusions. Finally, if patients are going to undergo TRK-based targeted therapy, only RNA-based NGS for detection of the specific fusion could tell the precise rearrangement information.
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http://dx.doi.org/10.3389/fonc.2021.669197DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8117224PMC
April 2021

The Synchronized Efforts to Decipher the Molecular Basis for Soybean Maturity Loci , , and That Regulate Flowering and Maturity.

Front Plant Sci 2021 28;12:632754. Epub 2021 Apr 28.

Department of Biotechnology, Graduate School of Engineering, Osaka University, Suita, Japan.

The general concept of photoperiodism, i.e., the photoperiodic induction of flowering, was established by Garner and Allard (1920). The genetic factor controlling flowering time, maturity, or photoperiodic responses was observed in soybean soon after the discovery of the photoperiodism. , , and were named in 1971 and, thereafter, genetically characterized. At the centennial celebration of the discovery of photoperiodism in soybean, we recount our endeavors to successfully decipher the molecular bases for the major maturity loci , , and in soybean. Through systematic efforts, we successfully cloned the gene in 2009, the gene in 2011, and the gene in 2012. Recently, successful identification of several circadian-related genes such as , , and has enriched the known major pathway. Further research progresses on the identification of new flowering and maturity-related genes as well as coordinated regulation between flowering genes will enable us to understand profoundly flowering gene network and determinants of latitudinal adaptation in soybean.
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http://dx.doi.org/10.3389/fpls.2021.632754DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113421PMC
April 2021

Secure key distribution based on bidirectional Michelson interferometers.

Opt Lett 2021 May;46(10):2264-2267

A scheme based on bidirectional Michelson interferometers to distribute secret keys through the phase of light wave is proposed and demonstrated. The structure uses two optical cable transmission schemes, lasers of short coherent length, random phase drift, polarization random disturbance, and vibration positioning technology to ensure the safe transmission of the secret key. The feasibility of 80 km secret key transmission is verified by experiments. When the secret key is transmitted at the frequency of 200 kHz, the bit error rate is less than 0.3%, and the disturbance positioning accuracy is within $\pm {100}\;{\rm m}$.
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http://dx.doi.org/10.1364/OL.423981DOI Listing
May 2021

Ultralight and Mechanically Robust Fibrous Sponges Tailored by Semi-Interpenetrating Polymer Networks for Warmth Retention.

ACS Appl Mater Interfaces 2021 Apr 9;13(15):18165-18174. Epub 2021 Apr 9.

State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, College of Textiles, Donghua University, Shanghai 201620, China.

People living in very cold climates urgently desire warmth retention equipment to remain healthy. However, creating materials that exhibit both effective warm retention and robust mechanical properties to maintain stable structures is extremely challenging. Herein, we report a facile and time-saving strategy for preparing ultralight, mechanically robust, and high-performance warmth retention materials via direct electrospinning and thermal crosslinking. Fluffy fibrous assemblies with stereoscopic fiber networks are fabricated with a humidity-induced electrospinning technique, followed by heating to create semi-interpenetrating polymer networks (semi-IPNs) within fibers to acquire fibrous sponges (FSs). The semi-IPN-based FSs (semi-IPN FSs) present integrated properties of high tensile stress (∼1 MPa), good fatigue resistance (∼0% plastic deformation after 1000 cyclic tensile or compressive tests), and nondestructive resilience in liquid nitrogen (-196 °C). Furthermore, the semi-IPN FSs exhibit a low volume density of ∼2.2 mg cm, effective heat preservation ability (low thermal conductivity ∼25.8 mW m K), and desired waterproofness and breathability. The successful synthesis of semi-IPN FSs provides a novel attempt to develop high-performance materials with robust mechanical properties for numerous applications.
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http://dx.doi.org/10.1021/acsami.1c03658DOI Listing
April 2021

Intrusion behavior classification method applied in a perimeter security monitoring system.

Opt Express 2021 Mar;29(6):8592-8605

A distributed optic fiber perimeter security system is proved to be an effective strategy for the security monitoring of some vital targets, such as power plants, power substations and telecommunication base stations. However, this method can hardly distinguish different categories of the intrusion behavior and is easily mis-triggered by different kinds of environmental interference. To distinguish different intrusion patterns and different interference events effectively, a vibration pattern recognition algorithm is proposed and demonstrated based on the merged Sagnac interferometer structure. The method consists of two parts: the pre-processing algorithm and the multi-layer perceptron neural networks (MLP-NNs). The pre-processing algorithm is applied to retrieve and extract the vibration signal from the captured source signal, and the MLP-NN is used to realize pattern recognition from each type of input. Typically, a high-dimensional vector group which contains hundreds of orders of vibration signal's power frequency is obtained to cover as many signalized features as possible. Moreover, results of the experiment deployed on a 10 kilometer long perimeter fence in the transformer substation show that the proposed classification-based model achieves 97.6% classification accuracy in the test. Through multiple comparison tests, the proposed model gives a solid performance in the subsequent integrated evaluation to classify each intrusion pattern.
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http://dx.doi.org/10.1364/OE.415929DOI Listing
March 2021

Typing FGFR2 translocation determines the response to targeted therapy of intrahepatic cholangiocarcinomas.

Cell Death Dis 2021 03 11;12(3):256. Epub 2021 Mar 11.

Department of Medical Genetics, Nanjing Medical University, Nanjing, 211166, Jiangsu Province, China.

Chromosomal translocations involving fibroblast growth factor receptor 2 (FGFR2) gene at the breakpoints are common genetic lesions in intrahepatic cholangiocarcinoma (ICC) and the resultant fusion protein products have emerged as promising druggable targets. However, predicting the sensitivity of FGFR2 fusions to FGFR kinase inhibitors is crucial to the prognosis of the ICC-targeted therapy. Here, we report identification of nine FGFR2 translocations out of 173 (5.2%) ICC tumors. Although clinicopathologically these FGFR2 translocation bearing ICC tumors are indistinguishable from the rest of the cohort, they are invariably of the mass-forming type originated from the small bile duct. We show that the protein products of FGFR2 fusions can be classified into three subtypes based on the breaking positions of the fusion partners: the classical fusions that retain the tyrosine kinase (TK) and the Immunoglobulin (Ig)-like domains (n = 6); the sub-classical fusions that retain only the TK domain without the Ig-like domain (n = 1); and the non-classical fusions that lack both the TK and Ig-like domains (n = 2). We demonstrate that cholangiocarcinoma cells engineered to express the classical and sub-classical fusions show sensitivity to FGFR-specific kinase inhibitors as evident by the suppression of MAPK/ERK and AKT/PI3K activities following the inhibitor treatment. Furthermore, the kinase-deficient mutant of the sub-classical fusion also lost its sensitivity to the FGFR-specific inhibitors. Taken together, our study suggests that it is essential to determine the breakpoint and type of FGFR2 fusions in the small bile duct subtype of ICC for the targeted treatment.
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http://dx.doi.org/10.1038/s41419-021-03548-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7946919PMC
March 2021

Lipoprotein glomerulopathy induced by ApoE Kyoto mutation in ApoE-deficient mice.

J Transl Med 2021 03 4;19(1):97. Epub 2021 Mar 4.

Department of Nephrology and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Sichuan, Guoxue Alley, 37#, Wuhou District, Chengdu, 610041, China.

Background: Lipoprotein glomerulopathy (LPG) is a rare autosomal dominant kidney disease that is most commonly caused by mutations in ApoE Kyoto (p.R43C) and ApoE Sendai (p.R163P). Differences in phenotype among the various ApoE mutations have been suggested, but the pathogenic role of ApoE Kyoto has not been validated in an animal model. This study intended to establish an ApoE Kyoto murine model and to further compare the pathologic differences between ApoE Kyoto and ApoE Sendai.

Method: Male ApoE-deficient mice, 3 months of age, were divided into five groups, including the AD-ApoE Sendai, AD-ApoE Kyoto, AD-ApoE3, AD-eGFP, and ApoE (-/-) groups. The first four groups received recombinant adenovirus that contained the entire coding regions of the human ApoE Sendai and ApoE Kyoto, apoE3, and eGFP genes, respectively. Fasting blood and urine samples were collected at multiple time points. Lipid profiles and urine albumin-creatinine ratio were measured. Renal and aortic histopathologic alterations were analyzed.

Results: After virus injection, plasma human ApoE was detected and rapidly reached the maximum level at 4-6 days in the AD-ApoE Kyoto and AD-ApoE Sendai groups (17.4 ± 3.1 µg/mL vs.: 22.2 ± 4.5 µg/mL, respectively) and at 2 days in the AD-ApoE3 group (38.4 µg/mL). The serum total cholesterol decreased by 63%, 65%, and 73% in the AD-ApoE Kyoto, AD-ApoE Sendai and AD-ApoE3 groups, respectively. There were no significant changes in serum triglyceride and urinary albumin-creatinine ratio among the five groups. Typical lipoprotein thrombi with positive ApoE staining were detected in the AD-ApoE Kyoto and AD-ApoE Sendai groups. The Oil-red O-positive glomerular area tended to be higher in the AD-ApoE Kyoto group (9.2%) than in the AD-ApoE Sendai (3.9%), AD-ApoE3 (4.8%), AD-eGFP (2.9%), and ApoE (-/-) (3.6%) groups. The atherosclerotic plaque area in the aorta was lower in the group injected with various ApoE mutations than in the group without injection of ApoE mutation.

Conclusions: In this animal study, we first established an ApoE Kyoto mutation murine model and confirmed its pathogenic role in LPG. Our results suggested that LPG may be more severe with the ApoE Kyoto than with the ApoE Sendai.
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http://dx.doi.org/10.1186/s12967-021-02765-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7934380PMC
March 2021

Valuation of SF-6Dv2 Health States in China Using Time Trade-off and Discrete-Choice Experiment with a Duration Dimension.

Pharmacoeconomics 2021 May 18;39(5):521-535. Epub 2021 Feb 18.

School of Health and Related Research, University of Sheffield, Sheffield, UK.

Objectives: Our objective was to generate a value set for the SF-6Dv2 using time trade-off (TTO) and a discrete-choice experiment with a duration dimension (DCE) in China.

Methods: A large representative sample of the Chinese general population was recruited from eight provinces/municipalities in China, stratified by age, sex, education level, and proportion of urban/rural residence. Respondents completed eight TTO tasks and ten DCE tasks during face-to-face interviews. Ordinary least squares (OLS), random-effects, fixed-effects, and Tobit models were used for TTO data, and conditional logit and mixed logit models were used for DCE. The monotonicity of model coefficients and the consistency of the predicted values according to intraclass correlation coefficient (ICC), mean absolute difference (MAD), and mean squared difference (MSD) were compared between the two approaches.

Results: In total, 3320 respondents (50.3% male; range 18-90 years) were recruited. The random-effects model and the conditional logit model were preferred for the TTO and DCE, respectively. The TTO values ranged from - 0.277 to 1, with 927 (4.94%) states considered as worse than dead (WTD). The corresponding range for DCE was - 0.535 to 1, with a higher WTD of 8.50%. DCE presented minor non-monotonicity with the coefficients in two dimensions. Values from the two approaches were highly consistent (ICC 0.9804, MAD 0.0588, MSD 0.0055), albeit those with DCE were slightly lower than those with TTO. The value set generated by TTO was preferred given the better monotonicity and the statistical significance of coefficients.

Conclusions: The Chinese value set for the SF-6Dv2 was established based on the TTO approach, but the DCE also performed well. Minor issues of non-monotonicity did present for DCE.
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http://dx.doi.org/10.1007/s40273-020-00997-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079294PMC
May 2021

Physiological responses of the diatoms Thalassiosira weissflogii and Thalassiosira pseudonana to nitrogen starvation and high light.

Mar Environ Res 2021 Apr 5;166:105276. Epub 2021 Feb 5.

School of Life Science, Ludong University, Yantai, 264025, China; Key Laboratory of Marine Biotechnology in Universities of Shandong, Ludong University,Yantai, 264025, China. Electronic address:

As oceans warm, the depth of the upper mixed layer is predicted to decrease, resulting in insufficient nutrient supply and higher solar radiation for phytoplankton. In order to understand the photophysiological responses of the key eukaryotic phytoplankton diatoms to high light and nutrient limitation, we grew two diatoms, Thalassiosira weissflogii and Thalassiosira pseudonana under N starvation conditions and exposed them to high visible light. It showed that the large-sized diatom T. weissflogii can maintain photosynthetic activity for a longer period of time under nitrogen starvation as compared with the small-sized diatom T. pseudonana. The electron transfer reaction was inhibited in both diatoms and the fast closing of reaction centers promoted the development of Q non-reducing PSII centers, thus facilitated the rapid induction of NPQ, however, the induction of NPQ depended on the degree of N starvation. N starvation exacerbated the photoinhibition caused by high light. The smaller-sized T. pseudonana had a higher σi value and was more sensitive to high-light, but its PSII repair rate was also higher. In contrast, T. weissflogii was more tolerant to high light with a lower σi value, but the tolerance was severely reduced under N-starvation. This study provides helpful insight into how climate change variables impact diatom's photosynthetic physiology.
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http://dx.doi.org/10.1016/j.marenvres.2021.105276DOI Listing
April 2021

Frequency and barriers of reporting workplace violence in nurses: An online survey in China.

Int J Nurs Sci 2021 Jan 3;8(1):65-70. Epub 2020 Dec 3.

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

Objectives: This study aimed to explore the reporting of workplace violence against nurses and the reasons why they did not reported.

Methods: A self-designed questionnaire regarding workplace violence and reporting was used to conduct a cross-sectional survey on nurses who submitted a manuscript to a Chinese nursing journal from 2016 to 2017. A total of 324 nurses agreed to participate in this study and 266 participants from 165 hospitals in 72 cities returned questionnaires.

Results: A total of 172 nurses (64.7%) experienced violent incidents during the past year. Of these incidents, 45.5% were reported; and the reporting rate of physical assaults (69.0%) was higher than those of verbal abuse (36.9%), threatening behavior (51.7%), and sexual harassment (60.0%). Formal reporting accounted for 25.4% (15.4% in written form and 10.0% through a computer-assisted reporting system). Almost half of the nurses (49.6%) stated that the hospital had no reporting system or they were uncertain about the reporting system. For reasons of not reporting, 51.9% of the nurses were unware of how and what types of violence to report, and 50.6% of the nurses believed that the hospital paid greater attention to patients rather than staff.

Conclusions: A clear definition of workplace violence and reporting procedures, establishment of a facile system for reporting, and supervisory support following a reporting are urgently required.
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http://dx.doi.org/10.1016/j.ijnss.2020.11.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859538PMC
January 2021

The expression of programmed death-ligand 1 in patients with invasive breast cancer.

Gland Surg 2020 Dec;9(6):2106-2115

Department of Oncology, The Affiliated Taikai Xianlin Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China.

Background: The purpose of this study is to investigate the association between protein expression of programmed death-ligand 1 (PD-L1) and the clinicopathological features of patients with invasive breast cancer.

Methods: Clinicopathological data of 651 patients with invasive breast carcinoma were collected over a 1-year period. Patients whose breast tissue samples did not express genes for the estrogen receptor (ER), progesterone receptor (PR), or human epidermal growth factor receptor-2 (HER2) were classified as triple-negative breast cancer (TNBC). The correlations of PD-L1 expression with clinicopathological features and overall survival were determined using Pearson's correlation coefficient and logistic binary regression analysis, respectively.

Results: Positive expression of PD-L1 was detected in 47% of patients with invasive breast carcinoma, compared with 69.3% of TNBC patients (P<0.05). Furthermore, expression of PD-L1 in patients with invasive breast carcinoma was significantly correlated with WHO grade, tumor size, vascular invasion, pathological stage, and the expression of ER, PR, nuclear associated antigen Ki67 (Ki67), gene, cytokeratin 5/6 (CK5/6), and epidermal growth factor receptor (EGFR) (P<0.05). Logistic binary regression analysis showed that WHO grade, Ki67, p53, and EGFR were independent risk factors for the expression of PD-L1 in patients with invasive breast cancer. Moreover, PD-L1 expression in TNBC patients was significantly correlated with WHO grade, neuro-invasion, Ki67, CK5/6, and EGFR (P<0.05), but it was not correlated with age, tumor size, vascular invasion, number of lymph nodes, pathological stage, or the expression of ER, PR, p53, androgen receptor (AR), or vascular endothelial growth factor receptor (VEGFR) (P>0.05).

Conclusions: The high expression rate of PD-L1 in invasive breast cancer is closely related to some clinicopathological features. Thus, immunotherapy with PD-L1 inhibitors could be a potential treatment strategy for patients with invasive breast cancer.
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http://dx.doi.org/10.21037/gs-20-824DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7804563PMC
December 2020

Assessing the reliability and validity of the ICECAP-A instrument in Chinese type 2 diabetes patients.

Health Qual Life Outcomes 2021 Jan 6;19(1). Epub 2021 Jan 6.

School of Public Administration, Southwestern University of Finance and Economics, Chengdu, 611130, China.

Purpose: We aimed to conduct psychometric tests for the Chinese version of ICECAP-A and compare the differences between ICECAP-A and EQ-5D-3L for patients with T2DM and explore the relationship between clinical conditions and ICECAP-A through diabetes-related clinical indicators.

Methods: Data were collected from a sample of 492 Chinese T2DM patients. The reliability and validity of the ICECAP-A were verified. Exploratory factor analysis (EFA), correlation analysis and regression analysis were conducted for both the ICECAP-A and EQ-5D-3L.

Results: Our results show that the Chinese version of ICECAP-A has good internal consistency with an overall Cronbach's Alpha coefficient of 0.721. The mean scores of ICECAP-A and EQ-5D-3L are 0.85 vs. 0.94. A weak correlation (r = 0.116) was found between the ICECAP-A tariff and EQ-5D-3L utility. EFA showed that although the five dimensions of the ICECAP-A and EQ-5D-3L scales were loaded into two different factors respectively. However, the two scales captured different dimensions of quality of life and can complement each other. The ICECAP-A, EQ-5D-3L, and EQ-VAS scores showed differences across different socio-demographic characteristics and clinic conditions groups.

Conclusion: The Chinese version of the ICECAP-A capability instrument can be for assessing outcomes in adults with T2DM. It may capture more dimensions of QoL than traditional Health-related QoL (HRQoL) instruments and may be useful for economic evaluations of health care and social care for people with T2DM or other chronic diseases.
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http://dx.doi.org/10.1186/s12955-020-01632-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7788876PMC
January 2021

Secure key generation and distribution scheme based on two independent local polarization scramblers.

Appl Opt 2021 Jan;60(1):147-154

We propose a practical secure key generation and distribution (SKGD) scheme for actual application. Based on the experiment results of the polarization properties of the actual optical-fiber link, we propose a SKGD method by the active modulation of the state of polarization of the optical-fiber by two polarization scramblers placed at the local end of the legal users in the point-to-point communication system. Experiment results prove that the signals received by legal users share high correlation using 20 km standard single-mode fiber and 1 KHz polarization scrambling rate, and the bit generation rate can reach to 1216 bit/s with a bit error rate of ∼0.33. Security of the system is also analyzed in terms of the polarization properties of the system; the theoretical and experimental results indicate that the proposed scheme possesses high security due to the invisibility of the key signal and the technical difficulty of the recovery of the key sequence.
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http://dx.doi.org/10.1364/AO.413171DOI Listing
January 2021

Influence of ocean acidification on thermal reaction norms of carbon metabolism in the marine diatom Phaeodactylum tricornutum.

Mar Environ Res 2021 Feb 3;164:105233. Epub 2020 Dec 3.

Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao, China; Function Laboratory for Marine Fisheries Science and Food Production Processes, Qingdao National Laboratory for Marine Science and Technology, Qingdao, China. Electronic address:

Under the present CO condition, the efficiency of biological pump mediating carbon sequestration is predicted to decline in the future because respiration tends to be more sensitive to rising temperature than is photosynthesis. However, it remains unknown whether the impacts of global warming on metabolic rates of phytoplankton can be modulated by elevated CO induced ocean acidification. Here we show that in the model diatom species Phaeodactylum tricornutum, E (activation energy) of photosynthesis (~0.5 eV) was significantly lower than that of respiration (1.8 eV), while CO concentration had no effect on the E value. E (deactivation energy) of respiration was increased to 2.5 eV, that was equivalent to E of photosynthesis in high CO-grown cells and 28.4% higher than that in low CO-grown ones. The respiration to photosynthesis ratio (R/P) was consistently higher in high CO condition, which increased with temperature at the beginning and subsequently decreased in both CO conditions. The ratio of R/P in high CO to R/P in low CO gradually increased with temperature above the optimal temperature. Our results imply that ocean acidification will aggravate the negative impacts or offset the alleviating effects of warming on the R/P ratio depending on the temperature range in Phaeodactylum tricornutum.
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http://dx.doi.org/10.1016/j.marenvres.2020.105233DOI Listing
February 2021

Chemerin/ChemR23 regulates cementoblast function and tooth resorption in mice via inflammatory factors.

J Periodontol 2020 Dec 1. Epub 2020 Dec 1.

College of Stomatology, Chongqing Medical University.

Background: Periodontitis and orthodontic treatment can lead to inflammatory root resorption (IRR) through an unclear mechanism. Chemerin, a novel chemoattractant protein, is closely associated with inflammation, affects osteoblast and osteoclast differentiation, and may play a role in IRR. We aimed to explore possible roles of the chemerin/ChemR23 interaction in cementoblast function and IRR and reveal a new IRR therapeutic target.

Methods: Cementoblast function-related gene and protein expression in the immortalized murine cementoblast cell line OCCM-30 after treatment with chemerin and siChemR23 was examined by qRT-PCR and Western blotting.The roles of the MAPK and PI3K-Akt signaling pathways were studied using specific inhibitors. Cementoblast cytokine production under different treatment conditions was measured by ELISA and qRT-PCR. Additionally, we modeled IRR in wild-type and chemerin-overexpressing mice and injected transgenic mice with anti-ChemR23 antibody to block ChemR23. We then calculated the root resorption volume and examined periodontal tissue cathepsin K, Runx2, TNF-α, and IL-6 expression.

Result: Chemerin suppressed cementoblast differentiation and mineralization and exerted a proinflammatory effect on cementoblasts. These effects were partially reversed by siChemR23 and reversed to different extents by p38, Erk1/2 and PI3K-Akt pathway inhibition, suggesting p38, Erk1/2 and PI3K-Akt pathways as signaling pathways downstream of chemerin/ChemR23. In vivo, chemerin overexpression worsened IRR. Moreover, chemerin expression was positively correlated with TNF-α, IL-6, and cathepsin K expression and negatively correlated with Runx2 expression. ChemR23 downregulation reversed these effects.

Conclusion: Chemerin/ChemR23 induced TNF-α and IL-6 expression dependent on Erk1/2, p38 MAPK and PI3K-Akt signaling pathway activation, thereby regulating cementoblast function and affecting IRR. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/JPER.20-0675DOI Listing
December 2020

A safety consideration of mesenchymal stem cell therapy on COVID-19.

Stem Cell Res 2020 12 24;49:102066. Epub 2020 Oct 24.

State Key Laboratory of Membrane Biology, School of Medicine, Tsinghua University, Beijing, China. Electronic address:

Due to the multi-potential differentiation and immunomodulatory function, mesenchymal stem cells (MSCs) have been widely used in the therapy of chronic and autoimmune diseases. Recently, the novel coronavirus disease 2019 (COVID-19) has grown to be a global public health emergency but no effective drug is available to date. Several studies investigated MSCs therapy for COVID-19 patients. However, it remains unclear whether MSCs could be the host cells of SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2) and whether they might affect the SARS-CoV-2 entry into other cells. Here, we report that human MSCs barely express ACE2 and TMPRSS2, two receptors required for the virus endocytosis, indicating that MSCs are free from SARS-CoV-2 infection. Furthermore, we observed that MSCs were unable to induce the expression of ACE2 and TMPRSS2 in epithelial cells and macrophages. Importantly, under different inflammatory challenge conditions, implanted human MSCs failed to up-regulate the expression of ACE2 and TMPRSS2 in the lung tissues of mice. Intriguingly, we showed that a SARS-CoV-2 pseudovirus failed to infect MSCs and co-cultured MSCs did not increase the risk of SARS-CoV-2 pseudovirus infection in epithelial cells. All these results suggest that human MSCs have no risk of assisting SARS-CoV-2 infection and the use of MSCs as the therapy for COVID-19 patients is feasible and safe.
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http://dx.doi.org/10.1016/j.scr.2020.102066DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7585498PMC
December 2020

An assessment of chromosomal alterations detected by fluorescence in situ hybridisation in pancreatobiliary tract malignancy.

BMC Gastroenterol 2020 Nov 4;20(1):367. Epub 2020 Nov 4.

Department of Pathology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, 321 Zhongshan Road, Nanjing, 210008, Jiangsu, China.

Background: Using fluorescence in situ hybridisation (FISH) to detect any gain of chromosomes 3, 7, or 17 and loss of the 9p21 locus has been proven to be sensitive in the diagnosis of pancreatobiliary tumors. However, both genetic and environmental factors contribute to the pathogenesis of pancreatobiliary tumors. Therefore, it is unknown whether this method is suitable for Chinese patients with pancreatobiliary tumors. This study aims to compare the sensitivity, specificity, predictive values and accuracy of cytology, ERCP/MRCP and FISH based on Chinese patients with pancreatobiliary tumors,and to analyze differences between brushing-based and formalin-fixed paraffin-embedded (FFPE)-based FISH.

Methods: A total of 66 brush cytology specimens obtained during ERCP were detected by FISH and cytology test respectively to compare the sensitivity, specificity, predictive values and accuracy. Besides, FFPE-based FISH was performed on 46 corresponding paraffin sections of pancreatobiliary tumors obtained by surgical resection.

Results: Our findings demonstrate that FISH greatly improves diagnostic sensitivity and negative predictive value compared to ERCP/MRCP and cytology without much reduction in specificity and positive predictive value. However, our results also indicate that FFPE-based FISH could not effectively identify the false-negative of brushing-based FISH.

Conclusions: We believe that FISH can effectively distinguish true positive and false positive results of cytological or radiological suspicions of malignancy. However, FFPE-based FISH still does not precisely recognize the false-negative of brushing-based FISH. Both cytology-based and PPFE-based FISH had limitation in some specimens.
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http://dx.doi.org/10.1186/s12876-020-01439-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7641847PMC
November 2020

Enhanced Chlorophyll Degradation Triggers the Pod Degreening of "Golden Hook," a Special Ecotype in Common Bean ( L.).

Front Genet 2020 6;11:570816. Epub 2020 Oct 6.

Key Laboratory of Soybean Molecular Design Breeding, Northeast Institute of Geography and Agroecology, Chinese Academy of Sciences, Harbin, China.

To reveal genetic factors or pathways involved in the pod degreening, we performed transcriptome and metabolome analyses using a yellow pod cultivar of the common bean "golden hook" ecotype and its green pod mutants yielded via gamma radiation. Transcriptional profiling showed that expression levels of red chlorophyll catabolite reductase (, ) involved in chlorophyll degradation was strongly enhanced at an early stage (2 cm long) in wild type but not in green pod mutants. The expression levels of genes involved in cellulose synthesis was inhibited by the pod degreening. Metabolomic profiling showed that the content of most flavonoid, flavones, and isoflavonoid was decreased during pod development, but the content of afzelechin, taxifolin, dihydrokaempferol, and cyanidin 3--rutinoside was remarkably increased in both wild type and green pod mutant. This study revealed that the pod degreening of the golden hook resulting from chlorophyll degradation could trigger changes in cellulose and flavonoids biosynthesis pathway, offering this cultivar a special color appearance and good flavor.
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http://dx.doi.org/10.3389/fgene.2020.570816DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7573562PMC
October 2020

Respiratory traits and coal workers' pneumoconiosis: Mendelian randomisation and association analysis.

Occup Environ Med 2021 02 23;78(2):137-141. Epub 2020 Oct 23.

Department of Occupational Medicine and Environmental Health and Key Laboratory of Modern Toxicology of Ministry of Education, Nanjing Medical University, Nanjing, Jiangsu, China

Objectives: Susceptibility loci of idiopathic pulmonary fibrosis and chronic obstructive pulmonary disease were also significantly associated with the predisposition of coal worker's pneumoconiosis (CWP) in recent studies. However, only a few genes and loci were targeted in previous studies.

Methods: To systematically evaluate the genetic associations between CWP and other respiratory traits, we reviewed the reported genome-wide association study loci of five respiratory traits and then conducted a Mendelian randomisation study and a two-stage genetic association study.

Results: Interestingly, we found that for each SD unit, higher lung function was associated with a 66% lower risk of CWP (OR=0.34, 95% CI: 0.15 to 0.77, p=0.010) using conventional Mendelian randomisation analysis (inverse variance weighted method). Moreover, we found susceptibility loci of interstitial lung disease (rs2609255, OR=1.29, p=1.61×10) and lung function (rs4651005, OR=1.39, p=1.62×10; rs985256, OR=0.73, p=8.24×10 and rs6539952, OR=1.28, p=4.32×10) were also significantly associated with the risk of CWP. Functional annotation showed these variants were significantly associated with the expression of (rs2609255, p=7.4 ×10), (rs4651005, p=5.4 ×10), (rs985256, p=1.1 ×10) and (rs6539952, p=7.1 ×10) in normal lung tissues, which were related to autophagy pathway simultaneously according to enrichment analysis.

Conclusions: These results provided a deeper understanding of the genetic predisposition basis of CWP.
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http://dx.doi.org/10.1136/oemed-2020-106610DOI Listing
February 2021
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