Publications by authors named "Hui Shen"

894 Publications

A transcriptome-wide association study to detect novel genes for volumetric bone mineral density.

Bone 2021 Jul 10;153:116106. Epub 2021 Jul 10.

Tulane Center for Biomedical Informatics and Genomics, Deming Department of Medicine, School of Medicine, Tulane University, New Orleans, LA, USA. Electronic address:

Transcriptome-wide association studies (TWAS) systematically investigate the association of genetically predicted gene expression with disease risk, providing an effective approach to identify novel susceptibility genes. Osteoporosis is the most common metabolic bone disease, associated with reduced bone mineral density (BMD) and increased risk of osteoporotic fractures, whereas genetic factors explain approximately 70% of the variance in phenotypes associated with bone. BMD is commonly assessed using dual-energy X-ray absorptiometry (DXA) to obtain measurements (g/cm) of areal BMD. However, quantitative computed tomography (QCT) measured 3D volumetric BMD (vBMD) (g/cm) has important advantages compared with DXA since it can evaluate cortical and trabecular microstructural features of bone quality, which can be used to directly predict fracture risk. Here, we performed the first TWAS for volumetric BMD (vBMD) by integrating genome-wide association studies (GWAS) data from two independent cohorts, namely the Framingham Heart Study (FHS, n = 3298) and the Osteoporotic Fractures in Men (MrOS, n = 4641), with tissue-specific gene expression data from the Genotype-Tissue Expression (GTEx) project. We first used stratified linkage disequilibrium (LD) score regression approach to identify 12 vBMD-relevant tissues, for which vBMD heritability is enriched in tissue-specific genes of the given tissue. Focusing on these tissues, we subsequently leveraged GTEx expression reference panels to predict tissue-specific gene expression levels based on the genotype data from FHS and MrOS. The associations between predicted gene expression levels and vBMD variation were then tested by MultiXcan, an innovative TWAS method that integrates information available across multiple tissues. We identified 70 significant genes associated with vBMD, including some previously identified osteoporosis-related genes such as LYRM2 and NME8, as well as some novel loci such as DNAAF2 and SPAG16. Our findings provide novel insights into the pathophysiological mechanisms of osteoporosis and highlight several novel vBMD-associated genes that warrant further investigation.
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http://dx.doi.org/10.1016/j.bone.2021.116106DOI Listing
July 2021

A subregion-based positron emission tomography/computed tomography (PET/CT) radiomics model for the classification of non-small cell lung cancer histopathological subtypes.

Quant Imaging Med Surg 2021 Jul;11(7):2918-2932

Research Center for Healthcare Data Science, Zhejiang Lab, Hangzhou, China.

Background: This study classifies lung adenocarcinoma (ADC) and squamous cell carcinoma (SCC) using subregion-based radiomics features extracted from positron emission tomography/computed tomography (PET/CT) images.

Methods: In this study, the standard F-fluorodeoxyglucose (FDG) PET/CT images of 150 patients with lung ADC and 100 patients with SCC were retrospectively collected from the PET Center of the First Affiliated Hospital, College of Medicine, Zhejiang University. First, the 3D feature vector of each tumor voxel (whose basis is PET value, CT value, and CT local dominant orientation) was extracted. Using K-means individual clustering and population clustering, each tumor was divided into 4 subregions that reflect intratumoral regional heterogeneity. Next, based on each subregion, 385 radiomics features were extracted. Clinical features including age, gender, and smoking history were included. Thus, there were a total of 1,543 features extracted from PET/CT images and clinical reports. Statistical tests were then used to eliminate irrelevant and redundant features, and the recursive feature elimination (RFE) algorithm was used to select the best feature subset to classify SCC and ADC. Finally, 7 types of classifiers were tested to achieve the optimized model for the classification: support vector machine (SVM) with linear kernel, SVM with radial basis function kernel (SVM-RBF), random forest, logistic regression, Gaussian process classifier, linear discriminant analysis, and the AdaBoost classifier. Furthermore, 5-fold cross-validation was applied to obtain the sensitivity, specificity, accuracy, and area under the curve (AUC) for performance evaluation.

Results: Our model exhibited the best performance with the subregion radiomics features and SVM-RBF classifier, with a 5-fold cross-validation sensitivity, specificity, accuracy, and AUC of 0.8538, 0.8758, 0.8623, and 0.9155, respectively. The interquartile range feature from subregion 2 of CT and the gender feature from the clinical reports are the 2 optimized features that achieved the highest comprehensive score.

Conclusions: Our proposed model showed that SCC and ADC could be classified successfully using PET/CT images, which could be a promising tool to assist radiologists or medical physicists during diagnosis. The subregion-based method illustrated that non-small cell lung cancer (NSCLC) depicts intratumoral regional heterogeneity on both CT and PET images. By defining these heterogeneities through a subregion-based method, the diagnostic performance was improved. The 3D feature vector (whose basis is PET value, CT value, and CT local dominant orientation) showed superiority in reflecting NSCLC intratumoral regional heterogeneity.
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http://dx.doi.org/10.21037/qims-20-1182DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8250013PMC
July 2021

Simultaneous visual diagnosis of acute hepatopancreatic necrosis disease and Enterocytozoon hepatopenaei infection in shrimp with duplex recombinase polymerase amplification.

J Fish Dis 2021 Jul 8. Epub 2021 Jul 8.

Key Laboratory of Molecular Biophysics of Ministry of Education, Department of Biomedical Engineering, College of Life Science and Technology, Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, China.

Shrimp is a globally popular seafood. Shrimp farming has been challenged by various infectious diseases that lead to significant economic losses. The prevention of two important shrimp infectious diseases, the acute hepatopancreatic necrosis disease (AHPND) and the Enterocytozoon hepatopenaei (EHP) infection, is highly dependent on early and accurate diagnostic. On-site monitoring of the two diseases in shrimp farming facilities demands point-of-care-testing (POCT) type of diagnostic assays. This study established a duplex recombinase polymerase amplification (RPA) and lateral flow dipstick (LFD) combined assay that could simultaneously diagnose the two diseases. The optimized RPA-LFD assay could finish the diagnostic in 35 min with good specificity, and the sensitivity reached 10 and 10 gene copies per reaction for EHP and AHPND, respectively, which were at the same level as the currently available molecular diagnostic assays. Test results of clinical samples showed 100% agreement of this assay with the industrial standard nested polymerase chain reaction (PCR) assays, and samples with both diseases were simultaneously identified. Because of the isothermal 37℃ amplification and the visual reading of the signal on dipsticks, the dependence on equipment is minimal. This duplex RPA-LFD assay is well suited for simultaneous POCT diagnostic of the two important shrimp infectious diseases. Moreover, the principle can be applied to multiplex POCT diagnostic of other infectious diseases in aquaculture.
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http://dx.doi.org/10.1111/jfd.13492DOI Listing
July 2021

A generalized kernel machine approach to identify higher-order composite effects in multi-view datasets, with application to adolescent brain development and osteoporosis.

J Biomed Inform 2021 Jul 6;120:103854. Epub 2021 Jul 6.

Tulane Center for Biomedical Informatics and Genomics, Tulane University, New Orleans, LA 70112, USA; Division of Biomedical Informatics and Genomics, Deming Department of Medicine, Tulane University, New Orleans, LA 70112, USA.

In recent years, a comprehensive study of complex disease with multi-view datasets (e.g., multi-omics and imaging scans) has been a focus and forefront in biomedical research. State-of-the-art biomedical technologies are enabling us to collect multi-view biomedical datasets for the study of complex diseases. While all the views of data tend to explore complementary information of disease, analysis of multi-view data with complex interactions is challenging for a deeper and holistic understanding of biological systems. In this paper, we propose a novel generalized kernel machine approach to identify higher-order composite effects in multi-view biomedical datasets (GKMAHCE). This generalized semi-parametric (a mixed-effect linear model) approach includes the marginal and joint Hadamard product of features from different views of data. The proposed kernel machine approach considers multi-view data as predictor variables to allow a more thorough and comprehensive modeling of a complex trait. We applied GKMAHCE approach to both synthesized datasets and real multi-view datasets from adolescent brain development and osteoporosis study. Our experiments demonstrate that the proposed method can effectively identify higher-order composite effects and suggest that corresponding features (genes, region of interests, and chemical taxonomies) function in a concerted effort. We show that the proposed method is more generalizable than existing ones. To promote reproducible research, the source code of the proposed method is available at.
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http://dx.doi.org/10.1016/j.jbi.2021.103854DOI Listing
July 2021

Sulfonate-Assisted Surface Iodide Management for High-Performance Perovskite Solar Cells and Modules.

J Am Chem Soc 2021 Jul 8;143(28):10624-10632. Epub 2021 Jul 8.

Pen-Tung Sah Institute of Micro-Nano Science and Technology, OSED, Jiujiang Research Institute, State Key Laboratory for Physical Chemistry of Solid Surfaces, Collaborative Innovation Center of Chemistry for Energy Materials, National & Local Joint Engineering Research Center of Preparation Technology of Nanomaterials, Innovation Laboratory for Sciences and Technologies of Energy Materials of Fujian Province, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, China.

Owing to the ionic nature of lead halide perovskites, their halide-terminated surface is unstable under light-, thermal-, moisture-, or electric-field-driven stresses, resulting in the formation of unfavorable surface defects. As a result, nonradiative recombination generally occurs on perovskite films and deteriorates the efficiency, stability, and hysteresis performances of perovskite solar cells (PSCs). Here, a surface iodide management strategy was developed through the use of cesium sulfonate to stabilize the perovskite surface. It was found that the pristine surface of common perovskite was terminated with extra iodide, that is, with an I/Pb ratio larger than 3, explaining the origination of surface-related problems. Through post-treatment of perovskite films by cesium sulfonate, the extra iodide on the surface was facilely removed and the as-exposed Pb cations were chelated with sulfonate anions while maintaining the original 3D perovskite structure. Such iodide replacement and lead chelating coordination on perovskite could reduce the commonly existing surface defects and nonradiative recombination, enabling assembled PSCs with an efficiency of 22.06% in 0.12 cm cells and 18.1% in 36 cm modules with high stability.
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http://dx.doi.org/10.1021/jacs.1c03419DOI Listing
July 2021

Nuclear Transglutaminase 2 interacts with topoisomerase II⍺ to promote DNA damage repair in lung cancer cells.

J Exp Clin Cancer Res 2021 Jul 5;40(1):224. Epub 2021 Jul 5.

Department of Radiation Medicine, Faculty of Naval Medicine, Naval Medical University, 800, Xiangyin Road, 200433, Shanghai, P.R. China.

Background: To block repairs of DNA damages, especially the DNA double strand break (DSB) repair, can be used to induce cancer cell death. DSB repair depends on a sequential activation of DNA repair factors that may be potentially targeted for clinical cancer therapy. Up to now, many protein components of DSB repair complex remain unclear or poorly characterized. In this study, we discovered that Transglutaminase 2 (TG2) acted as a new component of DSB repair complex.

Methods: A bioinformatic analysis was performed to identify DNA damage relative genes from dataset from The Cancer Genome Atlas. Immunofluorescence and confocal microscopy were used to monitor the protein localization and recruitment kinetics. Furthermore, immunoprecipitation and mass spectrometry analysis were performed to determine protein interaction of both full-length and fragments or mutants in distinct domain. In situ lung cancer model was used to study the effects cancer therapy in vivo.

Results: After DSB induction, cytoplasmic TG2 was extensively mobilized and translocated into nucleus after phosphorylated at T162 site by DNA-PKcs. Nuclear TG2 quickly accumulated at DSB sites and directly interacting with Topoisomerase IIα (TOPOIIα) with its TGase domain to promote DSB repair. TG2 deficient cells lost capacity of DSB repair and become susceptible to ionizing radiation. Specific inhibition of TG2-TOPOIIα interaction by glucosamine also significantly inhibited DSB repair, which increased sensitivity in lung cancer cells and engrafted lung cancers.

Conclusions: These findings elucidate new mechanism of TG2 in DSB repair trough directly interacting with TOPOIIα, inhibition of which provided potential target for overcoming cancer resistance.
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http://dx.doi.org/10.1186/s13046-021-02009-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8258933PMC
July 2021

Long non-coding RNA ANRIL promotes homologous recombination-mediated DNA repair by maintaining ATR protein stability to enhance cancer resistance.

Mol Cancer 2021 07 5;20(1):94. Epub 2021 Jul 5.

Department of Radiation Medicine, Faculty of Naval Medicine, Naval Medical University, 800, Xiangyin Road, Shanghai, 200433, P. R. China.

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http://dx.doi.org/10.1186/s12943-021-01382-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8256557PMC
July 2021

Expression and Prognostic Significance of PD-L2 in Diffuse Large B-Cell Lymphoma.

Front Oncol 2021 10;11:664032. Epub 2021 Jun 10.

Department of Pathology, Affiliated Tumor Hospital of Nantong University, Nantong, China.

Recent studies suggest that programmed death ligand-2 (PD-L2) constitutes an important antitumor immune response. Here, we investigated the relationship between PD-L2 expression and clinicopathological features in diffuse large B-cell lymphoma (DLBCL). Immunohistochemistry showed that positive expression of PD-L2 was observed in 45 of 181 newly diagnosed patients, including 14 cases with expression exclusively on tumor cells (TCs) and 31 cases with the expression on both TCs and immune cells (ICs) in the tumor microenvironment (TME). In 21 recurrent patients, positive expression of PD-L2 was present in six cases, including two cases with expression exclusively on TCs, and four cases with the expression on both TCs and ICs in the TME. Patients with PD-L2 tumor proportion score (TPS) ≥1% exhibited a better ECOG performance status (PS) (ECOG PS score <2, = 0.041), lower international prognostic index (IPI) score ( < 0.001), and early Ann Arbor stage (Ann Arbor stage I or II, = 0.010). Similarly, patients with PD-L2 immune proportion score (IPS) ≥1% also exhibited a better ECOG PS (ECOG PS score < 2, = 0.006) and lower IPI score ( = 0.001). Survival analysis showed that patients with PD-L2 TPS ≥1% exhibited prolonged overall survival (OS) and progression-free survival (PFS). However, survival analysis showed no prognostic significance based on expression of PD-L2 on ICs in the TME. TC PD-L2 expression was significantly associated with OS ( = 0.041) and PFS ( = 0.001). In the multivariate analysis, TC PD-L2 expression was an independent prognostic risk factor for PFS ( = 0.013), but not for OS ( = 0.249). Furthermore, we found that higher TC and IC PD-L2 expression was associated with higher objective response rate (ORR). Moreover, we demonstrated that the expression level of PD-L2 was positively correlated with the expression status of M1 macrophage markers CD86. Our findings highlight PD-L2 as a promising therapeutic target in DLBCL.
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http://dx.doi.org/10.3389/fonc.2021.664032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8222690PMC
June 2021

Choroidal changes in lens-induced myopia in guinea pigs.

Microvasc Res 2021 Jun 24;138:104213. Epub 2021 Jun 24.

Affiliated Eye Hospital of Shandong University of Traditional Chinese Medicine, No. 48#, Yingxiongshan Road, Jinan 250002, PR China; Shandong Provincial Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Therapy of Ocular Diseases, Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Therapy of Ocular Diseases in Universities of Shandong, Eye Institute of Shandong University of Traditional Chinese Medicine, No. 48#, Yingxiongshan Road, Jinan 250002, PR China. Electronic address:

Introduction: This study aimed to determine the role of the choroid in lens-induced myopia (LIM) in guinea pigs.

Methods: Guinea pigs were randomly divided into two groups: a normal control (NC) group and a LIM group. Refraction and axial length (AL) were measured by streak retinoscopy and A-scan ultrasonography. The choroidal thickness (ChT), vessel density of the choriocapillaris (VDCC) and vessel density of the choroidal layer (VDCL) were assessed by Spectral-domain Optical Coherence Tomography Angiography (SD-OCT). In addition, the choroidal expression of nitric oxide synthase (NOS) enzymes at the mRNA and protein levels was analyzed by real-time fluorescence quantitative PCR, enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry.

Results: In the LIM group, refraction and AL were increased significantly compared with those in the NC group at 2 weeks (refraction: LIM vs. NC, -4.23 ± 0.43 D vs. 2.20 ± 0.48 D; AL: LIM vs. NC, 8.36 ± 0.05 mm vs. 8.22 ± 0.03 mm) and 4 weeks (refraction: LIM vs. NC, -5.88 ± 0.49 D vs. 1.63 ± 0.41 D; AL: 8.57 ± 0.06 mm vs. 8.40 ± 0.04 mm). The ChT and VDCC were decreased significantly compared with those in the NC group at 2 weeks (ChT: LIM vs. NC, 60.92 ± 8.15 μm vs. 79.11 ± 7.47 μm; VDCC: LIM vs. NC, 23.43 ± 3.85% vs. 28.74 ± 4.11%) and 4 weeks (ChT: LIM vs. NC, 48.43 ± 6.85 μm vs. 76.38 ± 7.84 μm; VDCC: LIM vs. NC, 21.29 ± 2.17% vs. 27.64 ± 2.91%). The VDCL was also decreased compared with that in the NC group at 2 weeks and 4 weeks (NC vs. LIM, 24.87 ± 5.16% vs. 22.45 ± 3.26%; 23.37 ± 5.85% vs. 21.39 ± 2.62%; all P > 0.05). Moreover, the ChT was positively correlated with the VDCC and VDCL. The mRNA and protein expression of NOS enzymes (eNOS and nNOS) was increased.

Conclusions: During the development of myopia, the ChT, VDCC and VDCL were decreased, while NOS expression in the choroid was increased. The expression of NOS was negatively correlated with the ChT, VDCC and VDCL. NO may play an important role in regulating the choroid during myopia development.
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http://dx.doi.org/10.1016/j.mvr.2021.104213DOI Listing
June 2021

Multi-Dimensional Display of Wang's Lymph Node Map Using Virtual Bronchoscopic Navigation System.

Front Mol Biosci 2021 7;8:679442. Epub 2021 Jun 7.

Key Laboratory of Respiratory Disease of Zhejiang Province, Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.

Transbronchial needle aspiration (TBNA) is a classical technique for diagnosing mediastinal-hilar lymph node enlargement. However, the diagnostic value of conventional TBNA (cTBNA) is limited in small lymph nodes. Here, we generated an innovative multi-dimensional virtual lymph node map on top of Wang's lymph node map using a Lungpoint Virtual Bronchoscopic Navigation System. The virtual bronchoscopic navigation (VBN) system was combined with computed tomography (CT) images to generate extrabronchial, endobronchial, sagittal, coronal as well as horizontal views of the 11 intrathoracic lymph node stations and their adjacent tissues and blood vessels. We displayed the specific puncture site of each lymph node station. The 11 stations were divided into four groups: right mediastinal stations, left mediastinal stations, central mediastinal stations and hilar stations. The VBN system provides a precise view of the intrabronchial landmarks, which may increase the diagnostic accuracy of intrathoracic lymph node adenopathy and assist bronchoscopists with practicing TBNA.
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http://dx.doi.org/10.3389/fmolb.2021.679442DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8215157PMC
June 2021

miR-181d promotes pancreatic beta cell dysfunction by targeting IRS2 in gestational diabetes mellitus.

Ginekol Pol 2021 Jun 22. Epub 2021 Jun 22.

Shanghai Public Health Clinical Center, Shanghai, China.

Objectives: Hyperglycemia that develops during pregnancy is a diagnostic criterion of gestational diabetes mellitus (GDM). Current studies have shown that the expression of miRNA-181d is significantly enhanced in the glomeruli of type 2 diabetic. However, the relationship between miR-181d and GDM has never been reported before.

Material And Methods: The serum samples were collected from patients with GDM and subjected to qRT-PCR to verify the potential altered the miR-181d expression. In an in vitro GDM model, the miR-181d expression was induced by high glucose treatment, a miR-181d inhibitor was transfected into INS-1 cells to reduce miR-181d expression. Then, the level of insulin mRNA, cell viability, and content of total insulin were analyzed through ELISA, CCK-8 assay, and qRT-PCR assay. The relative apoptosis rates were detected by Annexin-V/PI assays. Finally, the shIRS2 transfection was performed to test whether in pancreatic β cells, IRS2 had similar insulin-enhancing functions as the miR-181d inhibitor.

Results: MiR-181d expression level was positively correlated with fasting blood glucose levels and the inhibition of miR-181d reduced insulin resistance, enhanced cells viability and suppressed high-glucose-induced apoptosis. In addition, the suppression of miR-181d improved the functions of INS-1 cells by targeting IRS2.

Conclusions: In summary, this study indicated that miR-181d modulated the process of insulin signaling and cell viability and apoptosis in pancreatic β cells by targeting IRS-2, suggesting that miR-181d inhibition is a potential target for GDM therapy.
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http://dx.doi.org/10.5603/GP.a2021.0077DOI Listing
June 2021

Evaluation of whole-genome DNA methylation sequencing library preparation protocols.

Epigenetics Chromatin 2021 Jun 19;14(1):28. Epub 2021 Jun 19.

Department of Epigenetics, Van Andel Research Institute, 333 Bostwick Avenue NE, Grand Rapids, MI, 49503, USA.

Background: With rapidly dropping sequencing cost, the popularity of whole-genome DNA methylation sequencing has been on the rise. Multiple library preparation protocols currently exist. We have performed 22 whole-genome DNA methylation sequencing experiments on snap frozen human samples, and extensively benchmarked common library preparation protocols for whole-genome DNA methylation sequencing, including three traditional bisulfite-based protocols and a new enzyme-based protocol. In addition, different input DNA quantities were compared for two kits compatible with a reduced starting quantity. In addition, we also present bioinformatic analysis pipelines for sequencing data from each of these library types.

Results: An assortment of metrics were collected for each kit, including raw read statistics, library quality and uniformity metrics, cytosine retention, and CpG beta value consistency between technical replicates. Overall, the NEBNext Enzymatic Methyl-seq and Swift Accel-NGS Methyl-Seq kits performed quantitatively better than the other two protocols. In addition, the NEB and Swift kits performed well at low-input amounts, validating their utility in applications where DNA is the limiting factor.

Results: The NEBNext Enzymatic Methyl-seq kit appeared to be the best option for whole-genome DNA methylation sequencing of high-quality DNA, closely followed by the Swift kit, which potentially works better for degraded samples. Further, a general bioinformatic pipeline is applicable across the four protocols, with the exception of extra trimming needed for the Swift Biosciences's Accel-NGS Methyl-Seq protocol to remove the Adaptase sequence.
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http://dx.doi.org/10.1186/s13072-021-00401-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8214260PMC
June 2021

In vitro activities of the tetrazole VT-1161 compared with itraconazole and fluconazole against and non- species.

Mycologia 2021 Jun 16:1-8. Epub 2021 Jun 16.

Department of Laboratory Medicine, Shanghai East Hospital, Tongji University School of Medicine, 1800 Yuntai Road, Pudong New District, Shanghai, China.

Recently, and non- (NAC) have emerged as health-threatening pathogens for clinical fungal infections. Due to their increased resistance to existing antifungal drugs, novel antifungals are urgently needed. In this study, we evaluated the antifungal effect of VT-1161 and its comparators itraconazole and fluconazole against common fluconazole-sensitive or -resistant and NAC strains. The tested strains were obtained from Chinese patients by the Invasive Fungal Infection Group within the past 2 years. The minimum inhibitory concentrations (MICs) of VT-1161 and other triazoles were measured according to the Clinical and Laboratory Standards Institute (CLSI) M27-Ed4 guidelines. We found that VT-1161 exhibited strong in vitro activity against spp.. VT-1161 (geometric mean MIC = 0.024 μg/mL) was 21.7-fold and 104.5-fold more potent than itraconazole and fluconazole, respectively. Against the seven isolates with higher fluconazole MICs (≥8 μg/mL based on the MIC value of this azole), VT-1161 maintained potent activities, with MICs ranging between 0.031 and 0.5 μg/mL. For NAC spp., VT-1161 (geometric mean MIC = 0.099 μg/mL) was 6.0-fold and 11.4-fold more effective than itraconazole and fluconazole, respectively. There is a positive correlation of the MICs between VT-1161 and itraconazole/fluconazole. The MIC values of VT-1161 against and were significantly lower than those of fluconazole, whereas for the differences in the MIC values between VT-1161 and fluconazole were not statistically significant. The results showed that tetrazole VT-1161 might be a promising candidate for treating and NAC infections.
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http://dx.doi.org/10.1080/00275514.2021.1913949DOI Listing
June 2021

Two-photon calcium imaging of neuronal and astrocytic responses: the influence of electrical stimulus parameters and calcium signaling mechanisms.

J Neural Eng 2021 Jul 2;18(4). Epub 2021 Jul 2.

School of Biomedical Engineering, Tianjin Medical University, 22 Qixiangtai Road, Tianjin 300070, China.

. Electrical brain stimulation has been used to ameliorate symptoms associated with neurologic and psychiatric disorders. The astrocytic activation and its interaction with neurons may contribute to the therapeutic effects of electrical stimulation. However, how the astrocytic activity is affected by electrical stimulation and its calcium signaling mechanisms remain largely unknown. This study is to explore the influence of electrical stimulus parameters on cellular calcium responses and corresponding calcium signaling mechanisms, with a focus on the heretofore largely overlooked astrocytes.. Usingtwo-photon microscopy in mouse somatosensory cortex, the calcium activity in neurons and astrocytes were recorded.. The cathodal stimulation evoked larger responses in both neurons and astrocytes than anodal stimulation. Both neuronal and astrocytic response profiles exhibited the unimodal frequency dependency, the astrocytes prefer higher frequency stimulation than neurons. Astrocytes need longer pulse width and higher current intensity than neurons to activate. Compared to neurons, the astrocytes were not capable of keeping sustained calcium elevation during prolonged electrical stimulation. The neuronal Cainflux involves postsynaptic effects and direct depolarization. The Casurge of astrocytes has a neuronal origin, the noradrenergic and glutamatergic signaling act synergistically to induce astrocytic activity.. The astrocytic activity can be regulated by manipulating stimulus parameters and its calcium activation should be fully considered when interpreting the mechanisms of action of electrical neuromodulation. This study brings considerable benefits in the application of electrical stimulation and provides useful insights into cortical signal transduction, which contributes to the understanding of mechanisms underlying the therapeutic efficacy of electrical stimulation for neurorehabilitation applications.
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http://dx.doi.org/10.1088/1741-2552/ac0b50DOI Listing
July 2021

Plasma Microbial Cell-Free DNA Sequencing Technology for the Diagnosis of Sepsis in the ICU.

Front Mol Biosci 2021 28;8:659390. Epub 2021 May 28.

Department of Laboratory Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.

Sepsis is a common life-threatening disease in the intensive care unit (ICU) that is usually treated empirically without pathogen identification. As a non-invasive and high-throughput technology, plasma microbial cell-free DNA (mcfDNA) sequencing can detect unknown pathogens independent of previous clinical or laboratory information. In this study, a total of 199 cases suspected of bloodstream infection (BSI) from January 2020 to June 2020 were collected, and potential pathogens were detected by simultaneous blood culture and plasma mcfDNA sequencing. Other clinical microbiological assays were performed within 7 days of plasma mcfDNA sequencing, including smear, culture of samples taken from relevant infected sites, and β-D-glucan/galactomannan (BDG/GM) tests, among others. The diagnoses were classified as sepsis [94 (47.2%)], non-sepsis [87 (43.7%)], and non-infectious disease [18 (9.0%)]. The sensitivity and specificity of plasma mcfDNA sequencing for diagnosing sepsis were 68.1 and 63.2%, respectively, which were significantly better than those of blood culture, especially for the common bacteria that cause hospital-acquired infection, namely, ( < 0.01) and ( < 0.01), and DNA viruses (plasma mcfDNA sequencing only, < 0.01). However, there was no significant difference in the rate of positivity between plasma mcfDNA sequencing and blood culture for antibiotic-non-exposed cases (43.6 vs. 30.9%, = 0.17). In the non-sepsis group, 44.8% of cases (13/29) detected only by plasma mcfDNA sequencing showed infections in other parts of the body, such as lower respiratory infection (LRI), intra-abdominal infection (IAI) and central nervous system infection (CNSI). For some common pathogens (not including anaerobes), turnaround time (TAT) 3 (TAT from the initiation of blood sample processing by nucleic acid extraction to the completion of sequencing analysis) was longer than TAT1 (TAT from blood culture bottles in Virtuo to off Virtuo). With disease progression, significant dynamic changes in microbial species were clearly detected by plasma mcfDNA sequencing.
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http://dx.doi.org/10.3389/fmolb.2021.659390DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194294PMC
May 2021

Discovery and Characterization of Benzimidazole Derivative XY123 as a Potent, Selective, and Orally Available RORγ Inverse Agonist.

J Med Chem 2021 Jun 14;64(12):8775-8797. Epub 2021 Jun 14.

Guangdong Provincial Key Laboratory of Biocomputing, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou 510530, China.

Receptor-related orphan receptor γ (RORγ) has emerged as an attractive therapeutic target for the treatment of cancer and inflammatory diseases. Herein, we report our effort on the discovery, optimization, and evaluation of benzothiazole and benzimidazole derivatives as novel inverse agonists of RORγ. The representative compound (designated as XY123) potently inhibited the RORγ transcription activity with a half-maximal inhibitory concentration (IC) value of 64 nM and showed excellent selectivity against other nuclear receptors. also potently suppressed cell proliferation, colony formation, and the expression of androgen receptor (AR)-regulated genes in AR-positive prostate cancer cell lines. In addition, demonstrated good metabolic stability and a pharmacokinetic property with reasonable oral bioavailability (32.41%) and moderate half-life ( = 4.98 h). Significantly, oral administration of compound achieved complete and long-lasting tumor regression in the 22Rv1 xenograft tumor model in mice. Compound may serve as a new valuable lead compound for further development of drugs for the treatment of prostate cancer.
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http://dx.doi.org/10.1021/acs.jmedchem.1c00763DOI Listing
June 2021

Single-cell RNA sequencing of human femoral head .

Aging (Albany NY) 2021 06 10;13(11):15595-15619. Epub 2021 Jun 10.

Center for System Biology, Data Sciences, and Reproductive Health, School of Basic Medical Science, Central South University, Yuelu, Changsha 410013, China.

The homeostasis of bone metabolism depends on the coupling and precise regulation of various types of cells in bone tissue. However, the communication and interaction between bone tissue cells at the single-cell level remains poorly understood. Thus, we performed single-cell RNA sequencing (scRNA-seq) on the primary human femoral head tissue cells (FHTCs). Nine cell types were identified in 26,574 primary human FHTCs, including granulocytes, T cells, monocytes, B cells, red blood cells, osteoblastic lineage cells, endothelial cells, endothelial progenitor cells (EPCs) and plasmacytoid dendritic cells. We identified () and () as novel bone metabolism-related genes. Additionally, we found that several subtypes of monocytes, T cells and B cells were related to bone metabolism. Cell-cell communication analysis showed that collagen, chemokine, transforming growth factor and their ligands have significant roles in the crosstalks between FHTCs. In particular, EPCs communicated with osteoblastic lineage cells closely via the "COL2A1-ITGB1" interaction pair. Collectively, this study provided an initial characterization of the cellular composition of the human FHTCs and the complex crosstalks between them at the single-cell level. It is a unique starting resource for in-depth insights into bone metabolism.
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http://dx.doi.org/10.18632/aging.203124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8221309PMC
June 2021

Design, synthesis and biological evaluation of novel molecules as potent PARP-1 inhibitors.

Bioorg Med Chem Lett 2021 Jun 6;47:128169. Epub 2021 Jun 6.

Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 211198, China; Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 211198, China. Electronic address:

Two series of novel compounds with inhibition activity against PARP-1 were designed and synthesized. All target compounds were evaluated for their PARP-1 inhibition activity, and compounds with high PARP-1 inhibition activity were selected to assess for cellular assays in vitro. Among them, compound II-4 displayed impressive results in both PARP-1 enzyme inhibition with IC value of 0.51 nM and anti-proliferation activity against HCT116 and HCC1937 cell lines with IC values of 6.62 nM and 12.65 nM, respectively. Also, II-4 exhibited good metabolic stability in vitro with t of 173.25 min and CL of 0.04 mL/min/mg. Prediction of molecular properties and protein docking were applied to structure design. Our study provides potential lead compounds and design directions for the development of PARP-1 inhibitors.
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http://dx.doi.org/10.1016/j.bmcl.2021.128169DOI Listing
June 2021

Duplex On-Site Detection of and by Recombinase Polymerase Amplification and Three-Segment Lateral Flow Strips.

Biosensors (Basel) 2021 May 12;11(5). Epub 2021 May 12.

Key Laboratory of Molecular Biophysics of Ministry of Education, Department of Biomedical Engineering, College of Life Science and Technology, Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan 430074, China.

and are two most reported foodborne pathogens related to seafood. Due to global ocean warming and an increase in seafood consumption worldwide, foodborne illnesses related to infection of these two bacteria are growing, leading to food safety issues and economic consequences. Molecular detection methods targeting species-specific genes are effective tools in the fight against bacterial infections for food safety. In this study, a duplex detection biosensor based on isothermal recombinase polymerase amplification (RPA) and a three-segment lateral flow strip (LFS) has been established. The biosensor used gene of and gene of as the detection markers based on previous reports. A duplex RPA reaction for both targets were constructed, and two chemical labels, FITC and DIG, of the amplification products were carefully tested for effective and accurate visualization on the strip. The biosensor demonstrated good specificity and achieved a sensitivity of 10 copies per reaction or one colony forming unit (CFU)/10 g of spiked food for both bacteria. Validation with clinical samples showed results consistent with that of real-time polymerase chain reaction. The detection process was simple and fast with a 30-min reaction at 37 °C and visualization on the strip within 5 min. With little dependence on laboratory settings, this biosensor was suitable for on-site detection, and the duplex system enabled simultaneous detection of the two important foodborne bacteria. Moreover, the principle can be extended to healthcare and food safety applications for other pathogens.
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http://dx.doi.org/10.3390/bios11050151DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8151630PMC
May 2021

Isolation and Characterization of Nocardia Species from Pulmonary Nocardiosis in a tertiary hospital in China.

Jpn J Infect Dis 2021 May 31. Epub 2021 May 31.

Department of Clinical Laboratory, Xiangya Hospital, Central South University, China.

The aim of this study was to investigate the clinical features, distribution and antimicrobial susceptibility of Nocardia species isolated from pulmonary nocardiosis cases in tertiary hospital in China. The species were collected from January 1, 2018 to May 31, 2019 and identified using MALDI-TOF MS or PCR. Antimicrobial susceptibility testing was performed using the broth microdilution method. Within the 44 Nocardia species, N. farcinica was the most frequently identified species (n = 36), followed by N. nova (n = 5), N. otitidiscaviarum (n = 1), N. cyriacigeorgica (n = 1), and N. transvalensis (n = 1). The top three predisposing factors of pulmonary nocardiosis were chronic obstructive pulmonary disease (45.5%), hypertension (34.1%), and tuberculosis (31.8%). All 44 Nocardia strains were susceptible to amikacin, trimethoprim / sulfamethoxazole, and linezolid. The resistance rates of Nocardia to amoxicillin-clavulanic acid, ciprofloxacin, clarithromycin, ceftriaxone, tobramycin, and imipenem were 4.5%, 9.1%, 79.5%, 72.7%, 63.6%, and 38.6%, respectively. Two Nocardia strains had decreased sensitivity to trimethoprim / sulfamethoxazole. In conclusion, N. farcinica was the most frequently isolated Nocardia species in the First Hospital of Changsha. All isolated clinical Nocardia strains showed susceptible to amikacin, trimethoprim / sulfamethoxazole, and linezolid, suggesting that these drugs can be primary therapeutic choices for treating Nocardia infections.
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http://dx.doi.org/10.7883/yoken.JJID.2020.1096DOI Listing
May 2021

Establishment of a visualized isothermal nucleic acid amplification method for on-site diagnosis of acute hepatopancreatic necrosis disease in shrimp farm.

J Fish Dis 2021 May 27. Epub 2021 May 27.

Jiangsu Key Laboratory of Marine Biological Resources and Environment, Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, Co-Innovation Center of Jiangsu Marine Bio-industry Technology, School of Pharmacy, Jiangsu Ocean University, Lianyungang, China.

Acute hepatopancreatic necrosis disease (AHPND) is a significant deadly infectious disease in the shrimp farming industry, causing serious economic losses globally every year. Because of the rapid progress speed, lack of effective treatment and high mortality rate of AHPND, monitoring with frequent diagnostic tests is vital for a successful prevention. The conventional histopathological diagnosis fell far short of the requirement for efficient monitoring, and the polymerase chain reaction (PCR)-based molecular diagnostic methods that rely on sophisticated thermocycler and trained personnel are hardly applicable in the field. Combining the recombinase polymerase amplification (RPA) and the lateral flow strips (LFSs), a diagnostic method suitable for on-site everyday monitoring of AHPND has been established in this study. This RPA-LFS method targeted the binary toxic photorhabdus insect-related genes PirA and PirB on a virulence plasmid of the AHPND-causative Vibrio parahaemolyticus strains. The diagnostic test was completed within 30 min at 37°C and showed good specificity and good sensitivity of 20 fg DNA of the AHPND shrimp or one colony-forming unit of the causative bacterium per reaction, which was better than the administration-approved standard AP4 assay. Crude templates from sample boiling could be directly used. Tests of clinical samples showed 100% consistency of this method with the standard AP4 assay. This RPA-LFS method can be a good choice for on-site diagnosis of AHPND with quick response time, easy procedure and low demand for resources, and should have significant value for the control of spreading of this dangerous disease in farmed shrimp.
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http://dx.doi.org/10.1111/jfd.13388DOI Listing
May 2021

Identification of key genes in calcific aortic valve disease via weighted gene co-expression network analysis.

BMC Med Genomics 2021 May 21;14(1):135. Epub 2021 May 21.

Department of Cardiology, Liyang People's Hospital, Liyang, 213300, China.

Background: Calcific aortic valve disease (CAVD) is the most common subclass of valve heart disease in the elderly population and a primary cause of aortic valve stenosis. However, the underlying mechanisms remain unclear.

Methods: The gene expression profiles of GSE83453, GSE51472, and GSE12644 were analyzed by 'limma' and 'weighted gene co-expression network analysis (WGCNA)' package in R to identify differentially expressed genes (DEGs) and key modules associated with CAVD, respectively. Then, enrichment analysis was performed based on Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, DisGeNET, and TRRUST database. Protein-protein interaction network was constructed using the overlapped genes of DEGs and key modules, and we identified the top 5 hub genes by mixed character calculation.

Results: We identified the blue and yellow modules as the key modules. Enrichment analysis showed that leukocyte migration, extracellular matrix, and extracellular matrix structural constituent were significantly enriched. SPP1, TNC, SCG2, FAM20A, and CD52 were identified as hub genes, and their expression levels in calcified or normal aortic valve samples were illustrated, respectively.

Conclusions: This study suggested that SPP1, TNC, SCG2, FAM20A, and CD52 might be hub genes associated with CAVD. Further studies are required to elucidate the underlying mechanisms and provide potential therapeutic targets.
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http://dx.doi.org/10.1186/s12920-021-00989-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8138987PMC
May 2021

TASP1 Promotes Proliferation and Migration in Gastric Cancer via EMT and AKT/P-AKT Pathway.

J Immunol Res 2021 29;2021:5521325. Epub 2021 Apr 29.

The Affiliated Huai'an Hospital of Xuzhou Medical University and The Second People's Hospital of Huai'an, No. 62, Huaihai Road (S.), Huaian 223002, China.

Threonine aspartase 1 (TASP1) was reported to function in the development of cancer. However, the regulatory mechanism of TASP1 in gastric cancer (GC) remains unclear. In this study, we determined the expression of TASP1 in tissues of GC patients, GC cells by qRT-PCR, and western blot and assessed the relationship between TASP1 and GC cell proliferation and migration via CCK-8 and transwell assay. It was found that the expression of TASP1 in GC tissues or GC cell lines was significantly higher than that in normal adjacent tissues or normal cells. The proliferation and migration of GC cells were inhibited upon TASP1 knockdown. Mechanism investigation revealed that TASP1 promoted GC cell proliferation and migration through upregulating the p-AKT/AKT expression. TASP1 induced GC cell migration via the epithelial -mesenchymal transition (EMT) pathway. In conclusion, TASP1 promotes GC progression through the EMT and AKT/p-AKT pathway, and it may serve as a new potential biomarker and therapeutic target for GC.
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http://dx.doi.org/10.1155/2021/5521325DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105097PMC
April 2021

α7 Nicotinic Acetylcholine Receptor Agonist PNU-282987 Ameliorates Cognitive Impairment Induced by Chronic Intermittent Hypoxia.

Nat Sci Sleep 2021 11;13:579-590. Epub 2021 May 11.

Institute of Respiratory Disease, The First Hospital of China Medical University, Shenyang, People's Republic of China.

Purpose: Cognitive impairment is an important complication of obstructive sleep apnea (OSA). Chronic intermittent hypoxia (CIH), the main pathophysiological characteristics of OSA, is closely related to cognitive dysfunction and may be mediated by alpha-7 nicotinic acetylcholine receptors (α7nAChR). This study investigated the effects and clarified the mechanisms of α7nAChR on the cognitive function of mice with CIH.

Methods: Thirty CD-1 mice were randomly divided into room air (RA), CIH-2 weeks (CIH2W), and CIH-4 weeks (CIH4W) groups. Cognitive function was evaluated by novel object recognition (NOR) and Morris water maze (MWM) tests after exposure. Then, 104 CD-1 mice were exposed to CIH for 4 weeks and randomly divided into four groups: CIH4W (control), with dimethyl sulfoxide (DMSO) (sham), with α7nAChR-specific agonist PNU-282987 (PNU), and with α7nAChR-specific inhibitor methyllycaconitine and PNU-282987 (MLA+PNU). In addition to the evaluation of cognitive function, apoptotic bodies in the hippocampus were detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, changes in p-CREB and BDNF were detected by immunohistochemistry, while those of ERK1/2, CREB, PGC-1α, FNDC5, and BDNF were detected by Western blotting in the hippocampal tissues of the mice.

Results: Compared to the CIH2W and RA groups, the CIH4W group showed cognitive dysfunction in the NOR and MWM tests. The changes in cognitive dysfunction were alleviated by PNU-282987; furthermore, MLA pretreatment offset the effect. In hippocampal tissues, TUNEL assays showed decreased apoptotic cells, immunohistochemical staining showed increased expressions of p-CREB and BDNF. The expression levels of p-ERK1/2/t-ERK1/2, p-CREB/t-CREB, PGC-1α, FNDC5, and BDNF were increased after PNU-282987 injection.

Conclusion: Four weeks of CIH caused cognitive dysfunction in mice. Activating α7nAChR might ameliorate this dysfunction by upregulating the ERK1/2/CREB signaling pathway; enhancing PGC-1α, FNDC5, and BDNF expression levels; and reducing cell apoptosis in the hippocampal tissue of mice.
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http://dx.doi.org/10.2147/NSS.S296701DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8123952PMC
May 2021

Interleukin-35 Regulates Angiogenesis Through P38 Mitogen-Activated Protein Kinase Signaling Pathway in Interleukin-1β-Stimulated SW1353 Cells and Cartilage Bioinformatics Analysis.

J Interferon Cytokine Res 2021 May;41(5):164-171

Department of Rheumatology and Immunology, The First Affiliated Hospital of China Medical University, Shenyang, P.R. China.

We aimed to investigate the effects of interleukin (IL)-35 on proangiogenic factors in IL-1β-pretreated chondrocyte-like SW1353 cells and screen-related genes that participated in osteoarthritis (OA) cartilage with IL-35, proangiogenic factors, and P38 mitogen-activated protein kinase (MAPK) signaling pathway. Different concentrations of IL-35 incubated with IL-1β stimulated SW1353 cells with or without SB203580 (inhibitor of P38 MAPK). Proangiogenic molecule expression was assessed by real-time polymerase chain reaction and enzyme-linked immunosorbent assay. Microarray datasets were downloaded from the Gene Expression Omnibus database of OA cartilage. Protein-protein interaction of genes was visualized by Search Tool for the Retrieval Interacting Genes and Cytoscape. Database for Annotation, Visualization, and Integrated Discovery was used to screen biological processes and pathways. IL-35 inhibited mRNA expression of proangiogenic factors in IL-1β-stimulated SW1353 cells through the P38 MAPK signaling pathway. IL-35 inhibited angiopoietin-2 secretion. We found that 8 related genes, 18 biological processes, and 6 pathways may associate with IL-35, P38 MAPK signaling pathway, and cartilage angiogenesis. IL-35 regulated the expression of proangiogenic factors through P38 MAPK signaling pathway in IL-1β-stimulated SW1353 cells. IL-35 and P38 MAPK pathway may participate in neovascularization of cartilage. Our findings may provide molecular mechanisms and possible genes target treatment for OA.
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http://dx.doi.org/10.1089/jir.2021.0016DOI Listing
May 2021

Roles of KLF4 and AMPK in the inhibition of glycolysis by pulsatile shear stress in endothelial cells.

Proc Natl Acad Sci U S A 2021 May;118(21)

Institute of Engineering in Medicine, University of California San Diego, La Jolla, CA 92093;

Vascular endothelial cells (ECs) sense and respond to hemodynamic forces such as pulsatile shear stress (PS) and oscillatory shear stress (OS). Among the metabolic pathways, glycolysis is differentially regulated by atheroprone OS and atheroprotective PS. Studying the molecular mechanisms by which PS suppresses glycolytic flux at the epigenetic, transcriptomic, and kinomic levels, we have demonstrated that glucokinase regulatory protein (GCKR) was markedly induced by PS in vitro and in vivo, although PS down-regulates other glycolysis enzymes such as hexokinase (HK1). Using next-generation sequencing data, we identified the binding of PS-induced Krüppel-like factor 4 (KLF4), which functions as a pioneer transcription factor, binding to the GCKR promoter to change the chromatin structure for transactivation of GCKR. At the posttranslational level, PS-activated AMP-activated protein kinase (AMPK) phosphorylates GCKR at Ser-481, thereby enhancing the interaction between GCKR and HK1 in ECs. In vivo, the level of phosphorylated GCKR Ser-481 and the interaction between GCKR and HK1 were increased in the thoracic aorta of wild-type AMPKα2 mice in comparison with littermates with EC ablation of AMPKα2 (AMPKα2). In addition, the level of GCKR was elevated in the aortas of mice with a high level of voluntary wheel running. The underlying mechanisms for the PS induction of GCKR involve regulation at the epigenetic level by KLF4 and at the posttranslational level by AMPK.
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http://dx.doi.org/10.1073/pnas.2103982118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166073PMC
May 2021

Removal of refractory organics in wastewater by coagulation/flocculation with green chlorine-free coagulants.

Sci Total Environ 2021 Sep 8;787:147654. Epub 2021 May 8.

State Key Laboratory of Heavy Oil Processing, Beijing Key Lab of Oil & Gas Pollution Control, China University of Petroleum, Beijing 102249, China; College of Chemical Engineering and Environment, China University of Petroleum, Beijing 102249, China. Electronic address:

Coagulation/flocculation is considered an economical and practical technology to remove refractory organic matter from wastewater. Coagulants containing chlorine may release chloride ions into water, thereby resulting in corrosion. A green chlorine-free coagulant of polyaluminum ferric silicate (PSAF) was synthesized to treat non-oily (e.g., humus wastewater) and oily refractory wastewaters (e.g., lubricating oil wastewater). Results showed that the highest removal efficiency of humus substances in non-oily wastewater achieved 96.0% at pH 7.0 using PSAF alone. When treating oily wastewater, the dosage and addition sequence of PAMALAM significantly affected the coagulation performance. The removal efficiencies of turbidity, chemical oxygen demand, and total nitrogen were increased by 0.3, 1.8, and 5.9 folds, respectively, with the optimal adding sequence of PSAF +0.08% PAMALAM. More fulvic acid-like substances can be removed during this process. The analysis of zeta potential and floc properties revealed that charge neutralization, sweep, and adsorption/entrapment mechanisms existed during the single PSAF coagulation process, and PAMALAM mainly improved the adsorption, bridging, and sweep function.
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http://dx.doi.org/10.1016/j.scitotenv.2021.147654DOI Listing
September 2021

The application of deep learning in electrocardiogram: Where we came from and where we should go?

Int J Cardiol 2021 08 14;337:71-78. Epub 2021 May 14.

Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210000, China.. Electronic address:

Electrocardiogram (ECG) is a commonly-used, non-invasive examination recording cardiac voltage versus time traces over a period. Deep learning technology, a robust artificial intelligence algorithm, can imitate the data processing patterns of the human brain, and it has experienced remarkable success in disease screening, diagnosis, and prediction. Compared with traditional machine learning, deep learning algorithms possess more powerful learning capabilities and can automatically extract features without extensive data pre-processing or hand-crafted feature extraction, which makes it a suitable tool to analyze complex structures of high-dimensional data. With the advances in computing power and digitized data availability, deep learning provides us an opportunity to improve ECG data interpretation with higher efficacy and accuracy and, more importantly, expand the original functions of ECG. The application of deep learning has led us to stand at the edge of ECG innovation and will potentially change the current clinical monitoring and management strategies. In this review, we introduce deep learning technology and summarize its advantages compared with traditional machine learning algorithms. Moreover, we provide an overview on the current application of deep learning in ECGs, with a focus on arrhythmia (especially atrial fibrillation during normal sinus rhythm), cardiac dysfunction, electrolyte imbalance, and sleep apnea. Last but not least, we discuss the current challenges and prospect directions for the following studies.
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http://dx.doi.org/10.1016/j.ijcard.2021.05.017DOI Listing
August 2021

Physical exercise increases peripheral brain-derived neurotrophic factors in patients with cognitive impairment: A meta-analysis.

Restor Neurol Neurosci 2021 May 10. Epub 2021 May 10.

Institute of Respiratory and Critical Care, the First Hospital of China Medical University, Shenyang, China.

Background: Physical exercise can improve cognitive dysfunction. Its specific mechanism remains unknown. Recent studies have indicated that elevating or peripherally overexpressing brain-derived neurotrophic factors (BDNF) improve cognitive impairment.

Objective: This meta-analysis aimed to investigate whether physical exercise improves cognitive performance in patients with cognitive dysfunction, such as mild cognitive impairment (MCI) or Alzheimer's disease (AD), by increasing peripheral BDNF.

Methods: PubMed, Embase, Cochrane Library, and Web of Science were searched up to June 2020 for studies that assayed the changes in peripheral BDNF levels in MCI and AD patients after exercise training.

Results: Peripheral BDNF levels were significantly elevated after a single exercise session (SMD = 0.469, 95% CI: 0.150-0.787, P = 0.004) or regular exercise interventions (SMD = 0.418, 95% CI: 0.105-0.731, P = 0.009). Subgroup analysis showed that only regular aerobic exercise interventions (SMD = 0.543, 95% CI: 0.038-1.049, P = 0.035) and intervention duration of 16 weeks or greater (SMD = 0.443, 95% CI: 0.154 -0.733, P = 0.003) significantly increased peripheral BDNF levels. Only plasma BDNF levels (SMD = 0.365, 95% CI:0.066-0.664, P = 0.017) were significantly increased after exercise interventions.

Conclusions: Acute and chronic physical exercises may improve cognitive impairment by increasing peripheral BDNF levels. Aerobic exercises and a longer duration of exercising increased BDNF levels. These findings also suggest that BDNF may be a suitable biomarker for evaluating the effect of exercise in patients with cognitive impairment, such as AD or MCI.
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http://dx.doi.org/10.3233/RNN-201060DOI Listing
May 2021

Mouse totipotent stem cells captured and maintained through spliceosomal repression.

Cell 2021 May 14;184(11):2843-2859.e20. Epub 2021 May 14.

MOE Key Laboratory of Cell Proliferation and Differentiation, School of Life Sciences, Peking University, Beijing 100871, China; Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China. Electronic address:

Since establishment of the first embryonic stem cells (ESCs), in vitro culture of totipotent cells functionally and molecularly comparable with in vivo blastomeres with embryonic and extraembryonic developmental potential has been a challenge. Here we report that spliceosomal repression in mouse ESCs drives a pluripotent-to-totipotent state transition. Using the splicing inhibitor pladienolide B, we achieve stable in vitro culture of totipotent ESCs comparable at molecular levels with 2- and 4-cell blastomeres, which we call totipotent blastomere-like cells (TBLCs). Mouse chimeric assays combined with single-cell RNA sequencing (scRNA-seq) demonstrate that TBLCs have a robust bidirectional developmental capability to generate multiple embryonic and extraembryonic cell lineages. Mechanically, spliceosomal repression causes widespread splicing inhibition of pluripotent genes, whereas totipotent genes, which contain few short introns, are efficiently spliced and transcriptionally activated. Our study provides a means for capturing and maintaining totipotent stem cells.
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http://dx.doi.org/10.1016/j.cell.2021.04.020DOI Listing
May 2021
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