Publications by authors named "Guan Li"

251 Publications

The optimization of total flavonoids from rhizoma drynariae by response surface methodology and the metal ion chelation activity assay.

Pak J Pharm Sci 2021 Mar;34(2):621-627

Department of Natural Medicinal Chemistry, Institute of Medicine, Xi'an Medical University, Xi'an, PR China.

Rhizoma Drynariae, the dried rhizome of Drynaria fortunei (Kunze), is rich in flavonoids and has varieties of pharmacological activities. To optimize the extract conditions for bioactive flavonoids, a response surface methodology (RSM) was utilized to assess the effects of three independent variables (liquid-to-solid ratio (mL/g), extract temperature (°C) and ethanol concentration (%) on the total flavonoids content (TFC). To test the chelation with metal ion, the UV-visible spectrophotometer was used to detect metal ion chelation of extracted flavonoids. Regression analysis displayed a good fit of the experimental data. The optimal condition was liquid-to-solid ratio with 50:1, extract temperature with 80 °C and ethanol concentration with 40.22%. The total flavonoids had a better chelation with metal ions Cu, Fe, Fe than Zn. These results suggested that the model employed is suitable and the application of RSM in optimizing the extract conditions is successful. The experimental values were in fine agreement (the yield 24.05±0.69mg/g) with predicted values. The total flavonoids from the extract presented good chelation against four metal ions (Cu, Zn, Fe and Fe), which provided a good evidence for Alzheimer's disease treatments.
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March 2021

STSRNet: Deep Joint Space-Time Super-Resolution for Vector Field Visualization.

IEEE Comput Graph Appl 2021 Jul 16;PP. Epub 2021 Jul 16.

We propose STSRNet, a joint space-time super-resolution deep learning based model for time-varying vector field data. Our method is designed to reconstruct high temporal resolution (HTR) and high spatial resolution (HSR) vector fields sequence from the corresponding low-resolution key frames. For large scale simulations, only data from a subset of time steps with reduced spatial resolution can be stored for post-hoc analysis. In this paper, we leverage a deep learning model to capture the non-linear complex changes of vector field data with a two-stage architecture: the first stage deforms a pair of low spatial resolution (LSR) key frames forward and backward to generate the intermediate LSR frames, and the second stage performs spatial super-resolution to output the high-resolution sequence. Our method is scalable and can handle different data sets. We demonstrate the effectiveness of our framework with several data sets through quantitative and qualitative evaluations.
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http://dx.doi.org/10.1109/MCG.2021.3097555DOI Listing
July 2021

Manipulation of TAMs functions to facilitate the immune therapy effects of immune checkpoint antibodies.

J Control Release 2021 Jul 9;336:621-634. Epub 2021 Jul 9.

Department of Pharmaceutics, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 44 Wenhua Xi Road, Jinan, Shandong Province 250012, China. Electronic address:

Immune checkpoint antibodies have emerged as novel therapeutics, while many patients are refractory. Researchers had identified tumor-associated macrophages (TAMs) is the pivotal factor involved in immune resistance and that manipulation of TAMs functions would improve the immunotherapies effectively. NF-κB pathway was one of the master regulators in TAMs manipulation. Inhibition of NF-κB pathway could achieve both re-polarization M2 TAMs and downregulation the expression of programmed cell death protein 1 (PD-1) ligand 1 (PD-L1) on TAMs to improve the effect of immunotherapies. Here, IMD-0354, inhibitor of NF-κB pathway was loaded in mannose modified lipid nanoparticles (M-IMD-LNP). Then, PD-1 antibody and M-IMD-LNP were co-loaded in matrix metalloproteinase 2 (MMP2) responsive and tumor target nanogels (P/ML-NNG). P/ML-NNG could co-deliver drugs to tumor site, disintegrated by MMP2 and release drugs to different targets. Evaluation of PD-1 expression, inhibition of NF-κB pathway, expression of PD-L1 on M2 TAMs and M2 TAMs re-polarization demonstrated that P/ML-NNG could block the PD-1/PD-L1 and NF-κB pathways simultaneously. Evaluation of CD4 T cells, CD8 T cells, Tregs, cytokines and antitumor immunity confirmed that IMD-0354 could improve the immunotherapies effectively. Those results provided forceful references for tumor immunetherapy.
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http://dx.doi.org/10.1016/j.jconrel.2021.07.009DOI Listing
July 2021

Tai Chi for Chronic Obstructive Pulmonary Disease (COPD): An Overview of Systematic Reviews.

Int J Gen Med 2021 29;14:3017-3033. Epub 2021 Jun 29.

Department of Rehabilitation, Chengdu University of Traditional Chinese Medicine, Chengdu, 610037, People's Republic of China.

Objective: Since current systematic reviews (SRs) show that results of effectiveness on Tai Chi for chronic obstructive pulmonary disease (COPD) are inconsistent, the purpose of this study is to find the reasons of the disparity by comprehensively appraising the related SRs.

Methods: Six databases were systematically searched from the inception date to April 17, 2021. The methodological quality, the risk of bias, the reporting quality, and the quality of evidence were independently assessed by two reviewers with the AMSTAR 2, ROBIS, PRISMA, and GRADE.

Results: A total of 12 studies met the inclusion criteria: 10 SRs were rated critically low quality and two SRs were low quality by AMSTAR 2. By the ROBIS, four out of 12 SRs were rated as "low risk". According to PRISMA, nine out of 12 SRs were adequately reported over 80%. With the GRADE tool, three out of 12 SRs rated the FEV1 as "Moderate", one out of 12 SRs (1/12, 9%) rated the FEV1/FVC (%) as "Moderate", three out of 12 SRs assessed the 6MWD as "Moderate", three out of 12 SRs evaluated the SGRQ as "Moderate", and the remaining evidence was fully rated as "Low" or "Very Low".

Conclusion: We found that the methodological quality, risk of bias, reporting quality, and quality of evidence of the included SRs on Tai Chi for COPD were suboptimal. These limitations may have a negative impact on SRs, consequently leading to inconsistent results. Further well-conducted SRs with less risk of bias, more rigorous methodology, normative reporting and high-quality of evidence are needed to provide robust evidence on Tai Chi for COPD.

Registration Number: This study has been registered in the PROSPERO International Prospective Register of Systematic Reviews (registration number: CRD42019126600).
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http://dx.doi.org/10.2147/IJGM.S308955DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8254601PMC
June 2021

High-Specific Isolation and Instant Observation of Circulating Tumour Cell from HCC Patients via Glypican-3 Immunomagnetic Fluorescent Nanodevice.

Int J Nanomedicine 2021 18;16:4161-4173. Epub 2021 Jun 18.

Department of Pharmaceutics, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, 250012, People's Republic of China.

Purpose: Specific targeting receptors for efficiently capturing and applicable nanodevice for separating and instant observing of circulating tumour cells (CTC) are critical for early diagnosis of cancer. However, the existing CTC detection system based on epithelial cell adhesion molecule (EpCAM) was seriously limited by low expression and poor specificity of targeting receptors, and not instant observation in clinical application.

Methods: Herein, an alternative glypican-3 (GPC3)-based immunomagnetic fluorescent system (C6/MMSN-GPC3) for high-specific isolation and instant observation of CTC from hepatocellular carcinoma (HCC) patients' peripheral blood was developed. The high-specific HCC targeting receptor, GPC3, was employed for improving the sensitivity and accuracy in CTC detection. GPC3 monoclonal antibody (mAb) was linked to immunomagnetic mesoporous silica for specific targeting capture and separate CTC, and fluorescent molecule coumarin-6 (C6) was loaded for instant detection of CTC.

Results: The cell recovery (%) of C6/MMSN-GPC3 increased in 10 HL-60 cells (from 49.7% to 83.0%) and in whole blood (from 42% to 80.3%) compared with MACS Beads. In clinical samples, the C6/MMSN-GPC3 could capture more CTC in the 13 cases of HCC patients and the capture efficiency was improved by 83.3%-350%. Meanwhile, the capture process of C6/MMSN-GPC3 was harmless, facilitating for the subsequent culture. Significantly, the C6/MMSN-GPC3 achieved the high-specific isolation and instant observation of CTC from HCC patients' blood samples, and successfully separated CTC from one patient with early stage of HCC (Stage I) and one post-surgery patient, further indicating the potential ability of C6/MMSN-GPC3 for HCC early diagnosis and prognosis evaluation.

Conclusion: Our study provides a feasible glypican-3 (GPC3)-based immunomagnetic fluorescent system (C6/MMSN-GPC3) for high-specific isolation and instant observation of HCC CTC.
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http://dx.doi.org/10.2147/IJN.S307691DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8219227PMC
June 2021

AtSEC22 Regulates Cell Morphogenesis via Affecting Cytoskeleton Organization and Stabilities.

Front Plant Sci 2021 4;12:635732. Epub 2021 Jun 4.

Key Laboratory of Saline-Alkali Vegetation Ecology Restoration, Ministry of Education, College of Life Sciences, Northeast Forestry University, Harbin, China.

The plant cytoskeleton forms a stereoscopic network that regulates cell morphogenesis. The cytoskeleton also provides tracks for trafficking of vesicles to the target membrane. Fusion of vesicles with the target membrane is promoted by SNARE proteins, etc. The vesicle-SNARE, Sec22, regulates membrane trafficking between the ER and Golgi in yeast and mammals. AtSEC22 might also regulate early secretion and is essential for gametophyte development. However, the role of AtSEC22 in plant development is unclear. To clarify the role of AtSEC22 in the regulation of plant development, we isolated an knock-down mutant, , and found that cell morphogenesis and development were seriously disturbed. exhibited shorter primary roots (PRs), dwarf plants, and partial abortion. More interestingly, the mutant had less trichomes with altered morphology, irregular stomata, and pavement cells, suggesting that cell morphogenesis was perturbed. Further analyses revealed that in , vesicle trafficking was blocked, resulting in the trapping of proteins in the ER and collapse of structures of the ER and Golgi apparatus. Furthermore, AtSEC22 defects resulted in impaired organization and stability of the cytoskeleton in . Our findings revealed essential roles of AtSEC22 in membrane trafficking and cytoskeleton dynamics during plant development.
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http://dx.doi.org/10.3389/fpls.2021.635732DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8211912PMC
June 2021

Development and application of the Faba_bean_130K targeted next-generation sequencing SNP genotyping platform based on transcriptome sequencing.

Theor Appl Genet 2021 Jun 12. Epub 2021 Jun 12.

National Key Facility for Crop Gene Resources and Genetic Improvement, Institute of Crop Sciences, Chinese Academy of Agricultural Sciences, Beijing, 100081, China.

Key Message: Large-scale faba bean transcriptome data are available, and the first genotyping platform based on liquid-phase probe targeted capture technology was developed for genetic and molecular breeding studies. Faba bean (Vicia faba L., 2n = 12) is an important food legume crop that is widely grown for multiple uses worldwide. However, no reference genome is currently available due to its very large genome size (approximately 13 Gb) and limited single nucleotide polymorphism (SNP) markers as well as highly efficient genotyping tools have been reported for faba bean. In this study, 16.7 billion clean reads were obtained from transcriptome libraries of flowers and leaves of 102 global faba bean accessions. A total of 243,120 unigenes were de novo assembled and functionally annotated. Moreover, a total of 1,579,411 SNPs were identified and further filtered according to a selection pipeline to develop a high-throughput, flexible, low-cost Faba_bean_130K targeted next-generation sequencing (TNGS) genotyping platform. A set of 69 Chinese faba bean accessions were genotyped with the TNGS genotyping platform, and the average mapping rate of captured reads to reference transcripts was 93.14%, of which 53.23% were located in the targeted regions. The TNGS genotyping results were validated by Sanger sequencing and the average consistency rate reached 93.6%. Comprehensive population genetic analysis was performed on the 69 Chinese faba bean accessions and identified four genetic subgroups correlated with the geographic distribution. This study provides valuable genomic resources and a reliable genotyping tool that could be implemented in genetic and molecular breeding studies to accelerate new cultivar development and improvement in faba bean.
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http://dx.doi.org/10.1007/s00122-021-03885-0DOI Listing
June 2021

Mixed reality models based on low-dose computed tomography technology in nephron-sparing surgery are better than models based on normal-dose computed tomography.

Quant Imaging Med Surg 2021 Jun;11(6):2658-2668

Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University, Nanjing, China.

Background: Nephron-sparing surgery has been widely applied in the treatment of renal tumors. Previous studies have confirmed the advantages of mixed reality technology in surgery. The study aimed to explore the optimization of mixed reality technology and its application value in nephron-sparing surgery.

Methods: In this prospective study of 150 patients with complex renal tumors (RENAL nephrometry score ≥7) who underwent nephron-sparing surgery, patients were randomly divided into Group A (the normal-dose mixed reality group, n=50), Group B (the low-dose mixed reality group, n=50), and Group C (the traditional computed tomography image group, n=50). Group A and Group C received the normal-dose computed tomography scan protocol: 120 kVp, 400 mA, and 350 mgI/mL, while Group B received the low-dose computed tomography scan protocol: 80 kVp, automatic tube current modulation, and 320 mgI/mL. All computed tomography data were transmitted to a three-dimensional visualization workstation and underwent modeling and mixed reality imaging. Two senior surgeons evaluated mixed reality quality. Objective indexes and perioperative indexes were calculated and compared.

Results: Compared with Group A, the radiation effective dose in Group B was decreased by 39.6%. The subjective scores of mixed reality quality in Group B were significantly higher than those of Group A (Z=-4.186, P<0.001). The inter-observer agreement between the two senior surgeons in mixed reality quality was excellent (K=0.840, P<0.001). The perioperative indexes showed that the mixed reality groups were significantly different from the computed tomography image group (all P<0.017). More cases underwent nephron-sparing surgery in the mixed reality groups than in the computed tomography image group (P<0.0017).

Conclusions: Low-dose computed tomography technology can be effectively applied to mixed reality optimization, reducing the effective dose and improving mixed reality quality. Optimized mixed reality can significantly increase the cases of successful nephron-sparing surgery and improve perioperative indexes.
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http://dx.doi.org/10.21037/qims-20-956DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107318PMC
June 2021

Studies on the electrostatic effects of stretched PVDF films and nanofibers.

Nanoscale Res Lett 2021 May 3;16(1):79. Epub 2021 May 3.

Sino-Danish Center for Education and Research (SDC), Interdisciplinary Nanoscience Center (iNANO), Aarhus University, DK-8000, Aarhus C, Denmark.

The electroactive β-phase in Poly (vinylidene fluoride, PVDF) is the most desirable conformation due to its highest pyro- and piezoelectric properties, which make it feasible to be used as flexible sensors, wearable electronics, and energy harvesters etc. In this study, we successfully developed a method to obtain high-content β-phase PVDF films and nanofiber meshes by mechanical stretching and electric spinning. The phase transition process and pyro- and piezoelectric effects of stretched films and nanofiber meshes were characterized by monitoring the polarized light microscopy (PLM) images, outputting currents and open-circuit voltages respectively, which were proved to be closely related to stretching ratio (λ) and concentrations. This study could expand a new route for the easy fabrication and wide application of PVDF films or fibers in wearable electronics, sensors, and energy harvesting devices.
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http://dx.doi.org/10.1186/s11671-021-03536-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093351PMC
May 2021

Mutations in ALK and TSC1 in a gastrointestinal stromal tumor: a case report.

BMC Surg 2021 Apr 20;21(1):202. Epub 2021 Apr 20.

Department of Gastrointestinal Surgery, Peking University Shenzhen Hospital, Shenzhen, 518036, Guangdong, People's Republic of China.

Background: Gastrointestinal stromal tumors rarely occur in children, but when they do, their biological behavior and histopathological patterns differ from those of adults.

Case Presentation: A 13-year-old boy with a gastrointestinal stromal tumor was characterized by a rare genetic mutation. The patient complained of "fatigue with intermittent abdominal pain for 1 month". According to the preoperative imaging examination, gastroscopy, and gastroscopic biopsy, the patient was diagnosed with a gastric stromal tumor. Postoperative pathology showed that the tumor cells were fusiform and ovoid, and mitotic figures were easily seen. Immunohistochemistry revealed that the tumor was S-100(+), SOX10(-), CD34(+), SMA(partially+), DOG-1(+), CD117(+), KI-67 (positive for 20% + of the subjects and 40% + of the hotspots), and SDHB(-). Genetic tests showed missense mutations in ALK and TSC1. With surgical treatment, the tumor was completely removed. The patient recovered well and was discharged on the ninth day after the operation. He is currently under follow-up.

Conclusions: In this case involving a patient with a gastrointestinal stromal tumor, immunohistochemistry indicated that the tumor was an "SDH-deficient type", and gene detection showed no KIT or PDGFRA mutation but rare ALK and TSC1 mutations, which adds to the knowledge of the types of gene mutations in children with gastrointestinal stromal tumors.
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http://dx.doi.org/10.1186/s12893-021-01208-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8059153PMC
April 2021

High-fidelity diffusion tensor imaging of the cervical spinal cord using point-spread-function encoded EPI.

Neuroimage 2021 08 20;236:118043. Epub 2021 Apr 20.

Center for Biomedical Imaging Research, Department of Biomedical Engineering, Tsinghua University, Beijing, China. Electronic address:

Diffusion tensor imaging (DTI) of the spinal cord is technically challenging due to the size of its structure and susceptibility-induced field inhomogeneity, which impedes clinical applications. This study aimed to achieve high-fidelity spinal cord DTI with reasonable SNR and practical acquisition efficiency. Particularly, a distortion-free multi-shot EPI technique, namely point-spread-function encoded EPI (PSF-EPI), was adopted for diffusion imaging of the cervical spinal cord (CSC). The shot number can be reduced to six for sagittal scans through titled-CAIPI acceleration and partial Fourier undersampling, consequently rendering this technique beneficial in clinics. Fifteen healthy volunteers and seven patients with metallic implants underwent sagittal scans using tilted-CAIPI PSF-EPI at 3T. Unsuppressed fat signals were further removed by retrospective water/fat separation using the intrinsic chemical-shift encoded signals. Compared with multi-shot interleaved EPI method, highly accelerated PSF-EPI method provided evidently improved distortion reduction and higher consistency with anatomical references even with metallic implants. Additionally, axial DTI scans using PSF-EPI were also evaluated quantitatively, and the measured DTI metrics are similar to those obtained from the zonal oblique multi-slice EPI (ZOOM-EPI) method and reported values. The high anatomical consistency, practical scan time and quantitative reliability indicate PSF-EPI's clinical potential for CSC diffusion imaging.
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http://dx.doi.org/10.1016/j.neuroimage.2021.118043DOI Listing
August 2021

AngioJet Thrombectomy Versus Catheter-Directed Thrombolysis for Lower Extremity Deep Vein Thrombosis: A Meta-Analysis of Clinical Trials.

Clin Appl Thromb Hemost 2021 Jan-Dec;27:10760296211005548

Department of Vascular Surgery, 370089Northern Jiangsu People's Hospital, Yangzhou, China.

Early catheter-directed thrombolysis (CDT) for lower extremity deep vein thrombosis (LEDVT) can reduce post-thrombotic morbidity and the AngioJet thrombectomy is a new therapy that can be selected for the treatment of LEDVT. We performed a systematic review and meta-analysis of clinical trials comparing AngioJet versus CDT to assess the efficacy and safety of AngioJet thrombectomy. We systematically searched PubMed and Embase for clinical trials that published before November 1, 2020 and compared AngioJet thrombectomy and CDT in the treatment of LEDVT. We meta-analyzed effective rate of treatment, serious complications, PTS, Villalta score, duration of treatment and drug dose. AngioJet does not result in a significant difference in the effective rate (OR 1.00, CI 0.73-1.36, = 0.98; I = 0%) and complications (OR 1.16 CI 0.84-1.61, = 0.36; I = 39%) compare to CDT. And there was a statistically significant decrease in incidence of PTS (OR 0.58 CI 0.37-0.91, = 0.02; I = 0%) and Villalta score (OR -1.86 CI -3.49 to -0.24, = 0.02; I = 34%) for AngioJet compared to CDT. In addition, there was a statistically significant decrease in duration of the treatment (OR -2.45 CI -2.75 to -2.15, < 0.0001; I = 95%) and drug dose (OR -3.15 CI -3.38 to -2.93, < 0.0001; I = 98%) between AngioJet and CDT. AngioJet results in a low severity of PTS compared to CDT therapy. Moreover, the average duration of treatment and thrombolysis time was shorter in the AngioJet group compared to the CDT group. However, the AngioJet group was not significantly different in effective rate of treatment and serious complications compared to the CDT group.
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http://dx.doi.org/10.1177/10760296211005548DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024451PMC
April 2021

Application of low-dose CT to the creation of 3D-printed kidney and perinephric tissue models for laparoscopic nephrectomy.

Cancer Med 2021 05 2;10(9):3077-3084. Epub 2021 Apr 2.

Department of Radiology, Jinling Hospital, Medical School of Nanjing University, Nanjing, China.

Purpose: The aim of this study was to explore the feasibility of 3D printing of kidney and perinephric fat based on low-dose CT technology.

Patients And Methods: A total of 184 patients with stage T1 complex renal tumors who underwent laparoscopic nephrectomy were prospectively enrolled and divided into three groups: group A (conventional dose kidney and perinephric fat 3D printing group, n = 62), group B (low-dose kidney and perinephric fat 3D printing, n = 64), and group C (conventional dose merely kidney 3D printing group, n = 58). The effective dose (ED), signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) were determined. The 3D printing quality was evaluated using a 4-point scale, and interobserver agreement was assessed using the intraclass correlation coefficient (ICC).

Results: The ED of group B was lower than that of group A, with a decrease of 55.1%. The subjective scores of 3D printing quality in all groups were 3 or 4 points. The interobserver agreement among the three observers in 3D printing quality was good (ICC = 0.84-0.92). The perioperative indexes showed that operation time (OT), warm ischemia time (WIT), estimated blood loss (EBL), and laparoscopic partial nephrectomy (LPN) conversion to laparoscopic radical nephrectomy (LRN) in groups A or B were significantly less than those in group C. LPN was more frequent in group A and group B than in group C (all p < 0.017). There were no significant differences in perioperative indexes between group A and group B (all p > 0.017).

Conclusion: Low-dose CT technology can be effectively applied to 3D printing of kidney and perinephric fat and reduce the patient's radiation dose without compromising 3D printing quality. 3D printing of kidney and perinephric fat can significantly increase the success rate of LPN and decrease OT, WIT, and EBL.
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http://dx.doi.org/10.1002/cam4.3851DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085913PMC
May 2021

The β3 Adrenergic Receptor Agonist CL316243 Ameliorates the Metabolic Abnormalities of High-Fat Diet-Fed Rats by Activating AMPK/PGC-1α Signaling in Skeletal Muscle.

Diabetes Metab Syndr Obes 2021 18;14:1233-1241. Epub 2021 Mar 18.

The Research Center of Basic Integrative Medicine, Basic Medical College, Guangzhou University of Chinese Medicine, University Town, Guangzhou, 510006, People's Republic of China.

Purpose: Skeletal muscle has a major influence on whole-body metabolic homeostasis. In the present study, we aimed to determine the metabolic effects of the β3 adrenergic receptor agonist CL316243 (CL) in the skeletal muscle of high-fat diet-fed rats.

Methods: Sprague-Dawley rats were randomly allocated to three groups, which were fed a control diet (C) or a high-fat diet (HF), and half of the latter were administered 1 mg/kg CL by gavage once weekly (HF+CL), for 12 weeks. At the end of this period, the serum lipid profile and glucose tolerance of the rats were evaluated. In addition, the phosphorylation and protein and mRNA expression of AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor γ coactivator (PGC)-1α, and carnitine palmitoyl transferase (CPT)-1b in skeletal muscle were measured by Western blot analysis and qPCR. The direct effects of CL on the phosphorylation (p-) and expression of AMPK, PGC-1α, and CPT-1b were also evaluated by Western blotting and immunofluorescence in L6 myotubes.

Results: CL administration ameliorated the abnormal lipid profile and glucose tolerance of the high-fat diet-fed rats. In addition, the expression of p-AMPK, PGC-1α, and CPT-1b in the soleus muscle was significantly increased by CL. CL (1 µM) also increased the protein expression of p-AMPK, PGC-1α, and CPT-1b in L6 myotubes. However, the effect of CL on PGC-1α protein expression was blocked by the AMPK antagonist compound C, which suggests that CL increases PGC-1α protein expression via AMPK.

Conclusion: Activation of the β3 adrenergic receptor in skeletal muscle ameliorates the metabolic abnormalities of high-fat diet-fed rats, at least in part via activation of the AMPK/PGC-1α pathway.
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http://dx.doi.org/10.2147/DMSO.S297351DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987271PMC
March 2021

LncRNA NORAD accelerates the progression of non-small cell lung cancer via targeting miRNA-455/CDK14 axis.

Minerva Med 2021 Mar 25. Epub 2021 Mar 25.

College of Clinical Medicine, Xi'an Medical University, Xi'an, China.

Background: To explore the potential involvement of long non-coding RNA (lncRNA) NORAD in regulating the progression of Non-small cell lung cancer (NSCLC), and its possible mechanism.

Methods: Relative level of NORAD in NSCLC tissues and cell lines was determined. Its level in NSCLC patients with different tumor staging (T1-T2, T3-T4) and either with lymphatic metastasis or not was examined as well. Kaplan-Meier curves were depicted for assessing the prognostic value of NORAD in NSCLC. Regulatory effects of NORAD on the proliferative ability of NCI-H1650 and HCC827 cells were evaluated. Dual-luciferase reporter gene assay was conducted to identify the binding between NORAD and miRNA-455, as well as between miRNA-455 and CDK14. At last, the role of NORAD/miRNA-455/CDK14 regulatory loop in influencing the progression of NSCLC was determined.

Results: NORAD was upregulated in NSCLC tissues and cells. Its level was higher in NSCLC patients with advanced stage or accompanied with lymphatic metastasis. Worse prognosis was observed in NSCLC patients presenting high level of NORAD. Silence of NORAD attenuated the proliferative ability of NCI-H1650 and HCC827 cells. MiRNA-455 was the downstream target binding to NORAD. Its level was negatively regulated by NORAD. Knockdown of miRNA-455 could reverse the role of NORAD in regulating the proliferative ability of NSCLC. Moreover, CDK14 was the target gene of miRNA-455. CDK14 level was negatively regulated by miRNA-455.

Conclusions: LncRNA NORAD is upregulated in NSCLC, which enhances the proliferative ability of tumor cells by targeting miRNA-455/CDK14 axis and thereby accelerates the progression of NSCLC.
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http://dx.doi.org/10.23736/S0026-4806.21.07194-9DOI Listing
March 2021

Hydroxyapatite Nanoparticles Facilitate Osteoblast Differentiation and Bone Formation Within Sagittal Suture During Expansion in Rats.

Drug Des Devel Ther 2021 1;15:905-917. Epub 2021 Mar 1.

Department of Plastic Surgery, Peking University Third Hospital, Beijing, 100191, People's Republic of China.

Background: The potential of relapse of craniofacial disharmony after trans-sutural distraction osteogenesis is high due to the failure to produce a stable bone bridge in the suture gap. The aim of this study is to evaluate whether hydroxyapatite nanoparticles (nHAP) have the effect of promoting osteoblast differentiation of suture-derived stem cells (SuSCs) and bone formation in sagittal suture during expansion.

Methods: SuSCs were isolated from sagittal sutures and exposed to various concentrations of nHAP (0, 25, 50, and 100 μg mL) to determine the optimal concentration of nHAP in osteoblast differentiation via performing Western Blotting and RT-qPCR. Twenty 4-week-old male Sprague-Dawley rats were randomly assigned into 4 groups: SHAM (sham-surgery), distraction, ACS (absorbable collagen sponge) and ACS+nHAP groups. In the ACS and ACS+nHAP groups, saline solution and nHAP suspended in a saline solution were delivered by ACS placed across the sagittal suture, respectively. In the latter three groups, the suture was expanded for 14 days by 50 g of constant force via a W shape expansion device. Suture gap area, bone volume fraction (BV/TV) and bone mineral density (BMD) of sagittal sutures were assessed via micro-CT, while the mechanical properties of sagittal sutures were evaluated via nanoindentation test. The efficacy of nHAP on bone formation in sagittal suture was also evaluated via BMP-2 immunohistochemistry staining.

Results: The expression of osteoblast related genes and proteins induced by 25μg mL nHAP were significantly higher than the other groups in vitro (p<0.05). Furthermore, treating with 25μg mL nHAP in vivo, the suture gap area was significantly reduced when compared with the distraction group. Correspondingly, the BV/TV, BMD, hardness and modulus of sagittal sutures were significantly increased in the ACS+nHAP group (p<0.05).

Conclusion: The 25μg mL dose of nHAP delivered by ACS can facilitate bone formation into the sagittal suture during expansion via inducing osteoblast differentiation of SuSCs.
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http://dx.doi.org/10.2147/DDDT.S299641DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7936535PMC
March 2021

The Feasibility of Assessing the Cortical Bone Trajectory Screw Placement Accuracy Using a Traditional Pedicle Screw Insertion Evaluation System.

Clin Spine Surg 2021 Mar;34(2):E112-E120

Department of Orthopedic Surgery, Beijing Chaoyang Hospital, Capital Medical University of China, Beijing, China.

Study Design: This was a retrospective observational study.

Objective: We aimed to characterize the feasibility of assessing the accuracy of cortical bone trajectory (CBT) screw placement in midline lumbar interbody fusion using a traditional pedicle screw insertion accuracy evaluation system based on computed tomography (CT).

Summary Of Background Data: Since Santoni and colleagues proposed CBT as an alternative approach for the treatment of lumbar degenerative disease, CBT has been biomechanically and clinically investigated in detail. The reported misplacement rate was 0%-12.5%. Therefore, these cortical screws may result in severe complications, such as nerve root, vascular, and spinal cord injuries. However, to the best of our knowledge, the accuracy of the current assessment system of cortical bone screw placement has not been described clearly.

Materials And Methods: Overall, 342 cortical screws of 69 consecutive patients with lumbar degenerative disease who underwent midline lumbar interbody fusion surgery in one surgeon's initial phase were examined retrospectively. A comprehensive and detailed pedicle screw accuracy classification and grading system was introduced in our study, including 5 types of misplacement: (1) medial and (2) lateral cortical bone perforation (MCP and LCP) of the corresponding pedicle, (3) anterior cortical bone perforation of the vertebral body, (4) endplate perforation, and (5) foraminal perforation (FP). The degree of interobserver and intraobserver agreement with regard to the screw positions based on CT were used as indicators of the reliability of the modified classification system. All patients were retrospectively assessed for screw placement-related complications throughout the entire treatment course to evaluate the relationship between the procedure adequacy and neurological symptoms.

Results: The interobserver and intraobserver agreements were substantial-to-almost perfect (κ=0.78 and 0.88, respectively) in distinguishing the acceptable-placed pedicle screws from those with partial or complete cortical perforation. In the MCP and LCP-the most common types of misplacement-the interobserver agreement was substantial (κ=0.70 and 0.76, respectively), and the intraobserver agreement was almost perfect (κ=0.85 and 0.89, respectively). In total, there are 7 (2.05%) MCP and 65 (19.01%) LCP screws. The screw placement-related complication rate is significantly higher in the MCP and FP groups than that in the LCP group.

Conclusions: Our study demonstrated that using a pedicle screw classification and grading system based on CT to assess the accuracy of CBT screw placement is feasible and practical. MCP and FP screws are more likely to cause neurological deficits with statistical significance, especially grade 2 MCP. We recommend inexperienced surgeons choose a lateral trajectory rather than a medial one if they cannot ensure accurate screw insertion.

Level Of Evidence: Level III.
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http://dx.doi.org/10.1097/BSD.0000000000001059DOI Listing
March 2021

Metal composite oxides BiMoO/IL membrane as matrix for constructing ultrasensitive electrochemical immunosensor.

Anal Bioanal Chem 2021 Feb 7;413(4):1173-1183. Epub 2021 Jan 7.

School of Environmental and Municipal Engineering, Xi'an University of Architecture and Technology, Xi'an, 710055, Shaanxi, China.

In the process of diagnosis and disease monitoring, it is important to quickly and easily detect protein biomarkers. The strategy reported here is an attempt to prepare BiMoO nanomaterial with new three-dimensional holes morphology surrounded by rod and sheet to construct a simple and sensitive sensing platform, where BiMoO/ionic liquid (IL) composite was modified on the carbon paste electrode (CPE). In order to monitor the assembly process of human IgG immunosensors, a plurality of electrochemical tests such as cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) was executed. The obtained BSA/anti-IgG/GA/BiMoO6/IL-CPE displayed prominent conductivity and high sensitivity in detecting human immunoglobulin G (human IgG). Under the optimal experimental conditions, the results by differential pulse voltammetry (DPV) showed that the constructed label-free IgG immunosensor can detect IgG in the range of 0.01 to 1000 ng mL, and limit of detection (LOD) was 4 pg mL. The immunosensor displayed good performances including selectivity, reproducibility, and stability. Based on preliminary experiments, BiMoO and its composite materials are very promising for the construction of a variety biosensors for the analysis of other biological substances. Graphical abstract.
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http://dx.doi.org/10.1007/s00216-020-03080-yDOI Listing
February 2021

F-FDG PET/CT imaging in a patient with solitary primary sacral lymphoma.

Hell J Nucl Med 2020 Sep-Dec;23(3):356-357. Epub 2020 Dec 14.

Department of Nuclear Medicine, West China Hospital; Sichuan University, No.37, Guoxue Alley, Chengdu, Sichuan (610041), People's Republic of China.

Solitary primary bone lymphoma of the sacrum is rare. We report a case of a 77-year-old male patient who presented with unexplained numbness and pain in the right lower extremity for over 2 months. Tumor markers and other laboratory were unremarkable. Fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (F-FDG PET/CT) revealed a solitary osteolytic bone lesion of the sacrum with intense F-FDG uptake (SUVmax=10.7). The subsequent biopsy confirmed the diagnosis of diffuse large B-cell lymphoma. After one cycle of R-CHOP, the neurological symptoms of the patient improved significantly.
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http://dx.doi.org/10.1967/s002449912215DOI Listing
December 2020

Depletion of circ-BIRC6, a circular RNA, suppresses non-small cell lung cancer progression by targeting miR-4491.

Biosci Trends 2021 Jan 10;14(6):399-407. Epub 2020 Nov 10.

Institute of Respiratory Disease, China Three Gorges University, Yichang Central People's Hospital, Yichang, Hubei, China.

Circular RNAs (circRNAs) are non-coding RNAs molecules consisting of a covalently closed continuous loop which have no 5'-3' polarity and contain no polyA tail. Accumulating evidence demonstrates that circRNAs are involved in the initiation and progression of human malignancies. In this study, we explored the expression profile and regulatory role of circ-baculoviral IAP repeat-containing 6 (circ-BIRC6), a circular RNA, in malignant behaviors in non-small cell lung cancer (NSCLC). Expression levels of circ-BIRC6 and miR-4491 were examined in NSCLC patient samples and cell lines using quantitative real time PCR (qRT-PCR). In vitro roles of circ-BIRC6 knockdown on cell viability, colony formation, and apoptosis were assessed using the CCK-8, colony formation assay, and flow cytometry, respectively. The interactions between circ-BIRC6 and miR-449 were assessed using luciferase reporter and qRT-PCR assays. The in vivo role of circ-BIRC6 knockdown on tumor growth and apoptosis was evaluated in a xenograft mouse model of NSCLC. We found that expression levels of circ-BIRC6 in NSCLC patient samples and cell lines were elevated. Small interfering RNA (siRNA)-mediated circ-BIRC6 knockdown suppressed cell proliferation, colony formation, migration and invasion, and promoted apoptosis in NCI-H460 and A549 cells. In addition, miR-4491 was identified as a tumor-suppressor miRNA in NSCLC and circ-BIRC6 functions as a molecular sponge for miR-4491. Furthermore, circ-BIRC6 knockdown suppressed Wnt2B/β-catenin pathway. In vivo assay showed that depletion of circ-BIRC6 suppressed tumor growth, enhanced apoptosis, and decreased miR-4491 levels in a mouse xenograft model. These findings demonstrate that circ-BIRC6 functions as a critical regulator of proliferation and apoptosis via binding to and negatively regulating miR-4491, suggesting that circ-BIRC6 might be a potential target for treatment of NSCLC.
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http://dx.doi.org/10.5582/bst.2020.03310DOI Listing
January 2021

-Substituted Thiazole Orange for Selective Fluorescence Detection to G-Quadruplex DNA and Molecular Docking Simulation.

ACS Omega 2020 Oct 2;5(40):26056-26062. Epub 2020 Oct 2.

Key Laboratory of Synthetic and Natural Functional Molecule of the Ministry of Education, National Demonstration Center for Experimental Chemistry Education, College of Chemistry and Materials Science, Northwest University, Xi'an 710127, P. R. China.

The cyanine dye thiazole orange (TO, including 2TO and 4TO) is widely used as a light-up fluorescent probe upon binding to almost all forms of DNA, but it exhibits poor selectivity for recognizing G-quadruplex DNA (G-DNA), which has significant biological functions in biological processes and therapeutic applications. Here, introducing benzyl substituent to the position of the methine chain of 2TO is expected to selectively recognize G-DNA. The spectroscopic titrations reveal that modified 2TO (-Bn-2TO) has almost no background fluorescence in solution and shows a preference to bind with G-DNA over ssDNA, dsDNA, and ct-DNA. Specifically, -Bn-2TO displays a strong fluorescent signal upon interaction with G-DNA and a very weak fluorescent signal upon interaction with ssDNA, dsDNA, and ct-DNA, displaying considerable selectivity for G-DNA. However, parent 2TO all gives a fluorescent signal in G-DNA, dsDNA, and ct-DNA. The fluorescence intensity of increases nearly 80-162 times when bound with different G-DNA. The binding constants of and 2TO to G-DNA htg22 are 3.16 and 1.52 μM, respectively. Molecular docking study of and 2TO with different DNA reveals that introducing benzyl substituent to the meso position methine chain of 2TO alters the planarity of the chromophore, thus enhancing the interactions with G-DNA and weakening the interactions with duplex DNA and therefore realizing selective detection to G-DNA.
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http://dx.doi.org/10.1021/acsomega.0c03556DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7557940PMC
October 2020

Histone H4 aggravates inflammatory injury through TLR4 in chlorine gas-induced acute respiratory distress syndrome.

J Occup Med Toxicol 2020 8;15:31. Epub 2020 Oct 8.

Research Center of Occupational Medicine, Peking University Third Hospital, No.49 North Garden Road, Haidian District, Beijing, 100191 China.

Background: Chlorine gas (Cl) exposure remains a public health concern in household, occupational, and transportation accidents around the world. The death rate associated with acute respiratory distress syndrome (ARDS) caused by high concentrations of Cl is very high, mainly because the pathogenesis of ARDS remains unclear. Histone H4 has been identified as an important endogenous pro-inflammatory molecule. The present study aimed to examine the pathogenic role of histone H4 in Cl-induced ARDS.

Methods: ARDS was induced by Cl exposure in male C57BL/6 mice. Circulating histone H4, blood gas, pulmonary edema, endothelial activation, and neutrophil infiltration were measured during acute lung injury (ALI). Histone H4 or anti-H4 antibody was administered through the tail vein 1 h prior to Cl exposure to study the pathogenic role of histone H4. Toll-like receptor 2 knock-out (-KO) and -KO mice were used in conjunction with blocking antibody against TLR1, TLR2, TLR4, or TLR6 to explore the mechanism involved in histone H4-mediated injury.

Results: Cl exposure induced a concentration-dependent ALI. The levels of circulating histone H4 were positively correlated with Cl concentrations. Pretreatment with intravenous histone H4 further aggravated lethality rate, blood gas, endothelial activation, and neutrophil infiltration, while anti-H4 antibody showed protective effects. deficiency improved lethality rate, blood gas, and pulmonary edema, and prevented endothelial and neutrophil activation caused by Cl exposure. More importantly, gene deletion greatly diminished the effect of histone H4 or anti-H4 antibody observed in wild-type (WT) mice. The impact of on inflammatory injury was not significant. The role of TLRs was also validated by endothelial activation mediated by histone H4 in vitro.

Conclusions: Circulating histone H4 played a pro-inflammatory role in ARDS caused by Cl. TLR4 was closely involved in histone H4-mediated inflammatory injury. Therefore, intervention targeting histone H4 is potentially protective.
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http://dx.doi.org/10.1186/s12995-020-00282-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7545935PMC
October 2020

CNNPruner: Pruning Convolutional Neural Networks with Visual Analytics.

IEEE Trans Vis Comput Graph 2021 Feb 28;27(2):1364-1373. Epub 2021 Jan 28.

Convolutional neural networks (CNNs) have demonstrated extraordinarily good performance in many computer vision tasks. The increasing size of CNN models, however, prevents them from being widely deployed to devices with limited computational resources, e.g., mobile/embedded devices. The emerging topic of model pruning strives to address this problem by removing less important neurons and fine-tuning the pruned networks to minimize the accuracy loss. Nevertheless, existing automated pruning solutions often rely on a numerical threshold of the pruning criteria, lacking the flexibility to optimally balance the trade-off between efficiency and accuracy. Moreover, the complicated interplay between the stages of neuron pruning and model fine-tuning makes this process opaque, and therefore becomes difficult to optimize. In this paper, we address these challenges through a visual analytics approach, named CNNPruner. It considers the importance of convolutional filters through both instability and sensitivity, and allows users to interactively create pruning plans according to a desired goal on model size or accuracy. Also, CNNPruner integrates state-of-the-art filter visualization techniques to help users understand the roles that different filters played and refine their pruning plans. Through comprehensive case studies on CNNs with real-world sizes, we validate the effectiveness of CNNPruner.
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http://dx.doi.org/10.1109/TVCG.2020.3030461DOI Listing
February 2021

Z-scheme [email protected]/CdZnS nanocomposites with efficient photocatalytic performance via one-step hydrothermal route.

Nanotechnology 2021 Jan;32(1):015706

School of Materials Science and Engineering, Zhengzhou University, Zhengzhou 450001 People's Republic of China.

Photocatalytic degradation of pollutants has been proved to be an effective strategy for wastewater treatment. Herein, TiO nanoparticles were synthesized on a TiC matrix by in situ growth, forming Z-scheme [email protected]/CdZnS (TO/CZS) multilevel structured nanocomposites via one-step hydrothermal route. The effects of hydrothermal temperature and CdZnS content on microstructure and properties of composites were assessed. TO/CZS nanocomposites were probed into phase composition, morphological and optical properties with x-ray diffractometer, infrared radiation, scanning electron microscope and UV-vis reflective spectra. Following the hydrothermal reaction at 160 °C for 12 h, TiO nanoparticles of 30 nm in diameter were generated in situ on TiC lamina and CdZnS particles were evenly distributed on the TiC matrix. The photocatalytic activity of TO/CZS composites were evaluated, which found that degradation rate constant (k = 0.028 min) of TO/CZS-40 on Rhodamine B was 5.19 times that of pure TiO and 4.48 times that of CdZnS. Through anchoring TiC as an electron transition mediator and combination with TiO and CdZnS, the new Z-scheme between TiO oxidized by TiC and CdZnS establishes a multilevel structure of separating electron-hole pairs. This work demonstrates a valid way to control electrons and hole transfer directions efficiently through designing multilevel semiconductor structural designs.
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http://dx.doi.org/10.1088/1361-6528/abb72fDOI Listing
January 2021

Charge and Size Dual Switchable Nanocage for Novel Triple-Interlocked Combination Therapy Pattern.

Adv Sci (Weinh) 2020 Sep 4;7(18):2000906. Epub 2020 Aug 4.

Department of Pharmaceutics Key Laboratory of Chemical Biology (Ministry of Education) School of Pharmaceutical Sciences Shandong University 44 Wenhuaxi Road Jinan Shandong 250012 China.

Combination therapy is a current hot topic in cancer treatment. Multiple synergistic effects elicited by combined drugs are essential in improving antitumor activity. Herein, a pH-triggered charge and size dual switchable nanocage co-loaded with abemaciclib and IMD-0354 (PA/PI-ND) is reported, exhibiting a novel triple-interlocked combination of chemotherapy, immunotherapy, and chemoimmunotherapy. The charge reversal polymer NGR-poly(ethylene glycol)-poly(l-lysine)-dimethylmaleic anhydride (NGR-PEG-PLL-DMA, ND) in PA/PI-ND promotes the pH-triggered charge reversal from negative to positive and size reduction from about 180 to 10 nm in an acidic tumor microenvironment, which greatly enhances cellular uptake and tumor tissue deep penetration. With the PA/PI-ND triple-interlocked combination therapy, the chemotherapeutic effect is enhanced by the action of abemaciclib to induce cell cycle arrest in the G1 phase, together with the reduction in cyclin D levels caused by IMD-0354. The dual anti-tumor promoting immunotherapy is achieved by abemaciclib selectively inhibiting the proliferation of regulatory T cells (Tregs) and by IMD-0354 promoting tumor-associated macrophage (TAM) repolarization from an M2 to M1 phenotype. Furthermore, PA/PI-ND has improved anti-tumor efficiency resulting from the third synergistic effect provided by chemoimmunotherapy. Taken together, PA/PI-ND is a promising strategy to guide the design of future drug delivery carriers and cancer combination therapy.
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http://dx.doi.org/10.1002/advs.202000906DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7509747PMC
September 2020

Synaptic Plasticity After Focal Cerebral Ischemia Was Attenuated by Gap26 but Enhanced by GAP-134.

Front Neurol 2020 26;11:888. Epub 2020 Aug 26.

Department of Physiology, School of Basic Medical Science, Guangzhou University of Chinese Medicine, Guangzhou, China.

Synaptic plasticity is critical for neurorehabilitation after focal cerebral ischemia. Connexin 43 (Cx43), the main component of the gap junction, has been shown to be pivotal for synaptic plasticity. The objective of this study was to investigate the role of the Cx43 inhibitor (Gap26) and gap junction modifier (GAP-134) in neurorehabilitation and to study their contribution to synaptic plasticity after focal ischemia. Time course expression of both total and phosphorylated Cx43 (p-Cx43) were detected by western blotting at 3, 7, and 14 d after focal ischemia. Gap26 and GAP-134 were administered starting from 3 d post focal ischemia. Neurological performances were evaluated by balance beam walking test and Y-maze test at 1, 3, and 7 d. Golgi staining and transmission electron microscope (TEM) detection were conducted at 7 d for observing dendritic spine numbers and synaptic ultrastructure, respectively. Immunofluorescent staining was used at 7 d for detection of synaptic plasticity markers, including synaptophysin (SYN) and growth-associated protein-43 (GAP-43). Expression levels of both total Cx43 and p-Cx43 were increased after focal cerebral ischemia, peaking at 7 d. Compared with the MCAO group, Gap26 worsened the neurological behavior and decreased the dendritic spine number while GAP-134 improved the neurobehavior and increased the number of dendritic spines. Moreover, Gap26 further destroyed the synaptic structure, concomitant with downregulated SYN and GAP-43, whereas GAP-134 alleviated synaptic destruction and upregulated SYN and GAP-43. These findings suggested that Cx43 or the gap junction was involved in synaptic plasticity, thereby promoting neural recovery after ischemic stroke. Treatments enhancing gap junctions may be potential promising therapeutic measures for neurorehabilitation after ischemic stroke.
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http://dx.doi.org/10.3389/fneur.2020.00888DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7479336PMC
August 2020

[Impact of gene dosage on recombinant transglutaminase production of Pichia pastoris].

Sheng Wu Gong Cheng Xue Bao 2020 Aug;36(8):1679-1688

Department of Pharmacy, Anhui Medical College, Hefei 230061, Anhui, China.

Based on the rDNA sequence of Pichia pastoris, a multi-copy gene expression vector of transglutaminase (pPICZα-rDNA-mtg) was constructed and transformed to the host strain (pGAP9-pro/GS115) expressing pro peptide, to obtain the co-expression strain pro/rDNA-mtg (GS115). Real-time fluorescence quantitative PCR (qPCR) was used to analyze transglutaminase gene copy number in the 4 positive strains. We further studied the effect of gene copy on the enzyme production of recombinant Pichia pastoris as well as high-density fermentation of higher expression strain in a 3-L fermenter. The mtg copy numbers of the 4 positive strains were 2.21, 3.36, 5.72 and 7.62 (mtg-2c, mtg-3c, mtg-6c and mtg-8c), respectively, and the enzyme production capacity and protein expression level were mtg-3c>mtg-2c>mtg-6c>mtg-8c. Mtg-3c and mtg-6c of high-density fermentation had the highest enzymatic activity and enzymatic activity per unit wet weight in the supernatant of 3.12 U/mL, 52.1 U/g (wet weight) and 2.07 U/mL and 36.5 U/g (wet weight), respectively. In terms of enzyme activity per unit wet weight, mtg-3c is 1.4 times higher than that of mtg-6c. The activity of purified enzyme (mtg-3c) was up to 7.21 U/mL and the protein concentration was 437.2 μg/mL. By analyzing the effect of mtg copy number on the enzyme production of recombinant strains, mtg-3c is suitable for the co-expression of two genes (pro and mtg) in pro/rDNA-mtg, and its enzyme activity is related to higher protein secretion of the strain.
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http://dx.doi.org/10.13345/j.cjb.190531DOI Listing
August 2020

Multi-shot echo-planar diffusion tensor imaging in cervical spondylotic myelopathy.

Bone Joint J 2020 Sep;102-B(9):1210-1218

Department of Orthopedic Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.

Aims: The aim of this study was to use diffusion tensor imaging (DTI) to investigate changes in diffusion metrics in patients with cervical spondylotic myelopathy (CSM) up to five years after decompressive surgery. We correlated these changes with clinical outcomes as scored by the Modified Japanese Orthopedic Association (mJOA) method, Neck Disability Index (NDI), and Visual Analogue Scale (VAS).

Methods: We used multi-shot, high-resolution, diffusion tensor imaging (ms-DTI) in patients with cervical spondylotic myelopathy (CSM) to investigate the change in diffusion metrics and clinical outcomes up to five years after anterior cervical interbody discectomy and fusion (ACDF). High signal intensity was identified on T2-weighted imaging, along with DTI metrics such as fractional anisotropy (FA). MJOA, NDI, and VAS scores were also collected and compared at each follow-up point. Spearman correlations identified correspondence between FA and clinical outcome scores.

Results: Significant differences in mJOA scores and FA values were found between preoperative and postoperative timepoints up to two years after surgery. FA at the level of maximum cord compression (MCL) preoperatively was significantly correlated with the preoperative mJOA score. FA postoperatively was also significantly correlated with the postoperative mJOA score. There was no statistical relationship between NDI and mJOA or VAS.

Conclusion: ms-DTI can detect microstructural changes in affected cord segments and reflect functional improvement. Both FA values and mJOA scores showed maximum recovery two years after surgery. The DTI metrics are significantly associated with pre- and postoperative mJOA scores. DTI metrics are a more sensitive, timely, and quantifiable surrogate for evaluating patients with CSM and a potential quantifiable biomarker for spinal cord dysfunction. Cite this article: 2020;102-B(9):1210-1218.
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http://dx.doi.org/10.1302/0301-620X.102B9.BJJ-2020-0468.R1DOI Listing
September 2020

CT Findings in a Novel Coronavirus Disease (COVID-19) Pneumonia at Initial Presentation.

Biomed Res Int 2020 15;2020:5436025. Epub 2020 Aug 15.

The First College of Clinical Medical Science, China Three Gorges University, Yichang, Hubei, China 443000.

Background: COVID-19 first broke out in China and spread rapidly over the world.

Objectives: To describe the CT features of COVID-19 pneumonia and to share our experience at initial diagnoses. . Data from 53 patients (31 men, 22 women; mean age, 53 years; age range, 16-83 years) with confirmed COVID-19 pneumonia were collected. Their complete clinical data was reviewed, and their CT features were recorded and analyzed.

Results: The average time between onset of illness and the initial CT scan was six days (range, 1-42 days). A total of 399 segments were involved and distributed bilaterally (left lung: 186 segments [46.6%], right lung: 213 segments [53.4%]) and peripherally (38 [71.7%] patients). Multiple lobes (45 [84.9%]) and bilateral lower lobes (left lower lobe: 104 [26.1%], right lower lobe: 107 [26.8%], and total: 211 [52.9%]) were the most commonly involved. Ground-glass opacity with consolidation (24 [45.3%]) and pure ground-glass opacity (28 [52.8%]) were the main findings. The other findings were crazy-paving (14 [26.4%]), bronchiectasis (12 [22.6%]), atelectasis (7 [13.2%]), parenchymal bands (6 [11.3%]), air bronchogram (6 [11.3%]), interlobular thickening (5 [9.4%]), reticular pattern (1 [1.9%]), and pleural effusion (1 [1.9%]).

Conclusions: Most COVID-19 pneumonia patients had abnormalities on chest CT images at initial presentation. Imaging features combined with patient's exposure history and onset symptoms could facilitate the identification of the suspected patient for further examinations.
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http://dx.doi.org/10.1155/2020/5436025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7436346PMC
September 2020

ACE2 expression in adipose tissue is associated with COVID-19 cardio-metabolic risk factors and cell type composition.

medRxiv 2020 Aug 14. Epub 2020 Aug 14.

COVID-19 severity has varied widely, with demographic and cardio-metabolic factors increasing risk of severe reactions to SARS-CoV-2 infection, but the underlying mechanisms for this remain uncertain. We investigated phenotypic and genetic factors associated with subcutaneous adipose tissue expression of Angiotensin I Converting Enzyme 2 ( ), which has been shown to act as a receptor for SARS-CoV-2 cellular entry. In a meta-analysis of three independent studies including up to 1,471 participants, lower adipose tissue expression was associated with adverse cardio-metabolic health indices including type 2 diabetes (T2D) and obesity status, higher serum fasting insulin and BMI, and lower serum HDL levels (P<5.32x10 ). expression levels were also associated with estimated proportions of cell types in adipose tissue; lower expression was associated with a lower proportion of microvascular endothelial cells (P=4.25x10 ) and higher macrophage proportion (P=2.74x10 ), suggesting a link to inflammation. Despite an estimated heritability of 32%, we did not identify any proximal or distal genetic variants (eQTLs) associated with adipose tissue expression. Our results demonstrate that at-risk individuals have lower background levels in this highly relevant tissue. Further studies will be required to establish how this may contribute to increased COVID-19 severity.
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http://dx.doi.org/10.1101/2020.08.11.20171108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7430606PMC
August 2020
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