Publications by authors named "Tong Gao"

104 Publications

Forming Cellulose Nanofibril-Reinforced Hyaluronic Acid Hydrogel for Cartilage Regeneration.

Biomacromolecules 2021 Nov 1. Epub 2021 Nov 1.

CAS Key Laboratory for Nano-Bio Interface, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Science, Suzhou 215000, China.

Hyaluronic acid (HA) based hydrogels are one of most functional natural biomaterials in the field of cartilage tissue engineering (CTE). Even with the promising advantages of HA hydrogels, the complicated mechanical properties of the native cartilage have not been realized, and fabricating HA hydrogels with excellent mechanical properties to make them practical in CTE still remains a current challenge. Here, a strategy that integrates hydrogels and nanomaterials is shown to form a HA hydrogel with sufficient mechanical loading for cartilage tissue production and recombination. Cellulose nanofibrils (CNFs) are promising nanomaterial candidates as they possess high mechanical strength and excellent biocompatibility. In this study, we developed methacrylate-functionalized CNFs that are able to photo-crosslink with methacrylated HA to fabricate HA/CNF nanocomposite hydrogels. The present composite hydrogels with a compressive modulus of 0.46 ± 0.05 MPa showed adequate compressive strength (0.198 ± 0.009 MPa) and restorability, which can be expected to employ as a stress-bearing tissue such as articular cartilage. Besides, this nanocomposite hydrogel could provide a good microenvironment for bone marrow mesenchymal stem cell proliferation, as well as chondrogenic differentiation, and exhibit prominent repair effect in the full-thickness cartilage defect model of SD rats. These results suggest that the HA/CNF nanocomposite hydrogel creates a new possibility for fabricating a scaffold in CTE.
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http://dx.doi.org/10.1021/acs.biomac.1c01063DOI Listing
November 2021

LncRNA TUG1 aggravates cardiomyocyte apoptosis and myocardial ischemia/reperfusion injury.

Histol Histopathol 2021 Oct 20:18381. Epub 2021 Oct 20.

Cardiology Department of Integrated Traditional Chinese and Western Medicine, China-Japan Friendship Hospital, Beijing, China.

Cardiomyocyte apoptosis is a fundamental pathogenic factor leading to myocardial ischemia/reperfusion (MI/R) injury. The long non-coding RNA (IncRNA) TUG1 regulates apoptosis in various cell types. We report here that TUG1 expression is induced in mouse heart following MI/R injury as well as in cardiomyocytes subjected to simulated ischemia/reperfusion (SI/R) in vitro. Clinically, TUG1 expression is also elevated in plasma from patients with acute myocardial infarction (AMI), which implies its potential application as a disease biomarker. Functionally, TUG1 overexpression promotes, and its knockdown reduces SI/R-induced lactate dehydrogenase (LDH) release and caspase-3 activity in cardiomyocytes in vitro, illustrating that TUG1 exacerbates SI/R-induced apoptosis. Furthermore, in vivo, TUG1 aggravates MI/R injury in a mouse model, and subsequent observations show concurrent increased apoptosis of cardiomyocytes. Hence, this study unveils a clinical relevance and functional role of TUG1 in MI/R injury, and also implicates that targeting TUG1 may have therapeutic effects in treating MI/R injury.
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http://dx.doi.org/10.14670/HH-18-381DOI Listing
October 2021

Evaluation of Bivalirudin-Associated Major Adverse Cardiac and Hemorrhagic Events in Acute Coronary Syndrome Patients on Chronic Dialysis Following Percutaneous Coronary Intervention.

J Invasive Cardiol 2021 Nov 15;33(11):E877-E883. Epub 2021 Oct 15.

China-Japan Friendship Hospital, Yinghua Dongjie 2, Chaoyang District, Beijing 100029, China.

Background And Aim: Patients with chronic dialysis dependency undergoing percutaneous coronary intervention (PCI) are at a greater risk of hemorrhagic and ischemic events. Due to their exclusion from randomized clinical trials, the optimal antithrombotic regimen for this population remains unknown. Bivalirudin has been associated with fewer hemorrhagic complications than unfractionated heparin (UFH) in patients undergoing PCI. We evaluated major adverse cardiac event (MACE) and hemorrhagic event rates for an antithrombotic regimen using bivalirudin or UFH during PCI in acute coronary syndrome (ACS) patients with chronic dialysis dependency.

Methods: A retrospective study was performed, including 211 patients on dialysis undergoing PCI due to ACS from January 2014 to April 2019 at the China-Japan Friendship Hospital. Patients were divided into 2 groups based on anticoagulation regimen: the bivalirudin group (86 cases) or the UFH group (125 cases) during and after PCI. Statistical analyses were used to compare MACE and hemorrhagic events between groups at 30 days after PCI.

Results: No patients experienced stent thrombosis within 30 days after PCI regardless of anticoagulant. There was no difference in the incidence of MACE in the bivalirudin group compared with the UFH group (6.98% vs 8.80%, respectively; P>.05). The rate of hemorrhagic events in the bivalirudin group was significantly lower than in the UHP group (5.81% vs 18.4%, respectively; P<.05), particularly for rates of mild bleeding (4.65% vs 15.2%, respectively; P<.05). There were no significant differences in rates of severe bleeding between the bivalirudin and UFH groups (1.16% vs 4.00%, respectively; P>.05), although fewer severe hemorrhagic events occurred in the bivalirudin group.

Conclusion: Bivalirudin was associated with fewer bleeding events following PCI in individuals with end-stage renal disease on dialysis.
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November 2021

Comparison of long-term clinical outcomes of percutaneous coronary intervention for chronic total occlusion between patients with and without diabetes mellitus: a single-center retrospective observational study.

Ann Palliat Med 2021 Sep;10(9):9993-10004

Cardiology Department of Integrated Traditional Chinese and Western Medicine, China-Japan Friendship Hospital, Beijing, China.

Background: The prognosis of percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) between patients with diabetes mellitus (DM) and those without DM is unknown. This study aimed to investigate whether DM has adverse effects on CTO PCI patients.

Methods: This single-center retrospective study included consecutive patients who underwent PCI for CTO at the China-Japan Friendship Hospital (Beijing, China) between January 2016 and April 2019. The clinical outcomes during follow-up were compared between patients with DM and those without DM.

Results: The analysis included 187 patients (152 males) aged 62.6±11.5 years. A total of 99 participants (52.9%) had DM, which involved a higher body mass index (BMI) and triglyceride level than those without DM (P<0.05). Participants with DM and those without DM had similar PCI success rates (89.9% vs. 95.4%, respectively) and complete revascularization rates (82.8% vs. 84.1%, respectively). There were no significant differences between groups in the rates of all-cause mortality, cardiac death, major adverse cardiovascular events (MACEs), readmission, recurrence of angina, target vessel revascularization (TVR), or myocardial infarction (MI) during a median follow-up of 20.5 months. Multivariable logistic regression revealed that CTO in a coronary branch vessel was associated with higher odds of all-cause death (odds ratio (OR): 53.56; 95% confidence interval (CI): 2.48 to 1,155.41; P<0.05) and failure of PCI for CTO (OR: 5.40; 95% CI: 1.263 to 23.098; P<0.05). Additionally, PCI for single CTO was associated with lower odds of MACEs (OR: 0.300; 95% CI: 0.118 to 0.765; P<0.05).

Conclusions: The performance of PCI for CTO has a high success rate in both patients with DM and those without DM, and clinical outcomes are comparable between groups.
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http://dx.doi.org/10.21037/apm-21-2354DOI Listing
September 2021

Allicin protects against myocardial I/R by accelerating angiogenesis via the miR-19a-3p/PI3K/AKT axis.

Aging (Albany NY) 2021 10 4;13(19):22843-22855. Epub 2021 Oct 4.

Graduate School of Peking Union Medical College, Beijing 100730, China.

Objectives: Allicin is an allyl 2-propenethiosulfinate or diallyl thiosulfinate acid with cardioprotective effects in myocardial ischemia/reperfusion (MI/R) injury. This study aims to examine the underlying mechanism by which Allicin protects against MI/R.

Methods: C57BL6 mice were subjected to either sham or MI/R surgery, and mice in the Allicin group were injected with Allicin (5 mg/ml) before the induction of ischemia. The cardiac function and histopathology of experimental mice were evaluated by ultrasound quantification and Masson staining. We next measured the capillary angiogenesis of the peri-infarct area by Masson staining and immunohistochemical staining. The miRNA microarray was carried out to examine the expressed miRNAs in MI/R tissues and corresponding normal tissues. Real-time quantitative polymerase chain reaction (q-PCR) was performed to validate the selected miRNA-19α-3p gene expression. Besides, we evaluated the myocardial lactate dehydrogenase and COX-2 by immunofluorescence staining. The western blot analysis was used to evaluate the protein levels of p-AKT, p-PI3K, p-mTOR, COX-2, and VEGF protein in the Allicin and Model group. study, LPS stimulated Tie2 expressing macrophages were cultured in an ischemic buffer. We evaluated the accumulation of VEGF by fura-2/AM fluorescence. Besides, Western blotting was performed to examine the protein levels of p-PI3K, p-AKT, p-mTOR, VEGF, COX2, and MMP2. The PI3K inhibitor was applied to investigate whether Allicin-induced myocardial ischemia-reperfusion injury protection is mediated via the PI3K/AKT pathway. And the miR-19α-3p mimic/inhibitor were transfected to promote/inhibit the expression of miR-19a-3p for verifying the regulation of miR-19a-3p on PI3K pathway.

Results: Allicin pretreatment significantly improved I/R-induced cardiac function damage. Furthermore, Allicin could repress cardiac fibrosis, as evidenced by reduced areas of cardiac fibrosis. Allicin's effect on the MI/R was associated with increased capillary angiogenesis. Microarray analysis exposed that miR-19a-3p down-regulated PIK3CA (PI3K) expression by directly targeting the PIK3CA gene. The regulation of the angiogenesis pathway and gene miRNA-19a-3p might affect the Allicin-induced MI/R protection. Immunofluorescence staining revealed that COX-2 and myocardial lactate dehydrogenase were significantly increased after Allicin treatment. Furthermore, western blot analysis demonstrated that p-AKT, p-PI3K, p-mTOR, COX-2, and VEGF protein levels were also increased in the Allicin group. study, the protein levels of p-PI3K, p-AKT, p-mTOR, VEGF, COX2, and MMP2 were significantly increased in the Allicin-treated Tie2 expressing macrophages. These effects were partially reversed by PI3K inhibitor (Wortmannin) treatment. MiR-19α-3p plays an important role in myocardial I/R injury. It could regulate the activity of the PI3K-AKT pathway. And inhibition of miR-19a-3p promoted angiogenesis by regulating PI3K/AKT pathway.

Conclusions: Allicin pretreatment protects against myocardial I/R and activating the miR-19a-3p/PI3K/AKT pathway.
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http://dx.doi.org/10.18632/aging.203578DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8544308PMC
October 2021

Dysfunction of miR-802 in tumors.

J Clin Lab Anal 2021 Nov 24;35(11):e23989. Epub 2021 Sep 24.

Medical Genetics Center, Ningbo University School of Medicine, Ningbo, China.

Recent studies have shown that miR-802 is abnormally expressed in many tumors. miR-802 is expressed at low levels in tissues and cells of gastric cancer, colorectal cancer, breast cancer, cervical cancer, epithelial ovarian cancer, tongue squamous cell carcinoma, oral squamous cell carcinoma, esophageal squamous cell carcinoma, laryngeal squamous cell carcinoma, and melanoma. In contrast, miR-802 is overexpressed in hepatocellular carcinoma, bladder urothelial cancer, osteosarcoma, and cholesteatoma tissue cells. It should be noted that the results of studies on the expression of miR-802 in pancreatic cancer, prostate cancer, and lung cancer are inconsistent. Current studies have found that miR-802 can target and regulate genes in different tumors, and affect the regulation of the Wnt signaling pathway, EMT signaling pathway, PI3K/AKT signaling pathway, ERK signaling pathway, and Hedgehog signaling pathway. At the same time, miR-802 is regulated by the endogenous competition of four ceRNAs, including circDONSON, IGFL2-AS1, MIR155HG, and MIR4435-2HG. This article reviews the abnormal expression of miR-802 in a variety of tumors, expounds the mechanism by which miR-802 affects tumor progression by regulating different target genes, and elaborates the network of miR-802-related ceRNAs. We also summarized the limitations of miR-802 research and looked forward to the potential application of miR-802 in the diagnosis and prognosis of tumors.
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http://dx.doi.org/10.1002/jcla.23989DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8605121PMC
November 2021

Sulfur-doped wood-derived porous carbon for optimizing electromagnetic response performance.

Nanoscale 2021 Oct 8;13(38):16084-16093. Epub 2021 Oct 8.

Key Laboratory for Anisotropy and Texture of Materials (MOE), School of Materials Science and Engineering, Northeastern University, Shenyang 110819, P. R. China.

Bio-mass materials have been selected as one of the advanced electromagnetic (EM) functional materials due to their natural porous framework for dynamically and flexibly optimizing the EM response property. Herein, we demonstrate sulfur-doped wood-derived porous carbon EM materials (SPC) for optimizing the EM response performance the coupling between doped heterostructures and the original 3D microchannels. The experimental results reveal that both the dielectric loss capacity and interfacial impedance matching could be increased by the sulfur-doped heterostructures. By tailoring the sulfur content, the microwave absorption (normalized RL) of SPC could be optimized to -15.90 dB mm, while the effective absorption bandwidth (EAB) could cover the K band. Moreover, the shielding effectiveness of SPC can be enhanced from 10 dB to 30 dB with the assistance of water, ascribed to the super-wettability performance. This present study provides a novel strategy to further optimize the EM response performance of wood-derived materials, and meanwhile could be widely extended to other bio-mass absorbers.
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http://dx.doi.org/10.1039/d1nr04232gDOI Listing
October 2021

PolyI:C suppresses TGF-β1-induced Akt phosphorylation and reduces the motility of A549 lung carcinoma cells.

Mol Biol Rep 2021 Sep 14;48(9):6313-6321. Epub 2021 Aug 14.

Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata, Kita-ku, Okayama, 700-8558, Japan.

Backgrounds: Epithelial mesenchymal transition (EMT) is a critical process involved in the invasion and metastasis of cancer, including lung cancer (LC). Transforming growth factor (TGF)-β is one of factors capable of inducing EMT. Polyinosinic-polycytidylic acid (polyI:C), a synthetic agonist for toll-like receptor (TLR) 3, can enhance immune responses and has been used as an adjuvant for cancer vaccines; however, it remains unclear whether it influences other process, such as EMT. In the present study, we examined the effects of polyI:C on TGF-β-treated A549 human LC cells.

Methods And Results: By in vitro cell proliferation assay, polyI:C showed no effect on the growth of A549 cells treated with TGF-β1 at the concentration range up to 10 μg/ml; however, it markedly suppressed the motility in a cell scratch and a cell invasion assay. By Western blotting, polyI:C dramatically decreased TGF-β1-induced Ak strain transforming (Akt) phosphorylation and increased phosphatase and tensin homologue (PTEN) expression without affecting the Son of mothers against decapentaplegic (Smad) 3 phosphorylation or the expression level of E-cadherin, N-cadherin or Snail, indicating that polyI:C suppressed cell motility independently of the 'cadherin switching'. The Akt inhibitor perifosine inhibited TGF-β1-induced cell invasion, and the PTEN-specific inhibitor VO-OHpic appeared to reverse the inhibitory effect of polyI:C.

Conclusion: PolyI:C has a novel function to suppress the motility of LC cells undergoing EMT by targeting the phosphatidylinositol 3-kinase/Akt pathway partly via PTEN and may prevent or reduce the metastasis of LC cells.
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http://dx.doi.org/10.1007/s11033-021-06625-1DOI Listing
September 2021

The protective effect of allicin on myocardial ischemia-reperfusion by inhibition of Ca overload-induced cardiomyocyte apoptosis via the PI3K/GRK2/PLC-γ/IP3R signaling pathway.

Aging (Albany NY) 2021 08 3;13(15):19643-19656. Epub 2021 Aug 3.

Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China.

Purpose: To investigate the protective effect and mechanism of allicin on myocardial ischemia-reperfusion (MI/R) injury.

Methods: We investigated the mechanisms by which allicin attenuated the MI/R injury by focusing on phosphoinositide 3-kinase, G protein coupled receptor kinases 2, phospholipase Cγ and cardiomyocyte apoptosis. Sixty male mice were randomly assigned into three groups: repeated MI/R (model), sham-operated (control), and MI/R+ allicin group (allicin). Ultrasound examination was used to examine the cardiac function. Masson staining was used to evaluate the myocardial infarct area. TUNEL assay was performed to examine the anti-apoptotic effect of allicin. Differentially expressed genes (DEGs) and pathways were analyzed by mRNA microarray analysis. Immunofluorescence staining and western blot were carried out to detect the effect of allicin on the PI3K. A pan-PLC activator, m-3M3FBS, was applied to investigate whether allicin induced cardiomyocyte apoptosis was via the GRK2/PLC/IP3R signaling pathway.

Results: Masson staining and the TUNEL assay revealed that allicin reduced infarct size and played an anti-apoptotic role in M/IR. Ultrasound examination revealed that allicin improved cardiac function after M/IR injury. Gene ontology analysis indicated that the calcium signaling pathway and PI3KCA(PI3K) were selected. Immunofluorescence staining and western blot exposed that PI3K was activated by allicin during MI/R injury. Fura-2AM staining revealed that the PI3K -mediated GRK2/PLC-γ/IP3R pathway may be involved in the protective effect of allicin on MI/R injury.

Conclusions: Allicin has a protective effect on MI/R injury. This effect might be associated with the inhibition of Ca overload-induced apoptosis and the inhibition of the PI3K -mediated GRK2/PLC-γ/IP3R signaling pathway.
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http://dx.doi.org/10.18632/aging.203375DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8386544PMC
August 2021

Efficient decolorization of azo dye wastewater with polyaniline/graphene modified anode in microbial electrochemical systems.

J Hazard Mater 2022 01 27;421:126740. Epub 2021 Jul 27.

MOE Key Laboratory of Pollution Processes and Environmental Criteria/Tianjin Key Laboratory of Environmental Remediation and Pollution Control/College of Environmental Science and Engineering, Nankai University, No. 38 Tongyan Road, Jinnan District, Tianjin 300350, China. Electronic address:

Azo dye pollution has become a worldwide issue, and the current treatment methods can hardly meet the expected emission standards. Microbial electrochemical systems (MESs) show promising applications for decolorization, but their performance critically depends on the microorganisms. Electrode modification is an interesting method of improving decolorization performance. However, the mechanisms of how the modification can affect microbial communities and the decolorization process remain unclear. Here, a modified anode with polyaniline (PANI) and graphene was fabricated via electro-deposition. Consequently, the highest decolorization efficiency was obtained. The Congo red (CR) decolorization rate of the MESs with the PANI/graphene-modified electrode (PG) reached 90% at 54 h. By contrast, the CR decolorization rates of the MESs with the PANI-modified electrode (P) and those of the MESs with the unmodified electrode (C) only reached 68% and 79%, respectively. Results of the microbial community analysis showed abundant Methanobrevibacter arboriphilus in PG (11%), which was 5.5 times that in C (2%) at 18 h. This phenomenon may be related to the rapid decolorization. The upregulated metabolism pathways, including arginine and proline metabolism, purine metabolism, arginine biosynthesis, and riboflavin metabolism, provided more electron shuttles and redox mediators that facilitated the extracellular electron transfer. Therefore, the PG-modified electrode facilitated the decolorization by altering certain metabolic pathways. This study can help to improve the guideline on the potential application of MESs for wastewater treatment.
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http://dx.doi.org/10.1016/j.jhazmat.2021.126740DOI Listing
January 2022

Effects of glycosaminoglycan from Urechis unicinctus on the P2Y1 receptor pathway and expression of related factors in rat platelets.

Pak J Pharm Sci 2021 Jan;34(1):129-134

Tianjin Marine Environmental Protection and Restoration Technology Engineering Center; Tianjin Key Laboratory of Marine Resource and Chemistry; College of Marine & Environment, Tianjin University of Science and Technology, Tianjin, China.

The aim of this study was to examine the effects of glycosaminoglycan (GAG) from Urechis unicinctus on the P2Y1 receptor pathway and expression of related factors in rat platelets. The concentration of calcium ion (Ca) in rat platelets was determined by double wavelength Fura-2 fluorescence spectrophotometry, and the concentrations of inositol trisphosphate (IP) and glycoprotein IIb/IIIa (GPIIb/IIIa) in rat platelets were measured using the enzymatic immunoassay method. The phosphorylation levels of phospholipase C (PLC), phospholipase A (PLA), protein kinase C (PKC), and p38 mitogen-activated protein kinase (p38MAPK) were also detected by Western blot. It was found that the GAG from U. unicinctus significantly reduced the Ca and IP3 levels in rat platelets (p<0.05, p<0.01). Moreover, medium and high concentrations of GAG significantly reduced the concentration of the platelet membrane GPIIb/IIIa in rats (p<0.05, p<0.01). The phosphorylation levels of PLC, PLA), PKC and p38MAPK in rat platelets were also inhibited by GAG and P)Y) receptor blocker MRS2179 (p<0.05, p<0.01). However, the degree of inhibition of GAG was lower than that of MRS2179. The results laid a foundation for further utilization of the glycosaminoglycan.
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January 2021

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

J Control Release 2021 08 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
August 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

Sirtuin 3 Ameliorates Lung Senescence and Improves Type II Alveolar Epithelial Cell Function by Enhancing the FoxO3a-Dependent Antioxidant Defense Mechanism.

Stem Cells Dev 2021 Sep 16;30(17):843-855. Epub 2021 Jul 16.

Department of Cardiovascular Surgery, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, China.

Lung aging alters the intrinsic structure of the lung and pulmonary surfactant system and increases the mortality and morbidity due to respiratory diseases in elderly individuals. We hypothesized that lung aging results from an insufficiency of type II alveolar epithelial cells (AECIIs) in the lung tissue. Sirtuin 3 (SIRT3) is a member of the sirtuin family of proteins that promote longevity in many organisms. Increased SIRT3 expression has been linked to an extended life span in humans. Hence, we speculated that the overexpression of SIRT3 may help to ameliorate lung senescence and improve AECII function. AECIIs were isolated from young and old patients with pneumothorax caused by pulmonary bullae. The expression of SIRT3, manganese superoxide dismutase, and catalase, as well as cell function and senescence indicators of young and old AECIIs, was measured before and after SIRT3 overexpression. After SIRT3 overexpression, the aged state of old AECIIs improved, and antiapoptotic activity, proliferation, and secretion were dramatically enhanced. Surfactant protein C (SPC), which is secreted by AECIIs, reduces alveolar surface tension, repairs the alveolar structure, and regulates inflammation. SPC deficiency in patients is associated with increased inflammation and delayed repair. SIRT3 deacetylated forkhead box O3a, thereby protecting mitochondria from oxidative stress and improving cell function and the senescent state of old AECIIs. These findings provide a possible direction for aging-delaying therapies and interventions for diseases of the respiratory system.
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http://dx.doi.org/10.1089/scd.2021.0099DOI Listing
September 2021

Nanoparticle-Loaded Polarized-Macrophages for Enhanced Tumor Targeting and Cell-Chemotherapy.

Nanomicro Lett 2020 Oct 27;13(1). Epub 2020 Oct 27.

Department of Pharmaceutics, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 44 Wenhuaxi Road, Jinan, 250012, People's Republic of China.

Cell therapy is a promising strategy for cancer therapy. However, its therapeutic efficiency remains limited due to the complex and immunosuppressive nature of tumor microenvironments. In this study, the "cell-chemotherapy" strategy was presented to enhance antitumor efficacy. M1-type macrophages, which are therapeutic immune cells with both of immunotherapeutic ability and targeting ability, carried sorafenib (SF)-loaded lipid nanoparticles (M1/SLNPs) were developed. M1-type macrophages were used both as therapeutic tool to provide immunotherapy and as delivery vessel to target deliver SF to tumor tissues for chemotherapy simultaneously. M1-type macrophages were obtained by polarizing macrophages using lipopolysaccharide, and M1/SLNPs were obtained by incubating M1-type macrophages with SLNP. Tumor accumulation of M1/SLNP was increased compared with SLNP (p < 0.01), which proved M1/SLNP could enhance tumor targeting of SF. An increased ratio of M1-type macrophages to M2-type macrophages, and the CD3CD4 T cells and CD3CD8 T cell quantities in tumor tissues after treatment with M1/SLNP indicated M1/SLNP could relieve the immunosuppressive tumor microenvironments. The tumor volumes in the M1/SLNP group were significantly smaller than those in the SLNP group (p < 0.01), indicating M1/SLNP exhibited enhanced antitumor efficacy. Consequently, M1/SLNP showed great potential as a novel cell-chemotherapeutic strategy combining both cell therapy and targeting chemotherapy.
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http://dx.doi.org/10.1007/s40820-020-00531-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187668PMC
October 2020

Lymph Node Delivery Strategy Enables the Activation of Cytotoxic T Lymphocytes and Natural Killer Cells to Augment Cancer Immunotherapy.

ACS Appl Mater Interfaces 2021 May 6;13(19):22213-22224. Epub 2021 May 6.

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 250012, China.

Lymph nodes are the main sites for immune activation and surveillance. Effective delivery of immunomodulators into lymph nodes to trigger antitumor immunity is essential for cancer treatment. Here, we propose a lymph node delivery strategy to modulate the immune response by activating cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells simultaneously. Novel pH/redox dual-sensitive micelles were prepared using poly(l-histidine)-poly(ethylene glycol) (PLH-PEG) as a skeleton, which can effectively deliver immunomodulators to the lymph nodes due to their suitable particle size. At 48 h after subcutaneous injection, the accumulation efficiency in lymph nodes increased 8.12-fold compared with the control group. Subsequently, Trp2/CpG-coloaded pH/redox dual-sensitive micelles (Trp2/CpG-NPs) acted on antigen-presenting cells, fully promoting CTL activation through dendritic cell antigen cross-presentation and macrophage repolarization. IL-15-loaded pH/redox dual-sensitive micelles (IL-15-NPs) were developed to activate the killing effect of NK cells by interacting with IL-15 receptors. In the tumor-bearing mice model, this lymph node delivery strategy showed significant antitumor efficiency and the tumor inhibition rate reached 93.76%. Meanwhile, the infiltration of CTLs and NK cells in tumor tissues increased, and the immunosuppressive microenvironment was relieved by the repolarization of macrophages from M2-type to M1-type. Overall, this study highlighted the potential of the lymph node delivery strategy for cancer immunotherapy.
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http://dx.doi.org/10.1021/acsami.1c03709DOI Listing
May 2021

Immune response induced by oral administration with a Saccharomyces cerevisiae-based SARS-CoV-2 vaccine in mice.

Microb Cell Fact 2021 May 5;20(1):95. Epub 2021 May 5.

College of Medicine, Southwest Jiaotong University, Chengdu, 610031, Sichuan, China.

Background: The global pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) highlights the need to develop safe and effective vaccines with a top priority. Multiple vaccine candidates are under development, and several vaccines are currently available. Efforts need to be undertaken to counter the threat of the global COVID-19 pandemic.

Results: We generated a Saccharomyces cerevisiae (S. cerevisiae)-based SARS-CoV-2 vaccine, EBY100/pYD1-RBD, in which the full-length receptor binding domain (RBD) of the spike protein of SARS-CoV-2 was expressed on the surface of yeast. Mice vaccinated orally with unadjuvanted EBY100/pYD1-RBD could produce significant humoral and mucosal responses as well as robust cellular immune responses. Notably, EBY100/pYD1-RBD elicited a mixed Th1/Th2-type cellular immune response with a Th1-biased immune response in a mouse model.

Conclusions: Our findings highlight the importance of the RBD as a key target to design and develop vaccines against SARS-CoV-2 and provide evidence of oral administration of a S. cerevisiae-based SARS-CoV-2 vaccine eliciting significant immune responses. Most importantly, the S. cerevisiae surface display system can serve as a universal technology platform and be applied to develop other oral viral or bacterial vaccines.
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http://dx.doi.org/10.1186/s12934-021-01584-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097247PMC
May 2021

Allicin attenuates myocardial apoptosis, inflammation and mitochondrial injury during hypoxia-reoxygenation: an in vitro study.

BMC Cardiovasc Disord 2021 04 21;21(1):200. Epub 2021 Apr 21.

Peking University China-Japan Friendship School of Clinical Medicine, 2 East Yinghuayuan Street, Hepingli, Beijing, 100029, China.

Background: Myocardial ischemia-reperfusion (IR) injury is a damage due to an initial reduction in blood flow to the heart, preventing it from receiving enough oxygen, and subsequent restoration of blood flow through the opening of an occluded coronary artery producing paradoxical harmful effects. The finding of new therapies to prevent IR is of utmost importance. Allicin is a compound isolated from garlic having the ability to prevent and cure different diseases, and a protective effect on the myocardium was also demonstrated. Therefore, the aim of this study was to evaluate the in vitro protective effect of Allicin against myocardial IR injury on cardiomyocytes.

Methods: We established an in vitro hypoxia-reoxygenation (HR) model of primary porcine cardiomyocytes to simulate myocardial IR injury. Primary porcine cardiomyocytes were extracted from Mini-musk swines (1 day old). After a period of adaptation of at least 2-3 days, cardiomyocytes in good condition were selected and randomly divided into control group (normal oxygen for 5 h), HR group (2 h of hypoxia/3 h of reoxygenation), and HR + Allicin group (hypoxia/reoxygenation + Allicin treatment).

Results: After the induction of hypoxia/reoxygenation, Allicin treatment enhanced the cell viability. Moreover, Allicin treatment resulted in a reduction of apoptosis from 13.5 ± 1.2% to 6.11 ± 0.15% compared with the HR group (p < 0.05), and the apoptosis related proteins were regulated as well, with a decreased expression of Bax, cleaved caspase-3 and cytosolic cytochrome C and an increase in Bcl-2 expression in the HR + Allicin group (all p < 0.01). Pro-inflammatory cytokines, such as interleukin-6 and tumor necrosis factor alpha were down-regulated by the treatment with Allicin (both p < 0.01). In addition, it significantly decreased intracellular reactive oxygen species generation (p < 0.01) and reduced the loss of mitochondrial membrane potential (p < 0.01). Furthermore, the expression of PPARγ coactivator-1α and endothelial nitric oxide synthase was up-regulated (both p < 0.01), while the expression of Endothelin-1, hypoxia inducing factor-1α and transforming growth factor beta was down-regulated (all p < 0.01) by Allicin treatment.

Conclusions: These results suggested that Allicin protected the cardiomyocytes against HR damage by reducing apoptosis, inflammation and mitochondrial injury, thus providing a basis for its potential use in the treatment of myocardial IR.
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http://dx.doi.org/10.1186/s12872-021-01918-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8059159PMC
April 2021

Assessment of AlN/Mg-8Al Composites Reinforced with In Situ and/or Ex Situ AlN Particles.

Materials (Basel) 2020 Dec 24;14(1). Epub 2020 Dec 24.

Key Laboratory for Liquid-Solid Structural Evolution and Processing of Materials, Ministry of Education, Shandong University, 17923 Jingshi Road, Jinan 250061, China.

In this paper, 8.2AlN/Mg-8Al composites reinforced with in situ and/or ex situ AlN particles have been synthesized. The in situ-formed AlN particles are nano-sized, performing as particle chains. It has been clarified that the in situ AlN particles are more efficient than ex situ particles for the enhancement of mechanical properties. The in situ-prepared composite exhibits improved density, hardness and compressive strength compared to the ex situ ones. This work may be referred to for designing particle-reinforced Mg composites by various methods.
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http://dx.doi.org/10.3390/ma14010052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7796081PMC
December 2020

Cross-protective immunity of the haemagglutinin stalk domain presented on the surface of against divergent influenza viruses in mice.

Virulence 2021 12;12(1):12-19

College of Medicine, Southwest Jiaotong University , Chengdu, China.

Most of the current approaches to influenza vaccine design focus on antibodies against influenza (HA). However, these influenza vaccines typically provide strain-specific protection against mostly homologous subtypes. There is an urgent need to develop a universal vaccine that confers cross-protection against influenza viruses. Of note, the HA stalk domain (HAsd) is a promising target for such an influenza vaccine. In this study, we generated recombinant ()/pNZ8150-phosphatidylglycerophosphate synthetase A (pgsA)-HAsd, in which pgsA was used as an anchor protein, and investigated the immunogenicity of HAsd in a mouse model by oral administration without the use of a mucosal adjuvant. Compared with /pNZ8150-pgsA, mice were orally vaccinated with /pNZ8150-pgsA-HAsd and then produced strong humoral and mucosal immune responses. Importantly, /pNZ8150-pgsA-HAsd provided cross-protection against H5N1, H3N2 and H1N1 virus infections. Our data support the hypothesis that HAsd presented on the surface of can provide cross-protective immunity against divergent influenza A viruses. Taken together, these findings suggest that /pNZ8150-pgsA-HAsd can be considered an alternative approach to developing a novel universal vaccine during an influenza A pandemic. HA, HAsd, HA stalk domain; ; SDS-PAGE, sodium dodecyl sulfate-polyacrylamide gel electrophoresis; IFA, immunofluorescence assay; PBS, phosphate-buffered saline; pgsA, phosphatidylglycerophosphate synthetase A; SPF, specific pathogen-free; CFU, colony-forming unit; BSL-3, biosafety level-3 laboratory; TCID, 50% tissue culture infective dose; ELISA, enzyme-linked immunosorbent assay; OD, optical density; LTB, liable enterotoxin B subunit; CTB, cholera toxin B subunit.
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http://dx.doi.org/10.1080/21505594.2020.1857162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7781637PMC
December 2021

Platelet-activating factor induces the stemness of ovarian cancer cells via the PAF/PAFR signaling pathway.

Am J Transl Res 2020 15;12(11):7249-7261. Epub 2020 Nov 15.

Department of Gynecology, Obstetrics and Gynecology Hospital of Fudan University Shanghai 200011, People's Republic of China.

Background: Cancer stem cells (CSCs) play an important role in tumor recurrence, metastasis, and chemoresistance. CSCs can shift between non-CSC and CSC states in certain tumor microenvironments. The mechanisms of this shift are not well understood. We previously demonstrated that platelet-activating factor (PAF), a lipid mediator of inflammation in the tumor microenvironment, can promote ovarian cancer progression and induce chemoresistance via PAF/PAFR-mediated inflammatory signaling pathways. Here, we investigated the role of PAF/PAFR signaling in the stemness of ovarian cancer cell.

Methods: The effects of PAF and PAFR antagonists on the stemness of SKOV3 and A2780 cells were evaluated using sphere-formation assays, FACS analysis and real-time PCR in vitro and a SKOV3 tumor-formation experiment in nude mice in vivo. The potential mechanism of the PAF effect on the stemness of ovarian cancer cells was evaluated by human cytokine antibody microarray analysis.

Results: PAF can promote spheroid formation and inhibit the transition of quiescent ovarian cancer cells into the cell cycle. The percentage of cancer stem cells increased significantly, and the expression of stemness genes increased in PAF-treated group. These effects could be blocked by PAFR inhibitors. Ginkgolide B (GB) inhibited tumor growth and decreased the CSC percentage in vivo. Human cytokine antibody microarray analysis showed that some stemness-maintaining proteins increased in PAF-treated group.

Conclusion: Our results suggest that PAF can regulate the stemness of ovarian cancer cells through the PAF/PAFR pathway, suggesting a new target for the treatment of ovarian cancer.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724322PMC
November 2020

Crystal structure of the FERM-folded talin head reveals the determinants for integrin binding.

Proc Natl Acad Sci U S A 2020 12 7;117(51):32402-32412. Epub 2020 Dec 7.

Molecular Therapeutics Program, Fox Chase Cancer Center, Philadelphia, PA 19111;

Binding of the intracellular adapter proteins talin and its cofactor, kindlin, to the integrin receptors induces integrin activation and clustering. These processes are essential for cell adhesion, migration, and organ development. Although the talin head, the integrin-binding segment in talin, possesses a typical FERM-domain sequence, a truncated form has been crystallized in an unexpected, elongated form. This form, however, lacks a C-terminal fragment and possesses reduced β3-integrin binding. Here, we present a crystal structure of a full-length talin head in complex with the β3-integrin tail. The structure reveals a compact FERM-like conformation and a tightly associated N-P-L-Y motif of β3-integrin. A critical C-terminal poly-lysine motif mediates FERM interdomain contacts and assures the tight association with the β3-integrin cytoplasmic segment. Removal of the poly-lysine motif or disrupting the FERM-folded configuration of the talin head significantly impairs integrin activation and clustering. Therefore, structural characterization of the FERM-folded active talin head provides fundamental understanding of the regulatory mechanism of integrin function.
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http://dx.doi.org/10.1073/pnas.2014583117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7768682PMC
December 2020

Immune evaluation of a Saccharomyces cerevisiae-based oral vaccine against Helicobacter pylori in mice.

Helicobacter 2021 Feb 20;26(1):e12772. Epub 2020 Nov 20.

College of Medicine, Southwest Jiaotong University, Chengdu, China.

Background: Helicobacter pylori (H. pylori) is a common human pathogenic bacterium that is associated with gastric diseases. The current leading clinical therapy is combination antibiotics, but this treatment has safety issues, especially the induction of drug resistance. Therefore, developing a safe and effective vaccine against H. pylori is one of the best alternatives.

Objective: To develop Saccharomyces cerevisiae (S. cerevisiae)-based oral vaccines and then demonstrate the feasibility of this platform for preventing H. pylori infection in the absence of a mucosal adjuvant.

Materials And Methods: Saccharomyces cerevisiae (S. cerevisiae)-based oral vaccines, including EBY100/pYD1-UreB and EBY100/pYD1-VacA, were generated and analyzed by Western blot, Immunofluorescence analysis, flow cytometric assay, and indirect enzyme-link immunosorbent assay (ELISA). Further, antibody responses induced by oral administration of EBY100/pYD1-UreB, EBY100/pYD1-VacA, or EBY100/pYD1-UreB + EBY100/pYD1-VacA were measured in a mouse model. Lastly, the vaccinated mice were infected with H. pylori SS1, and colonization in the stomach were evaluated.

Results: Saccharomyces cerevisiae-based H. pylori oral vaccines were successfully constructed. Mice orally administered with EBY100/pYD1-UreB, EBY100/pYD1-VacA, or EBY100/pYD1-UreB + EBY100/pYD1-VacA exhibited a significant humoral immune response as well as a mucosal immune response. Importantly, S. cerevisiae-based oral vaccines could effectively reduce bacterial loads with statistical significance after H. pylori infection.

Conclusions: Our study shows that S. cerevisiae-based platforms can serve as an alternative approach for the future development of promising bacterial oral vaccine candidates.
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http://dx.doi.org/10.1111/hel.12772DOI Listing
February 2021

A review on development of MUC1-based cancer vaccine.

Biomed Pharmacother 2020 Dec 21;132:110888. Epub 2020 Oct 21.

College of Medicine, Southwest Jiaotong University, Chengdu 610031, China. Electronic address:

Mucin 1 (MUC1) is a transmembrane mucin glycoprotein expressed on the surface of almost all epithelial cells. Aberrantly glycosylated MUC1 is associated with cellular transformation from a normal to malignant phenotype in human cancers. Therefore, MUC1 is the major target for the design and development of cancer vaccines. MUC1-based cancer vaccines are a promising strategy for preventing cancer progression and metastasis. This review summarizes the most significant milestones achieved to date in the development of different MUC-1-based vaccine approaches in clinical trials. Further, it provides perspectives for future research that may promote clinical advances in infection-associated cancers.
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http://dx.doi.org/10.1016/j.biopha.2020.110888DOI Listing
December 2020

Haemagglutinin displayed on the surface of Lactococcus lactis confers broad cross-clade protection against different H5N1 viruses in chickens.

Microb Cell Fact 2020 Oct 15;19(1):193. Epub 2020 Oct 15.

Department of Biotechnology, College of Life Science, Nanchang University, Jiangxi, 330031, China.

Background: The highly pathogenic avian influenza (HPAI) H5N1 virus poses a potential threat to the poultry industry. The currently available avian influenza H5N1 vaccines for poultry are clade-specific. Therefore, an effective vaccine for preventing and controlling H5N1 viruses belonging to different clades needs to be developed.

Results: Recombinant L. lactis/pNZ8148-Spax-HA was generated, and the influenza virus haemagglutinin (HA) protein of A/Vietnam/1203/2004 (H5N1) was displayed on the surface of Lactococcus lactis (L. lactis). Spax was used as an anchor protein. Chickens vaccinated orally with unadjuvanted L. lactis/pNZ8148-Spax-HA could produce significant humoral and mucosal responses and neutralizing activities against H5N1 viruses belonging to different clades. Importantly, unadjuvanted L. lactis/pNZ8148-Spax-HA conferred cross-clade protection against lethal challenge with different H5N1 viruses in the chicken model.

Conclusion: This study provides insights into the cross-clade protection conferred by unadjuvanted L. lactis/pNZ8148-Spax-HA, and the results might help the establishment of a promising platform for the development of a safe and effective H5N1 cross-clade vaccine for poultry.
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http://dx.doi.org/10.1186/s12934-020-01453-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7557258PMC
October 2020

Method for Fault Diagnosis of Temperature-Related MEMS Inertial Sensors by Combining Hilbert-Huang Transform and Deep Learning.

Sensors (Basel) 2020 Oct 1;20(19). Epub 2020 Oct 1.

School of Computer Science, Chongqing University, 174 Shazheng Street, Shapingba District, Chongqing 400044, China.

In this paper, we propose a novel method for fault diagnosis in micro-electromechanical system (MEMS) inertial sensors using a bidirectional long short-term memory (BLSTM)-based Hilbert-Huang transform (HHT) and a convolutional neural network (CNN). First, the method for fault diagnosis of inertial sensors is formulated into an HHT-based deep learning problem. Second, we present a new BLSTM-based empirical mode decomposition (EMD) method for converting one-dimensional inertial data into two-dimensional Hilbert spectra. Finally, a CNN is used to perform fault classification tasks that use time-frequency HHT spectrums as input. According to our experimental results, significantly improved performance can be achieved, on average, for the proposed BLSTM-based EMD algorithm in terms of EMD computational efficiency compared with state-of-the-art algorithms. In addition, the proposed fault diagnosis method achieves high accuracy in fault classification.
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http://dx.doi.org/10.3390/s20195633DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7583962PMC
October 2020

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

methylation is associated with hematologic improvement in low-risk myelodysplastic syndrome patients treated with Pai-Neng-Da.

J Int Med Res 2020 Sep;48(9):300060520956894

Department of Hematology, Ningbo First Hospital, Ningbo, Zhejiang, China.

Objective: The aim of this prospective randomized controlled clinical trial was to explore the relationship between methylation and Pai-Neng-Da (PND) in the treatment of patients with low-risk myelodysplastic syndrome (MDS).

Methods: There were 82 low-risk MDS patients who were randomly divided into the following two groups: androl, thalidomide, and PND capsule (ATP group, n = 41); or androl and thalidomide (AT group, n = 41). Hemoglobin and neutrophil and platelet counts and changes in methylation level were assessed.

Results: The plasma hemoglobin level increased in both groups after treatment. However, the platelet count increased only in the ATP group. Patients in the ATP group had a better platelet response than the AT group, and methylation markedly decreased after treatment with ATP but not after treatment with AT. Moreover, male patients had a significantly lower methylation level than female patients, while platelet counts from male patients increased dramatically after the ATP regimens compared with female patients. methylation changes were negatively correlated with platelet changes in ATP group.

Conclusion: PND can improve hematological parameters and decrease the methylation level. Decreasing methylation is associated with the hematologic response that includes platelet in methylation. http://www.chictr.org.cn/: ChiCTR-IOR-15006635.
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http://dx.doi.org/10.1177/0300060520956894DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7520939PMC
September 2020
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