Publications by authors named "Cheng Yang"

1,292 Publications

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Chiral covalent organic framework-monolith as stationary phase for high-performance liquid chromatographic enantioseparation of selected amino acids.

Anal Bioanal Chem 2021 Jul 31. Epub 2021 Jul 31.

Institute of Analytical Food Safety, School of Food Science and Technology, Jiangnan University, Wuxi, 214122, Jiangsu, China.

The separation of amino acid (AA) enantiomers shows significance for chemistry, food, and biology, but remains challenging due to their similar properties. A promising nanoporous chiral covalent organic framework (COF) as a stationary phase for high-performance liquid chromatography (HPLC) suffers from the irregularity and widely distributed particle size of the chiral COF. Herein, we show the facile preparation of a chiral COF-monolith as a stationary phase for HPLC enantiomeric separation of AAs via orthogonal experiments. The CTzDa-monolith is prepared by the incorporation of the model chiral COF named CTzDa into the porous poly(ethylene dimethacrylate-co-methacrylate) monolith and reveals great permeability and mechanical stability. The corresponding CTzDa-monolithic column gives better chiral HPLC separation of AAs than the commercial Poroshell 120 chiral-T column. Thermal dynamic analysis and molecular docking calculations imply the involvement of stereoscopic hydrogen, π-π, and van der Waals interactions between the CTzDa and AAs during HPLC enantioseparation. The facile incorporation of the chiral COF into the porous monolith will promote the potential of a chiral COF as a stationary phase for HPLC.
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http://dx.doi.org/10.1007/s00216-021-03574-3DOI Listing
July 2021

Molecular characterization and functional analysis of peroxiredoxin 4 in grass carp (Ctenopharyngodon idella).

Dev Comp Immunol 2021 Jul 26;125:104213. Epub 2021 Jul 26.

State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, China; Innovative Academy of Seed Design, Chinese Academy of Sciences, Beijing, 100101, China. Electronic address:

Peroxiredoxins (Prxs) are a group of evolutionarily conserved selenium-independent thiol-specific antioxidant proteins. In this study, the peroxiredoxin-4 (CiPrx4) gene from grass carp was identified and characterized. The full-length of CiPrx4 is 1339 bp, encoding 260 amino acids that contain two peroxiredoxin signature motifs and two GVL motifs. CiPrx4 belongs to the typical 2-Cys subfamily and shows the highest homology with Prx4 from Cyprinus carpio (95.4%). CiPrx4 mRNA was constitutively expressed in all tested tissues and was upregulated by grass carp reovirus and pathogen-associated molecular pattern (PAMP) stimulation. CiPrx4 was localized in the cytoplasm and co-localized with the endoplasmic reticulum. The purified CiPrx4 protein protected DNA from degradation in a dose-dependent manner. Moreover, the overexpression of CiPrx4 in Escherichia coli and fish cells showed apparent antioxidant and antiviral activities. Collectively, the results of the present study provide new insights for further understanding the functions of Prx4 in teleost fish.
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http://dx.doi.org/10.1016/j.dci.2021.104213DOI Listing
July 2021

Correction to "Synthetic Studies on Selective, Proapoptotic Isomalabaricane Triterpenoids Aided by Computational Techniques".

J Am Chem Soc 2021 Jul 28. Epub 2021 Jul 28.

Roger Adams Laboratory, Department of Chemistry, University of Illinois, Urbana, Illinois 61801, United States.

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http://dx.doi.org/10.1021/jacs.1c07261DOI Listing
July 2021

Effect of Schwann cell transplantation combined with electroacupuncture on axonal regeneration and remyelination in rats with spinal cord injury.

Anat Rec (Hoboken) 2021 Jul 28. Epub 2021 Jul 28.

Traditional Chinese Medicine College, Chongqing Medical University, Chongqing, China.

Axonal impairment and demyelination after compressed spinal cord injury lead to serious neurological dysfunction. Increasing studies have suggested that Schwann cells (SCs) transplantation is a reliable, effective, and promising method for treating spinal cord injury. However, single SCs transplantation is insufficient to promote the full recovery of neurological function. Additional approaches are required to support SCs transplantation as a treatment for spinal cord injury. In the study, we investigated whether the combination of electroacupuncture (EA) and SCs transplantation was a reliable intervention for spinal cord injury. We found that rats in the combination group had significantly higher functional locomotor scores than those received single treatment. By immunostaining, we found EA can not only improve survival and proliferation of transplanted SCs but also inhibit SC apoptosis and block the formation of an astrocytic scar. Additionally, EA promoted regenerated axons extending "bullet-shaped" growth cones into the lesion. Remarkably, EA can modify astrogliosis to promote axonal regeneration following SCs transplantation through inducing extension of astrocytic processes in the SCs graft interface. More importantly, the combination of SCs engraftment and EA can enhance corticospinal-tract axonal regeneration and remyelination after spinal cord injury through up-regulating neuregulin 1 type III in SCs and its downstream signaling mediators. Thus, it is concluded that SCs effectively promote axonal recovery after spinal cord injury when combined with EA stimulation. The experimental results have reinforced the theoretical basis of EA for its clinical efficacy in patients with spinal cord injury and merited further investigation for potential clinical application. : , ○ , (SCs) 、、○ , SCs ○ SCs ○ , SCs ○ ○ , EA SCs , SC ○ , EA ○ , EA SCs , SCs ○ , SCs EA EA SCs 1 III , ○ , SCs ○ , ○.
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http://dx.doi.org/10.1002/ar.24721DOI Listing
July 2021

Solvent-Driven Chirality Switching of a Pillar[4]arene[1]quinone Having a Chiral Amine-Substituted Quinone Subunit.

Front Chem 2021 7;9:713305. Epub 2021 Jul 7.

Key Laboratory of Green Chemistry and Technology of Ministry of Education, College of Chemistry, and Healthy Food Evaluation Research Center, Sichuan University, Chengdu, China.

Several new chiral pillar[4]arene[1]quinone derivatives were synthesized by reacting pillar[4]arene[1]quinone (), containing four 1,4-diethoxybenzene units and one benzoquinone unit, with various chiral amines Michael addition. Due to the direct introduction of chiral substituents on the rim of pillar[n]arene and the close location of the chiral center to the rim of , the newly prepared compounds showed unique chiroptical properties without complicated chiral resolution processes, and unprecedented high anisotropy factor of up to -0.018 at the charge transfer absorption band was observed. Intriguingly, the benzene sidearm attached pillar[4]arene[1]quinone derivative showed solvent- and complexation-driven chirality inversion. This work provides a promising potential for absolute asymmetric synthesis of pillararene-based derivatives.
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http://dx.doi.org/10.3389/fchem.2021.713305DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8293272PMC
July 2021

Afatinib in EGFR TKI-Naïve Patients with Locally Advanced or Metastatic EGFR Mutation-Positive Non-Small Cell Lung Cancer: A Pooled Analysis of Three Phase IIIb Studies.

Front Oncol 2021 9;11:709877. Epub 2021 Jul 9.

Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital and Guangdong Academy of Medical Sciences, Guangzhou, China.

Background: Afatinib is approved for first-line treatment of patients with epidermal growth factor receptor mutation-positive (m+) non-small-cell lung cancer (NSCLC). Here, we report findings from a combined analysis of three phase IIIb studies of afatinib in EGFR tyrosine kinase inhibitor (TKI)-naïve patients.

Methods: EGFR-TKI-naïve patients with m+ NSCLC received afatinib 40 mg/day. Dose reductions were permitted for adverse events (AEs). Efficacy endpoints included progression-free survival (PFS), time to symptomatic progression (TTSP), and tumor response. Subgroup analyses were performed by Eastern Cooperative Oncology Group performance status (ECOG PS), presence of brain metastasis, age and common/uncommon mutations (plus other factors).

Results: 1108 patients were treated. Median age was 61 years (range, 25-89); 19.2% had baseline brain metastases, 4.4% had ECOG PS ≥2, and 17.9% had tumors harboring uncommon mutations. Treatment-related AEs (TRAEs) were reported in 97.2%, most commonly diarrhea and rash. 41.6% had AEs leading to dose reduction. Median PFS was 13.0 months [95% confidence interval (CI): 12.0-13.8]; median TTSP was 14.8 months (95% CI: 13.9-16.1). Objective response rate (ORR) was 55.0%. Age, presence of baseline brain metastases, major (G719X, L861Q, S768I) or compound uncommon mutations had little/no effect on PFS, TTSP, or ORR, while outcomes were poorer in patients with ECOG PS 2 or exon 20 insertion/T790M mutations.

Conclusions: Afatinib was tolerable with no new safety signals. Afatinib demonstrated encouraging efficacy in a broad patient population, including those with brain metastases or uncommon mutations.
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http://dx.doi.org/10.3389/fonc.2021.709877DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8298067PMC
July 2021

Myeloid cells are enriched in tonsillar crypts providing insight into the host tropism of HPV.

Am J Pathol 2021 Jul 22. Epub 2021 Jul 22.

Division of Surgical Oncology, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA; Department of Otolaryngology-Head and Neck Surgery, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA. Electronic address:

Viruses are the second leading cause of cancer worldwide, and human papillomavirus (HPV)-associated head and neck cancers are increasing in incidence in the United States. HPV preferentially infects the crypts of the tonsils rather than the surface epithelium. The present study sought to characterize the unique microenvironment within the crypts to better understand the host tropism of HPV to a lymphoid rich organ. Laser-capture microdissection of distinct anatomic areas (crypts, surface epithelium, and germinal centers) of the tonsil coupled with transcriptional analysis and multi-parameter immunofluorescence staining was performed and demonstrated that the tonsillar crypts are enriched with myeloid populations which co-express multiple canonical and non-canonical immune checkpoints, including PD-L1, CTLA-4, HAVCR2 (TIM-3), ADORA2A, IDO1, BTLA, LGALS3, CDH1, CEACAM1, PVR, and C10orf54 (VISTA). The resident monocytes may foster a permissive microenvironment that facilitates HPV infection and persistence. Furthermore, the myeloid populations within HPV-associated tonsil cancers co-express the same immune checkpoints, providing insight into potential novel immunotherapeutic targets for HPV-associated head and neck cancers.
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http://dx.doi.org/10.1016/j.ajpath.2021.06.012DOI Listing
July 2021

A novel epigenetic drug conjugating flavonoid and HDAC inhibitor confers to suppression of acute myeloid leukemogenesis.

Clin Sci (Lond) 2021 Jul 20. Epub 2021 Jul 20.

Shenzhen University General Hospital, Shenzhen, China.

Epigenetic dysregulation has long been identified as a key driver of leukemogenesis in acute myeloid leukemia (AML). However, epigenetic drugs such as histone deacetylase inhibitors (HDACi) targeting epigenetic alterations in AML have obtained only limited clinical efficiency without clear mechanism. Fortunately, we screened out a novel epigenetic agent named Apigenin-Vorinostat-Conjugate (AVC), which provides us a possibility to handle the heterogenous malignancy. Its inhibition on HDACs was presented by HDACs expression, enzyme activity, and histone acetylation level. Its efficacy against AML was detected by cell viability assay and tumor progression of AML mouse model. Apoptosis is the major way causing cell death. We found AVC efficiently suppresses leukemogenesis whereas sparing the normal human cells. Kasumi-1 cells are at least twenty-fold higher sensitive to AVC (IC50=0.024μM) than vorinostat (IC50=0.513μM) and Ara-C (IC50=0.4366μM). Furthermore, it can efficiently regress the tumorigenesis in AML mouse model while keeping the pivotal organs safe, demonstrating a feasibility and favorable safety profile in treatment of AML. Collectively, these pre-clinical data suggest a promising potential utilizing flavonoid-HDACi-conjugate as a next-generation epigenetic drug for clinical therapy against AML.
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http://dx.doi.org/10.1042/CS20210571DOI Listing
July 2021

Chiroptical Sensing of Amino Acid Derivatives by Host-Guest Complexation with Cyclo[6]aramide.

Molecules 2021 Jul 2;26(13). Epub 2021 Jul 2.

Key Laboratory of Radiation Physics and Technology of Ministry of Education, College of Chemistry, Sichuan University, Chengdu 610064, China.

A hydrogen-bonded (H-bonded) amide macrocycle was found to serve as an effective component in the host-guest assembly for a supramolecular chirality transfer process. Circular dichroism (CD) spectroscopy studies showed that the near-planar macrocycle could produce a CD response when combined with three of the twelve L--amino acid esters (all cryptochiral molecules) tested as possible guests. The host-guest complexation between the macrocycle and cationic guests was explored using NMR, revealing the presence of a strong affinity involving the multi-point recognition of guests. This was further corroborated by density functional theory (DFT) calculations. The present work proposes a new strategy for amplifying the CD signals of cryptochiral molecules by means of H-bonded macrocycle-based host-guest association, and is expected to be useful in designing supramolecular chiroptical sensing materials.
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http://dx.doi.org/10.3390/molecules26134064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8271771PMC
July 2021

Ultrafast heating to boost the electrocatalytic activity of iridium towards oxygen evolution reaction.

Chem Commun (Camb) 2021 Jul 19. Epub 2021 Jul 19.

State Key Laboratory of New Ceramics and Fine Processing, School of Materials Science and Engineering, Tsinghua University, Beijing, 100084, P. R. China.

Efficient electrocatalysts are in great demand for renewable energy storage systems. Herein, we propose an ultrafast heating strategy to fabricate an efficient Ir/CP-UH catalyst for the oxygen evolution reaction (OER). Experimental results demonstrated that the ultrasmall Ir nanoparticles (≈1-3 nm) and clusters (<1 nm) were highly dispersed on the carbon paper support after a short thermal shock (∼5 s). The catalyst showed a low overpotential of 260 mV at 10 mA cm-2 and remarkable mass activity of about 13.8 times higher than that of the current state-of-the-art commercial Ir/C catalyst. This ultrafast heating strategy can also be applied to other catalyst systems for OER and other electrochemical reactions.
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http://dx.doi.org/10.1039/d1cc01999fDOI Listing
July 2021

Identifying Biomarkers from Transcriptomic Signatures in Renal Allograft Biopsies Using Deceased and Living Donors.

Front Immunol 2021 1;12:657860. Epub 2021 Jul 1.

Department of Cardiovascular Sciences, University of Leicester, Leicester, United Kingdom.

The survival of transplant kidneys using deceased donors (DD) is inferior to living donors (LD). In this study, we conducted a whole-transcriptome expression analysis of 24 human kidney biopsies paired at 30 minutes and 3 months post-transplantation using DD and LD. The transcriptome profile was found significantly different between two time points regardless of donor types. There were 446 differentially expressed genes (DEGs) between DD and LD at 30 minutes and 146 DEGs at 3 months, with 25 genes common to both time points. These DEGs reflected donor injury and acute immune responses associated with inflammation and cell death as early as at 30 minutes, which could be a precious window of potential intervention. DEGs at 3 months mainly represented the changes of adaptive immunity, immunosuppressive treatment, remodeling or fibrosis via different networks and signaling pathways. The expression levels of 20 highly DEGs involved in kidney diseases and 10 genes dysregulated at 30 minutes were found correlated with renal function and histology at 12 months, suggesting they could be potential biomarkers. These genes were further validated by quantitative polymerase chain reaction (qPCR) in 24 samples analysed by microarray, as well as in a validation cohort of 33 time point unpaired allograft biopsies. This analysis revealed that SERPINA3, SLPI and CBF were up-regulated at 30 minutes in DD compared to LD, while FTCD and TASPN7 were up-regulated at both time points. At 3 months, SERPINA3 was up-regulated in LD, but down-regulated in DD, with increased VCAN and TIMP1, and decreased FOS, in both donors. Taken together, divergent transcriptomic signatures between DD and LD, and changed by the time post-transplantation, might contribute to different allograft survival of two type kidney donors. Some DEGs including FTCD and TASPN7 could be novel biomarkers not only for timely diagnosis, but also for early precise genetic intervention at donor preservation, implantation and post-transplantation, in particular to effectively improve the quality and survival of DD.
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http://dx.doi.org/10.3389/fimmu.2021.657860DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8282197PMC
July 2021

Non-terminally exhausted tumor-resident memory HBV-specific T cell responses correlate with relapse-free survival in hepatocellular carcinoma.

Immunity 2021 Jul 10. Epub 2021 Jul 10.

Singapore Immunology Network, A(∗)STAR, 8A Biomedical Grove, Singapore 138648, Singapore; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N, Seattle, WA 98109, USA. Electronic address:

Hepatocellular carcinoma (HCC) often develops following chronic hepatitis B virus (HBV) infection and responds poorly to immune checkpoint blockade. Here, we examined the antigen specificities of HCC-infiltrating T cells and their relevance to tumor control. Using highly multiplexed peptide-MHC tetramer staining of unexpanded cells from blood, liver, and tumor tissues from 46 HCC patients, we detected 91 different antigen-specific CD8 T cell populations targeting HBV, neoantigen, tumor-associated, and disease-unrelated antigens. Parallel high-dimensional analysis delineated five distinct antigen-specific tissue-resident memory T (Trm) cell populations. Intratumoral and intrahepatic HBV-specific T cells were enriched for two Trm cell subsets that were PD-1TOX, despite being clonally expanded. High frequencies of intratumoral terminally exhausted T cells were uncommon. Patients with tumor-infiltrating HBV-specific CD8 Trm cells exhibited longer-term relapse-free survival. Thus, non-terminally exhausted HBV-specific CD8 Trm cells show hallmarks of active involvement and effective antitumor response, implying that these cells could be harnessed for therapeutic purposes.
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http://dx.doi.org/10.1016/j.immuni.2021.06.013DOI Listing
July 2021

BMI1 activates P-glycoprotein via transcription repression of and enhances chemoresistance of bladder cancer cell.

Aging (Albany NY) 2021 Jul 16;13(undefined). Epub 2021 Jul 16.

Department of Urology, The Third Affiliated Hospital of Southern Medical University, Guangzhou 510630, China.

Chemoresistance is the most significant reason for the failure of cancer treatment following radical cystectomy. The response rate to the first-line chemotherapy of cisplatin and gemcitabine does not exceed 50%. In our previous research, elevated BMI1 (B-cell specific Moloney murine leukemia virus integration region 1) expression in bladder cancer conferred poor survival and was associated with chemoresistance. Herein, via analysis of The Cancer Genome Atlas database and validation of clinical samples, BMI1 was elevated in patients with bladder cancer resistant to cisplatin and gemcitabine, which conferred tumor relapse and progression. Consistently, BMI1 was markedly increased in the established cisplatin- and gemcitabine-resistant T24 cells (T24/DDP&GEM). Functionally, BMI1 overexpression dramatically promoted drug efflux, enhanced viability and decreased apoptosis of bladder cancer cells upon treatment with cisplatin or gemcitabine, whereas BMI1 downregulation reversed this effect. Mechanically, upon interaction with p53, BMI1 was recruited on the promoter of gene concomitant with an increase in the mono-ubiquitination of histone H2A lysine 119, leading to transcription repression of gene followed by derepression of (ATP binding cassette subfamily B member 1) gene. Moreover, suppression of P-glycoprotein by miR-3682-3p mimics or its inhibitor XR-9576, could significantly reverse chemoresistance of T24/DDP&GEM cells. These results provided a novel insight into a portion of the mechanism underlying BMI1-mediated chemoresistance in bladder cancer.
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http://dx.doi.org/10.18632/aging.203277DOI Listing
July 2021

TRIM16 overexpression inhibits the metastasis of colorectal cancer through mediating Snail degradation.

Exp Cell Res 2021 Jul 13;406(1):112735. Epub 2021 Jul 13.

The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, 471003, China. Electronic address:

Tripartite motif containing 16 (TRIM16) is a member of the tripartite motif protein family and functions as a potential tumor suppressor in several cancers. However, the specific function and clinical significance of TRIM16 in colorectal cancer (CRC) remains unclear. In this study, we observed that low TRIM16 expression was detected frequently in primary colorectal cancer (CRC) tissues and was closely associated with a better prognosis. Functional studies demonstrate that TRIM16 overexpression notably inhibits the metastasis abilities of CRC in vivo and in vitro. Mechanistically, our results demonstrated that TRIM16 directly bound and ubiquitinated Snail family transcriptional repressor 1 (Snail), an important transcriptional factor of the epithelial-mesenchymal transition (EMT) process suppressing the EMT in CRC. Additionally, our data revealed that the inhibition effect of TRIM16 on cancer metastasis was dependent on Snail degradation. Collectively, our study is the first to report that TRIM16 plays a crucial anti-tumor role in CRC tumorigenesis. We also provided novel evidence that TRIM16 might act as a prognostic and therapeutic target to assess and inhibit CRC progression.
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http://dx.doi.org/10.1016/j.yexcr.2021.112735DOI Listing
July 2021

Diosmetin has therapeutic efficacy in colitis regulating gut microbiota, inflammation, and oxidative stress via the circ-Sirt1/Sirt1 axis.

Acta Pharmacol Sin 2021 Jul 14. Epub 2021 Jul 14.

The State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Key Laboratory of Molecular Drug Research, Nankai University, Tianjin, 300350, China.

Diosmetin (3',5,7 -trihydroxy-4'-methoxy flavone) is a natural flavonoid compound in the citrus species, it exhibits a variety of pharmacological activities, but little is known of its effects on colitis. In this study we evaluated the therapeutic effects of diosmetin on mouse models of chronic and acute colitis. Chronic colitis was induced in mice by drinking water containing 3% dextran sulfate sodium (DSS) from D0 to D8, followed by administration of diosmetin (25, 50 mg · kg · d) for another 8 days. Acute colitis was induced by drinking water containing 5% DSS from D0 to D7, the mice concomitantly received diosmetin (25, 50 mg · kg · d) from D1 to D7. During the experiments, body weight and disease activity index (DAI) were assessed daily. After the mice were sacrificed, colon tissue and feces samples were collected, and colon length was measured. We showed that in both models, diosmetin administration significantly decreased DAI score and ameliorated microscopic colon tissue damage; increased the expression of tight junction proteins (occludin, claudin-1, and zonula occludens-1), and reduced the secretion of proinflammatory cytokines IL-1β, IL-6, TNF-α, and Cox-2 in colon tissue. We found that diosmetin administration remarkably inhibited colon oxidative damage by adjusting the levels of intracellular and mitochondrial reactive oxygen species, GSH-Px, SOD, MDA and GSH in colon tissue. The protection of diosmetin against intestinal epithelial barrier damage and oxidative stress were also observed in LPS-treated Caco-2 and IEC-6 cells in vitro. Furthermore, we demonstrated that diosmetin markedly increased the expression of Nrf2 and HO-1 and reduced the ratio of acetylated NF-κB and NF-κB by activating the circ-Sirt1/Sirt1 axis, which inhibited oxidative stress and inflammation in vivo and in vitro. Diosmetin reversed the effects of si-circSirt1 and si-Sirt1 in LPS-treated Caco-2 and IEC-6 cells. When the gut microbiota was analyzed in the mouse model of colitis, we found that diosmetin administration modulated the abundance of Bacteroidetes, Actinobacteria, Cyanobacteria and Firmicutes, which were crucial for inflammatory bowel disease. Our results have linked colitis to the circ-Sirt1/Sirt1 signaling pathway, which is activated by diosmetin. The results imply that diosmetin may be a novel candidate to alleviate DSS-induced colitis and can be a lead compound for future optimization and modification.
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http://dx.doi.org/10.1038/s41401-021-00726-0DOI Listing
July 2021

Design and Synthesis of Fluorescent 1,3-Diaryl-β-carbolines and 1,3-Diaryl-3,4-dihydro-β-carbolines.

ACS Omega 2021 May 29;6(18):12238-12249. Epub 2021 Apr 29.

Key Laboratory of Green Chemistry & Technology, College of Chemistry, State Key Laboratory of Biotherapy and Healthy Food Evaluation Research Center, and Sino-British Materials Research Institute, College of Physical Sciences & Technology, Sichuan University, Chengdu, Sichuan 610064, P. R. China.

The 1,3-diaryl-β-carboline derivatives, including 3,4-dihydro variants, were synthesized via a multiple-step approach. These compounds possess rigid and twisted configurations, which are expected to exhibit unique optical properties. The absorption and fluorescence properties of the newly synthesized compounds were investigated. These synthetic 1,3-diaryl-β-carbolines displayed strong emission in the range of 387-409 nm and exhibited absolute photoluminescence quantum yields of up to 74%. Density functional theory calculations were performed to better elucidate the geometric, electronic, and optical properties of these novel 1,3-diaryl-β-carbolines.
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http://dx.doi.org/10.1021/acsomega.1c01116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8260278PMC
May 2021

Identification of Prognostic Signature and Gliclazide as Candidate Drugs in Lung Adenocarcinoma.

Front Oncol 2021 24;11:665276. Epub 2021 Jun 24.

Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China.

Background: Lung adenocarcinoma (LUAD) is the most common pathological type of lung cancer, with high incidence and mortality. To improve the curative effect and prolong the survival of patients, it is necessary to find new biomarkers to accurately predict the prognosis of patients and explore new strategy to treat high-risk LUAD.

Methods: A comprehensive genome-wide profiling analysis was conducted using a retrospective pool of LUAD patient data from the previous datasets of Gene Expression Omnibus (GEO) including GSE18842, GSE19188, GSE40791 and GSE50081 and The Cancer Genome Atlas (TCGA). Differential gene analysis and Cox proportional hazard model were used to identify differentially expressed genes with survival significance as candidate prognostic genes. The Kaplan-Meier with log-rank test was used to assess survival difference. A risk score model was developed and validated using TCGA-LUAD and GSE50081. Additionally, The Connectivity Map (CMAP) was used to predict drugs for the treatment of LUAD. The anti-cancer effect and mechanism of its candidate drugs were studied in LUAD cell lines.

Results: We identified a 5-gene signature (KIF20A, KLF4, KRT6A, LIFR and RGS13). Risk Score (RS) based on 5-gene signature was significantly associated with overall survival (OS). Nomogram combining RS with clinical pathology parameters could potently predict the prognosis of patients with LUAD. Moreover, gliclazide was identified as a candidate drug for the treatment of high-RS LUAD. Finally, gliclazide was shown to induce cell cycle arrest and apoptosis in LUAD cells possibly by targeting CCNB1, CCNB2, CDK1 and AURKA.

Conclusion: This study identified a 5-gene signature that can predict the prognosis of patients with LUAD, and Gliclazide as a potential therapeutic drug for LUAD. It provides a new direction for the prognosis and treatment of patients with LUAD.
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http://dx.doi.org/10.3389/fonc.2021.665276DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8264429PMC
June 2021

Development of a Ferroptosis-Related lncRNA Signature to Predict the Prognosis and Immune Landscape of Bladder Cancer.

Dis Markers 2021 20;2021:1031906. Epub 2021 Jun 20.

Department of Urology, The Third Affiliated Hospital of Southern Medical University, Guangzhou 510000, China.

The tight relationship between ferroptotic cell death and immune response demonstrated by recent studies enlightened us to detect the underlying roles of ferroptosis-related long noncoding RNAs (frlncRNAs) in the tumor microenvironment of bladder cancer (BCa). We collected 121 ferroptosis regulators from previous studies. Based on their expression values, 408 cases with BCa were clustered. The patients in different clusters showed diverse immune infiltration, immunotherapy response, and chemotherapy effectiveness, revalidating the tight correlation with ferroptosis and tumor immunity. Through differential, coexpression, Kaplan-Meier, Lasso, and Cox analysis, we developed a 22-lncRNA-pair signature to predict the prognosis of BCa based on gene-pair strategy, where there is no need for definite expression values. The areas under the curves are all over 0.8. The risk model also helped to predict immune infiltration, immunotherapeutic outcomes, and chemotherapy sensitivity. Totally, the prognostic assessment model indicated a promising predictive value, also providing clues for the interaction between ferroptosis and BCa immunity.
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http://dx.doi.org/10.1155/2021/1031906DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8238626PMC
June 2021

A Systematic Review and Meta-Analysis of Low-Residue Diet Versus Clear Liquid Diet: Which Is Better for Bowel Preparation Before Colonoscopy?

Gastroenterol Nurs 2021 Jul 1. Epub 2021 Jul 1.

Rui Wu, MD, is a student, Department of Gastroenterology, The Affiliated Wuxi People's Hospital to Nanjing Medical University, Wuxi, Jiangsu, China, and Department of Digestive Endoscopy, The First Affiliated Hospital with Nanjing Medical University, Nanjing, Jiangsu, China. Wen-ya Ji, MD, is a student, Department of Gastroenterology, The Affiliated Wuxi People's Hospital to Nanjing Medical University, Wuxi, Jiangsu, China. Cheng Yang, MD, PhD, is a visiting staff, Department of Gastroenterology, The Affiliated Wuxi People's Hospital to Nanjing Medical University, Wuxi, Jiangsu, China. Qiang Zhan, MD, PhD, is an archiater, Department of Gastroenterology, The Affiliated Wuxi People's Hospital to Nanjing Medical University, Wuxi, Jiangsu, China.

The goal of this systematic review was to compare the clear liquid diet and the low-residue diet to determine which is better for bowel preparation before colonoscopy. A literature search for randomized controlled trials on the effects of employing the clear liquid diet and low-residue diets before colonoscopy was conducted in major online English databases (PubMed, Web of Science, and Ovid EMBASE). After the systematic review of all 16 studies, the outcomes including quality of bowel preparation, tolerance, willingness to repeat, and adverse effects were analyzed through meta-analysis. The statistical analysis was performed by using RevMan 5.3 software. No statistically significant difference was observed between the low-residue diet and clear liquid diet groups (odds ratio [95% confidence interval] = 1.19 [0.79, 1.81]; p = .41). There was no statistically significant difference between the Boston Bowel Preparation Scale (standard mean difference [95% confidence interval] = -0.04 [-0.21, -0.14]; p = .68) Ottawa Bowel Preparation Scale (standard mean difference [95% confidence interval] = -0.04 [-0.19, 0.11]; p = .59) scores of the two groups. The quality indicators for colonoscopy of the two groups were not statistically significant. However, patient tolerance to the low-residue diet was higher (odds ratio [95% confidence interval] = 1.86 [1.47, 2.36]; p < .01). More patients in the low-residue diet group were willing to repeat the low-residue diet for bowel preparation (odds ratio [95% confidence interval] = 2.34 [1.72, 3.17]; p < .01). More patients in the clear liquid diet group experienced hunger, nausea, and vomiting. People who employed the low-residue diet before colonoscopy had the same quality of bowel preparation as those with clear liquid diet. Meanwhile, the tolerance of people with low-residue diet was better than people with clear liquid diet, and these people were more willing to repeat the colonoscopy with less adverse events.
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http://dx.doi.org/10.1097/SGA.0000000000000554DOI Listing
July 2021

A mechanical test of the tenertaxis hypothesis for leukocyte diapedesis.

Eur Phys J E Soft Matter 2021 Jul 8;44(7):93. Epub 2021 Jul 8.

Department of Chemical and Biological Engineering, University of British Columbia, Vancouver, BC, V6T 1Z3, Canada.

As part of the immune response, leukocytes can directly transmigrate through the body of endothelial cells or through the gap between adjacent endothelial cells. These are known, respectively, as the transcellular and paracellular route of diapedesis. What determines the usage of one route over the other is unclear. A recently proposed tenertaxis hypothesis claims that leukocytes choose the path with less mechanical resistance against leukocyte protrusions. We examined this hypothesis using numerical simulation of the mechanical resistance during paracellular and transcellular protrusions. By using parameters based on human lung endothelium, our results show that the required force to breach the endothelium through the transcellular route is greater than paracellular route, in agreement with experiments. Moreover, experiments have demonstrated that manipulation of the relative strength between the two routes can make the transcellular route preferable. Our simulations have demonstrated this reversal and thus tentatively confirmed the hypothesis of tenertaxis.
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http://dx.doi.org/10.1140/epje/s10189-021-00096-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8264968PMC
July 2021

Multi-Omics Sequencing Provides Insights Into Age-Dependent Susceptibility of Grass Carp () to Reovirus.

Front Immunol 2021 17;12:694965. Epub 2021 Jun 17.

State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China.

Grass carp () is an important aquaculture species in China that is affected by serious diseases, especially hemorrhagic disease caused by grass carp reovirus (GCRV). Grass carp have previously shown age-dependent susceptibility to GCRV, however, the mechanism by which this occurs remains poorly understood. Therefore, we performed transcriptome and metabolome sequencing on five-month-old (FMO) and three-year-old (TYO) grass carp to identify the potential mechanism. Viral challenge experiments showed that FMO fish were susceptible, whereas TYO fish were resistant to GCRV. RNA-seq showed that the genes involved in immune response, antigen presentation, and phagocytosis were significantly upregulated in TYO fish before the GCRV infection and at the early stage of infection. Metabolome sequencing showed that most metabolites were upregulated in TYO fish and downregulated in FMO fish after virus infection. Intragroup analysis showed that arachidonic acid metabolism was the most significantly upregulated pathway in TYO fish, whereas choline metabolism in cancer and glycerophospholispid metabolism were significantly downregulated in FMO fish after virus infection. Intergroup comparison revealed that metabolites from carbohydrate, amino acid, glycerophospholipid, and nucleotide metabolism were upregulated in TYO fish when compared with FMO fish. Moreover, the significantly differentially expressed metabolites showed antiviral effects both and . Based on these results, we concluded that the immune system and host biosynthesis and metabolism, can explain the age-dependent viral susceptibility in grass carp.
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http://dx.doi.org/10.3389/fimmu.2021.694965DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8247658PMC
June 2021

Myricetin Inhibits SARS-CoV-2 Viral Replication by Targeting M and Ameliorates Pulmonary Inflammation.

Front Pharmacol 2021 17;12:669642. Epub 2021 Jun 17.

State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Haihe Education Park, Tianjin, China.

The coronavirus disease 2019 (COVID-19) has spread widely around the world and has seriously affected the human health of tens of millions of people. In view of lacking anti-virus drugs target to SARS-CoV-2, there is an urgent need to develop effective new drugs. In this study, we reported our discovery of SARS-CoV-2 M inhibitors. We selected 15 natural compounds, including 7 flavonoids, 3 coumarins, 2 terpenoids, one henolic, one aldehyde and one steroid compound for molecular docking and enzymatic screening. Myricetin were identified to have potent inhibit activity with IC 3.684 ± 0.076 μM in the enzyme assay. The binding pose of Myricetin with SARS-CoV-2 M was identified using molecular docking method. In the binding pocket of SARS-CoV-2 M, the chromone ring of Myricetin interacts with His41 through -π stacking, and the 3'-, 4'- and 7-hydroxyl of Myricetin interact with Phe140, Glu166and Asp187 through hydrogen bonds. Significantly, our results showed that Myricetin has potent effect on bleomycin-induced pulmonary inflammation by inhibiting the infiltration of inflammatory cells and the secretion of inflammatory cytokines IL-6, IL-1α, TNF-α and IFN-γ. Overall, Myricetin may be a potential drug for anti-virus and symptomatic treatment of COVID-19.
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http://dx.doi.org/10.3389/fphar.2021.669642DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8248548PMC
June 2021

Super-elasticity at 4 K of covalently crosslinked polyimide aerogels with negative Poisson's ratio.

Nat Commun 2021 Jul 2;12(1):4092. Epub 2021 Jul 2.

Institute of Special materials and Technology, Fudan University, Shanghai, China.

The deep cryogenic temperatures encountered in aerospace present significant challenges for the performance of elastic materials in spacecraft and related apparatus. Reported elastic carbon or ceramic aerogels overcome the low-temperature brittleness in conventional elastic polymers. However, complicated fabrication process and high costs greatly limited their applications. In this work, super-elasticity at a deep cryogenic temperature of covalently crosslinked polyimide (PI) aerogels is achieved based on scalable and low-cost directional dimethyl sulfoxide crystals assisted freeze gelation and freeze-drying strategy. The covalently crosslinked chemical structure, cellular architecture, negative Poisson's ratio (-0.2), low volume shrinkage (3.1%), and ultralow density (6.1 mg/cm) endow the PI aerogels with an elastic compressive strain up to 99% even in liquid helium (4 K), almost zero loss of resilience after dramatic thermal shocks (∆T = 569 K), and fatigue resistance over 5000 times compressive cycles. This work provides a new pathway for constructing polymer-based materials with super-elasticity at deep cryogenic temperature, demonstrating much promise for extensive applications in ongoing and near-future aerospace exploration.
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http://dx.doi.org/10.1038/s41467-021-24388-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8253740PMC
July 2021

Chronic kidney disease: prevalence and association with handgrip strength in a cross-sectional study.

BMC Nephrol 2021 Jul 2;22(1):246. Epub 2021 Jul 2.

Department of Epidemiology, School of Public Health, Nanjing Medical University, 101 Longmian Avenue, 211166, Nanjing, China.

Background: Poor physical function is strongly associated with mortality and poor clinical outcomes in adults with chronic kidney disease (CKD). Handgrip strength (HGS) is an important index for physical function in the general population, and the association between HGS and CKD is worth investigating.

Methods: From September to November 2015, we conducted a cross-sectional study consisting of 10,407 participants in Jurong City, China. Age-related and sex-specific HGS percentile curves were constructed using the GAMLSS method. In addition, logistic regression was applied to estimate the association between HGS and the presence of CKD with odds ratios (ORs) and 95 % confidence intervals (CIs).

Results: Participants with low HGS tended to be older and were more likely to have CKD (8.73 %). Smoothed centile curves of HGS showed a similar shape in both sexes: participants peaked at approximately 20-35 years old and gradually decreased after the age of 50. In addition, independent of age and other factors, the decreased presence of CKD was significantly identified in individuals with moderate (OR: 0.64, 95 % CI: 0.49-0.83) and high HGS (OR: 0.37, 95 % CI: 0.23-0.58).

Conclusions: We concluded that HGS was significantly negatively associated with CKD in Chinese community-dwelling persons.
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http://dx.doi.org/10.1186/s12882-021-02452-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8252238PMC
July 2021

Three-dimensional SERS sensor based on the sandwiched [email protected]@G/PDMS film.

Talanta 2021 Oct 12;233:122481. Epub 2021 May 12.

School of Physics and Electronics, Shandong Normal University, Jinan, 250014, China. Electronic address:

Three-dimensional (3D) SERS substrate with the denser "hotspots" is synthesized by the constriction of PDMS film decorated with sandwiched [email protected]@graphene ([email protected]@G) nanostructure. Graphene layers above and below the AgNPs are used to absorb molecules onto the "hotspots", and prevent the oxidation of AgNPs in our design. PDMS films can be easily shrunk for 3D structures, causing advantages in enhancement ability and light-matter interaction. Benefiting from the above advantages, a detection limit of 10 M (CV) and enhancement factor (EF) of 3.9 × 10 were obtained in our experiment. Theoretical analyses (FDTD) were also used to study the enhancement mechanism. For practical purposes, in-situ detection of MG molecules on the fish surface and the label-free detection of DNA base of adenine (A) and cytosine (C) were also studied. The high enhancement factor, great sensitivity, reliability, and stability of substrate reasonably proved that it can be used as an excellent SERS substrate for biomolecular detection.
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http://dx.doi.org/10.1016/j.talanta.2021.122481DOI Listing
October 2021

Mechanism of Electrochemical Generation and Decomposition of Phthalimide--oxyl.

J Am Chem Soc 2021 Jul 2;143(27):10324-10332. Epub 2021 Jul 2.

Willard Henry Dow Laboratory, Department of Chemistry, University of Michigan, 930 North University Avenue, Ann Arbor, Michigan 48109, United States.

Phthalimide -oxyl (PINO) is a potent hydrogen atom transfer (HAT) catalyst that can be generated electrochemically from -hydroxyphthalimide (NHPI). However, catalyst decomposition has limited its application. This paper details mechanistic studies of the generation and decomposition of PINO under electrochemical conditions. Voltammetric data, observations from bulk electrolysis, and computational studies suggest two primary aspects. First, base-promoted formation of PINO from NHPI occurs via multiple-site concerted proton-electron transfer (MS-CPET). Second, PINO decomposition occurs by at least two second-order paths, one of which is greatly enhanced by base. Optimal catalytic efficiency in PINO-catalyzed oxidations occurs in the presence of bases whose corresponding conjugate acids have p's in the range of ∼11-15, which strikes a balance between promoting PINO formation and minimizing its decay.
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http://dx.doi.org/10.1021/jacs.1c04181DOI Listing
July 2021

Type 2 Nep1-Like Proteins from the Biocontrol Oomycete Suppress Infection in Solanaceous Plants.

J Fungi (Basel) 2021 Jun 22;7(7). Epub 2021 Jun 22.

The Key Laboratory of Plant Immunity, College of Plant Protection, Nanjing Agricultural University, Nanjing 210095, China.

As a non-pathogenic oomycete, the biocontrol agent is able to control plant diseases through direct mycoparasite activity and boosting plant immune responses. Several elicitors have been found to activate plant immunity as microbe-associated molecular patterns (MAMPs). Necrosis- and ethylene-inducing peptide 1 (Nep1)-like proteins (NLPs) are a group of MAMPs widely distributed in eukaryotic and prokaryotic plant pathogens. However, little is known about their distribution and functions in and its sister species . Here, we identified a total of 25 NLPs from (PyolNLPs) and (PypeNLPs). Meanwhile, we found that PyolNLPs/PypeNLPs genes cluster in two chromosomal segments, and our analysis suggests that they expand by duplication and share a common origin totally different from that of pathogenic oomycetes. Nine PyolNLPs/PypeNLPs induced necrosis in   by agroinfiltration. Eight partially purified PyolNLPs/PypeNLPs were tested for their potential biocontrol activity. PyolNLP5 and PyolNLP7 showed necrosis-inducing activity in via direct protein infiltration. At sufficient concentrations, they both significantly reduced disease severity and suppressed the in planta growth of in solanaceous plants including (tobacco), (tomato) and (pepper). Our assays suggest that the suppression effect of PyolNLP5 and PyolNLP7 is irrelevant to reactive oxygen species (ROS) accumulation. Instead, they induce the expression of antimicrobial plant defensin genes, and the induction depends on their conserved nlp24-like peptide pattern. This work demonstrates the biocontrol role of two NLPs for solanaceous plants, which uncovers a novel approach of utilizing NLPs to develop bioactive formulae for oomycete pathogen control with no ROS-caused injury to plants.
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http://dx.doi.org/10.3390/jof7070496DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8303654PMC
June 2021

Sulfur-Containing Compounds: Natural Potential Catalyst for the Isomerization of Phytofluene, Phytoene and Lycopene in Tomato Pulp.

Foods 2021 Jun 22;10(7). Epub 2021 Jun 22.

School of Food Science and Technology, Jiangnan University, Wuxi 214122, China.

The effects of some sulfur-containing compounds on the isomerization and degradation of lycopene, phytofluene, and phytoene under different thermal treatment conditions were studied in detail. Isothiocyanates such as allyl isothiocyanate (AITC) and polysulfides like dimethyl trisulfide (DMTS) had the effect on the configuration of PTF (phytofluene), PT (phytoene), and lycopene. The proportion of their naturally occurring -isomers (1,2-PTF and 15--PT) decreased and transformed into other isomers including all-trans configuration, while -lycopene increased significantly after thermal treatment, especially for 5--lycopene. The results showed that increase in heating temperature, time, and the concentration of DMTS and AITC could promote the isomerization reaction effectively to some extent. In addition, 15--PT and the newly formed 4-PTF were the predominant isomers in tomato at the equilibrium. Unlike the lycopene, which degraded significantly during heat treatment, the isomers of PTF and PT were stable enough to resist decomposition. Moreover, the isomerization of three carotenoids was enhanced, and the bioaccessibility of lycopene increased significantly with the addition of shii-take mushroom containing sulfur compounds, while there was no positive effect observed in that of PTF and PT.
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http://dx.doi.org/10.3390/foods10071444DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8307973PMC
June 2021

Secure Video Surveillance Framework in Smart City.

Sensors (Basel) 2021 Jun 28;21(13). Epub 2021 Jun 28.

Computer Science and Engineering, University of New South Wales, Sydney, NSW 2052, Australia.

In the construction process of smart cities, more and more video surveillance systems have been deployed for traffic, office buildings, shopping malls, and families. Thus, the security of video surveillance systems has attracted more attention. At present, many researchers focus on how to select the region of interest (RoI) accurately and then realize privacy protection in videos by selective encryption. However, relatively few researchers focus on building a security framework by analyzing the security of a video surveillance system from the system and data life cycle. By analyzing the surveillance video protection and the attack surface of a video surveillance system in a smart city, we constructed a secure surveillance framework in this manuscript. In the secure framework, a secure video surveillance model is proposed, and a secure authentication protocol that can resist man-in-the-middle attacks (MITM) and replay attacks is implemented. For the management of the video encryption key, we introduced the Chinese remainder theorem (CRT) on the basis of group key management to provide an efficient and secure key update. In addition, we built a decryption suite based on transparent encryption to ensure the security of the decryption environment. The security analysis proved that our system can guarantee the forward and backward security of the key update. In the experiment environment, the average decryption speed of our system can reach 91.47 Mb/s, which can meet the real-time requirement of practical applications.
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http://dx.doi.org/10.3390/s21134419DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8271794PMC
June 2021
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