Publications by authors named "Rong Sun"

316 Publications

Optimization of Effective Thermal Conductivity of Thermal Interface Materials Based on the Genetic Algorithm-Driven Random Thermal Network Model.

ACS Appl Mater Interfaces 2021 Sep 8. Epub 2021 Sep 8.

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

Polymer-based thermal interface materials (TIMs) are indispensable for reducing the thermal contact resistance of high-power electronic devices. Owing to the low thermal conductivity of polymers, adding multiscale dispersed particles with high thermal conductivity is a common approach to enhance the effective thermal conductivity. However, optimizing multiscale particle matching, including particle size distribution and volume fraction, for improving the effective thermal conductivity has not been achieved. In this study, three kinds of filler-loaded samples were prepared, and the effective thermal conductivity and average particle size of the samples were tested. The finite element model (FEM) and the random thermal network model (RTNM) were applied to predict the effective thermal conductivity of TIMs. Compared with the FEM, the RTNM achieves higher accuracy with an error less than 5% and higher computational efficiency in predicting the effective thermal conductivity of TIMs. Combining the abovementioned advantages, we designed a set of procedures for an RTNM driven by the genetic algorithm (GA). The procedure can find multiscale particle-matching ways to achieve the maximum effective thermal conductivity under a given filler load. The results show that the samples with 40 vol %, 50 vol %, and 60 vol % filler loading have similar particle size distribution and volume fractions when the effective thermal conductivity reaches the highest. It should be emphasized that the optimized effective thermal conductivity can be improved obviously with the increase in the volume fraction of the filler loading. The high efficiency and accuracy of the procedure show great potential for the future design of high-efficiency TIMs.
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http://dx.doi.org/10.1021/acsami.1c11963DOI Listing
September 2021

Stilbene glucoside: recent advances in pharmacology, bioinformatics investigation, toxicity and future opportunities.

Pharmazie 2021 Aug;76(8):351-358

State Key Laboratory of Generic Manufacture Technology of Chinese Traditional Medicine, Linyi; Lunan Pharmaceutical Group Co. Ltd., Linyi;, Email:

2,3,5,4'-Tetrahydroxystilbene-2--β-D-glucoside (TSG) from Thunb. (PMT), is a major bioactive component. This review is aimed to summarize the present development of TSG regarding pharmaceutics, pharmacology and toxicology, with a focus on the novel mechanism of drug-induced toxicity and provides insight for its potential developments and applications in the future on traditional Chinese medicine. : Studies about TSG's activities and toxicity were searched and summarized. Targets and mechanisms were predicted and analyzed with network pharmacology methods. Affinities and binding modes of key targets with TSG were verified by AutoDock Vina software. : TSG plays an essential role among the chemical components of PMT because of multiple pharmacological activities, which suggests a potential application of TSG for a variety of diseases, like atherosclerosis, Alzheimer's disease, Parkinson's disease, cerebral I/R injury, diabetes, osteoporosis, colitis. However, mild liver toxicity of TSG is also pointed out. : As a biologically active natural product in PMT, TSG has shown prospective pharmacological activities, particularly as an agent for cardiovascular protection and neuroprotection.
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http://dx.doi.org/10.1691/ph.2021.1393DOI Listing
August 2021

Sequential enzyme-activated macrotheranostic probe for selective tumor mitochondria targeting.

Acta Biomater 2021 Aug 8. Epub 2021 Aug 8.

National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou, 510006, P.R. China; Institutes for Life Sciences, School of Medicine, South China University of Technology, Guangzhou, 510006, P.R. China; Key Laboratory of Biomedical Materials and Engineering of the Ministry of Education and Innovation Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou, 510006, P.R. China. Electronic address:

Subcellular organelle targeted imaging and therapy are of enormous interest in cancer theranostics. However, the lack of tumor-selective organelle targeting has compromised their efficacy and safety. In this work, we found that the near-infrared (NIR) fluorophore hemicyanine (CyNH) can selectively target mitochondria with strong cytotoxicity through decreasing the mitochondrial membrane potential and increasing the intracellular reactive oxygen species (ROS) levels. A macrotheranostic probe (denoted as PLCy) based on conjugating CyNH with an acetylated lysine group was developed with masked fluorescence and cytotoxicity, which could both be unmasked through sequential activation by cancer cells overexpressing histone deacetylases (HDACs) and cathepsin L (CTSL) enzymes for selective cancer cell mitochondria-targeted imaging and therapy. In vitro and in vivo studies confirmed that the specific fluorescence turn-on and toxicity were restored in cancer cells and efficiently inhibited tumor growth. This macrotheranostic probe with sequential enzyme activation and mitochondrial targeting is expected to have promising applications in imaging-guided cancer therapy with high specificity and efficiency. STATEMENT OF SIGNIFICANCE: To improve the targeting efficiency and enhance the anti-cancer activities of macrotheranostic probe. We designed macrotheranostic probe PLCy that can be activated via sequential enzymes for selective tumor mitochondria targeting. More importantly, the activated CyNH can decrease the mitochondrial membrane potential and elevate the reactive oxygen species level in cancer cells without light irradiation, which can further induce apoptosis of tumor cells for chemotherapy. Therefore, the use of sequential enzyme activation and mitochondria targeting strategies in the context of enzymatic activation may provide a general strategy for organelle-targeted imaging and therapy with high specificity and efficiency.
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http://dx.doi.org/10.1016/j.actbio.2021.08.002DOI Listing
August 2021

Coexistence of magnetic and electric orderings in a divalent Cr-based multiaxial molecular ferroelectric.

Chem Sci 2021 Jul 15;12(28):9742-9747. Epub 2021 Jun 15.

Ordered Matter Science Research Center, Nanchang University Nanchang 330031 P. R. China

Multiferroic materials have attracted great interest because of their underlying new science and promising applications in data storage and mutual control devices. However, they are still very rare and highly imperative to be developed. Here, we report an organic-inorganic hybrid perovskite trimethylchloromethylammonium chromium chloride (TMCM-CrCl), showing the coexistence of magnetic and electric orderings. It displays a paraelectric-ferroelectric phase transition at 397 K with an Aizu notation of 6/, and spin-canted antiferromagnetic ordering with a Néel temperature of 4.8 K. The ferroelectricity originates from the orientational ordering of TMCM cations, and the magnetism is from the [CrCl] framework. Remarkably, TMCM-CrCl is the first experimentally confirmed divalent Cr-based multiferroic material as far as we know. A new category of hybrid multiferroic materials is pointed out in this work, and more Cr-based multiferroic materials will be expectedly developed in the future.
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http://dx.doi.org/10.1039/d1sc01871jDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8293986PMC
July 2021

Homochiral Ferromagnetic Coupling Dy Single-Molecule Magnets with Strong Magneto-Optical Faraday Effects at Room Temperature.

Inorg Chem 2021 Aug 4;60(16):12039-12048. Epub 2021 Aug 4.

State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, China.

By the bridging action of the 6-chloro-2-hydroxypyridine (Hchp) ligand and the terminal coordination role of the homochiral ligand, (-)/(+)-3-trifluoroacetyl camphor (l-Htfc/d-Htfc), a pair of enantiomerically pure dysprosium(III) dinuclear complexes, [Dy(l-tfc)(chp)(MeOH)] (l-) and [Dy(d-tfc)(chp)(MeOH)] (d-), was obtained. Their circular dichroism (CD) spectra verified their enantiomeric nature. Magnetic investigation indicated that they exhibit ferromagnetic interaction and good zero field single-molecule magnet (SMM) properties. The / values of l- and d- at 0 Oe are 180.5 and 181.3 K, respectively, which are large values for homochiral Dy(III) SMMs. A reasonable explanation for the magnetic properties of l- and d- was supplied by calculations. Remarkably, magnetic circular dichroism (MCD) investigation revealed that the chiral Dy enantiomers show a strong magneto-optical Faraday effect at room temperature, suggesting potential applications in magneto-optical devices.
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http://dx.doi.org/10.1021/acs.inorgchem.1c01218DOI Listing
August 2021

Prediction of breast cancer molecular subtypes using DCE-MRI based on CNNs combined with ensemble learning.

Phys Med Biol 2021 Aug 24;66(17). Epub 2021 Aug 24.

School of Medical Instrument and Food Engineering, University of Shanghai for Science and Technology, Shanghai, People's Republic of China.

To design an ensemble learning based prediction model using different breast DCE-MR post-contrast sequence images to distinguish two kinds of breast cancer subtypes (luminal and non-luminal). We retrospectively studied preoperative dynamic contrast enhanced-magnetic resonance imaging and molecular information of 266 breast cancer cases with either luminal subtype (luminal A and luminal B) or non-luminal subtype (human epidermal growth factor receptor 2 and triple negative). Then, multiple bounding boxes covering tumor lesions were acquired from three series of post-contrast DCE-MR sequence images which were determined by radiologists. Afterwards, three baseline convolutional neural networks (CNNs) with same architecture were concurrently trained, followed by preliminary prediction of probabilities from the testing database. Finally, the classification and evaluation of breast subtypes were realized by means of fusing predicted results from three CNNs employed via ensemble learning based on weighted voting. Taking advantage of 5-fold cross validation CV, the average prediction specificity, accuracy, precision and area under the ROC curve on testing dataset for the luminal versus non-luminal are 0.958, 0.852, 0.961, and 0.867, respectively, which empirically demonstrate that our proposed ensemble model has highly reliability and robustness. The breast DCE-MR post-contrast sequence image analysis utilizing the ensemble CNN model based on deep learning could show a valuable and extendible practical application on breast molecular subtype identification.
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http://dx.doi.org/10.1088/1361-6560/ac195aDOI Listing
August 2021

Tailoring Highly Ordered Graphene Framework in Epoxy for High-Performance Polymer-Based Heat Dissipation Plates.

ACS Nano 2021 Jul 26. Epub 2021 Jul 26.

Key Laboratory of Marine Materials and Related Technologies, Zhejiang Key Laboratory of Marine Materials and Protective Technologies, Ningbo Institute of Materials Technology and Engineering (NIMTE), Chinese Academy of Sciences, Ningbo 315201, People's Republic of China.

As the power density and integration level of electronic devices increase, there are growing demands to improve the thermal conductivity of polymers for addressing the thermal management issues. On the basis of the ultrahigh intrinsic thermal conductivity, graphene has exhibited great potential as reinforcing fillers to develop polymer composites, but the resultant thermal conductivity of reported graphene-based composites is still limited. Here, an interconnected and highly ordered graphene framework (HOGF) composed of high-quality and horizontally aligned graphene sheets was developed by a porous film-templated assembly strategy, followed by a stress-induced orientation process and graphitization post-treatment. After embedding into the epoxy (EP), the HOGF/EP composite (24.7 vol %) exhibits a record-high in-plane thermal conductivity of 117 W m K, equivalent to ≈616 times higher than that of neat epoxy. This thermal conductivity enhancement is mainly because the HOGF as a filler concurrently has high intrinsic thermal conductivity, relatively high density, and a highly ordered structure, constructing superefficient phonon transport paths in the epoxy matrix. Additionally, the use of our HOGF/EP as a heat dissipation plate was demonstrated, and it achieved 75% enhancement in practical thermal management performance compared to that of conventional alumina for cooling the high-power LED.
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http://dx.doi.org/10.1021/acsnano.1c01332DOI Listing
July 2021

Molecular Dynamics and Light Absorption Properties of Atmospheric Dissolved Organic Matter.

Environ Sci Technol 2021 08 21;55(15):10268-10279. Epub 2021 Jul 21.

State Key Laboratory of Organic Geochemistry and Guangdong Province Key Laboratory of Environmental Protection and Resources Utilization, Guangzhou Institute of Geochemistry, Chinese Academy of Sciences, Guangzhou 510640, China.

The light-absorbing organic aerosol referred to as brown carbon (BrC) affects the global radiative balance. The linkages between its molecular composition and light absorption properties and how environmental factors influence BrC composition are not well understood. In this study, atmospheric dissolved organic matter (ADOM) in 55 aerosol samples from Guangzhou was characterized using Fourier transform ion cyclotron resonance mass spectrometry and light absorption measurements. The abundant components in ADOM were aliphatics and peptide-likes (in structure), or nitrogen- and sulfur-containing compounds (in elemental composition). The light absorption properties of ADOM were positively correlated with the levels of unsaturated and aromatic structures. Particularly, 17 nitrogen-containing species, which are identified by a random forest, characterized the variation of BrC absorption well. Aggregated boosted tree model and nonmetric multidimensional scaling analysis show that the BrC composition was largely driven by meteorological conditions and anthropogenic activities, among which biomass burning (BB) and OH radical were the two important factors. BrC compounds often accumulate with elevated BB emissions and related secondary processes, whereas the photolysis/photooxidation of BrC usually occurs under high solar radiance/OH concentration. This study first illuminated how environmental factors influence BrC at the molecular level and provided clues for the molecular-level research of BrC in the future.
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http://dx.doi.org/10.1021/acs.est.1c01770DOI Listing
August 2021

Replication-Dependent Biogenesis of Turnip Crinkle Virus Long Noncoding RNAs.

J Virol 2021 Aug 25;95(18):e0016921. Epub 2021 Aug 25.

Department of Plant Pathology, Ohio Agricultural Research and Development Center, The Ohio State Universitygrid.261331.4, Wooster, Ohio, USA.

Long noncoding RNAs (lncRNAs) of virus origin accumulate in cells infected by many positive-strand (+) RNA viruses to bolster viral infectivity. Their biogenesis mostly utilizes exoribonucleases of host cells that degrade viral genomic or subgenomic RNAs in the 5'-to-3' direction until being stalled by well-defined RNA structures. Here, we report a viral lncRNA that is produced by a novel replication-dependent mechanism. This lncRNA corresponds to the last 283 nucleotides of the turnip crinkle virus (TCV) genome and hence is designated tiny TCV subgenomic RNA (ttsgR). ttsgR accumulated to high levels in TCV-infected Nicotiana benthamiana cells when the TCV-encoded RNA-dependent RNA polymerase (RdRp), also known as p88, was overexpressed. Both (+) and (-) strand forms of ttsgR were produced in a manner dependent on the RdRp functionality. Strikingly, templates as short as ttsgR itself were sufficient to program ttsgR amplification, as long as the TCV-encoded replication proteins p28 and p88 were provided in . Consistent with its replicational origin, ttsgR accumulation required a 5' terminal carmovirus consensus sequence (CCS), a sequence motif shared by genomic and subgenomic RNAs of many viruses phylogenetically related to TCV. More importantly, introducing a new CCS motif elsewhere in the TCV genome was alone sufficient to cause the emergence of another lncRNA. Finally, abolishing ttsgR by mutating its 5' CCS gave rise to a TCV mutant that failed to compete with wild-type TCV in . Collectively, our results unveil a replication-dependent mechanism for the biogenesis of viral lncRNAs, thus suggesting that multiple mechanisms, individually or in combination, may be responsible for viral lncRNA production. Many positive-strand (+) RNA viruses produce long noncoding RNAs (lncRNAs) during the process of cellular infections and mobilize these lncRNAs to counteract antiviral defenses, as well as coordinate the translation of viral proteins. Most viral lncRNAs arise from 5'-to-3' degradation of longer viral RNAs being stalled at stable secondary structures. Here, we report a viral lncRNA that is produced by the replication machinery of turnip crinkle virus (TCV). This lncRNA, designated ttsgR, shares the terminal characteristics with TCV genomic and subgenomic RNAs and overaccumulates in the presence of moderately overexpressed TCV RNA-dependent RNA polymerase (RdRp). Furthermore, templates that are of similar sizes as ttsgR are readily replicated by TCV replication proteins (p28 and RdRp) provided from nonviral sources. In summary, this study establishes an approach for uncovering low abundance viral lncRNAs, and characterizes a replicating TCV lncRNA. Similar investigations on human-pathogenic (+) RNA viruses could yield novel therapeutic targets.
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http://dx.doi.org/10.1128/JVI.00169-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8387050PMC
August 2021

Hormone silent giant adrenal incidentaloma-adrenal ganglioneuroma: case report and literature review.

Rofo 2021 Jun 17. Epub 2021 Jun 17.

Urology, Liaocheng People's Hospital, Liaocheng City, China.

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http://dx.doi.org/10.1055/a-1487-6740DOI Listing
June 2021

Nanoparticles as a Hedgehog signaling inhibitor for the suppression of cancer growth and metastasis.

Nanoscale 2021 Jul;13(25):11077-11085

Laboratory of Nanoscale Biochemical Analysis, Institute of Functional Nano and Soft Materials (FUNSOM) and Collaborative Innovation Center of Suzhou Nano Science and Technology, Soochow University, Suzhou 215123, China.

Nanoparticles (NPs) have been intensively explored for the treatment of tumors during the past decade, yet little information has been provided on the NPs' inherent therapeutic activity against cancers. With this goal in mind, we reveal that biocompatible silicon (Si) NPs (SiNPs) feature excellent anti-growth and anti-metastasis activities against prostate cancer cells that show aberrant activation of the Hedgehog (HH) signaling pathway. Without activation by the Sonic hedgehog (Shh)-agonist, mouse embryonic fibroblast (NIH3T3) cells show no response to SiNP exposure. The distinct inhibitory effect of SiNPs on the HH signaling pathway leads to significant suppression of the proliferation, migration, and invasion of human prostate cancer cells. Crucially, in two mouse tumor models, the growth and metastasis of prostate cancer cells are also efficiently inhibited by SiNPs.
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http://dx.doi.org/10.1039/d1nr02157eDOI Listing
July 2021

Targeted Noninvasive Treatment of Choroidal Neovascularization by Hybrid Cell-Membrane-Cloaked Biomimetic Nanoparticles.

ACS Nano 2021 06 26;15(6):9808-9819. Epub 2021 May 26.

Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangdong 510120, China.

Choroidal neovascularization (CNV) is the leading cause of vision loss in many blinding diseases, but current antiangiogenic therapies with invasively intravitreal injection suffer from poor patient compliance and a rate of devastating ocular complications. Here, we develop an alternative antiangiogenic agent based on hybrid cell-membrane-cloaked nanoparticles for noninvasively targeted treatment of CNV. The retinal endotheliocyte membrane coating provides as-fabricated nanoagents with homotypic targeting capability and binding ability to the vascular endothelial growth factor. The fusion of red blood cell membranes protects the hybrid membrane-coated nanoparticles from phagocytosis by macrophages. In a laser-induced wet age-related macular degeneration mouse model, a significantly enhanced accumulation is observed in CNV regions after intravenous delivery of the hybrid membrane-coated nanoparticles. Moreover, an excellent therapeutic efficacy is achieved in reducing the leakage and area of CNV. Overall, the biomimetic antiangiogenic nanoagents provide an effective approach for noninvasive treatment of CNV.
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http://dx.doi.org/10.1021/acsnano.1c00680DOI Listing
June 2021

Dihydroartemisinin inhibits endothelial cell migration via the TGF-β1/ALK5/SMAD2 signaling pathway.

Exp Ther Med 2021 Jul 3;22(1):709. Epub 2021 May 3.

Laboratory of Microvascular Medicine, Medical Research Center, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong 250014, P.R. China.

Anti-angiogenesis therapy is a novel treatment method for malignant tumors. Endothelial cell (EC) migration is an important part of angiogenesis. Dihydroartemisinin (DHA) exhibits strong anti-angiogenic and anti-EC migration effects; however, the underlying molecular mechanisms are yet to be elucidated. The TGF-β1/activin receptor-like kinase 5 (ALK5)/SMAD2 signaling pathway serves an important role in the regulation of migration. The present study aimed to explore the effects of DHA treatment on EC migration and the TGF-β1/ALK5/SMAD2 signaling pathway. The effects of DHA on human umbilical vein EC migration were assessed using wound healing and Transwell assays. The effects of DHA on the TGF-β1/ALK5/SMAD2 signaling pathway were detected using western blotting. DHA exhibited an inhibitory effect on EC migration in the wound healing and Transwell assays. DHA treatment upregulated the expression levels of ALK5 and increased the phosphorylation of SMAD2 in ECs. SB431542 rescued the inhibitory effect of DHA during EC migration. DHA inhibited EC migration via the TGF-β1/ALK5/SMAD2-dependent signaling pathway, and DHA may be a novel drug for the treatment of patients with malignant tumors.
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http://dx.doi.org/10.3892/etm.2021.10141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120513PMC
July 2021

Morphology-Tunable Synthesis of Intrinsic Room-Temperature Ferromagnetic γ-FeO Nanoflakes.

ACS Appl Mater Interfaces 2021 May 17;13(20):24051-24061. Epub 2021 May 17.

International Iberian Nanotechnology Laboratory (INL), Avenida Mestre José Veiga, Braga 4715-330, Portugal.

Intrinsic two-dimensional (2D) magnetic materials with room-temperature ferromagnetism and air stability are highly desirable for spintronic applications. However, the experimental observations of such 2D or ultrathin ferromagnetic materials are rarely reported owing to the scarcity of these materials in nature and for the intricacy in their synthesis. Here, we report a successful controllable growth of ultrathin γ-FeO nanoflakes with a variety of morphologies tunable by the growth temperature alone using a facile chemical vapor deposition method and demonstrate that all ultrathin nanoflakes still show intrinsic room-temperature ferromagnetism and a semiconducting nature. The γ-FeO nanoflakes epitaxially grown on α-AlO substrates take a triangular shape at low temperature and develop gradually in lateral size, forming eventually a large-scale γ-FeO thin film as the growth time increases due to a thermodynamic control process. The morphology of the nanoflakes could be tuned from triangular to stellated, petaloid, and dendritic crystalloids in sequence with the rise of precursor temperature, revealing a growth process from thermodynamically to kinetically dominated control. Moreover, the petaloid and dendritic nanoflakes exhibit enhanced coercivity compared with the triangular and stellated nanoflakes, and all the nanoflakes with diverse shapes possess differing electrical conductivity. The findings of such ultrathin, air-stable, and room-temperature ferromagnetic γ-FeO nanoflakes with tunable shape and multifunctionality may offer guidance in synthesizing other non-layered magnetic materials for next-generation electronic and spintronic devices.
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http://dx.doi.org/10.1021/acsami.1c05342DOI Listing
May 2021

Identification of a RAD52 Inhibitor Inducing Synthetic Lethality in BRCA2-Deficient Cancer Cells.

Front Pharmacol 2021 29;12:637825. Epub 2021 Apr 29.

Institute of Cancer Biology and Drug Discovery, Chengdu University, Chengdu, China.

The breast cancer susceptibility gene 1/2 (BRCA1/2) is frequently mutated in many malignant tumors, such as breast cancer and ovarian cancer. Studies have demonstrated that inhibition of RAD52 gene function in BRCA2-deficient cancer causes synthetic lethality, suggesting a potential application of RAD52 in cancer-targeted therapy. In this study, we have performed a virtual screening by targeting the self-association domain (residues 85-159) of RAD52 with a library of 66,608 compounds and found one compound, C791-0064, that specifically inhibited the proliferation of BRCA2-deficient cancer cells. Our biochemical and cell-based experimental data suggested that C791-0064 specifically bound to RAD52 and disrupted the single-strand annealing activity of RAD52. Taken together, C791-0064 is a promising leading compound worthy of further exploitation in the context of BRCA-deficient targeted cancer therapy.
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http://dx.doi.org/10.3389/fphar.2021.637825DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8118686PMC
April 2021

The endoribonuclease N4BP1 prevents psoriasis by controlling both keratinocytes proliferation and neutrophil infiltration.

Cell Death Dis 2021 05 14;12(5):488. Epub 2021 May 14.

Department of Pathogenic Biology, School of Medicine, Nantong University, 226001, Jiangsu, China.

Psoriasis is a common chronic skin disease, characterized by abnormal interplay between hyperproliferative epidermal keratinocytes and self-reactive immune cells with not fully addressed molecular mechanism. N4BP1 (NEDD4-binding protein 1) is considered as an immune regulator for a long time but its physiological role is not determined yet. Here, we found that the expression of N4BP1 in skin was highest among all 54 tested tissues, and its expression was further upregulated in psoriatic skin. N4BP1-deficient mice exhibited normal grossly, but developed severe and prolonged IMQ-induced psoriasis-like disease comparing to controls. N4BP1 mainly expressed in keratinocytes and located on nucleus. Up- but not downregulated genes in N4BP1-deficient skin were specifically enriched in keratinocyte proliferation and differentiation. The proliferation of N4BP1-deficient primary keratinocytes was faster compared to that of controls. The upregulated genes upon ablation of N4BP1 were highly enriched in targets of AP-1 transcription factor. Knocking out N4BP1 resulted in upregulation of JunB and FosB, and conversely, overexpression of N4BP1 greatly reduced their expression. Furthermore, N4BP1 binds with JunB and FosB encoding mRNAs and greatly reduces their stability. In addition, with a high expression in neutrophils, N4BP1 limits survival of neutrophils in blood and infiltration of neutrophils in psoriatic skin by targeting CXCL1, CCL20, and S100A8. These findings demonstrate that N4BP1 controls the proper function of keratinocytes and neutrophils by negatively regulating JunB, FosB, and CXCL1, respectively, and that is critical for psoriasis prevention.
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http://dx.doi.org/10.1038/s41419-021-03774-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8121926PMC
May 2021

Enhancing the magnetic performance of pyrazine-N-oxide bridged dysprosium chains through controlled variation of ligand coordination modes.

Dalton Trans 2021 May 4;50(20):7048-7055. Epub 2021 May 4.

Department of Chemistry and Beijing Key Laboratory of Energy Conversion and Storage Materials, Beijing Normal University, Beijing 100875, P. R. China.

While assembling superparamagnetic units in a controlled manner is crucial for future applications of molecular nanomagnets, optimizing their magnetic properties while achieving directional assembly of these units still remains a formidable challenge. Herein, we demonstrate how the assembly of two dysprosium chain complexes, namely, [Dy(L)Cl(CHOH)]·nCHOH (1) and [Dy(L)Cl(DMF)] (2) (HL = N'-(5-bromo-2-hydroxybenzylidene)pyrazine-N-oxide-carbohydrazide), can be successfully manipulated using an appropriate bridging ligand design. Both complexes contain similar dimeric units bridged by two alkoxido oxygens from an L ligand, but extended by its pyrazine-N-oxide group exhibiting two distinct coordination modes, namely, single and double pyrazine-N-oxide bridges, respectively. Magnetic studies reveal that both complexes display typical slow magnetic relaxation under zero direct-current field; however, the anisotropy barrier and the coercive field at 2 K for complex 2 are twice as much as that of 1. A further theoretical study indicates that switching the coordination mode from a single pyrazine-N-oxide bridge to double bridges can enhance both the magnetic anisotropy of dysprosium ions and magnetic coupling within the dimeric cores. The synergistic effect between the magnetic anisotropy of dysprosium ions and magnetic interactions among them directly contributes to the overall better performance of complex 2.
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http://dx.doi.org/10.1039/d1dt00635eDOI Listing
May 2021

Ziyuglycoside II inhibits the growth of digestive system cancer cells through multiple mechanisms.

Chin J Nat Med 2021 May;19(5):351-363

School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, China. Electronic address:

Digestive system cancers, including liver, gastric, colon, esophageal and pancreatic cancers, are the leading cause of cancers with high morbidity and mortality, and the question of their clinical treatment is still open. Previous studies have indicated that Ziyuglycoside II (ZYG II), the major bioactive ingredient extract from Sanguisorba officinalis L., significantly inhibits the growth of various cancer cells. However, the selective anti-tumor effects of ZYG II against digestive system cancers are not systemically investigated. In this study, we reported the anti-cancer effect of ZYG II on esophageal cancer cells (OE21), cholangiocarcinoma cells (HuCCT1), gastric cancer cells (BGC-823), liver cancer cells (HepG2), human colonic cancer cells (HCT116), and pancreatic cancer cells (PANC-1). We also found that ZYG II induced cell cycle arrest, oxidative stress and mitochondrial apoptosis. Network pharmacology analysis suggested that UBC, EGFR and IKBKG are predicted targets of ZYG II. EGFR signaling was suggested as the critical pathway underlying the anti-cancer effects of ZYG II and both docking simulation and western blot analysis demonstrated that ZYG II was a potential EGFR inhibitor. Furthermore, our results showed synergistic inhibitory effects of ZYG II and chemotherapy 5-FU on the growth of cancer cells. In summary, ZYG II are effective anti-tumor agents against digestive cancers. Further systemic evaluation of the anti-cancer activities in vitro and in vivo and characterization of underlying mechanism will promote the development of novel supplementary therapeutic strategies based on ZYG II for the treatment of digestive system cancers.
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http://dx.doi.org/10.1016/S1875-5364(21)60033-XDOI Listing
May 2021

Hydrothermal Synthesis of Zinc-Doped Silica Nanospheres Simultaneously Featuring Stable Fluorescence and Long-Lived Room-Temperature Phosphorescence.

Angew Chem Int Ed Engl 2021 Jul 9;60(28):15490-15496. Epub 2021 Jun 9.

Laboratory of Nanoscale Biochemical Analysis, Institute of Functional Nano and Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Soochow University, Jiangsu, Suzhou, 215123, China.

Fluorescence and phosphorescence are known as two kinds of fundamental optical signals, which have been used for myriad applications. To date, simultaneous activation of stable fluorescence and long-lived room-temperature phosphorescence (RTP) emission in the aqueous phase remains a big challenge. We prepare zinc-doped silica nanospheres ([email protected]) with fluorescence and RTP properties using a facile hydrothermal synthetic strategy. For the as-prepared [email protected], the recombination of electrons and holes in defects and defect-stabilized excitons derived from oxygen vacancy/C=N bonds lead to the production of stable fluorescence and long-lived RTP (emission lasting for ≈9 s, quantum yield (QY): ≈33.6 %, RTP lifetime: ≈236 ms). The internal Si-O bonded networks and hydrophilic surface in [email protected] can reduce nonradiative decay to form self-protective RTP, and also provide high water solubility, excellent pH- and photostability.
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http://dx.doi.org/10.1002/anie.202103200DOI Listing
July 2021

Efficacy and safety of endocrine therapy for breast-cancer prevention in high-risk premenopausal or postmenopausal women: a Bayesian network meta-analysis of nine randomized controlled trials.

Menopause 2021 04 12;28(5):589-600. Epub 2021 Apr 12.

Department of Oncology, Affiliated Hospital of Jining Medical University, Zaozhuang Municipal Hospital, Zaozhuang, China.

Importance: Findings in this work might provide certain guidance for current clinical work.

Objective: This study aimed to evaluate the efficacy and safety of these drugs based on the Bayesian network meta-analysis.

Evidence Review: Two researchers systematically and comprehensively searched PubMed, Embase, and the central databases of the Cochrane Library from inception to September 15, 2020. The number of specific events and sample size were extracted from each of the included studies. This Bayesian theory-based network meta-analysis included indirect comparisons and mixed treatment analysis. Indirect comparisons compare the efficacy of at least three interventions simultaneously and are mostly used when there are few direct comparison studies. In addition, indirect comparisons are conducted on the basis of direct comparisons through mixed treatment analysis, which can thus improve the accuracy of analysis.

Findings: A total of nine randomized controlled trials involving 60,732 participants were included. As a result, compared with placebo in high-risk pre- or postmenopausal women, endocrine therapy (ET) decreased the risks of total breast cancer (TBC, odds ratio [OR] 0.69, 95% confidence interval [CI] 0.56-0.85), invasive breast cancer (IBC, OR 0.69, 95% CI 0.53-0.89), estrogen receptor-positive breast cancer (ER+BC) (OR 0.49, 95% CI 0.38-0.64), and ductal carcinoma in situ (OR 0.74, 95% CI 0.56-0.98), but increased the risks of pulmonary embolism (OR 1.33, 95% CI 1.05-1.69), total venous thrombosis (OR 1.75, 95% CI 1.28-2.38), and endometrial carcinoma (EC, OR 1.84, 95% CI 1.17-2.88). In further network stratification analyses, anastrozole, exemestane, and tamoxifen were found to decrease the risks of TBC, IBC, and ER + BC relative to placebo. Similarly, raloxifene decreased the risk of IBC (OR 0.65, 95% CI 0.48-0.85), while tamoxifen increased the risk of EC (OR 2.42, 95% CI 1.10-7.35).

Conclusions And Relevance: To sum up, ET decreased the risks of TBC, IBC, ER + BC, and ductal carcinoma in situ, while increasing the risks of pulmonary embolism, total venous thrombosis, and EC in high-risk pre- or postmenopausal women. Meanwhile, anastrozole, exemestane, and tamoxifen possibly exerted potential protective effects on TBC, IBC and ER + BC. Typically, raloxifene might be effective on IBC, while tamoxifen might increase the risk of EC. Therefore, clinicians should fully weigh the benefits and risks of ET to develop a rational individualized treatment.
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http://dx.doi.org/10.1097/GME.0000000000001763DOI Listing
April 2021

Multiscale Structural Modulation of Anisotropic Graphene Framework for Polymer Composites Achieving Highly Efficient Thermal Energy Management.

Adv Sci (Weinh) 2021 Apr 19;8(7):2003734. Epub 2021 Feb 19.

Key Laboratory of Marine Materials and Related Technologies Zhejiang Key Laboratory of Marine Materials and Protective Technologies Ningbo Institute of Materials Technology and Engineering (NIMTE) Chinese Academy of Sciences Ningbo 315201 P. R. China.

Graphene is usually embedded into polymer matrices for the development of thermally conductive composites, preferably forming an interconnected and anisotropic framework. Currently, the directional self-assembly of exfoliated graphene sheets is demonstrated to be the most effective way to synthesize anisotropic graphene frameworks. However, achieving a thermal conductivity enhancement (TCE) over 1500% with per 1 vol% graphene content in polymer matrices remains challenging, due to the high junction thermal resistance between the adjacent graphene sheets within the self-assembled graphene framework. Here, a multiscale structural modulation strategy for obtaining highly ordered structure of graphene framework and simultaneously reducing the junction thermal resistance is demonstrated. The resultant anisotropic framework contributes to the polymer composites with a record-high thermal conductivity of 56.8-62.4 W m K at the graphene loading of ≈13.3 vol%, giving an ultrahigh TCE per 1 vol% graphene over 2400%. Furthermore, thermal energy management applications of the composites as phase change materials for solar-thermal energy conversion and as thermal interface materials for electronic device cooling are demonstrated. The finding provides valuable guidance for designing high-performance thermally conductive composites and raises their possibility for practical use in thermal energy storage and thermal management of electronics.
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http://dx.doi.org/10.1002/advs.202003734DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8025029PMC
April 2021

Remote Ischemic Preconditioning to Prevent Acute Kidney Injury After Cardiac Surgery: A Meta-Analysis of Randomized Controlled Trials.

Front Cardiovasc Med 2021 18;8:601470. Epub 2021 Mar 18.

Department of Thoracic and Cardiovascular Surgery, Shenzhen Baoan Women's and Children's Hospital, Jinan University, Guangzhou, China.

Randomized controlled trials (RCTs) evaluating the influence of remote ischemic preconditioning (RIPC) on acute kidney injury (AKI) after cardiac surgery showed inconsistent results. We performed a meta-analysis to evaluate the efficacy of RIPC on AKI after cardiac surgery. Relevant studies were obtained by search of PubMed, Embase, and Cochrane's Library databases. A random-effect model was used to pool the results. Meta-regression and subgroup analyses were used to determine the source of heterogeneity. Twenty-two RCTs with 5,389 patients who received cardiac surgery -2,702 patients in the RIPC group and 2,687 patients in the control group-were included. Moderate heterogeneity was detected ( for Cochrane's test = 0.03, = 40%). Pooled results showed that RIPC significantly reduced the incidence of AKI compared with control [odds ratio (OR): 0.76, 95% confidence intervals (CI): 0.61-0.94, = 0.01]. Results limited to on-pump surgery (OR: 0.78, 95% CI: 0.64-0.95, = 0.01) or studies with acute RIPC (OR: 0.78, 95% CI: 0.63-0.97, = 0.03) showed consistent results. Meta-regression and subgroup analyses indicated that study characteristics, including study design, country, age, gender, diabetic status, surgery type, use of propofol or volatile anesthetics, cross-clamp time, RIPC protocol, definition of AKI, and sample size did not significantly affect the outcome of AKI. Results of stratified analysis showed that RIPC significantly reduced the risk of mild-to-moderate AKI that did not require renal replacement therapy (RRT, OR: 0.76, 95% CI: 0.60-0.96, = 0.02) but did not significantly reduce the risk of severe AKI that required RRT in patients after cardiac surgery (OR: 0.73, 95% CI: 0.50-1.07, = 0.11). Current evidence supports RIPC as an effective strategy to prevent AKI after cardiac surgery, which seems to be mainly driven by the reduced mild-to-moderate AKI events that did not require RRT. Efforts are needed to determine the influences of patient characteristics, procedure, perioperative drugs, and RIPC protocol on the outcome.
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http://dx.doi.org/10.3389/fcvm.2021.601470DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8012491PMC
March 2021

Simultaneous Determination of Nine Residual Solvents in Sorafenib Tosylate by Gas Chromatography.

J AOAC Int 2021 Aug;104(4):1005-1009

China Pharmaceutical University, Department of Pharmaceutics, Nanjing 211198, China.

Background: Direct injection gas chromatography is convenient and quick. The residual solvent with a higher boiling point can be measured by using direct inhection gas chromatography. This method could be developed for residual solvents analysis of sorafenible tosylate.

Objective: In the present investigation, the injection method was developed and validated for the detection and quantification of residual solvents in sorafenib tosylate.

Method: The nine kinds of residual solvents were separated using direct injection gas chromatographic technology, and a quantitative analysis was performed. Analytical performance of the proposed injection method was validated as per the defined guidelines with respect to linearity, accuracy, precision, robustness, and specificity.

Results: Under the optimized conditions, simultaneous separation and determination of nine kinds of residual solvents, including methanol, acetonitrile, ethyl acetate, tetrahydrofuran, chlorobenzene, toluene, acetone, dichloromethane, and N, N-dimethylformamide were carried out using a DB-WAXETR polyethylene glycol Inertap Pure-WAX column (30 m × 0. 32 mm × 0.25 µm) for separation. The calibration plot was found to be linear, accurate, precise, robust, and specific for direct injection gas chromatography. The residual solvents in sorafenib tosylate were quantified by the developed method.

Conclusions: The present method was successfully applied for analysis of residual solvents in sorafenib tosylate. Similarly, the method can be used for quality control and stability testing of other medicines.

Highlights: A validated GC assay for the combined analysis of the nine solutions which offered a reference method for the detection of residual solvents in other medicines.
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http://dx.doi.org/10.1093/jaoacint/qsab041DOI Listing
August 2021

Ultrahigh-Aspect-Ratio Boron Nitride Nanosheets Leading to Superhigh In-Plane Thermal Conductivity of Foldable Heat Spreader.

ACS Nano 2021 Apr 18;15(4):6489-6498. Epub 2021 Mar 18.

Key Laboratory of Marine Materials and Related Technologies, Zhejiang Key Laboratory of Marine Materials and Protective Technologies, Ningbo Institute of Materials Technology and Engineering (NIMTE), Chinese Academy of Sciences, Ningbo, 315201, P. R. China.

The rapid development of integrated circuits and electronic devices creates a strong demand for highly thermally conductive yet electrically insulating composites to efficiently solve "hot spot" problems during device operation. On the basis of these considerations, hexagonal boron nitride nanosheets (BNNS) have been regarded as promising fillers to fabricate polymer matrix composites. However, so far an efficient approach to prepare ultrahigh-aspect-ratio BNNS with large lateral size while maintaining an atomically thin nature is still lacking, seriously restricting further improvement of the thermal conductivity for BNNS/polymer composites. Here, a rapid and high-yield method based on a microfluidization technique is developed to obtain exfoliated BNNS with a record high aspect ratio of ≈1500 and a low degree of defects. A foldable and electrically insulating film made of such a BNNS and poly(vinyl alcohol) (PVA) matrix through filtration exhibits an in-plane thermal conductivity of 67.6 W m K at a BNNS loading of 83 wt %, leading to a record high value of thermal conductivity enhancement (≈35 500). The composite film then acts as a heat spreader for heat dissipation of high-power LED modules and shows superior cooling efficiency compared to commercial flexible copper clad laminate. Our findings provide a practical route to produce electrically insulating polymer composites with high thermal conductivity for thermal management applications in modern electronic devices.
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http://dx.doi.org/10.1021/acsnano.0c09229DOI Listing
April 2021

Regional characteristics of atmospheric δS-SO over three parts of Asia monitored by quartz wool-based passive samplers.

Sci Total Environ 2021 Jul 5;778:146107. Epub 2021 Mar 5.

State Key Laboratory of Organic Geochemistry and Guangdong province Key Laboratory of Environmental Protection and Resources Utilization, Guangzhou Institute of Geochemistry, Chinese Academy of Sciences, Guangzhou 510640, China; CAS Center for Excellence in Deep Earth Science, Guangzhou 510640, China; Guangdong-Hong Kong-Macao Joint Laboratory for Environmental Pollution and Control, Guangzhou Institute of Geochemistry, Chinese Academy of Science, Guangzhou 510640, China.

A new method is presented for measuring atmospheric contents and δS-SO in airborne particulate matter using quartz wool disk passive air samplers (Pas-QW). The ability of Pas-QW samplers to provide time-integrated measurements of atmospheric SO was confirmed in a field calibration study. The average sampling rate of SO measured was 2.3 ± 0.3 m/day, and this was not greatly affected by changes in meteorological parameters. The results of simultaneous sampling campaign showed that the average SO contents in Pakistan and the Indochina Peninsula (ICP) were relatively lower than that of China. The spatial distribution of SO concentrations was largely attributed to the development of the regional economies. The range of δS values observed in Pakistan (4.3 ± 1.4‰) and the ICP (4.5 ± 1.2‰) were relatively small, while a large range of δS values was observed in China (3.9 ± 2.5‰). The regional distribution of sulfur isotope compositions was significantly affected by coal combustion. A source analysis based on a Bayesian mixing model showed that 80.4 ± 13.1% and 19.6 ± 13.1% of artificial sulfur dioxide (SO) sources in China could be attributed to coal combustion and oil combustion, respectively. The two sources differed greatly between regions, and the contribution of oil combustion in cities was higher than previously reported data obtained from emission inventories. This study confirmed that the Pas-QW is a promising tool for simultaneously monitoring atmospheric δS-SO over large regions, and that the results of the isotope models can provide a reference for the compilation of SO emission inventories.
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http://dx.doi.org/10.1016/j.scitotenv.2021.146107DOI Listing
July 2021

On-surface preparation of coordinated lanthanide-transition-metal clusters.

Nat Commun 2021 Mar 12;12(1):1619. Epub 2021 Mar 12.

Key Laboratory for the Physics and Chemistry of Nanodevices and Center for Carbon-based Electronics, Department of Electronics, Peking University, Beijing, China.

The study of lanthanide (Ln)-transition-metal (TM) heterometallic clusters which play key roles in various high-tech applications is a rapid growing field of research. Despite the achievement of numerous Ln-TM cluster compounds comprising one Ln atom, the synthesis of Ln-TM clusters containing multiple Ln atoms remains challenging. Here, we present the preparation and self-assembly of a series of Au-bridged heterometallic clusters containing multiple cerium (Ce) atoms via on-surface coordination. By employing different pyridine and nitrile ligands, the ordered coordination assemblies of clusters containing 2, 3 and 4 Ce atoms bridged by Au adatoms are achieved on Au(111) and Au(100), as revealed by scanning tunneling microscopy. Density functional theory calculations uncover the indispensable role of the bridging Au adatoms in constructing the multi-Ce-containing clusters by connecting the Ce atoms via unsupported Ce-Au bonds. These findings demonstrate on-surface coordination as an efficient strategy for preparation and organization of the multi-Ln-containing heterometallic clusters.
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http://dx.doi.org/10.1038/s41467-021-21911-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7954866PMC
March 2021

Numerical homogenization of thermal conductivity of particle-filled thermal interface material by fast Fourier transform method.

Nanotechnology 2021 Mar 2. Epub 2021 Mar 2.

School of Materials Science and Engineering, Georgia Institute of Technology, Atlanta, UNITED STATES.

Thermal interface material (TIM) is pivotal for the heat dissipation between layers of high-density electronic packaging. The most widely used TIMs are the particle-filled composite materials, in which the highly conductive particulate fillers are added into the polymer matrix to promote the heat conduction. The numerical simulation of heat transfer in the composites is essential for the design of TIMs, however, the widely used finite element method requires large memory and presents limited computational time for the composites with dense particles. In this work, a numerical homogenization algorithm based on fast Fourier transform was adopted to estimate the thermal conductivity of composites with randomly dispersed particles in 3D space. The unit cell problem is solved by means of a polarization based iterative scheme, which can accelerate the convergence procedure regardless of the contrast between various components. The algorithm shows good precision and requirs dramatically reduced computation time and cost comparing with finite element method. Moreover, the effect of particle volume fraction, interface thermal resistance between particles (R-PP), interface thermal resistance between particle and matrix (R-PM), and particle size have been estimated. It turns out that the effective conductivity of the particulate composites increases sharply at a critical filler volume fraction, after which it is sensitive to the variation of filler loading. We can observe that the effective thermal conductivity of the composites with low filler volume fraction is sensitive to R-PM, whereas the it is governed by R-PP for the compsosites with high filler content. The algorithm presents excellent efficiency and accuracy, showing potential for the future design of highly thermally conductive TIMs.
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http://dx.doi.org/10.1088/1361-6528/abeb3cDOI Listing
March 2021

Is Qi Fu Yin effective in clinical treatment of dementia?: A meta-analysis of 697 patients.

Medicine (Baltimore) 2021 Feb;100(5):e24526

College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan.

Background: Dementia, a kind of acquired and progressive intelligence-damaging syndrome, is induced by cerebral dysfunction. Ancient records show that Qi Fu Yin (QFY) has the advantages in age-related dementia treatment. This study aims to evaluate therapeutic efficacy of QFY on dementia through meta-analysis.

Methods: We comprehensively reviewed articles from various databases, including China National Knowledge Infrastructure (CNKI), Wanfang, VIP, Chinese Biomedical Literature (CBM), PubMed, and Web of Science published before June 2020, for all randomized controlled trials (RCTs) on dementia treatment with QFY. Then, we selected eligible literatures, extracted related data, and assessed risk of bias. Forest plots of total clinical effective rate, MMSE score, HDS score and ADL score illustrated the difference between the experimental group (treatment with QFY alone or combined with routine western medicine) and the control group (treatment with routine western medicine only). Random effects model and fixed effects model were adopted. Finally, publication bias was further analyzed using funnel plot, sensitivity analysis, Begg and Egger test.

Results: Finally, 9 RCTs, involving 697 patients, were included in this study. The results revealed that the total clinical effective rate of the experimental group was obviously higher than that of the control group (OR = 0.33, 95% CI [0.22, 0.50], P < .001). In comparison with the control group, the experimental group showed higher MMSE score (WMD = 2.60, 95% CI [2.16, 3.03], P < .001) and HDS score (WMD = 1.51, 95%CI [1.10, 1.92], P < .001). Due to few included studies, there were no statistically significance between experimental and control groups (WMD = -9.90, 95%CI [-26.09, 6.30], P = .231) regarding ADL score. In addition, there is no publication bias towards clinical effective rate and MMDE score.

Conclusions: QFY only or combined with western medicine therapy can significantly improve cognitive ability compared with only western medicine therapy in dementia. However, multiple samples, RCTs of high quality are still needed to verify our conclusions.
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http://dx.doi.org/10.1097/MD.0000000000024526DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7870270PMC
February 2021

[Study on construction of rat model of acute pancreatitis with syndrome of liver depression and Qi stagnation].

Zhongguo Zhong Yao Za Zhi 2020 Dec;45(23):5732-5737

Institute of Medical Sciences, the Second Hospital, Cheeloo College of Medicine, Shandong University Ji'nan 250033, China Advanced Medical Research Institute, Cheeloo College of Medicine, Shandong University Ji'nan 250012, China.

The aim of this paper was to construct a rat model of acute pancreatitis(AP) with syndrome of liver depression and Qi stagnation, and provide evaluation tools for pharmacodynamic research and efficacy network verification of related traditional Chinese medicine in view of the etiology, pathogenesis and clinical manifestations of AP. According to the Chinese and Western medicine diagnosis and treatment guidelines for AP with syndrome of liver depression and Qi stagnation, etiology, pathogenesis and clinical syndromes in TCM, Meta-analysis results, and evaluation strategy of establishing an animal model combining disease and syndrome in our laboratory, the biological surrogate outcomes suitable for the evaluation of animal models of AP with syndrome of liver depression and Qi stagnation were extracted then. The chronic unpredictable stress(CUS) method and chronic unpredictable stress +L-arginine(CUS +L-Arg) method were used to construct the rat model, and the above biological surrogate outcomes were used to evaluate whether an AP rat model was established. During the experiment, the weight and syndrome scores of the rats were observed and recorded. At the end of the experiment, the rats' serum, organs and tissues were collected from the operation to detect the various indicators. As compared with the normal group, the syndrome scores of the CUS group and CUS +L-Arg group were significantly increased(P<0.01); the anti-syndrome medicine Chaihu Shugan Pills could significantly reduce the syndrome scores of the two groups of rats(P<0.01), indicating that both modeling methods can replicate the syndrome of liver depression and Qi stagnation in the rat model. As compared with the normal group, the serum amylase(AMY) activity level was increased by 3 times in the CUS +L-Arg group(P<0.01), and the AMY activity level was also increased in CUS group, but not up to 3 times of the normal value. As compared with the normal group, the le-vels of TNF-α and IL-6 mRNA in the pancreatic tissues of the CUS +L-Arg group were significantly increased(P<0.01); the levels of TNF-α mRNA in the pancreatic tissues of the CUS group were significantly increased(P<0.05), but IL-6 mRNA level only showed a rising trend, indicating that only the CUS + L-Arg method can be used to replicate the AP damage in the disease-syndrome combination model. The CUS + L-Arg method can be used for continuous modeling for 4 weeks to establish a disease-syndrome combination model of AP rats with syndrome of liver depression and Qi stagnation. The model has the characteristics of repeatability, stability after mode-ling, low animal mortality, and similar clinical pathogenesis. It can be used for the evaluation of traditional Chinese medicine efficacy and the verification of efficacy network.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20200627.401DOI Listing
December 2020

Saikosaponin a contributed to CCIN treatment by promoting neutrophil bactericidal activity via activation CBL-dependent ERK pathway.

Phytomedicine 2021 Feb 26;82:153444. Epub 2020 Dec 26.

The Second Hospital, Cheeloo College of Medicine, Shandong University, No. 247 Beiyuan Street, Jinan, Shandong, 250033, China; Institute of Advanced Medical Research, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, China. Electronic address:

Background: Despite granulocyte colony-stimulating factor (GCSF) is widely used in clinical, cancer chemotherapy induced neutropenia (CCIN) infection and infection-related mortality is high for lack of functionally mature neutrophils. Generating functional neutrophils is new therapeutic approaches to reduce CCIN-associated infection and mortality. Saikosaponin a (SSA) is one of the major bioactive components of Radix Bupleuri (RB) and exerts immunoregulatory effects.

Purpose: The present study aims to investigate the efficacy and mechanism of SSA in CCIN therapy.

Methods: SSA was applied both in vitro and in vivo to assess the efficacy of CCIN therapy. The differentiation of neutrophils was measured by Nitroblue tetrazolium (NBT) reduction assay and Giemsa staining assay. The neutrophil differentiation related real-time transcription factors were detected by quantitative PCR (RT-qPCR) and Western Blot. Bacteria killing assay was used to assess the ability of fighting infection. Network pharmacology was employed to explore the mechanism network, and the predicted pathways were validated by Western Blot.

Results: We found that SSA contributed to generate functional mature neutrophils which capable of fighting infection both in vitro and in vivo. Network pharmacology prediction showed 55 pathways were predicted involved in SSA against CCIN. Further validation showed that CBL-ERK1/2 pathway was activated by SSA, which could upregulate PU.1 and CEBPβ expression leading to neutrophil differentiation.

Conclusions: Our findings suggest a natural regimen SSA regenerates microbicidal neutrophils to effectively reduce CCIN-associated infection via activating CBL-ERK1/2 pathway, providing a rationale for future therapeutic approaches.
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http://dx.doi.org/10.1016/j.phymed.2020.153444DOI Listing
February 2021
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