Publications by authors named "Qi Qin"

126 Publications

Intrauterine administration of peripheral blood mononuclear cells activated by human chorionic gonadotropin in patients with repeated implantation failure: A meta-analysis.

J Reprod Immunol 2021 Apr 15;145:103323. Epub 2021 Apr 15.

Jinxin Research Institute for Reproductive Medicine and Genetics, Chengdu Jinjiang Hospital for Maternal and Child Health Care, Chengdu, China. Electronic address:

The purpose of this study was to assess whether intrauterine administration of peripheral blood mononuclear cells (PBMCs) activated by human chorionic gonadotropin (hCG) could improve the pregnancy and live birth rates in women with repeated implantation failure (RIF), and whether the parameters of co-culture of hCG and PBMCs would affect the clinical outcomes. Six databases (PubMed, Ovid, Medline, NCBI, Cqvip and Wanfang) were searched up to October 2020 by two independent reviewers. Seven studies were included according to specific inclusion and exclusion criteria. A meta-analysis showed that the pregnancy and live birth rates were significantly increased in the case group compared with the control group (odds ratio [OR]: 3.43, 95 % confidence interval [CI]: 1.78-6.61; P =  0.0002 and OR: 2.79, 95 % CI: 1.09-7.15; P =  0.03), especially when hCG was cultured with PBMCs for 48 h or PBMCs administration was performed two or three days before embryo transfer (ET). Neither the dosage of the hCG co-cultured with PBMCs nor the mean concentration of the administered PBMCs appeared to influence the therapeutic efficiency. In conclusion, intrauterine administration of PBMCs co-cultured with hCG for 48 h, conducted two or three days before ET, could be an effective therapy for women experiencing RIF. Due to the limitations of sample size and quality of the included studies, further high-quality studies with large sample sizes are warranted to optimize the parameters of hCG and PBMC co-culture to help more RIF patients benefit from this therapy.
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http://dx.doi.org/10.1016/j.jri.2021.103323DOI Listing
April 2021

Stable, precisely controlled, and switchable thulium-doped fiber laser based on cascaded mode interference filters.

Opt Express 2021 Mar;29(7):9786-9796

This research experimentally demonstrates a switchable, single-wavelength, thulium-doped fiber laser based on the cascading of a multimode-single-mode-multimode (MSM) fiber filter and a two-mode fiber (TMF) filter. When the MSM fiber filter suffers from bending, the blue-shift of the output spectrum can be obtained. A switchable lasing wavelength output is realized by bending the MSM fiber filter to cover different channels of the TMF filter. The output wavelength can be switched from 1982.54 to 1938.81 nm with an optical signal-to-noise ratio of higher than 40 dB. The wavelength interval of the switchable output is an integral multiple of the wavelength interval of the TMF filter. The stability of the output wavelength was tested within 60 min, and the wavelength shift and output power fluctuation were found to be less than 0.01 nm and 0.31 dB, respectively, which demonstrates a stable output performance.
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http://dx.doi.org/10.1364/OE.419283DOI Listing
March 2021

High-Throughput Metabolomics for Discovering Potential Biomarkers and Identifying Metabolic Mechanisms in Aging and Alzheimer's Disease.

Front Cell Dev Biol 2021 25;9:602887. Epub 2021 Feb 25.

National Key Disciplines of Nutrition and Food Hygiene, Department of Nutrition and Food Hygiene, School of Public Health, Harbin Medical University, Harbin, China.

Alzheimer's disease (AD) is an aging-related neurodegenerative disease. We aimed to investigate the metabolic mechanisms of aging and AD and to identify potential biomarkers for the early screening of AD in a natural aging population. To analyze the plasma metabolites related to aging, we conducted an untargeted metabolomics analysis using ultra-high-performance liquid chromatography/quadrupole time-of-flight mass spectrometry in a two-stage cross-sectional study. Spearman's correlation analysis and random forest were applied to model the relationship between age and each metabolite. Moreover, a systematic review of metabolomics studies of AD in the PubMed, Cochrane and Embase databases were searched to extract the differential metabolites and altered pathways from original studies. Pathway enrichment analysis was conducted using Mummichog. In total, 669 metabolites were significantly altered with aging, and 12 pathways were enriched and correlated with aging. Three pathways (purine metabolism, arginine and proline metabolism, and the TCA cycle) were shared between aging and AD. Arginine and proline metabolism play a key role in the progression from healthy to mild cognitive impairment and to AD in the natural aging population. Three metabolites, 16-a-hydroxypregnenolone, stearic acid and PC[16:0/22:5(4Z,7Z,10Z,13Z,16Z)] were finally proposed as potential markers of AD in the natural aging population. The underlying mechanism shared between aging and AD and the potential biomarkers for AD diagnosis were proposed based on multistep comparative analysis.
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http://dx.doi.org/10.3389/fcell.2021.602887DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947003PMC
February 2021

Strategies for the detection of target analytes using microfluidic paper-based analytical devices.

Anal Bioanal Chem 2021 Apr 13;413(9):2429-2445. Epub 2021 Mar 13.

Department of Instrument Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, Shanghai Engineering Research Center for Intelligent Diagnosis and Treatment Instruments, Key Laboratory of Thin Film and Microfabrication (Ministry of Education), Shanghai, 200240, China.

Microfluidic paper-based analytical devices (μPADs) have developed rapidly in recent years, because of their advantages, such as small sample volume, rapid detection rates, low cost, and portability. Due to these characteristics, they can be used for in vitro diagnostics in the laboratory, or in the field, for a variety of applications, including food evaluation, disease screening, environmental monitoring, and drug testing. This review will present various detection methods employed by μPADs and their respective applications for the detection of target analytes. These include colorimetry, electrochemistry, chemiluminescence (CL), electrochemiluminescence (ECL), and fluorescence-based methodologies. At the same time, the choice of labeling material and the design of microfluidic channels are also important for detection results. The construction of novel nanocomponents and different smart structures of paper-based devices have improved the performance of μPADs and we will also highlight some of these in this manuscript. Additionally, some key challenges and future prospects for the use of μPADs are briefly discussed.
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http://dx.doi.org/10.1007/s00216-021-03213-xDOI Listing
April 2021

Polybrominated diphenyl ethers quinone-induced intracellular protein oxidative damage triggers ubiquitin-proteasome and autophagy-lysosomal system activation in LO2 cells.

Chemosphere 2021 Feb 23;275:130034. Epub 2021 Feb 23.

Key Laboratory of Luminescence Analysis and Molecular Sensing, Ministry of Education, College of Pharmaceutical Sciences, Southwest University, Chongqing, 400715, China; State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, China. Electronic address:

Polybrominated diphenyl ethers (PBDEs), a kind of flame retardants, were widely used in the furniture, textile and electronics industries. Because of their lipophilic, persistent and bio-accumulative properties, PBDEs were listed on the Stockholm Convention as typical persistent organic pollutants (POPs). We have previously reported that a highly active, quinone-type metabolite of PBDEs (PBDEQ) causes DNA damage and subsequently triggers apoptosis. However, it is remaining unclear whether PBDEQ provokes protein damage and stimulates corresponding signaling cascade. Using human normal liver (LO2) cells as an in vitro model, we demonstrated that PBDEQ causes oxidative protein damage through excess reactive oxygen species (ROS). Consistently, we found PBDEQ exposure causes the depletion of protein thiol group, the appearance of carbonyl group and the accumulation of protein aggregates. Endoplasmic reticulum (ER) stress was involved in the repair of oxidized proteins. Under the scenario of severe damage, LO2 cells degrade oxidized proteins through ubiquitin-proteasome system (UPS) and autophagy. The blockage of these protein degradation pathways aggravates PBDEQ-induced cytotoxicity in LO2 cells, whilst antioxidant N-acetyl-cysteine (NAC) rescues PBDEQ-induced oxidative protein damage conversely. In summary, our current study first demonstrated PBDEQ-induced protein oxidative damage in LO2 cells, which offer a better understanding of the cytotoxicity of PBDEs and corresponding metabolites.
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http://dx.doi.org/10.1016/j.chemosphere.2021.130034DOI Listing
February 2021

HPO enhanced catalytic activity of N, S, B, and O-codoped carbon nanosphere-armored CoS nanoparticles for organic pollutants degradation peroxymonosulfate activation: critical roles of superoxide radical, singlet oxygen and electron transfer.

Phys Chem Chem Phys 2021 Mar;23(9):5283-5297

School of Materials and Chemical Engineering, Zhongyuan University of Technology, Zhengzhou, Henan 450007, P. R. China.

In this study, we report a facile synthesis of a novel N, S, B, and O-codoped carbon nanosphere-armored Co9S8 nanoparticle composite (Co9S8@NSBOC) and its superior activation performance toward peroxymonosulfate (PMS) for methylene blue (MB) and ofloxacin degradation. The effects of various experimental parameters and the general applicability of the catalyst were investigated. Particularly, Co9S8@NSBOC exhibited high catalytic activity in a wide pH range of 3-12 and HPO42- exhibited a synergic catalytic effect with Co9S8@NSBOC in the degradation system. Radical quenching tests, EPR measurements and electrochemical analysis demonstrated that the degradation mechanism of pollutants in the Co9S8@NSBOC/PMS system included both radical and non-radical pathways, in which ˙O2-, 1O2 and electron transfer played dominant roles. Co2+, S2-, carbon defects, C[double bond, length as m-dash]O/C-O-C, pyridinic-N, graphitic-N, BC2O and C-S-C species on Co9S8@NSBOC, all contributed to PMS activation. The degradation pathways of MB and ofloxacin were proposed based on HPLC-MS/MS analysis of their degradation intermediates. This work not only presents a facile and practical synthetic method of cobalt sulfide-coupled multi-heteroatom-doped carbocatalysts, but also provides useful insights into their active sites and activation mechanisms toward PMS activation.
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http://dx.doi.org/10.1039/d0cp04773bDOI Listing
March 2021

Author Correction: A novel WEE1 pathway for replication stress responses.

Nat Plants 2021 Mar;7(3):376

College of Life Science and Technology, Huazhong Agricultural University, Wuhan, Hubei, China.

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http://dx.doi.org/10.1038/s41477-021-00883-4DOI Listing
March 2021

Cofilin: A Promising Protein Implicated in Cancer Metastasis and Apoptosis.

Front Cell Dev Biol 2021 4;9:599065. Epub 2021 Feb 4.

Yueyang Hospital of Integrative Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Cofilin is an actin-binding protein that regulates filament dynamics and depolymerization. The over-expression of cofilin is observed in various cancers, cofilin promotes cancer metastasis by regulating cytoskeletal reorganization, lamellipodium formation and epithelial-to-mesenchymal transition. Clinical treatment of cancer regarding cofilin has been explored in aspects of tumor cells apoptosis and cofilin related miRNAs. This review addresses the structure and phosphorylation of cofilin and describes recent findings regarding the function of cofilin in regulating cancer metastasis and apoptosis in tumor cells.
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http://dx.doi.org/10.3389/fcell.2021.599065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7890941PMC
February 2021

A novel WEE1 pathway for replication stress responses.

Nat Plants 2021 02 11;7(2):209-218. Epub 2021 Feb 11.

College of Life Science and Technology, Huazhong Agricultural University, Wuhan, Hubei, China.

DNA replication stress poses a severe threat to genome stability and is a hallmark of cancer as well as a target for cancer therapy. It is well known that the evolutionarily conserved protein kinase WEE1 regulates replication stress responses by directly phosphorylating and inhibiting the major cell cycle driver CDKs in many organisms. Here, we report a novel WEE1 pathway. We found that Arabidopsis WEE1 directly interacts with and phosphorylates the E3 ubiquitin ligase FBL17 that promotes the degradation of CDK inhibitors. The phosphorylated FBL17 is further polyubiquitinated and degraded, thereby leading to the accumulation of CDK inhibitors and the inhibition of CDKs. In strong support for this model, either loss of function of FBL17 or overexpression of CDK inhibitors suppresses the hypersensitivity of the wee1 mutant to replication stress. Intriguingly, human WEE1 also phosphorylates and destabilizes the FBL17 equivalent protein SKP2, indicating that this is a conserved mechanism. This study reveals that the WEE1-FBL17/SKP2-CKIs-CDKs axis is a molecular framework for replication stress responses, which may have clinical implications because the WEE1 inhibitor AZD1775 is currently in phase II clinical trial as an anticancer drug.
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http://dx.doi.org/10.1038/s41477-021-00855-8DOI Listing
February 2021

Long non-coding RNA SNHG20 promotes ovarian cancer development by targeting microRNA-338-3p to regulate MCL1 expression.

Oncol Lett 2021 Feb 18;21(2):130. Epub 2020 Dec 18.

Department of Gynecology, The Affiliated Renhe Hospital of China Three Gorges University, Yichang, Hubei 443001, P.R. China.

Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs/miRs) were reported to be associated with the development of ovarian cancer (OC). Increasing evidence demonstrated that lncRNA SNHG20 and miR-338-3p were involved in OC. However, the functional mechanism of lncRNA SNHG20 and miR-338-3p in OC development remains unknown. The expression of SNHG20, miR-338-3p and myeloid cell leukemia 1 (MCL1) was detected by reverse transcription-quantitative PCR. MTT assay, flow cytometry and transwell migration and invasion assays were used to assess cell proliferation, apoptosis, migration and invasion, respectively. The relative protein expression was detected by western blot analysis. The interaction between miR-338-3p and SNHG20 or MCL1 was predicted by starBase v3.0, and subsequently confirmed by dual-luciferase reporter assay. Besides, mouse xenograft assay was carried out to explore the effect of SNHG20 on tumor growth . The levels of SNHG20 and MCL1 were upregulated, while miR-338-3p level was downregulated in OC tissues and cells. SNHG20 knockdown repressed OC cell proliferation, migration, invasion and epithelial-mesenchymal transition, and induced apoptosis. Interestingly, SNHG20 targeted miR-338-3p to regulate MCL1 expression. miR-338-3p depletion or MCL1 overexpression could reverse the effects of SNHG20 knockdown on OC cells. Besides, SNHG20 knockdown impeded tumor growth . In conclusion, the present study demonstrated that SNHG20 regulates OC development via modulation of the miR-338-3p/MCL1 axis, providing the theoretical basis for the treatment of OC.
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http://dx.doi.org/10.3892/ol.2020.12391DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7798103PMC
February 2021

TREM2, microglia, and Alzheimer's disease.

Mech Ageing Dev 2021 Apr 28;195:111438. Epub 2021 Jan 28.

Innovation Center for Neurological Disorders, Department of Neurology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing, China; Neurodegenerative Laboratory of Ministry of Education of the People's Republic of China, Beijing Key Laboratory of Geriatric Cognitive Disorders, Beijing, China. Electronic address:

Triggering receptor expressed on myeloid cells 2 (TREM2) has been suggested to play a crucial role in Alzheimer's disease (AD) pathogenesis, as revealed by genome-wide association studies (GWAS). Since then, rapidly increasing literature related to TREM2 has focused on elucidating its role in AD pathology. In this review, we summarize our understanding of TREM2 biology, explore TREM2 functions in microglia, address the multiple mechanisms of TREM2 in AD, and raise key questions for further investigations to elucidate the detailed roles and molecular mechanisms of TREM2 in microglial responses. A major breakthrough in our understanding of TREM2 is based on our hypothesis suggesting that TREM2 may act as a multifaceted player in microglial functions in AD brain homeostasis. We conclude that TREM2 can not only influence microglial functions in amyloid and tau pathologies but also participate in inflammatory responses and metabolism, acting alone or with other molecules, such as apolipoprotein E (APOE). This review provides novel insight into the broad role of TREM2 in microglial function in AD and enables us to develop new strategies aimed at the immune system to treat AD pathogenesis.
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http://dx.doi.org/10.1016/j.mad.2021.111438DOI Listing
April 2021

Palladium Catalyzed Cascade Azidation/Carbonylation of Aryl Halides with Sodium Azide for the Synthesis of Amides.

Chem Asian J 2021 Mar 2;16(5):503-506. Epub 2021 Feb 2.

School of Biotechnology and Health Sciences, Wuyi University, 529020, Jiangmen, Guangdong, P. R. China.

Amide synthesis is one of the most important transformations in organic chemistry due to their ubiquitous presence in our daily life. In this communication, a palladium catalyzed cascade azidation/carbonylation of aryl halides for the synthesis of amides was developed. Both iodo- and bromobenzene derivatives were transformed to the corresponding amides using PdCl /xantphos as the catalyst system and sodium azide as the nitrogen-source. The reaction proceeds via a cascade azidation/carbonylation process. A range of alkyl and halogen substituted amides were prepared in moderate to good yields.
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http://dx.doi.org/10.1002/asia.202001463DOI Listing
March 2021

The ATR-WEE1 kinase module inhibits the MAC complex to regulate replication stress response.

Nucleic Acids Res 2021 02;49(3):1411-1425

College of Life Science and Technology, Huazhong Agricultural University, Wuhan, Hubei 430070, China.

DNA damage response is a fundamental mechanism to maintain genome stability. The ATR-WEE1 kinase module plays a central role in response to replication stress. Although the ATR-WEE1 pathway has been well studied in yeasts and animals, how ATR-WEE1 functions in plants remains unclear. Through a genetic screen for suppressors of the Arabidopsis atr mutant, we found that loss of function of PRL1, a core subunit of the evolutionarily conserved MAC complex involved in alternative splicing, suppresses the hypersensitivity of atr and wee1 to replication stress. Biochemical studies revealed that WEE1 directly interacts with and phosphorylates PRL1 at Serine 145, which promotes PRL1 ubiquitination and subsequent degradation. In line with the genetic and biochemical data, replication stress induces intron retention of cell cycle genes including CYCD1;1 and CYCD3;1, which is abolished in wee1 but restored in wee1 prl1. Remarkably, co-expressing the coding sequences of CYCD1;1 and CYCD3;1 partially restores the root length and HU response in wee1 prl1. These data suggested that the ATR-WEE1 module inhibits the MAC complex to regulate replication stress responses. Our study discovered PRL1 or the MAC complex as a key downstream regulator of the ATR-WEE1 module and revealed a novel cell cycle control mechanism.
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http://dx.doi.org/10.1093/nar/gkaa1082DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7897505PMC
February 2021

Stenotrophomonas-maltophilia inhibits host cellular immunity by activating PD-1/PD-L1 signaling pathway to induce T-cell exhaustion.

Mol Immunol 2021 02 21;130:37-48. Epub 2020 Dec 21.

Department of Laboratory Medicine, the Second Xiangya Hospital of Central South University, Changsha, Hunan, 410011, China. Electronic address:

Background: Smalotrophomonas maltophilia(S. maltophilia) is common in nosocomial infections. However, few studies have revealed the effect of S. maltophilia on cellular immunity in the host's immune system up to now. In clinical work, we accidentally discovered that S. maltophilia directly stimulated T cells to secrete IFN-γ.

Materials And Methods: S. maltophilia was co-cultured with PBMCs to detect secretion of cytokines (IFN-γ, TNF-α and IL-2) and expression of cell surface molecules (CD3, CD4, CD8, CD69, CD147 and CD152) of T cells. We used light microscopy and electron microscopy to observe the cell morphology and subcellular structure of S. maltophilia co-cultured with lymphocytes. Flow cytometry and Western Blot were used to detect the expression of PD-1/PD-L1 and annexin V in cells.

Results: T cells stimulated by S. maltophilia secreted a large amount of IL-2, IFN-γ, and TNF-α. The expression of CD4 and CD8 on the cell surface were declined, accompanied by the activation of the PD-1/PD-L1 pathway, which eventually led to the massive apoptosis of T cells. Electron microscopy showed that cells showed significant apoptotic morphology. Blocking the PD-1/PD-L1 pathway can inhibit the apoptosis-inducing effect of S. maltophilia on T cells.

Conclusions: These indicates that T cells are inhibited after being stimulated by S. maltophilia, and then accelerated to induce death without the initiation of an immunologic cascade. This paper demonstrates for the first time the inhibitory effect of S. maltophilia on cellular immunity, and the immunosuppressive effect induced by infection of S. maltophilia should be considered.
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http://dx.doi.org/10.1016/j.molimm.2020.12.019DOI Listing
February 2021

Polychlorinated biphenyl quinone induced the acquisition of cancer stem cells properties and epithelial-mesenchymal transition through Wnt/β-catenin.

Chemosphere 2021 Jan 28;263:128125. Epub 2020 Aug 28.

Key Laboratory of Luminescence Analysis and Molecular Sensing (Southwest University), Ministry of Education, College of Pharmaceutical Sciences, Southwest University, Chongqing, 400715, People's Republic of China. Electronic address:

Polychlorinated biphenyls (PCBs) are persistent industrial pollutants that have been linked to breast cancer progression. However, their molecular mechanism(s) are currently unclear. Our previous assessment suggested that the highly reactive PCB metabolite 2,3,5-trichloro-6-phenyl-[1,4]-benzoquinone (PCB29-pQ) induces the metastasis of breast cancer. Here, our data illustrate that PCB29-pQ increases cancer stem cell (CSC) marker expression, resulting in an increase in the epithelial-mesenchymal transition (EMT) in MDA-MB-231 breast cancer cells; further, the Wnt/β-catenin pathway also becomes activated by PCB29-pQ. When the Wnt/β-catenin pathway is inhibited, the promotion of CSC properties and EMT by PCB29-pQ were accordingly reversed. In addition, the overproduction of reactive oxygen species (ROS) mediated by PCB29-pQ plays a key role in Wnt/β-catenin activation. Collectively, our current data designated the regulatory role of Wnt/β-catenin in PCB29-pQ-triggered acquisition of CSC properties and EMT.
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http://dx.doi.org/10.1016/j.chemosphere.2020.128125DOI Listing
January 2021

Deep Learning on chromatographic data for Segmentation and Sensitive Analysis.

J Chromatogr A 2020 Dec 5;1634:461680. Epub 2020 Nov 5.

Department of Instrument Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, Yantai Information Technology Research Institute of SJTU, Shanghai Engineering Research Center for Intelligent diagnosis and treatment instrument, Shanghai 200240, China. Electronic address:

Lateral flow immunoassay (LFIA) is one of the most common methods in point-of-care testing, which is widely applied in some conditions for various applications. Image segmentation is an increasingly popular experimental paradigm to efficiently test the target area in LFIA. However, due to process pollution, and problems related to the experimental operation and irregular structure of the background of the reaction, currently available tools cannot be used to extract correct signals from these images, which affects the accuracy of detection. Machine learning has significantly improved modern biochemical analysis by pushing the limits of traditional techniques for the recognition and processing of images. In this paper, the U-Net, a variant of the convolutional neural network (CNN) is used for the quantitative analysis of LFIA images for the accurate quantification of single- and multi-target images. By graying, binarizing, and labeling different concentrations of test strips, the target area of LFIA images containing the T-/C-lines is extracted and obtained. Then it provides updated trends and directions for the development of LFIA technology. Several indicators are introduced to evaluate the proposed U-Net structure to verify the feasibility and effectiveness of its image processing capability. When the trained U-Net model was used to process images, the peak signal-to-noise ratio was 22.4 dB, significantly higher than prevalent methods in the area that have reported only a 4 dB improvement in the quality of the graphics. The intersection-over-union between samples also increased to above 93%. Our results show that the proposed method has significant potential for detecting a segmented target in an LFIA area, especially weak positive signals and multichannel detection. With other modifications, this deep learning method can be applied as a powerful tool to study rapid detection devices, systems, and biological images.
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http://dx.doi.org/10.1016/j.chroma.2020.461680DOI Listing
December 2020

Polychlorinated biphenyl quinone regulates MLKL phosphorylation that stimulates exosome biogenesis and secretion via a short negative feedback loop.

Environ Pollut 2021 Apr 9;274:115606. Epub 2020 Sep 9.

Key Laboratory of Luminescence Analysis and Molecular Sensing (Southwest University), Ministry of Education, College of Pharmaceutical Sciences, Southwest University, Chongqing, 400715, People's Republic of China. Electronic address:

Polychlorinated biphenyls (PCBs) are one of the most refractory organic environmental pollutants that ubiquitous existence in nature. Due to the polymorphism of their metabolic pathway and corresponding downstream metabolites, PCBs' toxicities are complicated and need extended investigation. In the present study, we discovered a novel regulatory mechanism of PCB quinone metabolite-driven programmed cell death (PCD), namely, necroptosis. We first confirmed that PCB quinone induces cancerous HeLa and MDA-MB-231 cells necroptosis via the phosphorylation of mixed lineage kinase domain-like MLKL (p-MLKL). Then, we found that PCB quinone-stimulated p-MLKL enhances exosome biogenesis and secretion. Exosome interacts with p-MLKL and releases p-MLKL to the outside of the cell, and ultimately alleviating PCB quinone-induced necroptosis. The inhibition of exosome secretion by GW4869 significantly elevated necroptotic level, indicating the establishment of a short negative feedback loop of MLKL-exosome secretion upon PCB quinone challenge. Since exosome-mediated signaling showed great implications in various human diseases, this work may provide a new mechanism for PCBs-associated toxicity.
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http://dx.doi.org/10.1016/j.envpol.2020.115606DOI Listing
April 2021

Nitrogen and phosphorus co-doped porous carbon framework with superior electrochemical activity for naphthol isomers sensing.

Anal Chim Acta 2020 Nov 4;1138:158-167. Epub 2020 Oct 4.

Key Laboratory for the Green Preparation and Application of Functional Materials, Key Laboratory for the Synthesis and Application of Organic Functional Molecules, Ministry of Education, Hubei Key Laboratory of Polymer Materials, School of Materials Science & Engineering, Hubei University, Wuhan, 430062, China. Electronic address:

Heteroatom-doped carbon has emerged as one of the most important electrode materials for electrochemical analysis. Thus, designing and synthesizing novel heteroatom-doped carbon material with superior electrochemical activity is highly desired. Herein, we report a simple and effective pyrolysis-activation strategy to synthesize nitrogen and phosphorus co-doped porous carbon (N, P-C) framework by using zeolitic imidazolate framework-67 (ZIF-67) as the precursor and phytic acid as the phosphorus source. It is found that the surface defect level, electrochemical active area and electrode reaction kinetics of N, P-C framework is greatly boosted compared with ZIF-67 derived N-doped porous carbon (N-C) framework. These features endow N, P-C framework with outstanding electrochemical activity for the oxidation of highly toxic environmental pollutants 1-naphthol and 2-naphthol. The oxidation peak currents of 1-naphthol and 2-naphthol increase linearly in the range from 25 nM to 2 μM. Besides, the limits of detection are estimated to be about 8.0 nM and 7.2 nM (three signal-to-noise ratio) for 1-naphthol and 2-naphthol with sensitivity of 87.3 μA μM cm and 84.6 μA μM cm, respectively.
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http://dx.doi.org/10.1016/j.aca.2020.09.064DOI Listing
November 2020

Engineering of Living Cells with Polyphenol-Functionalized Biologically Active Nanocomplexes.

Adv Mater 2020 Dec 4;32(49):e2003492. Epub 2020 Nov 4.

John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, 02138, USA.

Approaches to safely and effectively augment cellular functions without compromising the inherent biological properties of the cells, especially through the integration of biologically labile domains, remain of great interest. Here, a versatile strategy to assemble biologically active nanocomplexes, including proteins, DNA, mRNA, and even viral carriers, on cellular surfaces to generate a cell-based hybrid system referred to as "Cellnex" is established. This strategy can be used to engineer a wide range of cell types used in adoptive cell transfers, including erythrocytes, macrophages, NK cells, T cells, etc. Erythrocyte can enhance the delivery of cargo proteins to the lungs in vivo by 11-fold as compared to the free cargo counterpart. Biomimetic microfluidic experiments and modeling provided detailed insights into the targeting mechanism. In addition, Macrophage is capable of enhancing the therapeutic efficiency of anti-PD-L1 checkpoint inhibitors in vivo. This simple and adaptable approach may offer a platform for the rapid generation of complex cellular systems.
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http://dx.doi.org/10.1002/adma.202003492DOI Listing
December 2020

Tetrachlorobenzoquinone exposure triggers ferroptosis contributing to its neurotoxicity.

Chemosphere 2021 Feb 24;264(Pt 1):128413. Epub 2020 Sep 24.

Key Laboratory of Luminescence Analysis and Molecular Sensing (Southwest University), Ministry of Education, College of Pharmaceutical Sciences, Southwest University, Chongqing, 400715, People's Republic of China. Electronic address:

Halogenated quinones are representative metabolites of persistent organic pollutants. Tetrachlorobenzoquinone (TCBQ) is a reactive metabolite of the widely used fungicide hexachlorobenzene (HCB) and wood preservative pentachlorophenol (PCP). Our previous studies have demonstrated that TCBQ induced neuron-like cell apoptosis in a reactive oxygen species (ROS)-dependent manner. Here, we found that TCBQ caused lipid peroxidation and cellular morphological changes including shrinked mitochondrial size, suggesting the involvement of a recently uncovered form of programmed cell death (PCD), ferroptosis. Indeed, we then identified that ferroptosis is a novel PCD driven by TCBQ, which was correlated with a decrease in glutathione peroxidase 4 (GPX4) level and iron accumulation by altering iron metabolism. Notably, nuclear factor erythroid-derived 2-like 2 (Nrf2) is a negative regulator in modulating the outcomes of ferroptosis as an adaptive cellular defense response. Nrf2 activation enhanced iron storage capacity and GPX4 activity by elevating ferritin heavy chain 1 (FTH1) expression and glutathione (GSH) level, respectively. On the contrary, Nfe2l2 (Nrf2) deficiency enhanced PC12 cells susceptibility to ferroptosis.
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http://dx.doi.org/10.1016/j.chemosphere.2020.128413DOI Listing
February 2021

The APOE ε4 exerts differential effects on familial and other subtypes of Alzheimer's disease.

Alzheimers Dement 2020 12 3;16(12):1613-1623. Epub 2020 Sep 3.

Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing, China.

Introduction: The genetic risk effects of apolipoprotein E (APOE) on familial Alzheimer's disease (FAD) with or without gene mutations, sporadic AD (SAD), and normal controls (NC) remain unclear in the Chinese population.

Methods: In total, 15 119 subjects, including 311 FAD patients without PSEN1, PSEN2, APP, TREM2, and SORL1 pathogenic mutations (FAD [unknown]); 126 FAD patients with PSENs/APP mutations (FAD [PSENs/APP]); 7234 SAD patients; and 7448 NC were enrolled. The risk effects of APOE ε4 were analyzed across groups.

Results: The prevalence of the APOE ε4 genotype in FAD (unknown), FAD (PSENs/APP), SAD, and NC groups was 56.27%, 26.19%, 36.23%, and 19.54%, respectively. Further, the APOE ε4 positive genotype had predictive power for FAD (unknown) risk (odds ratio: 4.51, 95% confidence interval: 3.57-5.45, P < .001).

Discussion: APOE ε4 positive genotype may cause familial aggregation, and the investigation of multiple interventions targeting APOE pathological function to reduce the risk for this disease warrants attention.
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http://dx.doi.org/10.1002/alz.12153DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7984370PMC
December 2020

Gene mutations associated with early onset familial Alzheimer's disease in China: An overview and current status.

Mol Genet Genomic Med 2020 10 6;8(10):e1443. Epub 2020 Aug 6.

Innovation Center for Neurological Disorders, Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China.

Background: Mutations of three causative genes, namely presenilin 1 (PSEN1), presenilin 2 (PSEN2), and amyloid precursor protein (APP), have been identified as the major causes of early-onset familial Alzheimer's disease (EOFAD). The prevalence of causative gene mutations in patients with EOFAD has been reported in previous studies worldwide but remains unclear in China. The patients with these known mutations always show considerable clinical phenotypic variability. However, to date, there have been no detailed descriptions of the clinical phenotypes associated with these Chinese EOFAD mutations. Thus, the aim of this study was to describe all of the known mutations in three EOFAD causative genes and genotype-phenotype correlations in Chinese patients with EOFAD.

Method: We systematically searched the PubMed, MEDLINE, CNKI, VIP, and WAN-FANG databases to find Chinese EOFAD mutations in reports from inception through May 2020.

Result: We identified 31 studies reporting mutations of three causative genes in China. 10 mutations in APP gene, 27 mutations in PSEN1 gene and six mutations in PSEN2 were discovered in Chinese EOFAD. This review summarized all these probably pathogenic mutations as well as its clinical features. To the best of our knowledge, this is the first systemic review of causative gene mutations in patients with EOFAD in China.

Conclusion: The analysis of the genetic and clinical phenotype correlations in this review supports the idea that the clinical phenotype might be influenced by specific genetic defects. It also suggests genetic testing and genotype-phenotype correlations are important for the accurate diagnosis and for understanding disease-associated pathways and might also improve disease therapy and prevention.
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http://dx.doi.org/10.1002/mgg3.1443DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7549583PMC
October 2020

CRISPR/Cas12a Mediated Genome Editing Enhances Resistance to BmNPV.

Front Bioeng Biotechnol 2020 15;8:841. Epub 2020 Jul 15.

State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing, China.

CRISPR/Cas12a (Cpf1) is a single RNA-guided endonuclease that provides new opportunities for targeted genome engineering through the CRISPR/Cas9 system. Only AsCas12a has been developed for insect genome editing, and the novel Cas12a orthologs nucleases and editing efficiency require more study on insects. We compared three Cas12a orthologs nucleases, AsCas12a, FnCas12a, and LbCas12a, for their editing efficiencies and antiviral abilities. The three Cas12a efficiently edited the nucleopolyhedrovirus (BmNPV) genome and inhibited BmNPV replication in BmN-SWU1 cells. The antiviral ability of the FnCas12a system was more efficient than that of the SpCas9 system after infection by BmNPV. We created FnCas12a × gIE1 and SpCas9 × sgIE1 transgenic hybrid lines and evaluated the gene-editing efficiency of different systems at the same target site. We improved the antiviral ability using the FnCas12a system in transgenic silkworm. This study demonstrated the use of the CRISPR/Cas12a system to achieve high editing efficiencies, and increase disease resistance in the silkworm.
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http://dx.doi.org/10.3389/fbioe.2020.00841DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7373793PMC
July 2020

Skin characteristics associated with foot callus in people with diabetes: A cross-sectional study focused on desmocollin1 in corneocytes.

J Tissue Viability 2020 Nov 12;29(4):291-296. Epub 2020 Jun 12.

Department of Gerontological Nursing/Wound Care Management, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; Global Nursing Research Center, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. Electronic address:

Aim: The purpose of this study was to investigate the degradation of desmocollin-1 (DSC1), a member of the desmosomal cadherin family in patients with diabetes, as well as the factors associated with the suppression of DSC1 degradation.

Methods: This cross-sectional study included 60 cases of foot callus involving 30 patients with diabetes (DM) and 30 matched volunteers without diabetes (non-DM). DSC1 degradation in samples from debrided calluses was analysed using western blotting. Skin hydration, a factor reported to suppress DSC1 degradation, was measured using a mobile moisture device.

Results: Full-length DSC1 (approximately 100 kDa) was detected in six participants only in the DM group, and no relationship was found between the suppression of DSC1 degradation and decreased skin hydration in the DM group. There was no significant difference in skin hydration values between the DM and non-DM groups.

Conclusion: DSC1 degradation was suppressed in the DM group. There was no relationship between the suppression of DSC1 degradation and decreased skin hydration in the DM group. Current external force callus care would not be sufficient. This study highlights the need to develop novel callus care to enhance the degradation of DSC1.
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http://dx.doi.org/10.1016/j.jtv.2020.05.003DOI Listing
November 2020

Co nanoparticle-embedded N,O-codoped porous carbon nanospheres as an efficient peroxymonosulfate activator: singlet oxygen dominated catalytic degradation of organic pollutants.

Phys Chem Chem Phys 2020 Jul 19;22(27):15340-15353. Epub 2020 Jun 19.

School of Materials and Chemical Engineering, Zhongyuan University of Technology, Zhengzhou, Henan 450007, P. R. China.

In this study, Co nanoparticle-embedded N,O-codoped porous carbon nanospheres (C@Co) with abundant N and O doping, high graphitization, large specific surface area (319 m g) and a well-developed mesoporous structure were synthesized and characterized thoroughly, and were applied to activate peroxymonosulfate (PMS) for the degradation of methylene blue (MB). Various influential factors affecting the catalytic performance including C@Co dosage, PMS dosage, MB concentration, initial pH, temperature, and co-existing common anions and humic acid (HA) on the MB degradation were systematically investigated. The increase of the C@Co dosage (15-60 mg), PMS dosage (25-100 mg) and reaction temperature (278-308 K) promoted the MB degradation in the C@Co/PMS system. The best performance of the C@Co/PMS system was observed under weakly acidic or nearly neutral conditions. Both the MB concentration (25-100 mg L) and Cl (5-100 mM), NO (10-500 mM), CO (10-300 mM), HCO (1-30 mM) and HA (2-40 mg L) had an inhibitory effect on MB degradation, and the degree of decrease in MB degradation increased as their concentrations were enhanced. Interestingly, HPO (1-100 mM) had an overall inhibitory effect on the degradation process of MB; however, in comparison with lower concentrations (1-10 mM), an attenuation of the inhibitory effect at higher concentrations (50-100 mM) could be observed. Moreover, the C@Co/PMS system also exhibited general applicability in eliminating various organic pollutants from water such as methyl orange, malachite green, safranine T, Congo red, Rhodamine B, ofloxacin and tetracycline. Classical radical-quenching tests and EPR measurements showed that both the non-radical pathway (major route, involving O) and radical pathway (minor route, involving ˙OH, ˙SO and ˙O) contribute to the MB degradation. DFT calculations disclosed that the combination of Co-C interactions with graphitic N doping brought in catalytically active sites in C@Co where the charge states of some C atoms were significantly increased. The degradation intermediates of MB during the catalytic reaction were also identified by HPLC-MS and the possible degradation pathway was proposed. Overall, the resultant C@Co can be developed as a novel and efficient heterogeneous catalyst for activating PMS to degrade organic pollutants, and has potential application in environmental remediation.
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http://dx.doi.org/10.1039/d0cp00679cDOI Listing
July 2020

Polychlorinated Biphenyl Quinone Promotes Atherosclerosis through Lipid Accumulation and Endoplasmic Reticulum Stress via CD36.

Chem Res Toxicol 2020 06 29;33(6):1497-1507. Epub 2020 May 29.

College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, People's Republic of China.

Polychlorinated biphenyls (PCBs) are persistent organic environmental pollutants. According to previous epidemiological reports, PCBs exposure is highly related to atherosclerosis. However, studies of PCBs metabolites and atherosclerosis and corresponding mechanism studies are scarce. In this study, we evaluated the effect of 2,3,5-trichloro-6-phenyl-[1,4]-benzoquinone (PCB29-pQ), a presumptive PCB metabolite, on atherosclerosis. Aortic plaques were increased in PCB29-pQ-treated ApoE mice [intraperitoneally (i.p.) injection of 5 mg/kg body weight of PCB29-pQ once a week for 12 continuous weeks, high-fat feeding]. We observed lipids accumulation and the release of interleukin-1 beta (IL-1β), tumor necrosis factor alpha (TNF-α), and interleukin-6 (IL-6) in ApoE mice. In addition, we found that PCB29-pQ promoted the levels of total cholesterol, free cholesterol, triglyceride, and cholesteryl ester. Mechanism investigation indicated that PCB29-pQ induces the activation of three branches of endoplasmic reticulum (ER) stress response, that is, phosphorylated protein kinase R-like ER kinase (p-PERK), eukaryotic translation initiation factor 2α (eIF2α) and transcription factor 6 (ATF6), which is responsible for downstream necrosis. More importantly, we found the silence of CD36 is able to reverse PCB29-pQ-induced adverse effects completely. Overall, PCB29-pQ exposure resulted in lipid accumulation, ER stress response, apoptosis, and pro-inflammatory cytokines release via CD36, ultimately leading to atherosclerosis.
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http://dx.doi.org/10.1021/acs.chemrestox.0c00123DOI Listing
June 2020

Estimating the instant case fatality rate of COVID-19 in China.

Int J Infect Dis 2020 Aug 24;97:1-6. Epub 2020 Apr 24.

Department of Pharmacology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, PR China. Electronic address:

Objective: The outbreak of coronavirus disease 2019 (COVID-19) in China has been basically controlled. However, the global epidemic of COVID-19 is worsening. We established a method to estimate the instant case fatality rate (CFR) and cure rate of COVID-19 in China.

Methods: A total of 82 735 confirmed cases released officially by the Chinese authorities from December 8, 2019 to April 18, 2020 were collected. The estimated diagnosis dates of deaths and cured cases were calculated based on the median cure time or median death time of individual cases. Following this, the instant CFR was calculated according to the number of deaths and cured cases on the same estimated diagnosis date.

Results: In China, the instant CFR of COVID-19 was 3.8-14.6% from January 1 to January 17; it then declined gradually and stabilized at 5.7% in April. The average CFR in China was 6.1±2.9%, while the CFR was 1.0±0.4% in China except Hubei Province. The cure rate of COVID-19 was 93.9±2.9% in China, and stabilized at 94.3%, while it was 99.0±0.4% in China except Hubei Province.

Conclusions: The instant CFR of COVID-19 in China overall was much higher than that in China except Hubei Province. The CFR of COVID-19 in China was underestimated.
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http://dx.doi.org/10.1016/j.ijid.2020.04.055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7180353PMC
August 2020

Topical delivery of siRNA into skin using ionic liquids.

J Control Release 2020 07 24;323:475-482. Epub 2020 Apr 24.

John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA; Wyss Institute for Biologically Inspired Engineering, 52 Oxford St, Cambridge, MA 02138, USA. Electronic address:

Skin diseases such as lupus, cancer, psoriasis, and hyperhidrosis can potentially be treated effectively by suppressing allele-specific genes using small interfering RNA (siRNA). Injections of siRNA into skin, though effective, are painful and cover small surface areas and thus are not suitable as a long-term treatment option. Topical delivery of siRNA is an attractive alternative option to mediate RNA interference (RNAi). However, the barrier function of the epidermis impedes effective permeation of siRNA into the skin. Herein, we describe topical delivery of siRNA using ionic liquids (ILs) capable of complexing with siRNA non-covalently and delivering it effectively. Using complementary and synergistic strategies of ionic liquids, we report delivery of effective doses of siRNA into skin. The first strategy involved the use of hydrophobic cations to robe the siRNA and the second strategy involved the use of choline-geranic acid ionic liquid (CAGE) to enhance its dermal penetration. In vitro studies in porcine skin confirmed the synergistic effect of these strategies in enhancing epidermal and dermal penetration. In vivo application of siRNA formulation to SKH-1E hairless mice significantly suppressed GAPDH expression with no clinical evidence of toxicity. This is a simple, personalized, and scalable platform for effective topical delivery of siRNA for treating genetic skin diseases.
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http://dx.doi.org/10.1016/j.jconrel.2020.04.038DOI Listing
July 2020

[Regulatory effect of Di'ao Xinxuekang on TLR4/MyD88/NF-κB signaling pathway in atherosclerotic rats].

Zhongguo Zhong Yao Za Zhi 2020 Feb;45(3):602-608

School of Integrated Traditional and Western Medicine, Anhui University of Chinese Medicine Hefei 230038, China Key Laboratory of Chinese Compound Formula Research of Anhui Province Hefei 230038, China.

The aim of this paper was to observe the effect of Di'ao Xinxuekang(DXXK) on TLR4/MyD88/NF-κB signaling pathway in atherosclerotic rats, and to explore its anti-atherosclerotic mechanism. Sixty SD rats were randomly divided into normal group, model group, atorvastatin group(4.0 mg·kg~(-1)), and DXXK groups(100, 30, 10 mg·kg~(-1)), with 10 rats in each group. The atherosclerosis model was induced by high fat diet plus vitamin D_2. Experimental drugs were administered intragastrically once daily for 8 weeks starting from the 9 th week. Biochemical analyzers were used to detect levels of triglyceride(TG), total cholesterol(TC), low-density lipoprotein cholesterol(LDL-C) and high-density lipoprotein cholesterol(HDL-C) in blood lipid. The levels of serum tumor necrosis factor(TNF)-α, interleukin(IL)-6 and IL-1β were detected by ELISA. Pathological changes of aortic tissues were observed by using Sudan Ⅳ and HE staining. The mRNA and protein expressions of TLR4, MyD88 and NF-κB p65 in aortic tissues were detected by RT-PCR and Western blot, respectively. As compared with the model group, TC, TG, and LDL-C levels in serum were significantly decreased, HDL-C content was significantly increased, and levels of TNF-α, IL-6, and IL-1β in serum were significantly decreased in atorvastatin group and DXXK high and middle dose groups. Aortic lesions in atorvastatin group and DXXK group were significantly improved, and the mRNA and protein expressions of TLR4, MyD88, NF-κB p65 in the aorta were decreased. DXXK has a preventive and therapeutic effect on atherosclerosis in rats, and its mechanism may be related to inhibiting inflammatory reaction by regulating TLR4/MyD88/NF-κB signal transduction, thereby inhibiting the progression of atherosclerosis.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20190827.402DOI Listing
February 2020

Default mode network integrity changes contribute to cognitive deficits in subcortical vascular cognitive impairment, no dementia.

Brain Imaging Behav 2021 Feb;15(1):255-265

Department of Neurology, Innovation Center for Neurological Disorders, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, 45 Changchun Street, Beijing, 100053, China.

Vascular cognitive impairment, no dementia (VCIND) refers to cognitive deficits associated with underlying vascular causes that are insufficient to confirm a diagnosis of dementia. The default mode network (DMN) is a large-scale brain network of interacting brain regions involved in attention, working memory and executive function. The role of DMN white matter integrity in cognitive deficits of VCIND patients is unclear. Using diffusion tensor imaging (DTI), this study was carried out to investigate white matter microstructural changes in the DMN in VCIND patients and their contributions to cognitive deficits. Thirty-one patients with subcortical VCIND and twenty-two healthy elderly subjects were recruited. All patients underwent neuropsychological assessments and DTI examination. Voxel-based analyses were performed to extract fractional anisotropy (FA) and mean diffusivity (MD) measures in the DMN. Compared with the healthy elderly subjects, patients diagnosed with subcortical VCIND presented with abnormal white matter integrity in several key hubs of the DMN. The severity of damage in the white matter microstructure in the DMN significantly correlated with cognitive dysfunction. Mediation analyses demonstrated that DTI values could account for attention, executive and language impairments, and partly mediated global cognitive dysfunction in the subcortical VCIND patients. DMN integrity is significantly impaired in subcortical VCIND patients. The disrupted DMN connectivity could explain the attention, language and executive dysfunction, which indicates that the white matter integrity of the DMN may be a neuroimaging marker for VCIND.
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http://dx.doi.org/10.1007/s11682-019-00252-yDOI Listing
February 2021