Publications by authors named "Yizhi Zhang"

122 Publications

Presenilin enhancer2 is critical for the transition of apical progenitors to neurons but not basal progenitors in the developing hippocampus.

Development 2022 May 16. Epub 2022 May 16.

Ministry of Education (MOE) Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, 12 Xuefu Avenue, Nanjing, Jiangsu, 210061, China.

Recent evidence has shown that presenilin enhancer2 (Pen-2) plays an essential role in corticogenesis by regulating the switch of apical progenitors (APs) to basal progenitors (BPs). The hippocampus is a brain structure required for advanced functions including spatial navigation, learning and memory. However, it remains unknown whether Pen-2 is important for hippocampal morphogenesis. To address this question, we generated Pen-2 conditional knockout (cKO) mice, in which Pen-2 is inactivated in neural progenitor cells (NPCs) in the hippocampal primordium. We showed that Pen-2 cKO mice exhibited hippocampal malformation and decreased population of NPCs in the neuroepithelium of the hippocampus. We found that deletion of Pen-2 neither affected the proliferative capability of APs nor the switch of APs to BPs in the hippocampus, and that it caused enhanced transition of APs to neurons. We demonstrated that expression of Notch1 intracellular domain (N1ICD) significantly increased the population of NPCs in the Pen-2 cKO hippocampus. Collectively, this study uncovers a critical role of Pen-2 in the maintenance of NPCs during hippocampal development.
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http://dx.doi.org/10.1242/dev.200272DOI Listing
May 2022

Metformin inhibits multiple myeloma serum-induced endothelial cell thrombosis by down-regulating miR-532.

Ann Vasc Surg 2022 May 10. Epub 2022 May 10.

Department of Neurology, Karamay Central Hospital. Electronic address:

Objectives: Thrombotic complications in multiple myeloma (MM) impairs the quality of life of patients. Metformin has a certain effect on anti-thrombosis, but its role and mechanism in MM-induced thrombosis are still uncovered. Therefore, this study evaluated the effect of metformin on MM-induced thrombosis.

Methods: Human umbilical vein endothelial cells (HUVECs) were exposed to normal serum (15%), MM serum (15%), metformin (0.01 mmol/L), or MM serum and metformin simultaneously. The expression of tissue factor (TF) in HUVECs was detected by flow cytometry and quantitative real-time PCR (qRT-PCR). QRT-PCR was also used to determine the expressions of endothelial protein C receptor (EPCR) and miR-532. The generation of thrombin and activated protein C was measured by thrombin generation and protein C activation assays. And EPCR, extracellular signal-regulated kinase (ERK) 1/2, p38 mitogen activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) pathway related protein expressions were detected by western blot.

Result: MM serum increased the expressions of TF, EPCR and miR-532, and induced thrombin generation and protein C activation in HUVECs. Based on the MM serum treatment, metformin decreased these expressions and inhibited the thrombin generation and protein C activation in HUVECs. However, miR-532 mimic reversed the effect of metformin and promoted the levels of thrombosis related indicators in HUVECs. Moreover, metformin activated the EPCR, ERK 1/2, p38 MAPK and NF-κB pathways but miR-532 mimic suppressed the activation of pathways.

Conclusion: Metformin played an inhibitory effect on MM serum-induced HUVEC thrombosis, suggesting that metformin could serve as a novel antithrombotic approach for MM patients.
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http://dx.doi.org/10.1016/j.avsg.2022.04.035DOI Listing
May 2022

Diastereoselective Transfer of Tri(di)fluoroacetylsilanes-Derived Carbenes to Alkenes.

Angew Chem Int Ed Engl 2022 Apr 12:e202202175. Epub 2022 Apr 12.

Institute for Advanced Studies, Engineering Research Center of Organosilicon Compounds & Materials, Ministry of Education, Wuhan University, 299 Bayi Road, Wuhan, Hubei 430072, China.

Stereoselective cyclopropanation reaction of alkenes is usually achieved by metal complexes via singlet-metal-carbene intermediates. However, previous transition-metal-catalyzed cyclopropanation of alkenes with acylsilanes afforded low diastereoselectivity. Herein, we report the first visible-light-induced transition-metal-free cyclopropanation reaction of terminal alkenes with trifluoroacetylsilanes and difluoroacetylsilanes. Both aromatic and aliphatic alkenes as well as electron-deficient alkenes are suitable substrates for the highly cis-selective [2+1] cyclization reaction. A combination of experimental and computational studies identified triplet carbenes as being key intermediates in this transformation. The gram scale reaction and late-stage functionalization demonstrated the synthetic potential of this strategy.
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http://dx.doi.org/10.1002/anie.202202175DOI Listing
April 2022

Baicalin Attenuates Oxidative Stress in a Tissue-Engineered Liver Model of NAFLD by Scavenging Reactive Oxygen Species.

Nutrients 2022 Jan 26;14(3). Epub 2022 Jan 26.

Beijing Key Laboratory of Liver Failure and Artificial Liver Treatment, Department IV of Liver Diseases, Beijing Youan Hospital Affiliated to Capital Medical University, Beijing 100069, China.

Oxidative stress plays an important role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Baicalin has been shown to exert protective effects in various liver diseases. The mechanism of baicalin's antioxidative effect in NAFLD is currently unclear. The aim of this study was to investigate the effects and mechanisms of baicalin on oxidative stress in a new tissue-engineered liver model of NAFLD. The 3D model of NAFLD was induced by a fat-supplemented medium (fatty acids, FFA group) for 8 days and baicalin was administered on the 5th day. CCK-8 assay showed that baicalin at concentrations below 100 μM had no obvious cytotoxicity. Baicalin inhibited apoptosis and lactate dehydrogenase release in the FFA group. Baicalin reduced the levels of reactive oxygen species and malondialdehyde induced by FFA, and increased superoxide dismutase and glutathione amounts. However, it did not upregulate nuclear erythroid 2-related factor 2 compared with the FFA group. Mitochondrial morphology was partially restored after baicalin treatment, and ATP5A expression and mitochondrial membrane potential were increased. The superoxide anion scavenging ability of baicalin was enhanced in a dose-dependent manner. In summary, baicalin reduces oxidative stress and protects the mitochondria to inhibit apoptosis in the 3D NAFLD model via its own antioxidant activity.
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http://dx.doi.org/10.3390/nu14030541DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8840060PMC
January 2022

Altered cerebellar gray matter and cerebellar-cortex resting-state functional connectivity in patients with bipolar disorder Ⅰ.

J Affect Disord 2022 04 21;302:50-57. Epub 2022 Jan 21.

Guangzhou Huiai, Hospital, Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510370, China. Electronic address:

Background: Bipolar disorder (BP) is a common psychiatric disorder characterized by extreme fluctuations in mood. Recent studies have indicated the involvement of cerebellum in the pathogenesis of BP. However, no study has focused on the precise role of cerebellum exclusively in patients with bipolar I disorder (BP-I).

Methods: Forty-five patients with BP-I and 40 healthy controls were recruited. All subjects underwent clinical evaluation and Magnetic Resonance diffusion Tension Imaging scans. For structural images, we used a spatially unbiased infratentorial template toolbox to isolate the cerebellum and then preformed voxel-based morphometry (VBM) analyses to assess the difference in cerebellar gray matter volume (GMV) between the two groups. For the functional images, we chose the clusters that survived from VBM analysis as seeds and performed functional connectivity (FC) analysis. Between-group differences were assessed using the independent Students t test or the nonparametric Mann-Whitney U Test. For multiple comparisons, the results were further corrected with Gaussian random field (GRF) approach (voxel-level P < 0.001, cluster-level P < 0.05).

Results: Compared with healthy controls, BP-I patients showed significantly decreased GMV in left lobule V and left lobule VI (P < 0.05, GRF corrected). The FC of cerebellum with bilateral superior temporal gyrus, bilateral insula, bilateral rolandic operculum, right putamen, and left precentral gyrus was disrupted in BP-I patients (P < 0.05, GRF corrected).

Conclusions: BP-I patients showed decreased cerebellar GMV and disrupted cerebellar-cortex resting-state FC. This suggests that cerebellar abnormalities may play an important role in the pathogenesis of BP-I.
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http://dx.doi.org/10.1016/j.jad.2022.01.073DOI Listing
April 2022

Alternations in the gut microbiota and metabolome with newly diagnosed unstable angina.

J Genet Genomics 2022 Mar 6;49(3):240-248. Epub 2021 Dec 6.

Department of Occupational and Environmental Health, Key Laboratory of Environment and Health, Ministry of Education and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China. Electronic address:

Gut microbiota plays an important role in coronary heart disease, but its compositional and functional changes in unstable angina (UA) remain unexplored. We performed metagenomic sequencing of 133 newly diagnosed UA patients and 133 sex- and age-matched controls, and profiled the fecal and plasma metabolomes in 30 case-control pairs. The alpha diversity of gut microbiota was increased in UA patients: the adjusted odds ratios (ORs) per standard deviation increase in Shannon and Simpson indices were 1.30 (95% confidence interval, 1.01-1.70) and 1.36 (1.05-1.81), respectively. Two common species (depleted Klebsiella pneumoniae and enriched Streptococcus parasanguinis; P ≤ 0.002) and three rare species (depleted Weissella confusa, enriched Granulicatella adiacens and Erysipelotrichaceae bacterium 6_1_45; P ≤ 0.005) were associated with UA. The UA-associated gut microbiota was depleted in the pathway of L-phenylalanine degradation (P = 0.001), primarily contributed by Klebsiella pneumoniae. Consistently, we found increased circulating phenylalanine in UA patients (OR = 2.76 [1.17-8.16]). Moreover, Streptococcusparasanguinis was negatively correlated with fecal citrulline (Spearman's r = -0.470, P = 0.009), a metabolite depleted in UA patients (OR = 0.26 [0.08-0.63]). These findings are informative to help understand the metabolic connection between gut microbiota and UA.
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http://dx.doi.org/10.1016/j.jgg.2021.11.009DOI Listing
March 2022

Intervertebral Foramen Width Is an Important Factor in Deciding Additional Uncinate Process Resection in ACDF-a Retrospective Study.

Front Surg 2021 19;8:626344. Epub 2021 Nov 19.

Department of Spine Surgery, Shanghai Changzheng Hospital, Naval Medical University, Shanghai, China.

Anterior cervical discectomy and fusion (ACDF) has been established as a classic procedure for the management of cervical radiculopathy. However, it is unclear whether combined uncinate process resection (UPR) is necessary for treating cervical radiculopathy. Here, we investigated the clinical outcome of ACDF combined with UPR compared to ACDF alone to determine the necessity of UPR in treating cervical radiculopathy. Uncinate process resection may be necessary in certain patients along with ACDF to achieve better clinical outcomes of cervical radiculopathy. Fifty-five patients underwent ACDF with UPR, and 126 patients without UPR were reviewed. The width and height of the intervertebral foramen were measured by 45° oblique X-rays. We also measured the Japanese Orthopedic Association (JOA) score and visual analog scale (VAS) score. C2-C7 Cobb angles were obtained from all patients pre- and post-operatively. Meanwhile, linear regression analysis was used to evaluate the relationship between the clinical outcomes and the intervertebral foramen width before surgery. Linear regression analysis indicated that the improvement in the JOA and VAS scores was irrelevant to both the pre-operative width of the intervertebral foramen (wIVF) and the height of the intervertebral foramen (hIVF) in the ACDF+UPR group. However, pre-operative wIVF was associated with post-operative JOA and VAS scores in the ACDF alone group. Those with pre-operative wIVF <3 mm in the ACDF group had the least improvement in post-operative clinical symptoms due to the change in wIVF ( > 0.05). The ACDF group whose wIVF was over 3 mm showed similar clinical outcomes to the ACDF + UPR group, and wIVF significantly increased post-operatively ( < 0.05). The fusion rate and C2-C7 Cobb angles did not show significant differences between the two groups ( > 0.05). Our current findings suggest that UPR should be considered when wIVF is <3 mm pre-operatively. However, there is no need to sacrifice the uncovertebral joint in ACDF when the pre-operative wIVF is over 3 mm. Level III.
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http://dx.doi.org/10.3389/fsurg.2021.626344DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8639498PMC
November 2021

Acute-On-Chronic Liver Failure Defined by Asian Pacific Association for the Study of the Liver Should Include Decompensated Cirrhosis.

Front Med (Lausanne) 2021 15;8:750061. Epub 2021 Oct 15.

Fourth Department of Liver Disease (Difficult & Complicated Liver Diseases and Artificial Liver Center), Beijing You'an Hospital Affiliated to Capital Medical University, Beijing, China.

Acute-on-chronic liver failure (ACLF) is an acute deterioration of chronic liver disease with high short-term mortality. The inclusion or exclusion of previously decompensated cirrhosis (DC) in the diagnostic criteria of ACLF defined by the Asian Pacific Association for the Study of the Liver (APASL-ACLF) has not been conclusive. We aimed to evaluate the prognostic impact of decompensated cirrhosis in ACLF. We retrospectively collected a cohort of patients with a diagnosis of APASL-ACLF (with or without DC) hospitalized from 2012 to 2020 at three liver units in tertiary hospitals. Baseline characteristics and survival data at 28, 90, 180, 360, 540, and 720 days were collected. Of the patients assessed using APASL-ACLF criteria without the diagnostic indicator of chronic liver disease, 689 patients were diagnosed with ACLF, of whom 435 had no decompensated cirrhosis (non-DC-ACLF) and 254 had previously decompensated cirrhosis (DC-ACLF). The 28-, 90-, 180-, 360-, 540-, and 720-day mortality were 24.8, 42.9, 48.7, 57.3, 63.4, and 68.1%, respectively, in DC-ACLF patients, which were significantly higher than in non-DC-ACLF patients ( < 0.05). DC was independently associated with long-term (180/360/540/720 days) but not short-term (28/90 days) mortality in patients with ACLF. Age, total bilirubin, international normalized ratio, and hepatic encephalopathy were independent risk factors for short- and long-term mortality risk in ACLF patients ( < 0.05). Patients with DC-ACLF have a higher mortality rate, especially long-term mortality, compared to non-DC-ACLF patients. Therefore, DC should be included in the diagnostic criteria of APASL-ACLF and treated according to the ACLF management process.
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http://dx.doi.org/10.3389/fmed.2021.750061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8554226PMC
October 2021

Long-term performance, membrane fouling behaviors and microbial community in a hollow fiber anaerobic membrane bioreactor (HF-AnMBR) treating synthetic terephthalic acid-containing wastewater.

J Hazard Mater 2022 02 8;424(Pt B):127458. Epub 2021 Oct 8.

Shanghai Key Lab for Urban Ecological Processes and Eco-Restoration, School of Ecological and Environmental Sciences, East China Normal University, Shanghai 200241, PR China; Shanghai Engineering Research Center of Biotransformation of Organic Solid Waste, Shanghai 200241, PR China; Shanghai Institute of Pollution Control and Ecological Security, 1515 North Zhongshan Rd. (No. 2), Shanghai 200092, PR China; Technology Innovation Center for Land Spatial Eco-restoration in Metropolitan Area, Ministry of Natural Resources, 3663 N. Zhongshan Road, Shanghai 200062, PR China. Electronic address:

Purified terephthalic acid (PTA) wastewater with properties of poor biodegradation and high toxicity is produced from refining and synthesis of petrochemical products. In this study, a lab-scale hollow fiber membrane bioreactor (HF-AnMBR) fed with synthetic PTA wastewater was operated over 200 days with stepwise decreased hydraulic retention time (HRT) to investigate the long-term performance, membrane fouling mechanism and microbial community evolution. Results showed that a stable chemical oxygen demand (COD) removal rate of 65.8 ± 4.1% was achieved at organic loading rate of 3.1 ± 0.3 g-COD/L-reactor/d and HRT 24 h, under which the methane production rate reached 0.33 ± 0.02 L/L-reactor/d. Further shortening HRT, however, led to the decreased COD removal efficiency and low methane bioconversion. A mild membrane fouling occurred due to the production of colloidal biopolymers and the interaction between increased colloidal substances secreted/cracked by microorganisms and membrane interface. Further 16S rRNA analysis indicated that microbial diversity and richness had changed with the variation of HRT while Methanosaeta, and Methanolinea species were always the dominant methanogens responsible for methane production. The results verify that HF-AnMBR is an alternative technology for PTA wastewater treatment along with energy harvesting, and provide a new avenue toward sustainable petrochemical wastewater management.
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http://dx.doi.org/10.1016/j.jhazmat.2021.127458DOI Listing
February 2022

Integration of Molecular Inflammatory Interactome Analyses Reveals Dynamics of Circulating Cytokines and Extracellular Vesicle Long Non-Coding RNAs and mRNAs in Heroin Addicts During Acute and Protracted Withdrawal.

Front Immunol 2021 19;12:730300. Epub 2021 Aug 19.

National Health Commission (NHC) Key Laboratory of Drug Addiction Medicine (Kunming Medical University), The First Affiliated Hospital of Kunming Medical University, Kunming, China.

Heroin addiction and withdrawal influence multiple physiological functions, including immune responses, but the mechanism remains largely elusive. The objective of this study was to investigate the molecular inflammatory interactome, particularly the cytokines and transcriptome regulatory network in heroin addicts undergoing withdrawal, compared to healthy controls (HCs). Twenty-seven cytokines were simultaneously assessed in 41 heroin addicts, including 20 at the acute withdrawal (AW) stage and 21 at the protracted withdrawal (PW) stage, and 38 age- and gender-matched HCs. Disturbed T-helper(T)1/T2, T1/T17, and T2/T17 balances, characterized by reduced interleukin (IL)-2, elevated IL-4, IL-10, and IL-17A, but normal TNF-α, were present in the AW subjects. These imbalances were mostly restored to the baseline at the PW stage. However, the cytokines TNF-α, IL-2, IL-7, IL-10, and IL-17A remained dysregulated. This study also profiled exosomal long non-coding RNA (lncRNA) and mRNA in the plasma of heroin addicts, constructed co-expression gene regulation networks, and identified lncRNA-mRNA-pathway pairs specifically associated with alterations in cytokine profiles and T1/T2/T17 imbalances. Altogether, a large amount of cytokine and exosomal lncRNA/mRNA expression profiling data relating to heroin withdrawal was obtained, providing a useful experimental and theoretical basis for further understanding of the pathogenic mechanisms of withdrawal symptoms in heroin addicts.
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http://dx.doi.org/10.3389/fimmu.2021.730300DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8416766PMC
December 2021

SERS monitoring of local pH in encapsulated therapeutic cells.

Nanoscale 2021 Sep 16;13(34):14354-14362. Epub 2021 Aug 16.

CIC biomaGUNE, Basque Research and Technology Alliance (BRTA), Paseo de Miramon 182, 20014, Donostia San Sebastián, Spain.

Microencapsulation of therapeutic cells has widely advanced toward the development of treatments for various diseases, in particular seeking the protection of cell transplants from immune rejection. However, several challenges in cell therapy remain due to the lack of suitable methods to monitor in vivo microcapsule tracking, microcapsule stability and/or altered cell viability and proliferation upon transplantation. We propose in this work the incorporation of contrast agents in microcapsules, which can be easily visualized by SERS imaging. By placing SERS probes in the alginate extracellular layer, a high contrast can be obtained with negligible toxicity. Specifically, we used a pH-sensitive SERS tracking probe consisting of gold nanostars encoded with a pH-sensitive Raman-active molecule, and protected by a layer of biocompatible polymer coating, grafted on the nanoparticles via electrostatic interactions. This nanomaterial is highly sensitive within the biologically relevant pH range, 5.5-7.8. We demonstrate that this SERS-based pH sensor can provide information about cell death of microencapsulated cells, in a non-invasive manner. As a result, we expect that this approach should provide a general strategy to study biological interactions at the microcapsule level.
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http://dx.doi.org/10.1039/d1nr03969eDOI Listing
September 2021

Bivalirudin Attenuates Thrombin-Induced Endothelial Hyperpermeability via S1P/S1PR2 Category: Original Articles.

Front Pharmacol 2021 3;12:721200. Epub 2021 Aug 3.

Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang, China.

To explore the role of the Sphingosine 1-Phosphate (S1P)/Receptor2 (S1PR2) pathway in thrombin-induced hyperpermeability (TIP) and to test whether bivalirudin can reverse TIP via the S1P-S1PRs pathway. Using western blot, we demonstrated that Human umbilical vein endothelial cells (HUVECs) that were cultured with 2 U/ml thrombin showed significantly increased S1PR2 expression while S1PR1and three kept unchanged. Such increment was attenuated by JTE-013 pretreatment and by presence of bivalirudin. Exposure of 2 U/ml of thrombin brought a higher level of S1P both intracellularly and extracellularly within the HUVECs by using ELISA detecting. Thrombin induced S1P and S1PR2 increment was restored by usage of PF543 and bivalirudin. Bivalirudin alone did not influenced the level of S1P and S1PR1,2, and S1PR3 compare to control group. As a surrogate of cytoskeleton morphology, phalloidin staining and immunofluorescence imaging were used. Blurry cell edges and intercellular vacuoles or spaces were observed along thrombin-exposed HUVECs. Presence of JTE-013 and bivalirudin attenuated such thrombin-induced permeability morphological change and presence of heparin failed to show the protective effect. Transwell chamber assay and probe assay were used to measure and compare endothelial permeability . An increased TIP was observed in HUVECs cultured with thrombin, and coculture with bivalirudin, but not heparin, alleviated this increase. JTE-013 treatment yielded to similar TIP alleviating effect. , an Evans blue assay was used to test subcutaneous and organ microvascular permeability after the treatment of saline only, thrombin + saline, thrombin + bivalirudin, thrombin + heparin or thrombin + JTE-013. Increased subcutaneous and organ tissue permeability after thrombin treatment was observed in thrombin + saline and thrombin + heparin groups while treatment of bivalirudin and JTE-013 absent this effect. S1P/S1PR2 mediates TIP by impairing vascular endothelial barrier function. Unlike heparin, bivalirudin effectively blocked TIP by inhibiting the thrombin-induced S1P increment and S1PR2 expression, suggesting the novel endothelial protective effect of bivalirudin under pathological procoagulant circumstance.
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http://dx.doi.org/10.3389/fphar.2021.721200DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8369898PMC
August 2021

TiCT MXene-Loaded 3D Substrate toward On-Chip Multi-Gas Sensing with Surface-Enhanced Raman Spectroscopy (SERS) Barcode Readout.

ACS Nano 2021 Jul 30. Epub 2021 Jul 30.

Advanced Photonics Center, Southeast University, Nanjing 210096, China.

Gas sensors lie at the heart of various fields ranging from medical to environmental sciences, and the demand of gas sensors is instantly expanding. However, in the face of complex gas samples, how to maintain high sensitivity while performing multiplex detection still puzzles the researchers. Here, by introducing TiCT MXene into a microfluidic gas sensor with a three-dimensional (3D) transferable SERS substrate, a powerful gas sensor having both multiplex detecting ability and high sensitivity is demonstrated. The employ of MXene endows the sensor with a universal high adsorption efficiency for various gases while the generation of gas vortices in the sophisticated nanomicro structure extends the molecule residence time in SERS-active area, both leading to the increased sensitivity. In the proof-of-concept experiment, a limit of detection (LOD) of 10-50 ppb was achieved for three typical volatile organic compounds (VOCs) according to the intrinsic SERS signals of gas molecules. Besides, the well-designed periodic 3D structure solves the general repeatability problem of SERS substrates. In addition, the detailed composition of gas mixture was revealed using classic least-square analysis (CLS) with an average accuracy of 90.6%. Further, a chromatic barcode was developed based on the results of CLS to read out the complex composition of samples visually.
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http://dx.doi.org/10.1021/acsnano.1c01890DOI Listing
July 2021

Exposure to polycyclic aromatic hydrocarbons, DNA methylation and heart rate variability among non-current smokers.

Environ Pollut 2021 Nov 10;288:117777. Epub 2021 Jul 10.

Department of Occupational and Environmental Health, Key Laboratory of Environment and Health, Ministry of Education and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

Polycyclic aromatic hydrocarbons (PAHs) exposure is associated with heart rate variability (HRV) reduction, a widely used marker of cardiovascular autonomic dysfunction. The role of DNA methylation in the relationship between PAHs exposure and decreased HRV is largely unknown. This study aims to explore epigenome-wide DNA methylation changes associated with PAHs exposure and further evaluate their associations with HRV alternations among non-current smokers. We measured 10 mono-hydroxylated PAHs (OH-PAHs) in urine and DNA methylation levels in blood leukocytes among participants from three panels of Chinese non-current smokers (152 in WHZH, 99 in SY, and 53 in COW). We conducted linear regression analyses between DNA methylation and OH-PAHs metabolites with adjustment for age, gender, body mass index, drinking, blood cell counts, and surrogate variables in each panel separately, and combined the results by using inverse-variance weighted fixed-effect meta-analysis to obtain estimates of effect size. The median value of total OH-PAHs ranged from 0.92 × 10 in SY panel (62.6% men) to 13.82 × 10 μmol/mmol creatinine in COW panel (43.4% men). The results showed that methylation levels of cg18223625 (COL20A1) and cg07805771 (SLC16A1) were significantly or marginally significantly associated with urinary 2-hydroxynaphthalene [β(SE) = 0.431(0.074) and 0.354(0.068), FDR = 0.016 and 0.056, respectively], while methylation level of cg09235308 (PLEC1) was positively associated with urinary total OH-PAHs [β(SE) = 0.478(0.079), FDR = 0.004]. Hypermethylations of cg18223625, cg07805771, and cg09235308 were inversely associated with HRV indices among the WHZH and COW non-current smokers. However, we did not observe significant epigenome-wide associations for the other 9 urinary OH-PAHs. These findings provide new evidence that PAHs exposure is linked to differential DNA methylation, which may help better understand the influences of PAHs exposure on HRV alternations.
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http://dx.doi.org/10.1016/j.envpol.2021.117777DOI Listing
November 2021

Trace Analysis of Fenbutatin Oxide in Soil and Plant- and Animal-Derived Foods Using Modified QuEChERS Coupled with HPLC-MS/MS.

ACS Omega 2021 Apr 6;6(15):10260-10265. Epub 2021 Apr 6.

Chinese Academy of Agricultural Sciences Institute of Tobacco Research, Qingdao 266101, China.

A modified QuEChERS method in combination with high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was first developed for the determination of fenbutatin oxide in six types of samples (soil, tobacco, rice, milk, pork liver, and pork). Fenbutatin oxide was extracted with acetonitrile containing 1% formic acid (v/v) and purified by dispersive solid-phase extraction using primary secondary amine (PSA) and quantitatively analyzed by HPLC-MS/MS. In the range of 0.005-1 mg/kg, a good linear relationship exists between the concentration of fenbutatin oxide and the peak area, giving a coefficient of determination ( ) of >0.99. The recoveries of fenbutatin oxide at three spiked levels were 79.04-97.12% with the relative standard deviations (RSDs) of 3.30-10.96%, and the limit of quantification (LOQ) was 0.007 mg/kg. In addition, the developed method is consistent with the reference method ( = 0.9896, = 40). The method is demonstrated to be convenient and reliable for the routine monitoring of fenbutatin oxide in soil and plant- and animal-derived foods.
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http://dx.doi.org/10.1021/acsomega.1c00593DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8153780PMC
April 2021

Epigallocatechin-3-Gallate Provides Protection Against Alzheimer's Disease-Induced Learning and Memory Impairments in Rats.

Drug Des Devel Ther 2021 13;15:2013-2024. Epub 2021 May 13.

Department of Neurology, The Second Hospital of Jilin University, Changchun, 130041, People's Republic of China.

Purpose: Recent evidence has highlighted the anti-inflammatory properties of the constituent of Green Tea Polyphenols (GTP), epigallocatechin-3-gallate (EGCG) which has been suggested to exert a neuroprotective effect on Alzheimer's disease (AD). The current study aimed to elucidate the effect of EGCG on memory function in rats with AD.

Methods: AD rat models were initially established through an injection with Aβ 25-35 solution, followed by gavage with EGCG at varying doses to determine the effect of EGCG on learning and cognitive deficits in AD. Morris water maze test was conducted to evaluate the spatial memory function of the rats. Immunohistochemistry and Western blot analysis were performed to identify Tau phosphorylation. The expression of β-site amyloid precursor protein-cleaving enzyme 1 (BACE1) mRNA and protein in rat hippocampus was measured by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis. Acetylcholinesterase (AchE) activity, Aβ1-42 expression and Ach content were all detected using enzyme-linked immunosorbent assay (ELISA).

Results: EGCG intervention brought about a decrease in the escape latency period while increasing the time at the target quadrant among the AD rats. EGCG decreased the hyperphosphorylation of Tau in hippocampus. BACE1 expression and activity as well as the expression of Aβ1-42 were suppressed by EGCG. Moreover, EGCG promoted Ach content by diminishing the activity of AchE.

Conclusion: The current study demonstrates that EGCG may diminish the hyperphosphorylation of the Tau protein, downregulate BACE1 and Aβ1-42 expression to improve the antioxidant system and learning and memory function of rats with AD.
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http://dx.doi.org/10.2147/DDDT.S289473DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8128347PMC
November 2021

Naringin improves lipid metabolism in a tissue-engineered liver model of NAFLD and the underlying mechanisms.

Life Sci 2021 Jul 20;277:119487. Epub 2021 Apr 20.

Difficult & Complicated Liver Diseases and Artificial Liver Center & Beijing Municipal Key Laboratory of Liver Failure and Artificial Liver Treatment Research, Beijing YouAn Hospital, Capital Medical University, Beijing, China. Electronic address:

Aims: Nonalcoholic fatty liver disease (NAFLD) is a lipid metabolism disorder. Naringin (a main active ingredient in Ganshuang granules) is a flavanone that has been demonstrated to exert hepatoprotective and antifibrotic effects. The present study aimed to use a novel tissue-engineered fatty liver model to assess the effects and mechanisms of naringin on NAFLD.

Main Methods: Intracellular triglyceride (TG) was examined by oil red O staining and commercial kits. The proteins associated with lipid metabolism were measured by western blotting and/or qPCR. Very low-density lipoprotein (VLDL) was measured by ELISA. A CCK8 assay was used to assess the cytotoxicity of naringin. Molecular docking was used to predict the interactions and binding patterns between naringin and target proteins.

Key Findings: Naringin significantly reduced intracellular TG accumulation by 52.7% in tissue-engineered fatty (TEF) livers, and also the level of pyruvate dehydrogenase kinase 4. Naringin downregulated CD36 and proliferator activated-receptor γ expression, reducing the uptake of FFAs; naringin also downregulated de novo liposynthetases by reducing acetyl CoA carboxylase, fatty acid synthetase etc. in TEF livers. Moreover, naringin increased the expression of proliferator activated-receptor α (PPAR-α) and carnitine palmitoyltransferase 1 to improve the oxidation of fatty acids. The levels of VLDL secreted from TEF livers were reduced by 24.7% after naringin treatment. Molecular docking analyses determined the bioactivity of naringin through its specific binding to CD36 and PPAR-α.

Significance: Naringin improved lipid metabolism disorders in TEF livers by reducing fatty acid uptake and de novo lipogenesis and increasing fatty acid oxidation. CD36 and PPAR-α might be specific targets of naringin.
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http://dx.doi.org/10.1016/j.lfs.2021.119487DOI Listing
July 2021

Dual-Labeled Graphene Quantum Dot-Based Förster Resonance Energy Transfer Nanoprobes for Single-Molecule Localization Microscopy.

ACS Omega 2021 Apr 24;6(13):8808-8815. Epub 2021 Mar 24.

Advanced Photonics Center, Southeast University, Nanjing 210096, Jiangsu, China.

Single-molecule localization microscopy (SMLM)-based super-resolution imaging techniques (, photoactivated localization microscopy (PALM)/stochastic optical reconstruction microscopy (STORM)) require that the employed optical nanoprobes possess fluorescence intensity fluctuations under certain excitation conditions. Here, we present a dual-labeled graphene quantum dot (GQD)-based Förster resonance energy transfer (FRET) nanoprobe, which is suitable for SMLM imaging. The nanoprobe is constructed by attaching Alexa Fluor 488 (AF488) and Alexa Fluor 568 (AF568) dye molecules onto GQDs. Experimental results confirmed the FRET effect of the nanoprobes. Moreover, under a single 405 nm excitation, the FRET nanoprobe exhibits excellent blinking behavior. SMLM imaging of microtubules in MRC-5 cells is realized. The presented nanoprobe shows great potential in multicolor SMLM-based super-resolution imaging.
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http://dx.doi.org/10.1021/acsomega.0c05417DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8028002PMC
April 2021

The neuroprotection of deproteinized calf blood extractives injection against Alzheimer's disease via regulation of Nrf-2 signaling.

Aging (Albany NY) 2021 03 26;13(8):11150-11169. Epub 2021 Mar 26.

School of Life Sciences, Jilin University, Changchun 130012, China.

Alzheimer's disease (AD) is characterized by cognitive decline due to the accumulation of extracellular β-amyloid (Aβ) plaques and neurofibrillary tangles in the brain, which impair glutamate (Glu) metabolism. Deproteinized Calf Blood Extractive Injection (DCBEI) is a biopharmaceutical that contains 17 types of amino acids and 5 types of nucleotides. In this study, we found that DCBEI pretreatment reduced L-Glu-dependent neuroexcitation toxicity by maintaining normal mitochondrial function in HT22 cells. DCBEI treatment also reduced the expression of pro-apoptosis proteins and increased the expression of anti-apoptosis proteins. Furthermore, DCBEI attenuated AD-like behaviors (detected via the Morris water maze test) in B6C3-Tg (APPswePSEN1dE9)/Nju double transgenic (APP/PS1) mice; this effect was associated with a reduction in the amount of Aβ and neurofibrillary tangle deposition and the concomitant reduction of phospho-Tau in the hippocampus. Metabonomic profiling revealed that DCBEI regulated the level of neurotransmitters in the hippocampus of APP/PS1 mice. Label-free proteomics revealed that DCBEI regulated the expression of Nrf-2 and its downstream targets, as well as the levels of phospho-protein kinase B and mitogen-activated protein kinase. Together, these data show that DCBEI can ameliorate AD symptoms by upregulating Nrf2-mediated antioxidative pathways and thus preventing mitochondrial apoptosis.
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http://dx.doi.org/10.18632/aging.202776DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8109110PMC
March 2021

Parenting Style and Cyber-Aggression in Chinese Youth: The Role of Moral Disengagement and Moral Identity.

Front Psychol 2021 19;12:621878. Epub 2021 Feb 19.

The Lab of Mental Health and Social Adaptation, Faculty of Psychology, Southwest University, Chongqing, China.

Previous research has shown that parenting style is intricately linked to cyber-aggression. However, the underlying mechanisms of this relationship remain unclear, especially among young adults. Guided by the social cognitive theory and the ecological system theory, this study aimed to examine the effect of parenting style on cyber-aggression, the potential mediating role of moral disengagement, and the moderating role of moral identity in this relationship. Participants comprised 1,796 Chinese college students who anonymously completed questionnaires on parenting style, moral disengagement, moral identity, cyber-aggression, and demographic variables. After controlling for sex and age, parental rejection and over-protection were positively related to cyber-aggression; however, parental emotional warmth was non-significantly related to cyber-aggression. Mediation analysis revealed that parenting style was related to cyber-aggressive behavior through moral disengagement. Moderated mediation analysis further indicated that the indirect effect of parenting style on cyber-aggression was much stronger in college students with higher moral identity. The study carries important practical implications for parents and educators concerned about the destructive consequences of cyber-aggression.
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http://dx.doi.org/10.3389/fpsyg.2021.621878DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7933004PMC
February 2021

Profile of copper-associated DNA methylation and its association with incident acute coronary syndrome.

Clin Epigenetics 2021 01 27;13(1):19. Epub 2021 Jan 27.

Department of Occupational and Environmental Health, Key Laboratory of Environment and Health, Ministry of Education and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Rd., Wuhan, 430030, Hubei, China.

Background: Acute coronary syndrome (ACS) is a cardiac emergency with high mortality. Exposure to high copper (Cu) concentration has been linked to ACS. However, whether DNA methylation contributes to the association between Cu and ACS is unclear.

Methods: We measured methylation level at > 485,000 cytosine-phosphoguanine sites (CpGs) of blood leukocytes using Human Methylation 450 Bead Chip and conducted a genome-wide meta-analysis of plasma Cu in a total of 1243 Chinese individuals. For plasma Cu-related CpGs, we evaluated their associations with the expression of nearby genes as well as major cardiovascular risk factors. Furthermore, we examined their longitudinal associations with incident ACS in the nested case-control study.

Results: We identified four novel Cu-associated CpGs (cg20995564, cg18608055, cg26470501 and cg05825244) within a 5% false discovery rate (FDR). DNA methylation level of cg18608055, cg26470501, and cg05825244 also showed significant correlations with expressions of SBNO2, BCL3, and EBF4 gene, respectively. Higher DNA methylation level at cg05825244 locus was associated with lower high-density lipoprotein cholesterol level and higher C-reactive protein level. Furthermore, we demonstrated that higher cg05825244 methylation level was associated with increased risk of ACS (odds ratio [OR], 1.23; 95% CI 1.02-1.48; P = 0.03).

Conclusions: We identified novel DNA methylation alterations associated with plasma Cu in Chinese populations and linked these loci to risk of ACS, providing new insights into the regulation of gene expression by Cu-related DNA methylation and suggesting a role for DNA methylation in the association between copper and ACS.
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http://dx.doi.org/10.1186/s13148-021-01004-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7839231PMC
January 2021

MicroRNA-376b-5p targets SOX7 to alleviate ischemic brain injury in a mouse model through activating Wnt/β-catenin signaling pathway.

Life Sci 2021 Apr 19;270:119072. Epub 2021 Jan 19.

Department of Neurology, the Second Hospital of Jilin University, Changchun City 130041, Jilin Province, China. Electronic address:

Background: Accumulating evidence has reported the role of microRNA (miR) on ischemic brain injury. We aim to investigate the mechanism of miR-376b-5p/Sex-determining region Y-box 7 (SOX7)/Wnt/β-catenin axis in mice with ischemic brain injury.

Methods: Transient middle cerebral artery occlusion (tMCAO) model was established by suture method. Expression levels of miR-376b-5p, SOX7, and Wnt/β-catenin pathway-related proteins (Wnt3a and β-catenin) in brain tissues of tMCAO mice were determined by RT-qPCR and western blot analysis. The target relationship between miR-376b-5p and SOX7 was tested by bioinformatics analysis and luciferase activity assay. The neurological scores of mice were recorded and their behaviors were observed. Moreover, the brain damage, oxidative stress indices, hemoglobin (Hb) content, content of brain water, infarct area, TUNEL positive cells, blood-brain barrier permeability and the number of intact neurons in the ischemic-side brain tissues of tMCAO mice were detected via upregulated miR-376b-5p or downregulated SOX7.

Results: In mice with ischemic brain injury, miR-376b-5p targeted and downregulated SOX7 in brain tissues, thus activating the Wnt/β-catenin pathway. The tMCAO mice showed higher neurological scores, severe brain damage, decreased number of neurons, as well as elevated blood-brain barrier permeability, Hb content, cerebral edema and infarct area. These symptoms could be alleviated by miR-376b-5p elevation or SOX7 inhibition. SOX7 overexpression reversed the effects of miR-376b-5p elevation on tMCAO mice.

Conclusion: Our study suggests that miR-376b-5p could improve the blood-brain barrier permeability, relieve brain edema and decrease infarct area, thus improve ischemic brain injury via the inhibition of SOX7 and activation of Wnt/β-catenin pathway.
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http://dx.doi.org/10.1016/j.lfs.2021.119072DOI Listing
April 2021

Individualized identification of first-episode bipolar disorder using machine learning and cognitive tests.

J Affect Disord 2021 03 18;282:662-668. Epub 2020 Dec 18.

Department of Psychiatry, University of Alberta, Alberta, Canada.

Identifying cognitive dysfunction in the early stages of Bipolar Disorder (BD) can allow for early intervention. Previous studies have shown a strong correlation between cognitive dysfunction and number of manic episodes. The objective of this study was to apply machine learning (ML) techniques on a battery of cognitive tests to identify first-episode BD patients (FE-BD). Two cohorts of participants were used for this study. Cohort #1 included 74 chronic BD patients (CHR-BD) and 53 healthy controls (HC), while the Cohort #2 included 37 FE-BD and 18 age- and sex-matched HC. Cognitive functioning was assessed using the Cambridge Neuropsychological Test Automated Battery (CANTAB). The tests examined domains of visual processing, spatial memory, attention and executive function. We trained an ML model to distinguish between chronic BD patients (CHR-BD) and HC at the individual level. We used linear Support Vector Machines (SVM) and were able to identify individual CHR-BD patients at 77% accuracy. We then applied the model to Cohort #2 (FE-BD patients) and achieved an accuracy of 76% (AUC = 0.77). These results reveal that cognitive impairments may appear in early stages of BD and persist into later stages. This suggests that the same deficits may exist for both CHR-BD and FE-BD. These cognitive deficits may serve as markers for early BD. Our study provides a tool that these early markers can be used for detection of BD.
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http://dx.doi.org/10.1016/j.jad.2020.12.046DOI Listing
March 2021

Efficacy and Safety of Ultrasonic Bone Curette-assisted Dome-like Laminoplasty in the Treatment of Cervical Ossification of Longitudinal Ligament.

Orthop Surg 2021 Feb 5;13(1):161-167. Epub 2021 Jan 5.

Department of Spine Surgery, Changzheng Hospital, Naval Medical University, Shanghai, China.

Objective: To assess the efficacy and safety of ultrasonic bone curette-assisted dome-like laminoplasty in the treatment of ossification of longitudinal ligament (OPLL) involving C .

Methods: A total of 64 patients with OPLL involving C level were enrolled. Thirty-eight patients who underwent ultrasonic bone curette-assisted dome-like laminoplasty were defined as ultrasonic bone curette group (UBC), and 28 patients who underwent traditional high-speed drill-assisted dome-like laminoplasty were defined as high-speed drill group (HSD). Patient characteristics such as age, sex, body mass index (BMI), symptomatic duration, and other information like the type of OPLL, the time of surgery, blood loss, C -C Cobb angle change and complications were all recorded and compared. The Japanese Orthopaedic Association (JOA) score, the nerve root functional improvement rate (IR), and the visual analogue scale (VAS) were used to assess neurological recovery and pain relief. The change of the distance between the apex of ossification and a continuous line connecting the anterior edges of the lamina was measured to assess the spinal expansion extent. The measured data were statistically processed and analyzed using SPSS 21.0 software, and the measurement data were expressed as mean ± SD.

Results: In ultrasonic bone curette (UBC) group and high-speed drill group (HSD) group, the average time for laminoplasty was 52.3 ± 18.2 min and 76.0 ± 21.8 min and the mean bleeding loss volume was 155.5 ± 41.3 mL and 177.4 ± 54.7 mL, respectively, with a statistically significant difference between the groups. Both groups demonstrated a significant improvement in neurological function. However, the VAS score in UBC group was lower than in HSD group at the 6-month follow-up (P < 0.05), but there was no significant difference at 1-year follow-up. We found that the loss of lordosis was 1.5° ± 1.0° in UBC group, which is significantly lower than that of HSD group at 1-year follow-up (3.8° ± 1.2°, P < 0.05). According to the change of canal dimension, we found that the expansion extent of the spinal canal in UBC group was similar to that of HSD group (P > 0.05). Only one patient in the UBC group and five patients in the HSD group displayed cerebrospinal fluid (CSF) leakag.

Conclusions: With the use of ultrasonic bone curette in OPLL dome-like decompression, the decompression surgery could be completed relatively safely and quickly. It effectively reduced the amount of intraoperative blood loss and complications, and had better initial recovery of neck pain.
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http://dx.doi.org/10.1111/os.12858DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7862153PMC
February 2021

Identification of Tamoxifen-Resistant Breast Cancer Cell Lines and Drug Response Signature.

Front Mol Biosci 2020 4;7:564005. Epub 2020 Dec 4.

Department of Bioinformatics, Key Laboratory of Ministry of Education for Gastrointestinal Cancer, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China.

Breast cancer cell lines are frequently used to elucidate the molecular mechanisms of the disease. However, a large proportion of cell lines are affected by problems such as mislabeling and cross-contamination. Therefore, it is of great clinical significance to select optimal breast cancer cell lines models. Using tamoxifen survival-related genes from breast cancer tissues as the gold standard, we selected the optimal cell line model to represent the characteristics of clinical tissue samples. Moreover, using relative expression orderings of gene pairs, we developed a gene pair signature that could predict tamoxifen therapy outcomes. Based on 235 consistently identified survival-related genes from datasets GSE17705 and GSE6532, we found that only the differentially expressed genes (DEGs) from the cell line dataset GSE26459 were significantly reproducible in tissue samples (binomial test, = 2.13E-07). Finally, using the consistent DEGs from cell line dataset GSE26459 and tissue samples, we used the transcriptional qualitative feature to develop a two-gene pair (, ; , ) for predicting clinical tamoxifen resistance in the training data (logrank = 1.98E-07); this signature was verified using an independent dataset (logrank = 0.009909). Our results indicate that the cell line model from dataset GSE26459 provides a good representation of the characteristics of clinical tissue samples; thus, it will be a good choice for the selection of drug-resistant and drug-sensitive breast cancer cell lines in the future. Moreover, our signature could predict tamoxifen treatment outcomes in breast cancer patients.
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http://dx.doi.org/10.3389/fmolb.2020.564005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746845PMC
December 2020

Neuroprotective effect of emodin against Alzheimer's disease via Nrf2 signaling in U251 cells and APP/PS1 mice.

Mol Med Rep 2021 02 10;23(2). Epub 2020 Dec 10.

School of Life Sciences, Jilin University, Changchun, Jilin 130012, P.R. China.

Emodin is a naturally‑occurring medicinal herbal ingredient that possesses numerous pharmacological properties, including anti‑inflammatory and antioxidant effects. In the present study, potential neuroprotective effects associated with the antioxidant activity of emodin were assessed in U251 cells that were subjected to β‑amyloid peptide (Aβ)‑induced apoptosis and in amyloid precursor protein (APP)/presenilin‑1 (PS1) double‑transgenic mice. U251 is a type of human astroglioma cell line (cat. no. BNCC337874; BeNa Culture Collection). In apoptotic U251 cells, 3‑h emodin pre‑treatment prior to 24‑h Aβ co‑exposure improved cell viability, suppressed lactate dehydrogenase leakage and caspase‑3, ‑8 and ‑9 activation to inhibit apoptosis. Compared with those after Aβ exposure alone, emodin ameliorated the dissipation of the mitochondrial membrane potential, inhibited the over‑accumulation of reactive oxygen species, enhanced the expression levels of nuclear factor‑erythroid‑2‑related factor 2 (Nrf2), haemeoxygenase‑1, superoxide dismutase 1, Bcl‑2 and catalase in addition to decreasing the expression levels of Bax. In APP/PS1 mice, an 8‑week course of emodin administration improved spatial memory and learning ability and decreased anxiety. Emodin was also found to regulate key components in the Nrf2 pathway and decreased the deposition of Aβ, phosphorylated‑τ and 4‑hydroxy‑2‑nonenal in APP/PS1 mice. Taken together, the present data suggest that emodin may serve as a promising candidate for the treatment of Alzheimer's disease.
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http://dx.doi.org/10.3892/mmr.2020.11747DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7723071PMC
February 2021

Effects of Microplastics on the Adsorption and Bioavailability of Three Strobilurin Fungicides.

ACS Omega 2020 Dec 17;5(47):30679-30686. Epub 2020 Nov 17.

Laboratory of Tobacco and Aromatic Plants Quality and Safety Risk Assessment, Tobacco Research Institute of Chinese Academy of Agricultural Sciences, Qingdao 266101, China.

Microplastics (MPs) and fungicides have been recognized as two main pollutants in ecological environments, especially in aqueous ecosystems. In this study, the adsorption behavior of three typical strobilurins (azoxystrobin, picoxystrobin, and pyraclostrobin) on polystyrene (PS) and polyethylene (PE) was investigated, and the effects of adsorption on the residual behavior and bioavailability of pyraclostrobin were evaluated. The results showed that MPs had strong adsorption capacity for the three kinds of strobilurins. Under similar conditions, the adsorption capacity was the highest for pyraclostrobin, followed by picoxystrobin and azoxystrobin, which was consistent with their octanol-water partition coefficients. Moreover, the adsorption capacity of PS was slightly higher than that of PE. The pH of aqueous solution had little effect on adsorption capacity, while an increase in ionic strength increased the adsorption capacity of azoxystrobin and picoxystrobin. The Fourier transform infrared spectra of MPs showed that no new chemical groups were formed during the adsorption process. Thus, it is speculated that hydrophobic interactions may be the driving force behind the adsorption of strobilurins on the MPs. Additionally, the adsorption of pyraclostrobin on MPs significantly reduced its residual amount in the aqueous solution, which reduced the adsorption and bioavailability of pyraclostrobin in black bean seedlings. The study provides effective information for environmental safety risk assessments with regard to the combined pollution risks of MPs and strobilurins.
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http://dx.doi.org/10.1021/acsomega.0c04787DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7711943PMC
December 2020

Microglia-Derived Extracellular Vesicles Carrying miR-711 Alleviate Neurodegeneration in a Murine Alzheimer's Disease Model by Binding to Itpkb.

Front Cell Dev Biol 2020 6;8:566530. Epub 2020 Nov 6.

Department of Neurology, The Second Hospital of Jilin University, Changchun, China.

Neurodegeneration in Alzheimer's disease (AD) results in microglial activation, which may participate in the inflammatory cascade accelerating tissue damage. In this study, we sought to characterize the alleviatory role of microRNA-711 (miR-711) encapsulated in microglia-derived extracellular vesicles (EVs) in a model of AD. Ultracentrifugation was employed to extract EVs from microglia (BV2 cells), which were identified using Western blot analysis of the EVs marker proteins Alix and CD63. A repetitive mild traumatic brain injury (rmTBI) mouse model was induced by controlled cortical impact. After overexpressing miR-711 or 1,4,5-trisphosphate 3-kinase B (Itpkb) in BV2 cells, we evaluated the inflammation in BV2 cells and the ratio of microglia M2/M1. Further, we injected BV2 cell-secreted EVs with overexpressed miR-711 or Itpkb into rmTBI mice through a tail vein to investigate the inflammation markers in mouse serum and, the M2/M1 phenotype ratio of microglia in brain tissues, and to evaluate neurological deficit and cognitive function. The EVs obtained by ultracentrifugation were verified by the presence of Alix and CD63 expression. Mechanistic studies suggested that miR-711 targeted and inhibited Itpkb, thereby repressing Tau phosphorylation and increasing the ratio of M2/M1. Furthermore, miR-711-containing EVs reduced the score of neurological deficits and improved cognitive function in rmTBI mice. The administration of microglia-derived EVs loaded with miR-711, which mediated the hyperphosphorylation of Tau protein in the Itpkb pathway, effectively alleviated neurodegenerative changes and cognitive dysfunction in AD.
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http://dx.doi.org/10.3389/fcell.2020.566530DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7677138PMC
November 2020

Blood Test Results of Pregnant COVID-19 Patients: An Updated Case-Control Study.

Front Cell Infect Microbiol 2020 7;10:560899. Epub 2020 Oct 7.

Obstetric Department, Maternal and Child Health Hospital of Hubei Province, Wuhan, China.

Coronavirus disease (COVID-19) is a current global public health emergency. However, current research on the blood test results of pregnant women with COVID-19 is insufficient. A case-control study was carried out based on clinical blood test results. Pregnant COVID-19 patients, pregnant COVID-19 patients with diabetes, and pregnant COVID-19 patients with hypertension, were assessed in this study. Also, 120 controls were matched by age, parity, fetus number, and presence of chronic disease. -tests, Chi-square tests, Wilcoxon signed-rank tests, and Kruskal-Wallis tests were used to compare data from the blood tests and liver function indices among the selected groups. Between January 24 and March 14, 2020, 60 pregnant COVID-19 patients delivered at the Maternal and Child Health Hospital of Hubei Province. The average maternal age of pregnant COVID-19 patients was 30.97 years and the mean gestational period was 37.87 weeks. 71.67% (43/60) of pregnant COVID-19 patients gave birth by cesarean delivery. In total, 21.67% (13/60) were diagnosed with diabetes and 18.33% (11/60) were diagnosed with hypertension during pregnancy. Compared to controls, pregnant COVID-19 patients showed significantly lower numbers of blood lymphocytes and higher numbers of neutrophils, as well as higher levels of C-reactive protein and total bilirubin. Among the three groups, pregnant COVID-19 patients with diabetes had significantly higher levels of neutrophils and lower levels of total protein. Aspartate transaminase levels were higher in pregnant COVID-19 patients with hypertension than in pregnant COVID-19 patients with no comorbidities and controls with hypertension. Blood and liver function indices indicate that chronic complications, including hypertension and diabetes, could increase the risk of inflammation and liver injury in pregnant COVID-19 patients.
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http://dx.doi.org/10.3389/fcimb.2020.560899DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7575733PMC
November 2020

Live-Cell Surface-Enhanced Raman Spectroscopy Imaging of Intracellular pH: From Two Dimensions to Three Dimensions.

ACS Sens 2020 10 14;5(10):3194-3206. Epub 2020 Oct 14.

CIC biomaGUNE, Basque Research and Technology Alliance (BRTA), Paseo de Miramón 182, 20014 Donostia-San Sebastián, Spain.

Visualization of intracellular pH (i-pH) using surface-enhanced Raman spectroscopy (SERS) plays an important role toward understanding of cellular processes including their interactions with nanoparticles. However, conventional two-dimensional SERS imaging often fails to take into consideration changes occurring in the whole-cell volume. We therefore aimed at obtaining a comprehensive i-pH profile of living cells by means of three-dimensional (3D) SERS imaging, thereby visualizing dynamic i-pH distribution changes in a single cell. We devised here a biocompatible and highly stable SERS pH probe, comprising plasmonic gold nanostars functionalized with a pH-sensitive Raman reporter tag-4-mercaptobenzoic acid-and protected by a cationic biocompatible polymer, poly-l-arginine hydrochloride (PA). The positively charged PA coating plays a double role in enhancing cell uptake and providing chemical and colloidal stability in cellular environments. The SERS-active pH probe allowed visualization of local changes in i-pH, such as acidification during nanoparticle (NP) endocytosis. We provide evidence of i-pH changes during NP endocytosis via high-resolution 3D SERS imaging, thereby opening new avenues toward the application of SERS to intracellular studies.
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http://dx.doi.org/10.1021/acssensors.0c01487DOI Listing
October 2020
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