Publications by authors named "Yizhi Zhang"

105 Publications

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

Life Sci 2021 Apr 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
April 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 Mar 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
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 Jan 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

Neuroprotective effects of verbascoside against Alzheimer's disease via the relief of endoplasmic reticulum stress in Aβ-exposed U251 cells and APP/PS1 mice.

J Neuroinflammation 2020 Oct 18;17(1):309. Epub 2020 Oct 18.

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

Background: Endoplasmic reticulum (ER) stress is involved in the progression of Alzheimer's disease (AD). Verbascoside (VB), an active phenylethanoid glycoside that was first isolated from Verbascum sinuatum (the wavyleaf mullein), possesses anti-inflammatory, antioxidative, and anti-apoptotic effects. The purpose of this study was to elucidate the beneficial effects of VB in amyloid β (Aβ)-damaged human glioma (U251) cells and in APPswe/PSEN1dE9 transgenic (APP/PS1) mice.

Methods: U251 cells were co-incubated with 10 μM of Aβ and treated with VB. The protective effects of VB were investigated by using 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium bromide assay, flow cytometry, fluorescence staining, and transmission electron microscopy. APP/PS1 transgenic mice were treated for 6 weeks with VB. Learning and memory were evaluated using a Morris water maze test. Immunohistochemistry, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling, thioflavin-S staining, and proteomics analysis were performed to study the potential neuroprotective mechanism. Enzyme-linked immunosorbent assays and western blot were performed to analyze altered protein levels of brain lysates in APP/PS1 mice and/or Aβ-damaged U251 cells.

Results: In Aβ-damaged U251 cells, VB significantly improved cell viability, inhibited apoptosis, reduced calcium accumulation and the intracellular concentrations of reactive oxygen species, and improved the morphology of mitochondria and ER. In APP/PS1 mice, 6-week administration of VB significantly improved memory and cognition. VB inhibited apoptosis, reduced the deposition of Aβ, reduced the formation of neurofibrillary tangles formed by hyperphosphorylated tau protein, and downregulated the expression levels of 4-hydroxynonenal and mesencephalic astrocyte-derived neurotrophic factor in the brains of APP/PS1 mice. Proteomics analysis of mouse hippocampus suggested that the neuroprotective effect of VB may be related to the reduction of ER stress. This was indicated by the fact that VB inhibited the three branches of the unfolded protein response, thereby attenuating ER stress and preventing apoptosis.

Conclusions: The results confirmed that VB possesses significant neuroprotective effects, which are related to the reduction of ER stress. These findings support the status of VB as a potentially effective treatment for AD and warrant further research.
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http://dx.doi.org/10.1186/s12974-020-01976-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7570123PMC
October 2020

Forsythoside B attenuates memory impairment and neuroinflammation via inhibition on NF-κB signaling in Alzheimer's disease.

J Neuroinflammation 2020 Oct 15;17(1):305. Epub 2020 Oct 15.

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

Background: Neuroinflammation is a principal element in Alzheimer's disease (AD) pathogenesis, so anti-inflammation may be a promising therapeutic strategy. Forsythoside B (FTS•B), a phenylethanoid glycoside isolated from Forsythiae fructus, has been reported to exert anti-inflammatory effects. However, no studies have reported whether the anti-inflammatory properties of FTS•B have a neuroprotective effect in AD. In the present study, these effects of FTS•B were investigated using amyloid precursor protein/presenilin 1 (APP/PS1) mice, BV-2 cells, and HT22 cells.

Methods: APP/PS1 mice were administered FTS•B intragastrically for 36 days. Behavioral tests were then carried out to examine cognitive functions, including the Morris water maze, Y maze, and open field experiment. Immunohistochemistry was used to analyze the deposition of amyloid-beta (Aβ), the phosphorylation of tau protein, and the levels of 4-hydroxynonenal, glial fibrillary acidic protein, and ionized calcium-binding adapter molecule 1 in the hippocampus. Proteins that showed marked changes in levels related to neuroinflammation were identified using proteomics and verified using enzyme-linked immunosorbent assay and western blot. BV-2 and HT22 cells were also used to confirm the anti-neuroinflammatory effects of FTS•B.

Results: In APP/PS1 mice, FTS•B counteracted cognitive decline, ameliorated the deposition of Aβ and the phosphorylation of tau protein, and attenuated the activation of microglia and astrocytes in the cortex and hippocampus. FTS•B affected vital signaling, particularly by decreasing the activation of JNK-interacting protein 3/C-Jun NH2-terminal kinase and suppressing WD-repeat and FYVE-domain-containing protein 1/toll-like receptor 3 (WDFY1/TLR3), further suppressing the activation of nuclear factor-κB (NF-κB) signaling. In BV-2 and HT22 cells, FTS•B prevented lipopolysaccharide-induced neuroinflammation and reduced the microglia-mediated neurotoxicity.

Conclusions: FTS•B effectively counteracted cognitive decline by regulating neuroinflammation via NF-κB signaling in APP/PS1 mice, providing preliminary experimental evidence that FTS•B is a promising therapeutic agent in AD treatment.
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http://dx.doi.org/10.1186/s12974-020-01967-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7565774PMC
October 2020

Identification of bipolar disorder using a combination of multimodality magnetic resonance imaging and machine learning techniques.

BMC Psychiatry 2020 10 6;20(1):488. Epub 2020 Oct 6.

Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou Huiai Hospital, Guangzhou, Guangdong, China.

Background: Bipolar disorder (BPD) is a common mood disorder that is often goes misdiagnosed or undiagnosed. Recently, machine learning techniques have been combined with neuroimaging methods to aid in the diagnosis of BPD. However, most studies have focused on the construction of classifiers based on single-modality MRI. Hence, in this study, we aimed to construct a support vector machine (SVM) model using a combination of structural and functional MRI, which could be used to accurately identify patients with BPD.

Methods: In total, 44 patients with BPD and 36 healthy controls were enrolled in the study. Clinical evaluation and MRI scans were performed for each subject. Next, image pre-processing, VBM and ReHo analyses were performed. The ReHo values of each subject in the clusters showing significant differences were extracted. Further, LASSO approach was recruited to screen features. Based on selected features, the SVM model was established, and discriminant analysis was performed.

Results: After using the two-sample t-test with multiple comparisons, a total of 8 clusters were extracted from the data (VBM = 6; ReHo = 2). Next, we used both VBM and ReHo data to construct the new SVM classifier, which could effectively identify patients with BPD at an accuracy of 87.5% (95%CI: 72.5-95.3%), sensitivity of 86.4% (95%CI: 64.0-96.4%), and specificity of 88.9% (95%CI: 63.9-98.0%) in the test data (p = 0.0022).

Conclusions: A combination of structural and functional MRI can be of added value in the construction of SVM classifiers to aid in the accurate identification of BPD in the clinic.
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http://dx.doi.org/10.1186/s12888-020-02886-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7542439PMC
October 2020

MicroRNA-181 regulates the development of Ossification of Posterior longitudinal ligament via Epigenetic Modulation by targeting PBX1.

Theranostics 2020 12;10(17):7492-7509. Epub 2020 Jun 12.

Department of Orthopedics, Changzheng Hospital Affiliated to Second Military Medical University, 415th Feng Yang Road, Shanghai, 200003, PR China.

Ossification of the posterior longitudinal ligament (OPLL) presents as the development of heterotopic ossification in the posterior longitudinal ligament of the spine. The etiology of OPLL is genetically linked, as shown by its high prevalence in Asian populations. However, the molecular mechanism of the disease remains obscure. In this study, we explored the function and mechanism of OPLL-specific microRNAs. The expression levels of the ossification-related OPLL-specific miR-181 family were measured in normal or OPLL ligament tissues. The effect of miR-181a on the ossification of normal or pathogenic ligament cells was tested using real-time polymerase chain reaction (PCR), Western blot, alizarin red staining and alkaline phosphatase (ALP) staining. The candidate targets of miR-181 were screened using a dual luciferase reporter assay and functional analysis. The link between miR-181a and its target PBX1 was investigated using chromatin immunoprecipitation, followed by real-time PCR detection. Histological and immunohistochemical analysis as well as micro-CT scanning were used to evaluate the effects of miR-181 and its antagonist using both tip-toe-walking OPLL mice and bone formation assays. Using bioinformatic analysis, we found that miR-181a-5p is predicted to play important roles in the development of OPLL. Overexpression of miR-181a-5p significantly increased the expression of ossification-related genes, staining level of alizarin red and ALP activity, while the inhibition of miR-181a-5p by treatment with an antagomir had the opposite effects. Functional analysis identified PBX1 as a direct target of miR-181a-5p, and we determined that PBX1 was responsible for miR-181a-5p's osteogenic phenotype. By chromatin immunoprecipitation assay, we found that miR-181a-5p controls ligament cell ossification by regulating PBX1-mediated modulation of histone methylation and acetylation levels in the promoter region of osteogenesis-related genes. Additionally, using an model, we confirmed that miR-181a-5p can substantially increase the bone formation ability of posterior ligament cells and cause increased osteophyte formation in the cervical spine of tip-toe-walking mice. Our data unveiled the mechanism by which the miR-181a-5p/PBX1 axis functions in the development of OPLL, and it revealed the therapeutic effects of the miR-181a-5p antagomir in preventing OPLL development both and . Our work is the first to demonstrate that microRNA perturbation could modulate the development of OPLL through epigenetic regulation.
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http://dx.doi.org/10.7150/thno.44309DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7359103PMC
May 2021

A SERS-colorimetric dual-mode aptasensor for the detection of cancer biomarker MUC1.

Anal Bioanal Chem 2020 Sep 6;412(23):5707-5718. Epub 2020 Jul 6.

Advanced Photonics Center, School of Electronic Science and Engineering, Southeast University, Nanjing, 210096, Jiangsu, China.

Human mucin-1 (MUC1) has attracted considerable attention owing to its overexpression in diverse malignancies. Here, for the rapid and efficient detection of MUC1, we present a SERS-colorimetric dual-mode aptasensor, by integrating SERS probes with magnetic separation, which has several distinctive advantages. Using such a dual-mode aptasensor, the colorimetric functionality is distinguishable by the naked eye, providing a fast and straightforward screening ability for the detection of MUC1. Moreover, SERS-based detection greatly improves the detection sensitivity, reaching a limit of detection of 0.1 U/mL. In addition, the combination of SERS and colorimetric method holds the advantages of these two techniques and thereby increases the reliability and efficiency of MUC1 detection. On the one hand, the magnetic nanobeads functionalized with MUC1-specific aptamer were utilized as an efficient capturing substrate for separating MUC1 from biological complex medium. On the other hand, the gold-silver core-shell nanoparticles modified with Raman reporters and the complementary sequences of MUC1 were used as the signal indicator, which could simultaneously report the SERS signal and colorimetric change. This strategy can achieve a good detection range and realize MUC1 analysis in real patients' samples. Thus, we anticipate that this kind of aptasensor would provide promising potential applications in the diagnosis and prognosis of cancers. Graphical abstract.
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http://dx.doi.org/10.1007/s00216-020-02790-7DOI Listing
September 2020

Quaternary-Ammonium-Modulated Surface-Enhanced Raman Spectroscopy Effect: Discovery, Mechanism, and Application for Highly Sensitive Sensing of Acetylcholine.

Anal Chem 2020 07 9;92(14):9706-9713. Epub 2020 Jul 9.

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

Quaternary ammonium (QA) plays multiple roles in biological functions, whose dysregulation may result in multiple diseases. However, how to efficiently detect QA-based materials such as acetylcholine (ACh) still remains a great challenge, especially in complex biological environments. Here, a new effect [called quaternary-ammonium-modulated surface-enhanced Raman spectroscopy (QAM-SERS) effect] is discovered, showing that the existence of QA will modulate the intensity of SERS signals in a concentration-dependent manner. When the QAM-SERS effect is used, a new method is easily developed for detection of ACh with an extremely high sensitivity and an ultrawide dynamic range. Particularly, the linear dynamic range can be freely tuned to adapt for various physiological samples. As a proof-of-concept experiment, the time-dependent secretion of ACh from PC12 cells was successfully monitored using the QAM-SERS method, which were under either the stimulation of potassium ions or the incubation of drugs. The discovery of the QAM-SERS effect provides an easy and universal strategy for detecting ACh as well as other QA-contained molecules, which can also inspire new insights into the roles that QA could play in biology and chemistry.
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http://dx.doi.org/10.1021/acs.analchem.0c01061DOI Listing
July 2020

Corrigendum to "Glutamate dehydrogenase plays an important role in ammonium detoxification by submerged macrophytes" [Sci. Total Environ. 722 (2020) 137859].

Sci Total Environ 2020 Sep 28;733:139640. Epub 2020 May 28.

Key Laboratory of Aquatic Botany and Watershed Ecology, Wuhan Botanical Garden, Chinese Academy of Sciences, Wuhan 430074, Hubei, PR China; Sino-Africa Joint Research Centre, Chinese Academy of Sciences, Wuhan 430074, Hubei, PR China. Electronic address:

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http://dx.doi.org/10.1016/j.scitotenv.2020.139640DOI Listing
September 2020

The relationship between preoperative cervical sagittal balance and clinical outcome of laminoplasty treated cervical ossification of the posterior longitudinal ligament patients.

Spine J 2020 09 28;20(9):1422-1429. Epub 2020 May 28.

Spine Center, Department of Orthopedics, Changzheng Hospital, Second Military Medical University, 415th Feng Yang Road, Shanghai 200003, PR China. Electronic address:

Background Context: Laminoplasty is a common surgical method used to treat patients with cervical ossification of the posterior longitudinal ligament (OPLL). Although laminoplasty is preferred over traditional laminectomy, the factors affecting the complications and outcomes are unclear. Recently, sagittal balance indexes have been revealed to be predictors of clinical outcomes in patients with cervical degenerative diseases, but their relationships with laminoplasty-treated OPLL outcomes remains unknown.

Purpose: The purpose of this study is to evaluate the relationship of preoperative cervical sagittal balance indexes and clinical outcome in laminoplasty treated OPLL patients.

Study Design: This is a retrospective case study.

Patient Population: Between January 2015 and January 2017, 181 consecutively included patients who underwent cervical laminoplasty for OPLL were enrolled (male:female ratio=126:75; mean age=60.2 years). Cervical spine lateral radiographs in neutral, flexion, and extension positions were taken before and 2 years after the surgery.

Outcome Measures: The C2-C7 Cobb angle, T1 slope, C1-C7 sagittal vertical axis (SVA), C2-C7 SVA, CGH (center of gravity of the head)-C7 SVA, cervical JOA (Japanese Orthopedic Association) score, and neck VAS (visual analogue scale) score were measured preoperatively and postoperatively at the 2-year follow-up.

Methods: The patients were divided into two groups according to changes in the lordotic angle or the recovery rate of the JOA score. The relationships between the postoperative lordosis loss or the clinical outcome and the preoperative variables, including the patient's age, JOA score, C2-C7 Cobb angle, T1 slope, C1-C7 SVA, C2-C7 SVA, and CGH-C7 SVA, were investigated.

Results: The patients were divided into two groups according to the postoperative change in the C2-C7 Cobb angle. There were no differences in the age, preoperative C2-C7 Cobb angle, C1-C7 SVA, or C2-C7 SVA; there was only a difference in the preoperative CGH-C7 SVA and T1 slope level (p=.038, p=.042). The postoperative JOA and JOA recovery rate were related to the postoperative lordosis loss in cervical alignment (p=.048, p=.031). We again divided the patients into two groups according to the JOA recovery rate and found that only the preoperative CGH-C7 SVA and C1-C7 SVA were related to the neurological outcome (p=.011, p=.047). According to the multivariate logistic regression analysis, higher preoperative CGH-C7 SVA levels were significantly associated with decreases in the lordosis angle postoperatively and the clinical outcome (p=.018, OR=1.225; p=.034, OR=1.654). The ROC (receiver operating characteristic) analysis revealed that the proper cutoff value of preoperative CGH-C7 SVA for predicting the postoperative loss of lordosis and clinical outcomes is 3.8 cm.

Conclusion: Preoperative cervical sagittal balance indexes are related to the outcomes of OPLL patients after laminoplasty. Patients with high preoperative CGH-C7 SVA levels have a high probability of developing sagittal imbalances and neurological symptoms of the cervical spine, and this measurement can be used as a predictor of outcomes in laminoplasty-treated cervical OPLL patients.
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http://dx.doi.org/10.1016/j.spinee.2020.05.542DOI Listing
September 2020

Dynamic Epidemiology and Virulence Characteristics of Carbapenem-Resistant in Wenzhou, China from 2003 to 2016.

Infect Drug Resist 2020 31;13:931-940. Epub 2020 Mar 31.

Department of Clinical Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People's Republic of China.

Purpose: To investigate transitions in resistance mechanisms, virulence characteristics and molecular epidemiology of carbapenem-resistant (CRKP) during 2003-2016 in a major Eastern Chinese medical center.

Patients And Methods: From a total of 2299 clinical strains collected from 2003 to 2016, 214 were found to be CRKP isolates and were selected for further study. Characterization of these was conducted by molecular detection of antibiotic resistance markers and virulence determinants, modified carbapenem inactivation method and multilocus sequence typing (MLST).

Results: In this study, the prevalence of CRKP was increasing over the 14-year period, mirroring a national trend. These CRKP strains were resistant to most of the tested, clinically relevant drugs. The majority of these CRKP strains were positive for carbapenemases, with the carbapenemase (KPC) found to be the dominant type (207/210, 98.6%). The carrier rates of virulence genes and increased in 2016, while the  and showed a relatively constant trend. From MLST data, ST11 (88.8%, 190/214) was the preponderant sequence type (ST), followed by ST15 (1.9%, 4/214) and ST656 (1.4%, 3/214). Several strains with less common STs (ST690, ST895, ST1823 and ST1384) were also detected, and these too showed high levels of antimicrobial resistance.

Conclusion: The average national rise in CRKP across China is mirrored in this in-depth analysis of a single hospital, while the prevalence of hypervirulent CRKP (such as ST15) was relatively low as of 2016. Continuous monitoring is necessary to keep track of CRKP and should include the prospect of newly emerging strains with less common STs and the prospect of detecting carbapenem-resistant, carbapenemase-negative .
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http://dx.doi.org/10.2147/IDR.S243032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7128075PMC
March 2020

Glutamate dehydrogenase plays an important role in ammonium detoxification by submerged macrophytes.

Sci Total Environ 2020 Jun 11;722:137859. Epub 2020 Mar 11.

Key Laboratory of Aquatic Botany and Watershed Ecology, Wuhan Botanical Garden, Chinese Academy of Sciences, Wuhan 430074, Hubei, PR China; Sino-Africa Joint Research Centre, Chinese Academy of Sciences, Wuhan, 430074, Hubei, PR China. Electronic address:

Ammonium is a paradoxical chemical because it is a nutrient but also damages ecosystems at high concentration. As the most eco-friendly method of water restoration, phytoremediation technology still faces great challenges. To provide more theoretical support, we exploited six common submerged macrophytes and selected the most ammonium-tolerant and -sensitive species; then further explored and compared the mechanisms underlying ammonium detoxification. Our results showed the activity of glutamate dehydrogenase (GDH) in the ammonium-tolerant species Myriophyllum spicatum leaves performed a dose-response curve (increased 169% for NADH-dependent GDH and 103% for NADPH-dependent GDH) with the [NH-N] increasing from 0 to 100 mg/L while glutamine synthetase (GS) activity slightly changed. But for the ammonium-sensitive species, Potamogeton lucens, the activity of GDH recorded no major changes, while the GS increased slightly (17%). Based on this, we conclude that the alternative pathway of GDH is more important than the pathway catalyzed by GS in determining the tolerance of submerged macrophytes to high ammonium concentration (up to 100 mg N/L). Our present study identifies submerged macrophytes that are tolerant of high concentrations of ammonium and provides mechanistic support for practical water restoration by aquatic plants.
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http://dx.doi.org/10.1016/j.scitotenv.2020.137859DOI Listing
June 2020

Hyper-expression of the efflux pump gene adeB was found in Acinetobacter baumannii with decreased triclosan susceptibility.

J Glob Antimicrob Resist 2020 09 9;22:367-373. Epub 2020 Mar 9.

School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang Province, China. Electronic address:

Objectives: Triclosan is usually employed as a disinfectant in a wide range of medical and consumer care products, which may have imposed a selective pressure on bacteria. This study was designed to evaluate the resistance mechanisms of triclosan and molecular epidemiology of triclosan-resistant isolates of Acinetobacter baumannii in Wenzhou, China.

Methods: A collection of 626 A. baumannii were isolated from the First Affiliated Hospital of Wenzhou Medical University during 2016-2017 and antimicrobial susceptibility testing of these isolates were performed via agar dilution method. Molecular mechanisms of triclosan resistance, including the existence of mutations in reductase (FabI) were investigated by PCR and sequencing. Furthermore, quantitative RT-PCR was conducted to evaluate the expression levels of the fabI gene and efflux pump genes (adeB, adeG, adeJ, abeM, amvA and abeS) at normal condition and sub-inhibitory concentration of triclosan, and the epidemiological characteristics were analyzed by PFGE and MLST.

Results: 2.7% (17/626) of A. baumannii exhibited resistance to triclosan. The FabI mutation Gly95Ser was found in one triclosan resistant strain. The expression of fabI and adeB gene were significant difference between triclosan-resistant and susceptible strains (P < 0.05). The expression of fabI, adeG, adeJ and abeM were increased after triclosan induction. The clones of these resistant isolates were diverse and sporadic.

Conclusions: The hyper-expression of fabI was probably the main mechanism of triclosan resistance in this study, and the efflux pump AdeB, AdeG, AdeJ and AbeM might also be related to decreased triclosan susceptibility.
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http://dx.doi.org/10.1016/j.jgar.2020.02.027DOI Listing
September 2020

CACNB2 rs11013860 polymorphism correlates of prefrontal cortex thickness in bipolar patients with first-episode mania.

J Affect Disord 2020 05 3;268:82-87. Epub 2020 Feb 3.

The Mental Health Center, West China Hospital, Sichuan University, Chengdu, Sichuan, PR China.

Background: The β2 subunit of the voltage-gated l-type calcium channel gene(CACNB2) rs11013860 polymorphism is a putative genetic susceptibility marker for bipolar disorder (BD). However, the neural effects of CACNB2 rs11013860 in BD are largely unknown.

Methods: Forty-six bipolar patients with first-episode mania and eighty-three healthy controls (HC) were genotyped for CACNB2 rs11013860 and were scanned with a 3.0 Tesla structural magnetic resonance imaging system to measure cortical thickness of prefrontal cortex (PFC) components (superior frontal cortex, orbitofrontal cortex, middle and inferior frontal gyri).

Results: Cortical thickness was thinner in patients on all PFC measurements compared to HC (p < 0.050). Moreover, we found a significant interaction between CACNB2 genotype and diagnosis for the right superior frontal cortical thickness (F = 8.190, p = 0.040). Bonferroni corrected post-hoc tests revealed that, in CACNB2 A-allele carriers, patients displayed thinner superior frontal thickness compared to HC (p < 0.001). In patients, CACNB2 A-allele carriers also exhibited reduced superior frontal thickness compared to CACNB2 CC-allele carriers (p = 0.016).

Limitations: Lithium treatment may influence our results, and the sample size in our study is relatively small.

Conclusions: Our results suggest that the CACNB2 rs11013860 might impact PFC thickness in patients with first-episode mania. These findings provide evidence to support CACNB2 rs11013860 involvement in the emotion-processing neural circuitry abnormality in the early stage of BD, which will ultimately contribute to revealing the link between the variation in calcium channel genes and the neuropathological mechanism of BD.
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http://dx.doi.org/10.1016/j.jad.2020.02.007DOI Listing
May 2020

Inflammatory-sensitive CHI3L1 protects nucleus pulposus via AKT3 signaling during intervertebral disc degeneration.

FASEB J 2020 03 29;34(3):3554-3569. Epub 2020 Jan 29.

Spine Center, Department of Orthopedics, Changzheng Hospital Affiliated to Second Military Medical University, Shanghai, China.

Intervertebral disc degeneration (IDD) is the main cause of low back pain and the mechanism of which is far from fully revealed. Although inflammation directed nucleus pulposus (NP) extracellular matrix metabolism dysregulation is known to be the main cause of the degeneration process, few is known about the protective factors. Using high-throughput label-free proteomics, we found that inflammation-related autocrine factor Chitinase-3-like protein 1 (CHI3L1, or YKL-40) is highly expressed in the NP cells during degeneration. Immunohistochemical analysis show that the expression of CHI3L1 is NP tissue specific, and increase significantly during degeneration. Overexpression of CHI3L1 significantly decrease the catabolism, and increase the anabolism of extracellular matrix. Knockdown of CHI3L1 using siRNAs show the opposite results, which imply that the protective role of CHI3L1 in IDD. Using high-throughput RNA sequencing and functional analyses, we find that AKT3 expression and its phosphorylation is mainly regulated by CHI3L1. And lastly, the mechanism of which is also validated using human and mouse degenerated NP tissues. In summary, our findings show that the inflammation-related autocrine factor CHI3L1 is NP specific, and it protects IDD by promoting the AKT3 signaling, which may serve as a potential therapeutic target in intervertebral disc degeneration.
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http://dx.doi.org/10.1096/fj.201902096RDOI Listing
March 2020

MicroRNA-384-5p Promotes Endothelial Progenitor Cell Proliferation and Angiogenesis in Cerebral Ischemic Stroke through the Delta-Likeligand 4-Mediated Notch Signaling Pathway.

Cerebrovasc Dis 2020 10;49(1):39-54. Epub 2020 Jan 10.

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

Background: MicroRNAs (miRs) have a crucial regulatory role in endothelial cell function and tumor angiogenesis by inhibiting the expressions of their target genes. The participation of microRNA-384-5p (miR-384-5p) has been prominently reported in various ischemia-induced diseases such as myocardial ischemia and atherosclerosis. Hence, the present study aimed at exploring the effect of miR-384-5p on proliferation, apoptosis, and angiogenesis of endothelial progenitor cells (EPCs) in cerebral ischemic stroke and investigating the associated underlying mechanism.

Methods: A middle cerebral artery occlusion (MCAO) mouse model was established, with determination of the expression of cluster of differentiation 31 (CD31) and vascular endothelial growth factor (VEGF) proteins. Next, the MCAO mice and EPCs separated from MCAO mice were injected or transfected with mimics or inhibitors of miR-384-5p, or small interference RNA Delta-likeligand 4 (si-DLL4) in order to evaluate their effect on brain infarct size, cell proliferation, apoptosis, and angiogenesis. The relationship among miR-384-5p, DLL4, and the Notch signaling pathway was then verified by a series of experiments.

Results: In MCAO mice, an increased brain infarct size and cell apoptosis in brain tissues were evident, with decreased expression of miR-384-5p, VEGF, and CD31, as well as increased DLL4 expression. After miR-384-5p mimic or si-DLL4 treatment, the brain infarct size and cell apoptosis in the brain tissues were reduced in compliance with an increased expression of VEGF and CD31. Our findings demonstrated that miR-384-5p negatively regulated the expression of DLL4, which further downregulated the Notch signaling pathway. When miR-384-5p was overexpressed or DLL4 silenced, the cell proliferation and angiogenesis of EPCs were promoted and cell apoptosis was inhibited.

Conclusions: Our study demonstrated that overexpressed miR-384-5p targeting DLL4 could stimulate proliferation and angiogenesis, while inhibiting apoptosis of EPCs in mice with cerebral ischemic stroke through the Notch signaling pathway.
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http://dx.doi.org/10.1159/000503950DOI Listing
September 2020

Zebrafish and : Models to Identify the Subsequent Infection and Evaluate the Immunological Differences in Different Intestinal Colonization Strains.

Front Microbiol 2019 2;10:2750. Epub 2019 Dec 2.

Department of Clinical Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

The intestine is the main reservoir of bacterial pathogens in most organisms. is an important opportunistic pathogen associated with nosocomial bacterial infections. Intestinal colonization with has been shown to be associated with an increased risk of subsequent infections. However, not all strains in the intestine cause further infection, and the distinction of the difference among strains that cause infection after colonization and the ones causing only asymptomatic colonization is unclear. In this study, we report a case of a hospitalized patient from the ICU. We screened out two intestine colonization strains (FK4111, FK4758) to analyze the subsequent infection conditions. We set up infection models of zebrafish and to establish the differences in the potential for causing subsequent infection and the immunological specificities after intestine colonization. Sudan Black B and neutral red staining results indicated that FK4758 was more responsive to neutrophil recruitment and phagocytosis of macrophages than FK4111. The results of the assessment of the organ bacterial load revealed that FK4111 and FK4758 both had the highest bacterial loads in the zebrafish intestine compared to those in other organs. However, in the zebrafish spleen, liver, and heart, the FK4758 load was significantly higher than that of FK4111. The ST37 strain FK4111, which does not produce carbapenemase, did not cause infection after colonization, whereas the ST11 strain FK4758, which produces carbapenemase, caused infection after intestinal colonization. Our finding demonstrated that not all intestinal colonization of subsequently caused infections, and the infections of after colonization are different. Therefore, the infection models we established provided possibility for the estimation of host-microbial interactions.
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http://dx.doi.org/10.3389/fmicb.2019.02750DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6900958PMC
December 2019

Array-Assisted SERS Microfluidic Chips for Highly Sensitive and Multiplex Gas Sensing.

ACS Appl Mater Interfaces 2020 Jan 24;12(1):1395-1403. Epub 2019 Dec 24.

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

A novel kind of array-assisted surface-enhanced Raman spectroscopy (SERS) microfluidic chip (ArraySERS chip) is demonstrated for gas sensing, which has the advantages of both ultrahigh sensitivity and multiplex sensing ability. On the one hand, the introduction of a microstructured triangular array can greatly increase the multiple collision probability between gas molecules and sensing interfaces in the channel. Compared with traditional gas sensors using sealed boxes, where gaseous molecules move only by diffusion, the ArraySERS chip exhibits significantly improved sensitivity. On the other hand, a composite nanoparticle is fabricated as a SERS probe for reading out the fingerprint spectral data, which consists of metal-organic framework (MOF) materials [Zeolitic Imidazolate framework-8 (ZIF-8)] and Au@Ag nanocubes, as well as cysteamine (CA) that serves as the gas-capturing agent. The experimental results show that such a structure of the SERS probe can further increase the sensing ability because of better adsorption of ZIF-8 for gas and the lower SERS background of CA itself. In addition, the simultaneous detection of multiplex gases was easily performed according to their own intrinsic SERS signals. Taking aldehyde gas as a model of a typical air pollutant, trace and multicomponent detection was realized using the ArraySERS chip. The limit of detection value was as low as 1 ppb, which is 2 magnitudes lower than that obtained by traditional methods. This strategy can be well extended for the detection of universal gases and help unleash the potential of existing gas sensors, especially for samples at low concentrations in air.
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http://dx.doi.org/10.1021/acsami.9b19358DOI Listing
January 2020