Publications by authors named "Hui Gu"

126 Publications

PIWI-interacting RNA sequencing profiles in maternal plasma-derived exosomes reveal novel non-invasive prenatal biomarkers for the early diagnosis of nonsyndromic cleft lip and palate.

EBioMedicine 2021 Mar 24;65:103253. Epub 2021 Feb 24.

Key Laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital, China Medical University, Shenyang, PR China. Electronic address:

Background: Congenital malformations are common birth defects with high neonatal morbidity and mortality. It is essential to find simpler and more efficient biomarkers for early prenatal diagnosis. Therefore, we investigated PIWI-interacting RNAs (piRNAs) as potential prenatal biomarkers in plasma-derived exosomes from pregnant women carrying foetuses with congenital malformations.

Methods: Small RNA sequencing was used to screen piRNA biomarkers in plasma-derived exosomes of five pregnant women carrying foetuses with nonsyndromic cleft lip and palate (nsCLP) and five women carrying normal foetuses. Differentially expressed piRNAs were verified in 270 pregnant women, including 111 paired women carrying foetuses with congenital malformations and normal foetuses (at 24 gestational weeks), 10 paired women carrying foetuses with nsCLP and normal foetuses (at 15-19 gestational weeks), and 28 women at different stages of normal pregnancy. piRNA biomarkers were also verified in placentas, umbilical cords, fetal medial calf muscles, and lip tissues of nsCLP and normal foetuses.

Findings: We identified a biomarker panel of three pregnancy-associated exosomal piRNAs (hsa-piR-009228, hsa-piR-016659, and hsa-piR-020496) could distinguish nsCLP foetuses from normal foetuses. These three piRNAs had better diagnostic accuracy for nsCLP at the early gestational stage, at which time typical malformations were not detected upon prenatal ultrasound screening, and had diagnostic value for neural tube defects (NTDs) and congenital heart defects (CHDs).

Interpretation: Our work revealed the potential clinical applications of piRNAs for predicting nsCLP, NTDs, and CHDs.

Funding: National Key Research and Development Program, National Natural Science Foundation of China, and LiaoNing Revitalization Talents Program .
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http://dx.doi.org/10.1016/j.ebiom.2021.103253DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921467PMC
March 2021

Efficacy of ultrasound-guided percutaneous transluminal angioplasty for arteriovenous fistula stenosis or occlusion at juxta-anastomosis-a three-year follow-up cohort study.

J Vasc Surg 2020 Dec 16. Epub 2020 Dec 16.

Department of Nephrology, The First Affiliated Hospital of Chongqing Medical University, Youyi Road 1, Chongqing 400042, China.

Objective: Arteriovenous fistula (AVF) is the preferred access for hemodialysis. Percutaneous transluminal angioplasty(PTA) has become a choice for AVF stenosis and ultrasound has been used in PTA more frequently.

Methods: This single-center retrospective cohort study analyzed 129 patients who underwent PTA in the First Affiliated Hospital of Chongqing Medical University from January 2016 to December 2016. Angioplasty was performed using a non-compliant high-pressure balloon. The process was visualized by duplex scan. Our inclusion criteria were as follows: (1)stenoses or occlusions were located at the juxta-anastomosis site:the first 5cm of the vein distal to the anastomosis;(2) stenosis was confirmed with the following conditions:(a)flow ratesare <500ml/min in the brachial artery and<200ml/min in the fistula during dialysis, and(b)the stenosis diameter is<1.7mm.We used Kaplan-Meier curve to show the postintervention primary and secondary patency rates of patients with stenosis and occlusion.

Results: Altogether,129 patients with 76 males were analyzed. Moreover,104 have AVFs on left arm,and only one had ulna-basilic AVF, while others had radial-cephalic AVF.The postintervention primary patency rates are better in occlusion cases(P<0.05),while secondary patency rates have no difference.The postintervention primary patency rates are better in patients without diabetes mellitus(P<0.05),while the secondary patency rates had no difference.

Conclusion: For juxta-anastomosis site stenosis or occlusion,PTA can be used to obtain satisfactory results.
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http://dx.doi.org/10.1016/j.jvs.2020.11.041DOI Listing
December 2020

Prognostic Value of Atherosclerosis Progression for Prediction of Cardiovascular Events in Patients with Nonobstructive Coronary Artery Disease.

Acad Radiol 2020 Oct 22. Epub 2020 Oct 22.

Department of Radiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Shandong University, Jinan, Shandong 250021, People's Republic of China. Electronic address:

Rationale And Objectives: Coronary CT angiography (CCTA) is a noninvasive reliable cardiovascular imaging technology to assess coronary atherosclerosis progression. However, there is limited data available to investigate the relationship between the atherosclerosis progression and cardiovascular events in patients with nonobstructive coronary artery disease (CAD).

Materials And Methods: A total of 757 patients (53.4 ± 9.5 years, 61.2% male) with nonobstructive CAD (1%-49% diameter stenosis) who underwent baseline and follow-up CCTA were retrospectively included in this study. Coronary atherosclerosis and its changing were analyzed by these following semi-quantitative scores: (1) obstructive plaque scores (three-vessel plaque score and severe proximal plaque score); (2) scores exhibiting plaque distribution and extent (segment stenosis score and segment involvement score); (3) coronary artery calcium score. The end points of this study were the major adverse cardiac events (MACE), which included cardiac death, coronary revascularization, nonfatal myocardial infarction and hospitalization due to unstable angina.

Results: The average time between scans was 2.0 years. After their second scan, 82 (10.8%) patients experienced MACE during 4.9 ± 1.0 years follow-up. Combined baseline and follow-up CCTA together, we found that the progression of coronary atherosclerosis was significantly higher in patients with MACE than those without (all p < 0.05). Diabetes mellitus (hazard ratio [HR] = 3.17, p < 0.001), dyslipidemia (HR = 1.69, p = 0.046), and family history of CAD (HR = 1.79, p = 0.005) were independently associated with MACE. Three vessel plaque progression (HR = 2.37, p = 0.026) and severe proximal plaque progression (HR = 3.65, p = 0.003) were strong predictors of MACE.

Conclusion: Coronary atherosclerosis progression had a predictive value of MACE in patients with nonobstructive CAD.
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http://dx.doi.org/10.1016/j.acra.2020.06.038DOI Listing
October 2020

T1 Stage Clear Cell Renal Cell Carcinoma: A CT-Based Radiomics Nomogram to Estimate the Risk of Recurrence and Metastasis.

Front Oncol 2020 4;10:579619. Epub 2020 Nov 4.

School of Medicine, Shandong University, Jinan, China.

Objectives: To develop and validate a radiomics nomogram to improve prediction of recurrence and metastasis risk in T1 stage clear cell renal cell carcinoma (ccRCC).

Methods: This retrospective study recruited 168 consecutive patients (mean age, 53.9 years; range, 28-76 years; 43 women) with T1 ccRCC between January 2012 and June 2019, including 50 aggressive ccRCC based on synchronous metastasis or recurrence after surgery. The patients were divided into two cohorts (training and validation) at a 7:3 ratio. Radiomics features were extracted from contrast enhanced CT images. A radiomics signature was developed based on reproducible features by means of the least absolute shrinkage and selection operator method. Demographics, laboratory variables (including sex, age, Fuhrman grade, hemoglobin, platelet, neutrophils, albumin, and calcium) and CT findings were combined to develop clinical factors model. Integrating radiomics signature and independent clinical factors, a radiomics nomogram was developed. Nomogram performance was determined by calibration, discrimination, and clinical usefulness.

Results: Ten features were used to build radiomics signature, which yielded an area under the curve (AUC) of 0.86 in the training cohort and 0.85 in the validation cohort. By incorporating the sex, maximum diameter, neutrophil count, albumin count, and radiomics score, a radiomics nomogram was developed. Radiomics nomogram (AUC: training, 0.91; validation, 0.92) had higher performance than clinical factors model (AUC: training, 0.86; validation, 0.90) or radiomics signature as a means of identifying patients at high risk for recurrence and metastasis. The radiomics nomogram had higher sensitivity than clinical factors mode (McNemar's chi-squared = 4.1667, p = 0.04) and a little lower specificity than clinical factors model (McNemar's chi-squared = 3.2, p = 0.07). The nomogram showed good calibration. Decision curve analysis demonstrated the superiority of the nomogram compared with the clinical factors model in terms of clinical usefulness.

Conclusion: The CT-based radiomics nomogram could help in predicting recurrence and metastasis risk in T1 ccRCC, which might provide assistance for clinicians in tailoring precise therapy.
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http://dx.doi.org/10.3389/fonc.2020.579619DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7672185PMC
November 2020

Simultaneously Breaking the Double Schottky Barrier and Phonon Transport in SrTiO-Based Thermoelectric Ceramics via Two-Step Reduction.

ACS Appl Mater Interfaces 2020 Nov 12;12(47):52721-52730. Epub 2020 Nov 12.

State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, College of Materials Science and Engineering, Donghua University, Shanghai 201620, China.

The low powder factor (PF) of polycrystalline oxide perovskites induced by the resistive grain boundaries or known as double Schottky barrier (DSB) greatly restricts their thermoelectric performance in application. Here, a general protocol including (i) powder and (ii) bulk reduction in H/Ar forming gas is demonstrated to break the DSB in La and Nb codoped SrTiO. While the powder reduction guarantees a high carrier concentration by fully stimulating the donor doping effect, the bulk reduction effectively lowers the DSB by influencing the point defects at grain boundaries, which is proved by the combination of cathode luminescence spectra and energy-dispersive X-ray spectroscopy in transmission electron microscopy. The Hall mobility can approach 10 cm V s after two-step reduction, which is similar to the level of single crystals. However, the Seebeck coefficient is not compromised, giving rise to high PF values up to 1.70 mW m K under proper reduction strength. Meanwhile, the reduction process also promotes mild precipitation of Nb nanoparticles, thus effectively lowering the lattice thermal conductivity by scattering phonons. As a result, a remarkable figure of merit reaching 0.4 at 700 K is obtained, which validates the two-step reduction as a reliable strategy toward "electron crystal-phonon glass" behavior in SrTiO-based perovskites.
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http://dx.doi.org/10.1021/acsami.0c16084DOI Listing
November 2020

Altered mRNA and lncRNA expression profiles in the striated muscle complex of anorectal malformation rats.

Pediatr Surg Int 2020 Nov 11;36(11):1287-1297. Epub 2020 Sep 11.

Department of Pediatric Surgery, Shengjing Hospital, China Medical University, 36 Sanhao Street, Shenyang, Liaoning, 110004, People's Republic of China.

Background: Striated muscle complex (SMC) dysplasia has been confirmed to contribute to postoperative defecation dysfunction of patients with anorectal malformations (ARMs). To date, the potential molecular mechanisms of SMC dysplasia underlying the development of ARMs have not been clearly explained. This study examined the expression profiles of mRNAs and lncRNAs in the malformed SMC of ARM rats using RNA sequencing (RNA-seq).

Methods: A rat model of ARMs was established by the intragastric administration of 1% ethylene thiourea (ETU) on an embryonic day 10 (E10). The rats were subjected to euthanasia and the SMC samples were collected on E19. The expression of mRNAs and lncRNAs was analyzed by RNA-seq on the Illumina HiSeq2500 platform. qRT-PCR was used to confirm the results of RNA-seq.

Results: Compared with the levels in control rats, 1408 mRNAs and 472 lncRNAs were differentially expressed in the SMC of E19 ARM rats. GO and KEGG pathway analyses showed that the top enriched GO terms were mainly related to muscle development and the enriched pathways were associated with muscle and synaptic development. Protein-protein interaction network analysis was also performed using the STRING database. The network map revealed the interaction between the WNT3 protein and NTRK1, NTF4, MUSK, and BMP5 proteins. Finally, the qRT-PCR results further confirmed the RNA-seq data.

Conclusion: Our findings indicate the involvement of these dysregulated mRNAs and lncRNAs in the pathogenesis of SMC dysplasia in ARMs, providing a theoretical foundation for developing interventions to improve postoperative defecation function.
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http://dx.doi.org/10.1007/s00383-020-04741-wDOI Listing
November 2020

Complement factors and alpha-fetoprotein as biomarkers for noninvasive prenatal diagnosis of neural tube defects.

Ann N Y Acad Sci 2020 10 5;1478(1):75-91. Epub 2020 Aug 5.

Key Laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital, China Medical University, Shenyang, China.

Neural tube defects (NTDs) are serious congenital malformations. In this study, we aimed to identify more specific and sensitive maternal serum biomarkers for noninvasive NTD screenings. We collected serum from 37 pregnant women carrying fetuses with NTDs and 38 pregnant women carrying normal fetuses. Isobaric tags for relative and absolute quantitation were conducted for differential proteomic analysis, and an enzyme-linked immunosorbent assay was used to validate the results. We then used a support vector machine (SVM) classifier to establish a disease prediction model for NTD diagnosis. We identified 113 differentially expressed proteins; of these, 23 were either up- or downregulated 1.5-fold or more, including five complement proteins (C1QA, C1S, C1R, C9, and C3); C3 and C9 were downregulated significantly in NTD groups. The accuracy rate of the SVM model of the complement factors (including C1QA, C1S, and C3) was 62.5%, with 60% sensitivity and 67% specificity, while the accuracy rate of the SVM model of alpha-fetoprotein (AFP, an established biomarker for NTDs) was 62.5%, with 75% sensitivity and 50% specificity. Combination of the complement factor and AFP data resulted in the SVM model accuracy of 75%, and receiver operating characteristic curve analysis showed 75% sensitivity and 75% specificity. These data suggest that a disease prediction model based on combined complement factor and AFP data could serve as a more accurate method of noninvasive prenatal NTD diagnosis.
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http://dx.doi.org/10.1111/nyas.14443DOI Listing
October 2020

Transamniotic mesenchymal stem cell therapy for neural tube defects preserves neural function through lesion-specific engraftment and regeneration.

Cell Death Dis 2020 07 13;11(7):523. Epub 2020 Jul 13.

Key Laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital, China Medical University, Shenyang, China.

Neural tube defects (NTDs) lead to prenatal mortality and lifelong morbidity. Currently, surgical closure of NTD lesions results in limited functional recovery. We previously suggested that nerve regeneration was critical for NTD therapy. Here, we report that transamniotic bone marrow-derived mesenchymal stem cell (BMSC) therapy for NTDs during early development may achieve beneficial functional recovery. In our ex vivo rat embryonic NTD model, BMSCs injected into the amniotic cavity spontaneously migrated into the defective neural tissue. Hepatocyte growth factor and its receptor c-MET were found to play critical roles in this NTD lesion-specific migration. Using the in vivo rat fetal NTD model, we further discovered that the engrafted BMSCs specifically differentiated into the cell types of the defective tissue, including skin and different types of neurons in situ. BMSC treatment triggered skin repair in fetuses, leading to a 29.9 ± 5.6% reduction in the skin lesion area. The electrophysiological functional recovery assay revealed a decreased latency and increased motor-evoked potential amplitude in the BMSC-treated fetuses. Based on these positive outcomes, ease of operation, and reduced trauma to the mother and fetus, we propose that transamniotic BMSC administration could be a new effective therapy for NTDs.
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http://dx.doi.org/10.1038/s41419-020-2734-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7354991PMC
July 2020

Double molecular recognition strategy based on boronic acid-diol and NHS ester-amine for selective electrochemical detection of cerebral dopamine.

Anal Bioanal Chem 2020 Jun 29;412(15):3727-3736. Epub 2020 Apr 29.

Department of Anesthesiology, The First People's Hospital of Foshan, Foshan, 528000, Guangdong, China.

Electrochemical detection of dopamine (DA) usually depends on electrochemical oxidation of DA. This conventional method can hardly provide sufficient sensitivity and selectivity in the determination of the cerebral DA down to nanomolar level, because the ability of DA to be electrochemically oxidized is limited and many electroactive interferents are also oxidized at a similar potential with DA. Here, an electrochemical assay based on a double molecular recognition strategy has been proposed and proved to be of high sensitivity and selectivity for DA measurement in the cerebral system. 3,3'-Dithiodipropionic acid di(N-hydroxysuccinimide ester) (DSP) was anchored on the electrode surface to capture DA target through the specific reaction between N-hydroxysuccinimide (NHS) ester and amine. The captured DA endowed the electrode with a layer of diol groups, which further reacted with the boronic acid to trap of 4-mercaptophenylboronic acid (MBA) molecules, thus leading to the conjunction of electroactive thionine (Th) molecules on the electrode for signal readout. In addition, an Au nanostructure was employed to enhance signal amplification and facilitate the double molecular recognition process. As a consequence, this method was able to quantify DA from 1 to 300 nM with a detection limit of 0.74 nM, which exhibited a high specificity against cerebral interferents. Furthermore, the practicability of this platform was successfully demonstrated through determination of the dynamics of cerebral DA in the events of high K and nomifensine retromicrodialysis. Graphical abstract.
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http://dx.doi.org/10.1007/s00216-020-02624-6DOI Listing
June 2020

Accuracy improvement of electrochemical whole blood ketone sensor based on HCT compensation algorithm.

Electrophoresis 2020 09 28;41(16-17):1446-1449. Epub 2020 May 28.

National Chengdu Center for Safety Evaluation of Drugs, West China Hospital of Sichuan University, Chengdu, P. R. China.

In this manuscript, we demonstrated an electrochemical test strip with HCT (hematocrit) compensation algorithm to improve the accuracy of blood ketone sensor. In the conventional electrochemical sensor, the electrochemical current was directly resolved into the concentration value of the determinant without HCT compensation. For lower or higher HCT blood sample, the measured result was inaccurate. In the proposed design, the blood impedance can be measured to estimate the HCT, which was utilized to compensate the electrochemical current to resolve the more accurate concentration of determinant. The practical blood sample tests demonstrated the proposed design can provide more believable and reliable measured result in clinical point-of-care setting.
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http://dx.doi.org/10.1002/elps.201900472DOI Listing
September 2020

Intra-Amniotic Delivery of CRMP4 siRNA Improves Mesenchymal Stem Cell Therapy in a Rat Spina Bifida Model.

Mol Ther Nucleic Acids 2020 Jun 19;20:502-517. Epub 2020 Mar 19.

Key Laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital, China Medical University, Shenyang 110004, P.R. China. Electronic address:

Neural tube defects (NTDs) result in prenatal mortality and lifelong morbidity, and available treatments have limited efficacy. We previously suggested that prenatal bone marrow-derived mesenchymal stem cell (BMSC) transplantation could treat neuron deficiency in NTD rats; however, BMSC-based therapy is limited by the low survival rate of BMSCs when used to treat severe NTDs. Herein, a new therapy using combined BMSC transplantation and small interfering RNA of collapsin response mediator protein 4 (CRMP4 siRNA), which was identified as a novel potential target for the NTD treatment, is proposed. The intra-amniotic CRMP4 siRNA, BMSC, and CRMP4 siRNA + BMSC injections repaired skin lesions, improved motor neural function, reduced neuronal apoptosis, and promoted expression of neural differentiation-related molecules and neurotrophic factors in the spinal cord of spina bifida rat fetuses. Therapeutic effects in the CRMP4 siRNA + BMSC injection group were superior to those of the CRMP4 siRNA only or BMSC only injection groups. CRMP4 siRNA + BMSC injection resulted in a 45.38% reduction in the skin lesion area and significantly shorter latency and higher amplitude of motor-evoked potentials (MEPs) in spina bifida fetuses. Our results suggest that intrauterine Ad-CRMP4 siRNA delivery with BMSCs is an innovative platform for developing fetal therapeutics to safely and efficaciously treat NTDs.
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http://dx.doi.org/10.1016/j.omtn.2020.03.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7177192PMC
June 2020

miR-322 treatment rescues cell apoptosis and neural tube defect formation through silencing NADPH oxidase 4.

CNS Neurosci Ther 2020 09 24;26(9):902-912. Epub 2020 Apr 24.

Key Laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital, China Medical University, Shenyang, China.

Aims: Failure of neural tube closure resulting from excessive apoptosis leads to neural tube defects (NTDs). NADPH oxidase 4 (NOX4) is a critical mediator of cell growth and death, yet its role in NTDs has never been characterized. NOX4 is a potential target of miR-322, and we have previously demonstrated that miR-322 was involved in high glucose-induced NTDs. In this study, we investigated the effect of NOX4 on the embryonic neuroepithelium in NTDs and reveal a new regulatory mechanism for miR-322 that disrupts neurulation by ameliorating cell apoptosis.

Methods: All-trans-retinoic acid (ATRA)-induced mouse model was utilized to study NTDs. RNA pull-down and dual-luciferase reporter assays were used to confirm the interaction between NOX4 and miR-322. In mouse neural stem cells and whole-embryo culture, Western blot and TUNEL were carried out to investigate the effects of miR-322 and NOX4 on neuroepithelium apoptosis in NTD formation.

Results: NOX4, as a novel target of miR-322, was upregulated in ATRA-induced mouse model of NTDs. In mouse neural stem cells, the expression of NOX4 was inhibited by miR-322; still further, NOX4-triggered apoptosis was also suppressed by miR-322. Moreover, in whole-embryo culture, injection of the miR-322 mimic into the amniotic cavity attenuated cell apoptosis in NTD formation by silencing NOX4.

Conclusion: miR-322/NOX4 plays a crucial role in apoptosis-induced NTD formation, which may provide a new understanding of the mechanism of embryonic NTDs and a basis for potential therapeutic target against NTDs.
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http://dx.doi.org/10.1111/cns.13383DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7415201PMC
September 2020

MiR-34a may Function as Potential Biomarker for Remission after Traumatic Spinal Cord Injury.

Clin Lab 2020 Apr;66(4)

Background: Emerging evidence has manifested that many microRNAs (miRNAs) exert crucial roles in the responses and remission process of traumatic spinal cord injury (TSCI). The present study aimed to investigate clinical significance of miR-34a concerning the assessment of neurological remission and prognosis after TSCI.

Methods: We examined the serum levels of miR-34a in patients with TSCI and healthy controls through real-time polymerase chain reaction (RT-qPCR) assay. Then, receiver operating characteristic (ROC) curve was used to determine the diagnostic value of miR-34a in TSCI. Finally, we detected the expression levels of miR-34a from serum samples over a 12-week period.

Results: The results of our study demonstrated that miR-34a was significantly down-regulated in TSCI patients compared with healthy controls. miR-34a may function a potential biomarker for TSCI diagnosis with an area under curve (AUC) of 0.8020. The expression of miR-34a was increased in the remission group compared to the non-remission group after 12 weeks post-injury. The expression of miR-34a was negatively related to TNF-alpha, IL-6, and IL-8.

Conclusions: Measuring serum expression level of miR-34a over time may be used in tracking the process and neurological remission of TSCI.
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http://dx.doi.org/10.7754/Clin.Lab.2019.190916DOI Listing
April 2020

MiR-195-5p Inhibits Malignant Progression of Cervical Cancer by Targeting YAP1.

Onco Targets Ther 2020 30;13:931-944. Epub 2020 Jan 30.

Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang 110000, People's Republic of China.

Purpose: Our previous studies have shown that miR-195 is reduced in cervical cancer tissues, and that upregulation of miR-195 suppressed cervical cancer cell growth and induced a cell cycle block. In this study, we aimed to further elucidate the mechanism of action between miR-195-5p and Yes-associated protein 1 (YAP1) in the malignant progression of cervical cancer.

Methods: MiR-195-5p and YAP1 were detected using qRT-PCR in cervical cancer cells transfected with miR-195-5p mimics or inhibitor. Cell proliferation, migration, and invasion ability were detected using MTT, wound healing, and transwell invasion assays. Dual luciferase reporter assay, qRT-PCR, and Western blot analysis were used to demonstrate that YAP1 was a target of miR-195-5p.

Results: Our results showed that miR-195-5p is negatively correlated with YAP1 protein levels but not with mRNA expression. Moreover, upregulation of miR-195-5p by transient transfection with miR-195-5p mimics in HeLa and SiHa cells inhibited cell proliferation, migration ability, invasiveness, and the EMT. Conversely, miR-195-5p downregulation produced opposite results. In addition, multiple miRNA target prediction sites showed that YAP1 was a potential target gene; this was confirmed by dual luciferase assay. Rescue experiments further confirmed that YAP1 is involved in miR-195-5p-mediated inhibition of proliferation, migration ability, invasiveness, and the EMT of cervical cancer cells.

Conclusion: Taken together, our data suggest that miR-195-5p may act as a tumor suppressor which could provide a theoretical basis for cervical cancer patient targeted therapy.
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http://dx.doi.org/10.2147/OTT.S227826DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6996614PMC
January 2020

Therapeutic potential of adenovirus-encoding brain-derived neurotrophic factor for spina bifida aperta by intra-amniotic delivery in a rat model.

Gene Ther 2020 Dec 24;27(12):567-578. Epub 2020 Feb 24.

Key Laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital, China Medical University, No. 36, Sanhao Street, Heping District, Shenyang, PR China.

Spina bifida aperta is a type of neural tube defect (NTD). Although prenatal fetal surgery has been an available and effective treatment for it, the neurological functional recovery is still need to be enhanced. Our previous results revealed that deficiencies of sensory, motor, and parasympathetic neurons were primary anomalies that occurred with the spinal malformation. Therefore, we emphasized that nerve regeneration is critical for NTD therapy. We delivered an adenoviral construct containing genes inserted for green fluorescent protein and brain-derived neurotrophic factor (Ad-GFP-BDNF) into the amniotic fluid to investigate its prenatal therapeutic potential for rat fetuses with spina bifida aperta. Using immunofluorescence, TdT-mediated dUTP nick-end labeling staining, and real-time polymerase chain reaction analysis, we assessed cell apoptosis in the defective spinal cord and Brn3a positive neuron survival in the dorsal root ganglion (DRG); a protein array was used to investigate the microenvironmental changes of the amniotic fluid. We found that most of the overexpressed BDNF was present on the lesions of the spina bifida fetuses, the number of apoptosis cells in Ad-GFP-BDNF-transfected spinal cords were reduced, mRNA levels of Bcl2/Bax were upregulated and Casp3 were downregulated compared with the controls, the proportion of Brn3a positive neurons in DRG were increased by activating the BDNF/TrkB/Akt signaling pathway, and most of the significant changes in cytokines in the amniotic fluid were related to the biological processes of regulation of apoptotic process and generation of neurons. These results suggest that intra-amniotic Ad-GFP-BDNF gene delivery might have potential as a supplementary approach to treat congenital malformations of neural tubes.
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http://dx.doi.org/10.1038/s41434-020-0131-2DOI Listing
December 2020

Evaluating cervical artery dissections in young adults: a comparison study between high-resolution MRI and CT angiography.

Int J Cardiovasc Imaging 2020 Jun 20;36(6):1113-1119. Epub 2020 Feb 20.

Department of Radiology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250021, China.

To compare the diagnostic values of high-resolution magnetic resonance (HR-MRI) with computed tomographic angiography (CTA) in young adults with ischemic stroke due to cervical artery dissections. Totally 42 symptomatic patients were recruited in this study. All the 42 patients underwent both HR-MRI and CTA, including 28 patients with dissections confirmed by Digital Subtraction Angiography (DSA) and 4 patients with vertebral artery dissections diagnosed by follow-up. CTA and HR-MRI images were separately and blindly analyzed by two radiologists. The sensitivity, specificity, positive and negative predictive value of HR-MRI and CTA were calculated. The receiver operating characteristic (ROC) curves and AUC of each imaging modality were generated. A total of 20 carotid artery dissections, 12 vertebral artery dissections and 10 non-dissected cervical arteries were involved. The inter-observer concordance of HR-MRI and CTA was good (κ = 0.806 vs. 0.776). The sensitivity and specificity of HR-MRI and CTA on detecting the dissections were 87.5% vs. 62.5%, and 90.0% vs. 80.0%, respectively. Area under the ROC curve of HR-MRI [0.94 (95% CI 0.86-0.97)] was greater than that of CTA [0.87 (95% CI 0.71-1.0)]. Compared to CTA, HR-MRI is more sensitive and specific for the diagnosis of cervical artery dissections in high-risk symptomatic patients. This study supports the value of HR-MRI in non-invasive diagnosis of young adults with cervical artery dissections.
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http://dx.doi.org/10.1007/s10554-020-01799-4DOI Listing
June 2020

Facile Ratiometric Electrochemical Sensor for In Vivo/Online Repetitive Measurements of Cerebral Ascorbic Acid in Brain Microdiaysate.

Anal Chem 2020 03 20;92(5):3981-3989. Epub 2020 Feb 20.

A Key Laboratory of Theoretical Organic Chemistry and Functional Molecule of Ministry of Education, School of Chemistry and Chemical Engineering, Hunan University of Science and Technology, Xiangtan, Hunan 411201, P. R. China.

The in vivo monitoring of ascorbic acid (AA) following physiological and pathological events is of great importance because AA plays a critical role in brain functions. The conventional electrochemical sensors (ECSs) usually suffered from poor selectivity and sluggish electron transfer kinetics for cerebral AA oxidation. The exploitation of ECSs adapt to the electrochemical detection (ECD)-microdialysis system, here we reported a facile ratiometric electrochemical sensor (RECS) for in vivo/online repetitive measurements of cerebral AA in brain microdiaysate. The sensor were constructed by careful electrodeposition of graphene oxide (GO) onto glassy carbon (GC) electrodes. Methylene blue (MB) was electrostatically adsorbed onto the GO surface as a built-in reference to achieve ratiometric detection of AA. The subsequent proper electroreduction treatment was able to readily facilitate the oxidation of AA at a relatively negative potential (-100 mV) and the oxidation of MB at separated potential (-428 mV). The in vitro experiments demonstrated that the RECS exhibited high sensitivity (detection limit: 10 nM), selectivity, and stability toward AA determination, enabling the in vivo/online repetitive measurement of cerebral AA in brain microdiaysate with high reliability. As a result, the designed RECS was successfully applied in the ECD-microdialysis system to in vivo/online repetitive monitoring the dynamic change of cerebral AA in the progress of the global cerebral ischemia/reperfusion events. More, the microinjection of endogenous AA and AA oxidase (AAOx) verified the reliability of the proposed RECS for in vivo/online repetitive cerebral AA detection. This proposed sensor filled the gap that no rational electrochemical sensor has been developed for the ECD-microdialysis system since its creation by the Mao group in 2005, which provided a reliable and effective method for brain chemistry research.
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http://dx.doi.org/10.1021/acs.analchem.9b05484DOI Listing
March 2020

Interface engineering of microelectrodes toward ultrasensitive monitoring of β-amyloid peptides in cerebrospinal fluid in Alzheimer's disease.

Analyst 2020 Mar 7;145(6):2331-2338. Epub 2020 Feb 7.

School of Chemistry and Molecular Engineering, Shanghai Key Laboratory for Urban Ecological Processes and Eco-Restoration, East China Normal University, 500 Dongchuan Road, Shanghai 200241, People's Republic of China.

Ultrasensitive detection of monomeric β-amyloid peptides is of fundamental significance for studying the pathological progression of Alzheimer's disease (AD). In this article, by facilely engineering a gold microelectrode interface, we developed a novel electrochemical biosensor for sensitive and selective monitoring of β-amyloid peptide (Aβ) monomers in cerebrospinal fluid (CSF). Through specific Cu-Aβ-hemin coordination, Aβ directed the assembly of Cu-PEI/AuNPs-hemin nanoprobes into network aggregates on a microelectrode interface, which promoted the enrichment of Aβ monomers on the microelectrode. Furthermore, the AuNP aggregate promotes the deposition of silver nanoparticles, which were utilized for the electrochemical stripping analysis of the Aβ monomer. The proposed method displayed ultra-sensitivity for Aβ monomers with the detection limit down to 0.2 pM. Besides, high selectivity toward Aβ monomers was observed. These remarkable analytical performances render the electrochemical biosensor useful for evaluating the dynamic change of Aβ monomer level in CSF of live mice with AD, promoting the investigation of the role that Aβ monomers play in brain events.
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http://dx.doi.org/10.1039/c9an02285fDOI Listing
March 2020

Dynamic Indicators That Impact the Outcomes of Thoracic Endovascular Aortic Repair in Complicated Type B Aortic Dissection.

J Vasc Interv Radiol 2020 05 22;31(5):760-768.e1. Epub 2020 Jan 22.

Department of Radiology, Shandong Provincial Hospital, Shandong Provincial Key Laboratory of Diagnosis and Treatment of Cardio-Cerebral Vascular Disease, Shandong University, #324, Jingwu Road, Jinan, Shandong 250021, China. Electronic address:

Purpose: To investigate dynamic variables obtained from retrospective computed tomography angiography for ability to predict thoracic endovascular aortic repair (TEVAR) outcomes in patients with complicated type B aortic dissection (cTBAD).

Materials And Methods: Seventy-nine patients with cTBAD who received TEVAR from March 2009 to June 2018 were retrospectively enrolled. Relative true lumen area (r-TLA) was computed at the level of tracheal bifurcation every 5% of all R-R intervals. Parameters that reflect the state of intimal motion were evaluated, including difference between maximum and minimum r-TLA (D-TLA) and true lumen collapse. The endpoints comprised early (≤ 30 days) and late (> 30 days) outcomes after intervention.

Results: Overall early mortality rate was 13.9% (11/79), and early adverse events rate was 24.1% (19/79). Patients who received TEVAR within 2 days of symptom onset demonstrated the worst outcomes. A longer time of r-TLA < 25% in 1 cardiac cycle (P = .049) and larger D-TLA (P < .001) were correlated to an increased early death. In addition, D-TLA was an independent predictor of early mortality. Area under the curve of D-TLA was 0.849 (95% confidence interval 0.730-0.967) for predicting early mortality and 0.742 (95% CI 0.611-0.873) for predicting early adverse events. Survival and event-free survival rates during follow-up were decreased in the D-TLA > 21.5% group compared with the D-TLA ≤ 21.5% group (all P < .001).

Conclusions: Larger D-TLA is correlated with worse postoperative outcomes and might be a crucial parameter for future risk stratification in patients with cTBAD.
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http://dx.doi.org/10.1016/j.jvir.2019.11.010DOI Listing
May 2020

Dynamic Imaging Features of Retrospective Cardiac Gating CT Angiography Influence Delayed Adverse Events in Acute Uncomplicated Type B Aortic Dissections.

Cardiovasc Intervent Radiol 2020 Apr 17;43(4):620-629. Epub 2019 Dec 17.

Department of Radiology, Shandong Provincial Hospital, Shandong Provincial Key Laboratory of Diagnosis and Treatment of Cardio-Cerebral Vascular Disease, Shandong University, #324, Jingwu Road, Jinan, 250021, Shandong, People's Republic of China.

Purpose: To investigate the correlation between dynamic morphological parameters of retrospective cardiac gating CT angiography (CTA) and delayed adverse event (DAE) in uncomplicated type B acute aortic dissection (uTB-AAD) patients.

Materials And Methods: Eighty-seven patients initially diagnosed with uTB-AAD were retrospectively reviewed. Dynamic variables obtained by dose-regulated retrospective CTA were recorded, including the minimum relative true lumen diameter (RTLA), ratio of the minimum to maximum true lumen relative area (r-RTLA), the maximum diameter of the descending aorta, false lumen, and primary entry tear. Outcome analysis comprised incidences of DAE and early mortality within 3 to 14 days since symptom occurring.

Results: Twenty-six patients (29.9%) developed DAE, and two of which (7.7%) died before any interventions. Smaller values of RTLA (P = 0.01) and r-RTLA at the upper thoracic descending aorta (UTDA) (P < 0.001), and r-RTLA at the renal artery level (P = 0.016) demonstrated higher incidences of DAE; maximum diameter of the descending aorta (P < 0.001), the false lumen (P = 0.008), and entry tear size (P = 0.007) were positively associated with the occurrence of DAE. r-RTLA at the UTDA level yielded the highest diagnostic accuracy (82.0%) in detecting DAE at an optimal cutoff value of 61.7% (AUC = 0.839). Performance of dynamic characteristics was superior to static features obtained from single-phase image in the detection of DAE (P < 0.001).

Conclusion: Dynamic morphological features of retrospective cardiac gating CTA might aid in identifying a high risk of DAE in uTB-AAD patients and guiding early targeted interventions.
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http://dx.doi.org/10.1007/s00270-019-02395-3DOI Listing
April 2020

Expression profiles of long noncoding RNAs and messenger RNAs in the border zone of myocardial infarction in rats.

Cell Mol Biol Lett 2019 2;24:63. Epub 2019 Dec 2.

Shengjing Hospital, China Medical University, Shenyang, China.

Background: The participation of long noncoding RNAs (lncRNAs) in myocardial infarction has recently been noted. However, their underlying roles in the border zone of myocardial infarction remain unclear. This study uses microarrays to determine the profiles of lncRNAs and mRNAs in the border zone.

Methods: Bioinformatics methods were employed to uncover their underlying roles. Highly dysregulated lncRNAs was further validated via PCR.

Results: Four hundred seven lncRNAs and 752 mRNAs were upregulated, while 132 lncRNAs and 547 mRNAs were downregulated in the border zone of myocardial infarction. A circos graph was constructed to visualize the chromosomal distribution and classification of the dysregulated lncRNAs and mRNAs. The upregulated mRNAs in the border zone were most highly enriched in cytokine activity, binding, cytokine receptor binding and related processes, as ascertained through Go analysis. Pathway analysis of the upregulated mRNAs showed the most significant changes were in the TNF signaling pathway, cytokine-cytokine receptor interaction and chemokine signaling pathway and similar pathways and interactions. An lncRNA-mRNA co-expression network was established to probe into the underlying functions of the 10 most highly dysregulated lncRNAs based on their co-expressed mRNAs. In the co-expression network, we found 16 genes directly involved in myocardial infarction, including Alox5ap, Itgb2 and B4galt1. The lncRNAs AY212271, EF424788 and MRAK088538, among others, might be associated with myocardial infarction. BC166504 is probably a key lncRNA in the border zone of myocardial infarction.

Conclusions: The results may have revealed some aberrantly expressed lncRNAs and mRNAs that contribute to the underlying pathophysiological mechanisms of myocardial infarction.
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http://dx.doi.org/10.1186/s11658-019-0185-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6889673PMC
May 2020

Suppressing Sponge-Like Li Deposition via AlN-Modified Substrate for Stable Li Metal Anode.

ACS Appl Mater Interfaces 2019 Nov 1;11(45):42261-42270. Epub 2019 Nov 1.

Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences , Ningbo 315201 , China.

Sponge-like lithium (Li) deposition results in high-surface-area morphology that harmfully accelerates the side reactions between Li and electrolyte, arousing serious safety issues of next high energy density Li metal batteries (LMBs). Herein, we propose a strategy to suppress the sponge-like Li deposition by plating Li metal on aluminum nitride (AlN)-modified substrates. For a practical Li deposition of 4 mAh cm on a AlN-modified copper (Cu) electrode, the roughness and thickness of the as-deposited Li layer are only ∼10% and ∼50% of those for the Li layer deposited on bare Cu. Only based on the compacted Li deposition layer without any other protective remedies, the AlN-modified Cu electrode could provide a Li cycling life of 5 times longer than that on bare Cu, and an AlN-modified carbon felt was proved as an efficient interlayer to boost the cycling stability of Li||LiFePO batteries. These results demonstrate the high importance of suppressing the sponge-like Li deposition for high energy density LMBs.
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http://dx.doi.org/10.1021/acsami.9b15468DOI Listing
November 2019

Maternal, paternal, and neonatal risk factors for neural tube defects: A systematic review and meta-analysis.

Int J Dev Neurosci 2019 Nov 26;78:227-235. Epub 2019 Sep 26.

Key Laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital, China Medical University, Shenyang, PR China.

Objective: Neural tube defects [NTDs] are severe congenital anomalies. The etiology of NTDs is not fully known, and studies on the potential risk factors of NTDs present inconsistent results. Thus, we conducted a systematic review and meta-analysis to investigate the maternal, paternal, and neonatal risk factors for NTDs.

Study Design: We systematically reviewed relative original studies published through October 6, 2018 available in Pubmed, Embase and the Cochrane Library without restrictions for language. The selected studies measured maternal, paternal, and neonatal risk factors and examined their associations with NTDs. A meta-analysis, including subgroup analysis and sensitivity analysis, was conducted to estimate the pooled effect measures. Two reviewers independently extracted data using a predesigned data collection form.

Results: Forty-five studies were eligible for inclusion in the meta-analysis, and twelve potential risk factors were analyzed. The factors that were associated with NTDs risk included stressful life events [odds ratio [OR],1.61; 95% confidence interval [CI], 1.24-2.08; p < 0.001; I = 59.2%], low maternal education level [OR, 1.42; 95% CI, 1.19-1.70; p < 0.001; I = 47.7%], pregestational diabetes [OR, 2.24; 95% CI, 1.21-4.12; p < 0.010; I = 56.3%], low paternal age [OR, 1.41; 95% CI, 1.10-1.81; p = 0.007; I = 0.0%], low birth weight [OR, 5.53; 95% CI, 1.95-15.70; p = 0.001; I = 98.5%], and neonatal female gender [OR, 1.54; 95% CI, 1.10-2.14; p = 0.012; I = 67.8%].

Conclusion: Stressful life events, pregestational diabetes, low birth weight, and neonatal female gender are risk factors associated with NTDs. Low maternal education level and low paternal age are factors that are moderately associated with NTDs. Further cohort studies are required to verify the factors associated with NTDs and control the risk of this severe birth defect.
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http://dx.doi.org/10.1016/j.ijdevneu.2019.09.006DOI Listing
November 2019

Temperature and CO Dual-Responsive Pickering Emulsions Using Jeffamine M2005-Modified Cellulose Nanocrystals.

Langmuir 2019 10 10;35(42):13663-13670. Epub 2019 Oct 10.

Key Laboratory of Colloid and Interface Chemistry, Ministry of Education , Shandong University , Jinan , Shandong 250100 , P. R. China.

Cellulose nanocrystals (CNCs) with excellent biodegradability are promising biomaterials for use as responsive Pickering emulsifiers. However, the high hydrophilicity of CNCs limits their emulsification ability. Some existing studies have utilized complicated covalent modification procedures to increase the hydrophobicity of CNCs. To simplify the modification process, we prepared hydrophobically modified CNCs (CNCs-M2005) via simple and controllable electrostatic interactions with thermosensitive M2005. The obtained CNCs-M2005 exhibited temperature and CO dual-responsive properties. Subsequently, stable oil/water Pickering emulsions were prepared using the partially hydrophobic CNCs-M2005 at 20 °C. However, demulsification occurred when the temperature increased to 60 °C. This temperature-induced demulsification resulted from the dehydration of polyethylene oxide and polypropylene oxide, causing the aggregation of the CNCs-M2005, as shown by dynamic light scattering and transmission electron microscopy experiments. In addition, demulsification was also achieved after bubbling CO, which was attributed to the dissociation of the partially hydrophobic CNCs-M2005. The temperature and CO dual-responsive biosafe Pickering emulsions open up opportunity for the design of intelligent food, cosmetic, and drug delivery systems.
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http://dx.doi.org/10.1021/acs.langmuir.9b02497DOI Listing
October 2019

In vivo monitoring of superoxide anion from Alzheimer's rat brains with functionalized ionic liquid polymer decorated microsensor.

Biosens Bioelectron 2019 Nov 31;144:111665. Epub 2019 Aug 31.

Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, 221004, Jiangsu, PR China; Department of Pharmaceutical Analysis, School of Pharmacy, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, 221004, Jiangsu, PR China. Electronic address:

The superoxide anion (O) is an important reactive oxygen species (ROS) in the brain system, which has been associated with the development of many neurological diseases, including Alzheimer's disease (AD). Herein, we introduced a carbon fiber microelectrode (CFME) based in vivo technique for specific and sensitive monitoring of the O radical in the living brains of both normal and AD model rats. Compared with other reported superoxide dismutase (SOD) electrochemical biosensors, the microsensor presented in our work was featured in the coating of a functionalized ionic liquid polymer (PIL) onto PB nanoparticles (PBNPs) and carbon nanotubes (CNT). It was demonstrated that the cationic and carboxyl-rich PILs provided abundant interaction sites with SOD to prevent enzyme leakage from sensor, which was beneficial for the enhancement of sensitivity. Additionally, CCK-8 assay and autoxidation of pyrogallol tests showed that MCF-7 cells maintained a high viability after incubated with PIL and most of the SOD bioactivity was retained in the presence of PIL, which implied the PIL itself possessed an excellent biocompatibility. These properties allow the sensor to track the fluctuation of O levels in vivo between normal and AD rats. This is the first report on application of functionalized PIL to reveal the O related pathological process of AD.
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http://dx.doi.org/10.1016/j.bios.2019.111665DOI Listing
November 2019

Cocaine induces differential circular RNA expression in striatum.

Transl Psychiatry 2019 08 21;9(1):199. Epub 2019 Aug 21.

National Chengdu Center for Safety Evaluation of Drugs, State Key Lab of Biotherapy/Collaborative Innovation Center of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, 610041, China.

Circular RNA (circRNA), a novel type of endogenous non-coding RNA, plays natural miRNA sponge effect that represses the activities of corresponding miRNAs through binding with them, thus modulating transcriptional expression of genes. Recent studies indicate that circRNAs are significantly enriched in the brain and some of them are derived from synaptic protein-coding genes. In addition, miRNAs are involved in synaptic plasticity, memory formation, and cocaine addiction. However, the role of circRNAs in cocaine reward is unclear. This study aimed to investigate the expression profile of striatal circRNAs in the mice after cocaine self-administration. By using circRNA microarray analysis, we observed that 90 striatal circRNAs were differentially expressed in cocaine self-administering mice, of which 18 circRNAs were up-regulated and 72 down-regulated. Six circRNAs were selected randomly for validation by using quantitative reverse transcription-PCR, and their expression levels showed consistency with microarray analysis. We backward predicted the circRNAs and their binding sites of miRNAs associated with neuroplasticity. In functional validation test, mmu_circRNA_002381 may modulate the transcription of certain genes associated with neuroplasticity, such as limk1 and bdnf. Taken together, circRNAs may participate in cocaine behavioral effect via interacting with miRNAs. Our findings reveal a potential role of circRNAs in cocaine effect.
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http://dx.doi.org/10.1038/s41398-019-0527-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6704174PMC
August 2019

In vivo monitoring of cerebral glucose with an updated on-line electroanalytical system.

Anal Bioanal Chem 2019 Sep 23;411(23):5929-5935. Epub 2019 Jul 23.

Lab of Biochemical Sensing Technology, School of Chemistry and Molecular Engineering, Shanghai Key Laboratory for Urban Ecological Processes and Eco-Restoration, East China Normal University, 500 Dongchuan Road, Shanghai, 200241, China.

Because cerebral species involve rapid events, increasing the temporal resolution to realize in vivo near-real-time measurements is desirable. Here, we aimed to improve the low resolution of our previous on-line electroanalytical system by decreasing the dead volume and reducing molecular dispersion. This updated system has advantages of elevated time resolution and accelerated analysis for on-line monitoring of glucose versus the previous system. Finally, this new system was successfully applied to continuous measurement of cerebral glucose in vivo during global ischemia/reperfusion events. This study is expected to offer a reliable on-line analytical platform for continuous monitoring of important species associated with fast physiological and pathological events in vivo. Graphical abstract.
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http://dx.doi.org/10.1007/s00216-019-02002-xDOI Listing
September 2019

Extraordinary n-Type Mg SbBi Thermoelectrics Enabled by Yttrium Doping.

Adv Mater 2019 Sep 5;31(36):e1903387. Epub 2019 Jul 5.

Interdisciplinary Materials Research Center, School of Materials Science and Engineering, Tongji University, 4800 Caoan Road, Shanghai, 201804, China.

Advancing thermoelectric n-type Mg Sb alloys requires both high carrier concentration offered by effective doping and high carrier mobility enabled by large grains. Existing research usually involves chalcogen doping on the anion sites, and the resultant carrier concentration reaches ≈3 × 10 cm or below. This is much lower than the optimum theoretically predicted, which suggets that further improvements will be possible once a highly efficient dopant is found. Yttrium, a trivalent dopant, is shown to enable carrier concentrations up to and above ≈1 × 10 cm when it is doped on the cation site. Such carrier concentration allows for in-depth understand of the electronic transport properties over a broad range of carrier concentrations, based on a single parabolic band approximation. As well as reasonably high carrier mobility in coarse-grain materials sintered by hot deforming and fusing of large pieces of ingots synthesized by melting, higher thermoelectric performance than earlier experimentally reported for n-type Mg Sb is found. In particular, the thermoelectric figure of merit, zT, is even higher than that of any known n-type thermoelectric, including Bi Te alloys, within 300-500 K. This might pave the way for Mg Sb alloys to become a realistic material for n-type thermoelectrics for sustainable applications.
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http://dx.doi.org/10.1002/adma.201903387DOI Listing
September 2019

Chronic alcohol causes alteration of lipidome profiling in brain.

Toxicol Lett 2019 Oct 11;313:19-29. Epub 2019 May 11.

National Chengdu Center for Safety Evaluation of Drugs, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Collaborative Innovation Center for Biotherapy, Chengdu 610041, China. Electronic address:

Much efforts have been tried to clarify the molecular mechanism of alcohol-induced brain damage from the perspective of genome and protein; however, the effect of chronic alcohol exposure on global lipid profiling of brain is unclear. In the present study, by using Q-TOF/MS-based lipidomics approach, we investigated the comprehensive lipidome profiling of brain from the rats orally administrated with alcohol daily, continuously for one year. Through systematically analysis of all lipids in prefrontal cortex (PFC) and striatum region, we found that long-term alcohol exposure profoundly modified brain lipidome profiling. Notably, three kinds of lipid classes, glycerophospholipid (GP), glycerolipid (GL) and fatty acyls (FA), were significantly increased in these two brain regions. Interestingly, most of the modified lipids were involved in synthetic pathways of endoplasmic reticulum (ER), which may result in ER stress-related metabolic disruption. Moreover, alcohol-modified lipid species displayed long length of carbon chain with high degree of unsaturation. Taken together, our results firstly present that chronic alcohol exposure markedly modifies brain lipidomic profiling, which may activate ER stress and eventually result in neurotoxicity. These findings provide a new insight into the mechanism of alcohol-related brain damage.
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http://dx.doi.org/10.1016/j.toxlet.2019.05.010DOI Listing
October 2019

On-line regeneration of electrochemical biosensor for in vivo repetitive measurements of striatum Cu under global cerebral ischemia/reperfusion events.

Biosens Bioelectron 2019 Jun 9;135:111-119. Epub 2019 Mar 9.

School of Chemistry and Chemical Engineering, Key Laboratory of Theoretical Organic Chemistry and Functional Molecule of Ministry of Education, Hunan University of Science and Technology, Xiangtan, Hunan 411201, PR China. Electronic address:

The detection of Cu ion, one of the metal ions substantial in cerebral physiology, is critical in studying brain activities and understanding brain functions. However, repetitive measurements of Cu in the progress of physiological and pathological events is still challenging, because lack of the platform for repetitive on-line detection-regeneration cycle. Herein we report the design of a regenerated electrochemical biosensor combined with the in vivo microdialysis system. In this biosensor, hyperbranched polyethyleneimine (hPEI) acts as a regenerated recognition unit for Cu. Just by a simple rinse of ethylenediaminetetraacetic acid (EDTA) disodium salt, the Cu and Cu ions on the biosensor interface were chelated with EDTA disodium salt, thus achieving the regeneration of the biosensor. In addition, 6-(ferrocenyl)hexanethiol (FcHT) serves as the inner reference moiety to elevate the sensing accuracy over regeneration cycles. As a result, this ratiometric electrochemical biosensor not only revealed high sensitivity and selectivity, but also exhibited excellent stability during multiple regeneration processing. This biosensor was capable of determining Cu with a linear range between 0.05 and 12 μM and low detection limit (LOD) of 13 nM. Then, the platform has been successfully applied in repetitive Cu analysis in rat brain under global cerebral ischemia/reperfusion events. The combination of results from 7 rats indicates global cerebral ischemia caused an obvious increase of the Cu level, while reperfusion brought this level back to normal.
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http://dx.doi.org/10.1016/j.bios.2019.03.014DOI Listing
June 2019