Publications by authors named "Hui Wen"

145 Publications

ZIF-67-based catalysts for oxygen evolution reaction.

Nanoscale 2021 Jul 7;13(28):12058-12087. Epub 2021 Jul 7.

School of Materials Science and Engineering, Northeastern University, Shenyang 110819, China.

As a new type of crystalline porous material, the imidazole zeolite framework (ZIF) has attracted widespread attention due to its ultra-high surface area, large pore volume, and unique advantage of easy functionalization. Developing different methods to control the shape and composition of ZIF is very important for its practical application as catalyst. In recent years, nano-ZIF has been considered an electrode material with excellent oxygen evolution reaction (OER) performance, which provides a new way to research electrolyzed water. This review focuses on the morphological engineering of the original ZIF-67 and its derivatives (core-shell, hollow, and array structures) through doping (cation doping, anion doping, and co-doping), derivative composition engineering (metal oxide, phosphide, sulfide, selenide, and telluride), and the corresponding single-atom catalysis. Besides, combined with DFT calculations, it emphasizes the in-depth understanding of actual active sites and provides insights into the internal mechanism of enhancing the OER and proposes the challenges and prospects of ZIF-67 based electrocatalysts. We summarize the application of ZIF-67 and its derivatives in the OER for the first time, which has significantly guided research in this field.
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http://dx.doi.org/10.1039/d1nr01669eDOI Listing
July 2021

Boosting the charge transfer of FeOOH/Ni(OH) for excellent oxygen evolution reaction Cr modification.

Dalton Trans 2021 Jul;50(28):9746-9753

School of Materials Science and Engineering, Northeastern University, Shenyang 110819, China. and School of Resources and Materials, Northeastern University at Qinhuangdao, 066004, China.

For the electrocatalytic oxygen evolution reaction (OER) in alkaline media, there is an urgent need to optimize the adsorption strength of OH*. Here, a flower-like hybrid of Cr-doped FeOOH/Ni(OH)2 was used as an OER catalyst with a low overpotential of 291 mV at 50 mA cm-2. The results showed that faster charge transfer was achieved at the electrode/solution interface during the OER process after the FeOOH/Ni(OH)2 was modified by Cr, which facilitates the rate-determining step of the Volmer reaction. Furthermore, the results of faradaic efficiency and X-ray photoelectron spectroscopy (XPS) measurements confirmed that the synergistic effect between the ternary metal and oxygen vacancies led to excellent OER performance. This work provides a new strategy for the preparation of high-efficiency and low-cost oxygen evolution electrocatalysts.
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http://dx.doi.org/10.1039/d1dt01469bDOI Listing
July 2021

Water-soluble brown carbon in atmospheric aerosols along the transport pathway of Asian dust: Optical properties, chemical compositions, and potential sources.

Sci Total Environ 2021 Oct 24;789:147971. Epub 2021 May 24.

Key Laboratory for Semi-Arid Climate Change of the Ministry of Education, College of Atmospheric Sciences, Lanzhou University, Lanzhou 730000, China; Institute of Surface-Earth System Science, School of Earth System Science, Tianjin University, Tianjin 300072, China. Electronic address:

As an important type of light-absorbing aerosol, brown carbon (BrC) has the potential to affect the atmospheric photochemistry and Earth's energy budget. A comprehensive field campaign was carried out along the transport pathway of Asian dust during the spring of 2016, including a desert site (Erenhot), a rural site (Zhangbei), and an urban site (Jinan), in northern China. Optical properties, bulk chemical compositions, and potential sources of water-soluble brown carbon (WS-BrC) were investigated in atmospheric total suspended particulate (TSP) samples. Samples from Zhangbei had higher mass absorption efficiency at 365 nm (MAE, 1.32 ± 0.34 m g) than those from Jinan (1.00 ± 0.23 m g) and Erenhot (0.84 ± 0.30 m g). Compere to the non-dust samples, elevated water-soluble organic carbon (WSOC) concentrations and MAE values of dust samples from Erenhot are related to the input of high molecular weight organic compounds and biogenic matter from the Gobi Desert, while lower values from Zhangbei and Jinan are attributed to the dilution effect caused by strong northwesterly winds. Based on fluorescence excitation-emission matrix spectra and parallel factor analysis, two humic-like (C1 and C2) and two protein-like (C3 and C4) substances were identified. Together, C1 and C2 accounted for ~64% of total fluorescence intensity at the highly polluted urban Jinan site; C3 represented ~45% at the rural Zhangbei site where local biomass burning affects; and C4 contributed ~24% in the desert region (Erenhot) due to dust-sourced biogenic substances. The relative absorptive forcing of WS-BrC compared to black carbon at 300-400 nm was about 31.3%, 13.9%, and 9.2% during non-dust periods at Erenhot, Zhangbei, and Jinan, respectively, highlighting that WS-BrC may significantly affect the radiative balance of Earth's climate system and should be included in radiative forcing models.
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http://dx.doi.org/10.1016/j.scitotenv.2021.147971DOI Listing
October 2021

[Development and trends of real-world research based on bibliometric and knowledge map analysis].

Sheng Wu Yi Xue Gong Cheng Xue Za Zhi 2021 Apr;38(2):317-325

Chinese Evidence-based Medicine Center, West China Hospital, Sichuan University, Chengdu 610041, P.R.China.

To explore the focus and trends in real-world studies in Chinese through knowledge mapping method, databases CNKI, VIP, Wanfang and Sinomed were retrieved, with 1 757 relevant articles published before September 30rd, 2020 finally included, whose bibliographical records were imported into NoteExpress to avoid duplication and check relativity. VOSviewer, a bibliometric analysis tool, was used to analyze their development. It was found that real-world studies have mainly taken shape after 2010, in which traditional Chinese medicine research plays an important role. was the leading journal with 120 papers, the China Academy of Chinese Medical Sciences the most contribution institution with 338 papers, and Xie Yanming from the institution the most contribution author with 250 papers. This study helps clinicians and researchers in better understanding the evolution of real-world research over more than two decades in China.
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http://dx.doi.org/10.7507/1001-5515.202101006DOI Listing
April 2021

Strain-Engineered Nano-Ferroelectrics for High-Efficiency Piezocatalytic Overall Water Splitting.

Angew Chem Int Ed Engl 2021 Jul 9;60(29):16019-16026. Epub 2021 Jun 9.

School of Materials Science and Engineering, University of New South Wales, Sydney, New South, Wales, 2052, Australia.

Developing nano-ferroelectric materials with excellent piezoelectric performance for piezocatalysts used in water splitting is highly desired but also challenging, especially with respect to reaching large piezo-potentials that fully align with required redox levels. Herein, heteroepitaxial strain in BaTiO nanoparticles with a designed porous structure is successfully induced by engineering their surface reconstruction to dramatically enhance their piezoelectricity. The strain coherence can be maintained throughout the nanoparticle bulk, resulting in a significant increase of the BaTiO tetragonality and thus its piezoelectricity. Benefiting from high piezoelectricity, the as-synthesized blue-colored BaTiO nanoparticles possess a superb overall water-splitting activity, with H production rates of 159 μmol g  h , which is almost 130 times higher than that of the pristine BaTiO nanoparticles. Thus, this work provides a generic approach for designing highly efficient piezoelectric nanomaterials by strain engineering that can be further extended to various other perovskite oxides, including SrTiO , thereby enhancing their potential for piezoelectric catalysis.
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http://dx.doi.org/10.1002/anie.202103112DOI Listing
July 2021

A Random Forest Model for Predicting Social Functional Improvement in Chinese Patients with Schizophrenia After 3 Months of Atypical Antipsychotic Monopharmacy: A Cohort Study.

Neuropsychiatr Dis Treat 2021 19;17:847-857. Epub 2021 Mar 19.

Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.

Purpose: Impaired social functions contribute to the burden of schizophrenia patients and their families, but predictive tools of social functioning prognosis and specific factors are undefined in Chinese clinical practice. This article explores a machine learning tool to identify whether patients will achieve significant social functional improvement after 3 months of atypical antipsychotic monopharmacy and finds the defined risk factors using a multicenter clinical study.

Patients And Methods: A multicenter study on atypical antipsychotic (AAP) treatment in Chinese patients with schizophrenia (SALT-C) was conducted from July 2011 to August 2018. Data from 550 patients with AAP monopharmacy from their baseline to their 3-month follow-up were used to establish machine learning tools after screening. The positive outcome was an increase in the Personal and Social Performance (PSP) scale score by ≥10 points. The predictors were a range of investigator-rated assessments on symptoms, functioning, the safety of AAPs and illness history. The Least Absolute Shrinkage and Selection Operator (LASSO) was used for the feature screening and ranking of the predicted variables. The random forest algorithm and five-fold cross-validation for optimizing the model were selected to ensure the generalizability and precision.

Results: There were 137 patients (mean [SD] age, 41.1 [16.8] years; 77 [58.8%] female) who had a good social functional prognosis. A lower PSP score, taking a mood stabilizer, a high total Positive and Negative Symptom Scale (PANSS) and PANSS general subscale score, unemployment, a hepatic injury with medication, comorbid cardiovascular disease and being male predicted poor PSP outcomes. The generalizability of the PSP predictive tool was estimated with the precision-recall curve (accuracy of 79.5%, negative predictive value of 92.6% and positive predictive value of 57.1%) and receiver operating characteristic curve (ROC) (specificity of 81.8% and sensitivity of 78.7%).

Conclusion: The machine learning tool established using our current real-world data could assist in predicting PSP outcome by several clinical factors.
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http://dx.doi.org/10.2147/NDT.S280757DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7989048PMC
March 2021

Hydrogen Bond Association to Prepare Flame Retardant Polyvinyl Alcohol Film with High Performance.

ACS Appl Mater Interfaces 2021 Feb 19;13(4):5508-5517. Epub 2021 Jan 19.

The State Key Laboratory of Polymer Materials Engineering, Polymer Research Institute of Sichuan University, Chengdu 610065, China.

It has always been the goal of flame retardant research to improve the flame retardancy of a polymer efficiently without compromising comprehensive properties such as mechanical properties. For polyvinyl alcohol (PVA), inspired by the multiple hydrogen bonding in spider silk, we design a new type of compound containing phosphorus and nitrogen with multiple hydrogen-bonding reaction sites (,',''-tris(2-aminoethyl)phosphoric triamide (TE)) as it is flame retardant. The dynamic cross-linking structure is constructed, and the hyperdispersion of flame retardancy is achieved by the hydrogen bond self-assembly between TE and PVA, thus the high-performance flame retardant PVA is obtained. With only a 10 wt % addition of TE, the PVA film with a thickness of 0.15 mm can reach the UL94 VTM-0 level, and its tensile strength, ductility, and initial decomposition temperature can be increased by 33, 15, and 12 °C, respectively. In addition, the hydrogen-bonding effect and flame retardant mechanism are characterized and studied. This work overcomes the shortcomings of traditional flame retarding approaches and provides an effective strategy for the preparation of flame retardant polymers with an excellent performance.
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http://dx.doi.org/10.1021/acsami.0c19093DOI Listing
February 2021

Synthesis and evaluation of benzenesulfonic acid derivatives as human neutrophil elastase (hNE) inhibitors.

Med Chem Res 2021 Jan 12:1-12. Epub 2021 Jan 12.

State Key Laboratory of Bioactive Substances and Function of Natural Medicine, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, 1 Xiannongtan Street, Beijing, 100050 China.

Herein we report our investigation concerning the development of Human neutrophil elastase (hNE) inhibitors for the treatment of Acute Respiratory Distress Syndrome (ARDS). Various benzenesulfonic acid derived compounds were synthesized and evaluated as competitive inhibitors of hNE. Biological screening revealed that compound shows moderate inhibitory activity (IC = 35.2 μM) against hNE. Compound was also superimposed onto the active center of hNE to understand the binding mode.
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http://dx.doi.org/10.1007/s00044-020-02684-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7801566PMC
January 2021

Response by Hui et al to Letter Regarding, "Efficacy and Safety of Recanalization Therapy for Acute Ischemic Stroke With Large Vessel Occlusion".

Stroke 2021 01 28;52(1):e47. Epub 2020 Dec 28.

Department of Neurosurgery (X.J.), Xuanwu Hospital, Capital Medical University, Beijing, China.

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http://dx.doi.org/10.1161/STROKEAHA.120.032522DOI Listing
January 2021

Determining Essential Requirements for Fluorophore Selection in Various Fluorescence Applications Taking Advantage of Diverse Structure-Fluorescence Information of Chromone Derivatives.

J Med Chem 2021 01 14;64(2):1001-1017. Epub 2020 Dec 14.

State Key Laboratory of Bioactive Substances and Function of Natural Medicine, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, 1 Xiannongtan Street, Beijing 100050, China.

Herein, we report our work exploring the essential requirements for fluorophore selection during the development of various fluorescence applications. We assembled a library of chromone-derived fluorophores with diverse structure-fluorescence properties, which allowed us to choose the fluorophore pairs with similar structures but differing fluorescence properties and compared the performance of the selected fluorophore pairs in three types of commonly used fluorescence applications. We found that the selection standard of a suitable fluorophore is variable depending on the application. (1) In fluorescence imaging, fluorophores with strong and constant fluorescence under various conditions, such as a large pH range, are preferred. Notably, (2) in the detection of bioactive species, fluorophores with relatively lower fluorescence quantum yield favor the detection sensitivity. Furthermore, (3) in enzymatic assays employing fluorescence, the key parameter is the binding affinity between the fluorophore and the enzyme.
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http://dx.doi.org/10.1021/acs.jmedchem.0c01508DOI Listing
January 2021

Gut-on-chip: Recreating human intestine in vitro.

J Tissue Eng 2020 Jan-Dec;11:2041731420965318. Epub 2020 Nov 18.

CAS Key Laboratory of Quantitative Engineering Biology, Guangdong Provincial Key Laboratory of Synthetic Genomics, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.

The human gut is important for food digestion and absorption, as well as a venue for a large number of microorganisms that coexist with the host. Although numerous in vitro models have been proposed to study intestinal pathology or interactions between intestinal microbes and host, they are far from recapitulating the real intestinal microenvironment in vivo. To assist researchers in further understanding gut physiology, the intestinal microbiome, and disease processes, a novel technology primarily based on microfluidics and cell biology, called "gut-on-chip," was developed to simulate the structure, function, and microenvironment of the human gut. In this review, we first introduce various types of gut-on-chip systems, then highlight their applications in drug pharmacokinetics, host-gut microbiota crosstalk, and nutrition metabolism. Finally, we discuss challenges in this field and prospects for better understanding interactions between intestinal flora and human hosts, and then provide guidance for clinical treatment of related diseases.
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http://dx.doi.org/10.1177/2041731420965318DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7682210PMC
November 2020

The latest development of CoOOH two-dimensional materials used as OER catalysts.

Chem Commun (Camb) 2020 Dec 20;56(98):15387-15405. Epub 2020 Nov 20.

School of Materials Science and Engineering, Northeastern University, Shenyang 110819, China.

Electrocatalytic water splitting, which is driven by renewable energy input to produce oxygen, has been widely regarded as a promising strategy in the future energy portfolio. The two-dimensional structure based on CoOOH nanosheets is easy to handle in the preparation process, low in cost, and has a small overpotential during water decomposition. Therefore, CoOOH two-dimensional materials have been widely used as electrocatalysts for the oxygen evolution reaction (OER). In this paper, we summarize the application of two-dimensional CoOOH nanosheets in the field of oxygen production from electrocatalytic water splitting. First, the different preparation methods of two-dimensional CoOOH nanosheets are briefly introduced. The structure-activity relationship of the two-dimensional CoOOH catalyst was analyzed from different viewpoints, such as doping, defects, etc. Finally, different catalytic mechanisms of CoOOH-based catalysts are discussed, and studies at the density functional theory (DFT) level are also provided to support the above mechanisms. To improve the readability of this review, a concise overview at the end of each section is given to illustrate some of the characteristics and trends of the studies in the corresponding part. The opportunities and challenges of two-dimensional CoOOH as an electrocatalyst in the future are summarized in the Conclusion section. This work will provide new insights and perspectives to the readers to understand the role of CoOOH nanosheets in the OER process.
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http://dx.doi.org/10.1039/d0cc05876aDOI Listing
December 2020

Hair Cortisol Is Associated With Social Support and Symptoms in Schizophrenia.

Front Psychiatry 2020 24;11:572656. Epub 2020 Sep 24.

State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic & Developmental Sciences, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China.

Introduction: Psychosocial stressors may worsen psychotic symptoms in schizophrenia, while social support could protect against the effects of stress in schizophrenia. Hypothalamus-pituitary-adrenal axis dysfunction has been associated with schizophrenia. Hair cortisol concentrations (HCC) allow assessment of cumulative cortisol secretion over the preceding 3 months. The relationship between HCC, psychosocial stressors, social support, and the clinical characteristics of schizophrenia needs to be explored.

Methods: One hundred nine schizophrenia patients and 86 healthy controls between the ages of 18 and 60 were enrolled in the study. Three-centimeter samples of hair were collected from the scalp and HCC were measured using ELISA kits. Linear regression and factor analysis were employed to examine the relationship between HCC, childhood trauma, the number of stressful life events (SLE), the amount of social support in the 3 months prior to the hair cortisol assessment and clinical characteristics of schizophrenia.

Results: Schizophrenia patients experience more SLE in their lifetime, receive less social support, and have lower HCC in the recent 3 months compared to healthy controls. In the schizophrenia patients, HCC are positively associated with the amount of social support and negatively associated with the severity of delusions. The interaction between social support and SLE predicts decreased HCC. Factor analysis shows that a subgroup of schizophrenia patients who experience childhood trauma and SLE are characterized by decreased HCC.

Conclusions: Findings indicate social support could be a moderator for the relationship between SLE and HCC which may attenuate the effects of SLE in schizophrenia.
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http://dx.doi.org/10.3389/fpsyt.2020.572656DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7541838PMC
September 2020

Integrated analysis of lncRNAs and mRNAs reveals key trans-target genes associated with ETEC-F4ac adhesion phenotype in porcine small intestine epithelial cells.

BMC Genomics 2020 Nov 10;21(1):780. Epub 2020 Nov 10.

Key Laboratory of Animal Genetics, Breeding and Reproduction, Ministry of Agriculture & National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, P. R. China.

Background: Long non-coding RNAs (lncRNAs) play crucial roles in gene regulation at the transcriptional and post-transcriptional levels. LncRNAs are belonging to a large class of transcripts with ≥200 nt in length which do not code for proteins, have been widely investigated in various physiological and pathological contexts by high-throughput sequencing techniques and bioinformatics analysis. However, little is known about the regulatory mechanisms by which lncRNAs regulate genes that are associated with Enterotoxigenic Escherichia coli F4 fimbriae (ETEC-F4ac) adhesion phenotype in small intestine epithelial cells of Large White piglets. To address this, we used RNA sequencing to profile lncRNAs and mRNAs of small intestine epithelial cells in Large White piglets differing in their ETEC-F4 adhesion phenotypes and ITGB5 genotypes. Eight male piglets were used in this study and were divided into two groups on the basis of their adhesion phenotype and ITGB5 genotypes, a candidate gene for F4ac receptor. Non-adhesive group (n = 4) with CC genotype and adhesive group (n = 4) with TT genotype.

Results: In total, 78 differentially expressed lncRNAs (DE-lncRNA) and 223 differentially expressed mRNAs (log2 |FC| > 1, P < 0.05) were identified in the comparison of non-adhesive vs. adhesive small intestine epithelial cells. Furthermore, cis- and trans-regulatory target genes of DE-lncRNAs were identified, then interaction networks of lncRNAs and their cis- and trans-target differentially expressed genes (DEGs) were constructed separately. A total of 194 cis-targets were involved in the lncRNAs-cis genes interaction network and 61 trans-targets, were involved in lncRNA-trans gene interaction network that we constructed. We determined that cis-target genes were involved in alcoholism, systemic lupus erythematosus, viral carcinogenesis and malaria. Whereas trans-target DEGs were engaged in three important pathways related to the ETEC-F4 adhesion phenotype namely cGMP-PKG signaling pathway, focal adhesion, and adherens junction. The trans-target DEGs which directly involved in these pathways are KCNMB1 in cGMP-PKG signaling pathway, GRB2 in focal adhesion pathway and ACTN4 in focal adhesion and adherens junction pathways.

Conclusion: The findings of the current study provides an insight into biological functions and epigenetic regulatory mechanism of lncRNAs on porcine small intestine epithelial cells adhesion to ETEC-F4-ac and piglets' diarrhea susceptibility/resistance.
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http://dx.doi.org/10.1186/s12864-020-07192-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7653856PMC
November 2020

Hybrids of Upconversion Nanoparticles and Silver Nanoclusters Ensure Superior Bactericidal Capability Combined Sterilization.

ACS Appl Mater Interfaces 2020 Nov 5;12(46):51285-51292. Epub 2020 Nov 5.

Research Center for Analytical Sciences, Department of Chemistry, College of Sciences, Northeastern University, Shenyang 110819, China.

It is highly desired to develop new antibacterial agents with superior bactericidal efficiency for minimizing the damage to biological cells. We developed a combined antibacterial nanohybrid exhibiting a superb bactericidal effect and excellent biocompatibility by integrating upconversion nanoparticles (UCNPs) with silver nanoclusters (AgNCs). UCNPs and methylene blue (MB) molecules were encapsulated with silica microspheres microemulsion, with MB as the photosensitizer. Silver ions (Ag) were reduced by amino groups on the surface of silica spheres, wherein silver nanoclusters (AgNCs) were formed to produce the nanohybrid, [email protected](MB)@AgNCs. UCNPs emit visible light at 655 nm under excitation by near-infrared radiation (NIR, 980 nm). MB absorbs the emission from UCNPs to generate toxic singlet oxygen (O), which leads to the apoptosis of bacteria cells. Meanwhile, silver ions released from AgNCs destroy the bacteria membrane structure. Upon NIR irradiation at 980 nm for 10 min, 8.33 μg mL nanohybrid results in a 100% killing rate for both Gram-positive (+) and Gram-negative (-).
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http://dx.doi.org/10.1021/acsami.0c15710DOI Listing
November 2020

Association between copy-number alteration of +20q, -14q and -18p and cross-sensitivity to tyrosine kinase inhibitors in clear-cell renal cell carcinoma.

Cancer Cell Int 2020 6;20:482. Epub 2020 Oct 6.

Department of Urology, Huashan Hospital, Fudan University, Shanghai, 200040 People's Republic of China.

Background: We aim to explore association between copy number alteration (CNA) and sensitivity to common tyrosine kinase inhibitors (TKIs) used in clear-cell renal cell carcinoma (ccRCC) treatment.

Methods: CNA with related sensitivity profiles were extracted from the Genomics of Drug Sensitivity in Cancer (GDSC) dataset and was cross-referenced with common CNA in ccRCC in the Cancer Genome Atlas (TCGA) dataset. Functional annotation was profiled using GSEA and NET-GE. Target genes within cytobands of interest were screened in silico and validated in vitro using proliferation assays in A498 and 786-O ccRCC cells.

Results: Four TKIs (Sunitinib, Cabozantinib, Axitinib and Sorafenib) that were clinically used in ccRCC were selected. In silico analysis showed gain of 20q (+20q) occurred in ~ 23% of cases and was associated with resistance to all four TKIs; loss of 14q (-14q) occurred in ~ 39% of cases and was associated with resistance to Sunitinib and Sorafenib; loss of 18p (-18p) occurred in ~ 39% of cases and was associated with sensitivity to Sunitinib and Sorafenib. All 3 CNAs were associated with worsened prognosis, respectively. Candidate target genes included of RBL1 on 20q, KLHL33 on 14q and ARHGAP28 on18q. In vitro validation showed RBL1 overexpression induced resistance to Sunitinib and Cabozantinib; KLHL33 silencing induced resistance to Sunitinib; ARHGAP28 silencing induced sensitivity to Cabozantinib. Functional annotation indicated FoxO signaling, hypoxic response and Wnt pathway, and Rho-related cellular adhesion were mechanistically associated with +20q, -14q and -18p, respectively.

Conclusion: Common CNAs in ccRCC are associated with cancer-intrinsic cross-sensitivity to common TKIs. Further validation and functional analyses are therefore needed.
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http://dx.doi.org/10.1186/s12935-020-01585-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7541266PMC
October 2020

Cerebral blood microcirculation measurement in APP/PS1 double transgenic mice at the preclinical stage of Alzheimer's disease: preliminary data on the early intervention of anodal transcranial direct current stimulation

Annu Int Conf IEEE Eng Med Biol Soc 2020 07;2020:3557-3560

Anodal transcranial direct current stimulation (AtDCS) can improve memory and cognitive dysfunction in patients with Alzheimer's disease (AD), which has been proven in basic and clinical studies. Intervention of AD in preclinical stage is important to prevent progression of AD in the aging society. At the same time, there is increasing evidence that a close link exists between cerebrovascular dysfunction and AD disease. Here we investigated the changes of local cerebral blood microcirculation in preclinical AD mouse model after AtDCS based on the previous studies. Twenty-four 6-month-old male APP/PS1 double transgenic mice were randomly divided into three groups: a model group (AD), a model sham stimulation (ADST) group and a model stimulation group (ATD). Eight 6-month-old male C57 wild-type mice served as a control group (CTL). Mice in the ATD group received 10 AtDCS sessions. Two months after the end of AtDCS in the ATD group, the microcirculation parameters of the frontal cortex of the mice in each group, including cerebral blood flow (CBF), blood flow velocity (Velo), oxygen saturation (SO) and relative hemoglobin content (rHb), were obtained by the non-invasive laser-Doppler spectrophotometry system "Oxygen-to-See (O2C)". The results showed that AtDCS increased CBF, Velo and SO, and reduce rHb in APP/PS1 double transgenic mice at the preclinical stage of AD.Clinical Relevance-This shows the positive effect of AtDCS on preclinical AD in cerebrovascular function, and provides effective basic research facts for AtDCS to intervene and delay the clinical application of AD disease.
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http://dx.doi.org/10.1109/EMBC44109.2020.9175875DOI Listing
July 2020

Two engineered site-specific antibody-drug conjugates, HLmD4 and HLvM4, have potent therapeutic activity in two DLL4-positive tumour xenograft models.

Am J Cancer Res 2020 1;10(8):2387-2408. Epub 2020 Aug 1.

State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University Nanjing 210009, China.

The humanized Delta-like 4 (DLL4) monoclonal antibody H3L2 with a quite high affinity for hrDLL4 inhibits the DLL4-mediated human umbilical vein endothelial cell (HUVEC) phenotype, inducing dysfunctional angiogenesis and tumour cell apoptosis, which effectively arrests breast cancer cell growth . To develop a more effective therapy, an engineered cysteine residue at alanine 121 (Kabat numbering) on each H3L2 heavy chain or at valine 207 (Kabat numbering) on each H3L2 light chain was established by site-directed mutagenesis. Three engineered antibodies, THL4, TH2 and TL2, were identified, and the specific-site antibody-drug conjugates (ADCs) THL4-mpeoDM1 (named HLmD4), TH2-mpeoDM1 (named HmD2), TL2-mpeoDM1 (named LmD2) and THL4-vcMMAE (named HLvM4), were produced, which exhibit much more potent antitumour activity than the naked antibody. The engineered ADCs can be directed against DLL4 and effectively internalized, followed by the release of small molecule cytotoxic agents, e.g., DM1 or MMAE, into the cytosol, which inhibit the synthesis of microtubules and induce G2/M phase growth arrest and cell death through the induction of apoptosis. ADC-conjugated DM1 was highly potent against DLL4-expressing cells . We systematically compared the potency and the preclinical efficacy and safety profiles of the heterogeneous conventional ADC, H3L2-mpeoDM1 (named JmD4) with that of the homogeneous engineered conjugate HLmD4. The engineered anti-DLL4 ADCs, particularly HLmD4, showed more potent antitumour activity than Docetaxel and superior safety compared with JmD4 in two xenograft tumour models. Our findings indicate that engineered ADCs have promising potential as effective preclinical therapies for cancers.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7471348PMC
August 2020

G551D mutation impairs PKA-dependent activation of CFTR channel that can be restored by novel GOF mutations.

Am J Physiol Lung Cell Mol Physiol 2020 11 2;319(5):L770-L785. Epub 2020 Sep 2.

Department of Cell, Developmental, and Integrative Biology, University of Alabama at Birmingham, Birmingham, Alabama.

G551D is a major disease-associated gating mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) protein, an ATP- and phosphorylation-dependent chloride channel. G551D causes severe cystic fibrosis (CF) disease by disrupting ATP-dependent channel opening; however, whether G551D affects phosphorylation-dependent channel activation is unclear. Here, we use macropatch recording and Ussing chamber approaches to demonstrate that G551D impacts on phosphorylation-dependent activation of CFTR, and PKA-mediated phosphorylation regulates the interaction between the x-loop in nucleotide-binding domain 2 (NBD2) and cytosolic loop (CL) 1. We show that G551D not only disrupts ATP-dependent channel opening but also impairs phosphorylation-dependent channel activation by largely reducing PKA sensitivity consistent with the reciprocal relationship between channel opening/gating, ligand binding, and phosphorylation. Furthermore, we identified two novel GOF mutations: D1341R in the x-loop near the ATP-binding cassette signature motif in NBD2 and D173R in CL1, each of which strongly increased PKA sensitivity both in the wild-type (WT) background and when introduced into G551D-CFTR. When D1341R was combined with a second GOF mutation (e.g., K978C in CL3), we find that the double GOF mutation maximally increased G551D channel activity such that VX-770 had no further effect. We further show that a double charge-reversal mutation of D1341R/D173R-CFTR exhibited similar PKA sensitivity when compared with WT-CFTR. Together, our results suggest that charge repulsion between D173 and D1341 of WT-CFTR normally inhibits channel activation at low PKA activity by reducing PKA sensitivity, and negative allostery by the G551D is coupled to reduced PKA sensitivity of CFTR that can be restored by second GOF mutations.
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http://dx.doi.org/10.1152/ajplung.00262.2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7701354PMC
November 2020

Complete genome analysis of PaGz-1 and PaZq-1, two novel phages belonging to the genus Pakpunavirus.

Arch Virol 2020 Oct 27;165(10):2393-2396. Epub 2020 Jul 27.

CAS Key Laboratory of Quantitative Engineering Biology, Guangdong Provincial Key Laboratory of Synthetic Genomics, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China.

Pseudomonas phages PaGz-1 and PaZq-1, two new phages infecting Pseudomonas aeruginosa, were isolated from fresh water in Guangdong province, China. The genomes of these two phages consist of 93,975 bp and 94,315 bp and contain 175 and 172 open reading frames (ORFs), respectively. The genome sequences of PaGz-1 and PaZq-1 share 95.8% identity with a query coverage of 94%, suggesting that these two phages belong to two different species. Based on results of nucleotide sequence alignment, gene annotation, and phylogenetic analysis, we propose PaGz-1 and PaZq-1 as representative isolates of two species in the genus Pakpunavirus within the family Myoviridae.
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http://dx.doi.org/10.1007/s00705-020-04745-wDOI Listing
October 2020

Taking advantage of the aromatisation of 7-diethylamino-4-methyl-3,4-dihydrocoumarin in the fluorescence sensing of superoxide anion.

Chem Commun (Camb) 2020 Sep 27;56(68):9827-9829. Epub 2020 Jul 27.

State Key Laboratory of Bioactive Substances and Function of Natural Medicine, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, 1 Xiannongtan Street, Beijing, 100050, China.

The aromatisation of 7-diethylamino-3,4-dihydrocoumarin provides an alternative fluorescent probing technique to selectively detect the concentration of superoxide anion in solution. In addition, we reported the advantage of evaluating O˙ sensing probes in anhydrous DMSO instead of in aqueous buffers when using KO as the surrogate of O˙.
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http://dx.doi.org/10.1039/d0cc02282aDOI Listing
September 2020

Comprehensive analysis of copy number variance and sensitivity to common targeted therapy in clear cell renal cell carcinoma: In silico analysis with in vitro validation.

Cancer Med 2020 08 6;9(16):6020-6029. Epub 2020 Jul 6.

Department of Urology, Huashan Hospital, Fudan University, Shanghai, PR China.

Background: Chromosomal rearrangements are common in clear cell renal cell carcinoma (ccRCC) and their roles in mediating sensitivity to tyrosine kinase inhibitors (TKIs) and mTOR inhibitors (mTORi) remain elusive.

Methods: We developed an in silico strategy by screening copy number variance (CNV) that was potentially related to TKI or mTORi sensitivity in ccRCC by reproducing the TCGA and GDSC datasets. Candidate genes should be both significantly prognostic and related to drug sensitivity or resistance, and were then validated in vitro.

Results: ADCYAP1 loss and GNAS gain were associated with sensitivity and resistance and to Cabozantinib, respectively. ACRBP gain and CTBP1 loss were associated with sensitivity and resistance and to Pazopanib, respectively. CDKN2A loss and SULT1A3 gain were associated with sensitivity and resistance and to Temsirolimus, respectively. CCNE1 gain was associated with resistance to Axitinib and LRP10 loss was associated with resistance to Sunitinib. Mutivariate analysis showed ADCYAP1, GNAS, and CCNE1 remained independently prognostic when adjusted for the rest.

Conclusion: Here we show CNVs of several genes that are associated with sensitivity and resistance to commonly used TKIs and mTORi in ccRCC. Further validation and functional analyses are therefore needed.
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http://dx.doi.org/10.1002/cam4.3281DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7433817PMC
August 2020

Ivacaftor Reverses Airway Mucus Abnormalities in a Rat Model Harboring a Humanized G551D-CFTR.

Am J Respir Crit Care Med 2020 11;202(9):1271-1282

Department of Medicine.

Animal models have been highly informative for understanding the characteristics, onset, and progression of cystic fibrosis (CF) lung disease. In particular, the CFTR rat has revealed insights into the airway mucus defect characteristic of CF but does not replicate a human-relevant CFTR (cystic fibrosis transmembrane conductance regulator) variant. We hypothesized that a rat expressing a humanized version of CFTR and harboring the ivacaftor-sensitive variant G551D could be used to test the impact of CFTR modulators on pathophysiologic development and correction. In this study, we describe a humanized-CFTR rat expressing the G551D variant obtained by zinc finger nuclease editing of a human complementary DNA superexon, spanning exon 2-27, with a 5' insertion site into the rat gene just beyond intron 1. This targeted insertion takes advantage of the endogenous rat promoter, resulting in appropriate expression compared with wild-type animals. The bioelectric phenotype of the epithelia recapitulates the expected absence of CFTR activity, which was restored with ivacaftor. Large airway defects, including depleted airway surface liquid and periciliary layers, delayed mucus transport rates, and increased mucus viscosity, were normalized after the administration of ivacaftor. This model is useful to understand the mechanisms of disease and the extent of pathology reversal with CFTR modulators.
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http://dx.doi.org/10.1164/rccm.202002-0369OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7605185PMC
November 2020

The relationship between clinics and the venom of the causative Amazon pit viper (Bothrops atrox).

PLoS Negl Trop Dis 2020 06 8;14(6):e0008299. Epub 2020 Jun 8.

Instituto Butantan, São Paulo, Brazil.

Snake venoms are complex mixtures of proteins with toxic activities, with many distinct isoforms, affecting different physiological targets, comprised in a few protein families. It is currently accepted that this diversity in venom composition is an adaptive advantage for venom efficacy on a wide range of prey. However, on the other side, variability on isoforms expression has implications in the clinics of human victims of snakebites and in the efficacy of antivenoms. B. atrox snakes are responsible for most of the human accidents in Brazilian Amazon and the type and abundance of protein families on their venoms present individual variability. Thus, in this study we attempted to correlate the individual venom proteome of the snake brought to the hospital by the patient seeking for medical assistance with the clinical signs observed in the same patient. Individual variability was confirmed in venoms of the 14 snakes selected for the study. The abundance of each protein family was quite similar among the venom samples, while the isoforms composition was highly variable. Considering the protein families, the SVMP group presented the best correlation with bleeding disorders and edema. Considering individual isoforms, some isoforms of venom metalloproteinase (SVMP), C-type lectin-like toxins (CTL) and snake venom serine proteinases (SVSP) presented expression levels that with statistically significant positive correlation to signs and symptoms presented by the patients as bleeding disorders, edema, ecchymosis and blister formation. However, some unexpected data were also observed as the correlation between a CTL, CRISP or LAAO isoforms with blister formation, still to be confirmed with a larger number of samples. Although this is still a small number of patient samples, we were able to indicate that venom composition modulates clinical manifestations of snakebites, to confirm at the bedside the prominent role of SVMPs and to include new possible toxin candidates for the development of toxin inhibitors or to improve antivenom selectiveness, important actions for the next generation treatments of snakebites.
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http://dx.doi.org/10.1371/journal.pntd.0008299DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7302866PMC
June 2020

Efficacy and Safety of Recanalization Therapy for Acute Ischemic Stroke With Large Vessel Occlusion: A Systematic Review.

Stroke 2020 07 3;51(7):2026-2035. Epub 2020 Jun 3.

Cerebrovascular Diseases Research Institute, Xuanwu Hospital (C.W., W.Z., X.J.), Capital Medical University, Beijing, China.

Background And Purpose: The optimal recanalization strategy for acute ischemic stroke with large vessel occlusion continues to be an area of active interest. Network meta-analysis can provide insight when direct comparative evidence is lacking.

Methods: A systematic review of the literature using PubMed, Embase, the Cochrane Central Register of Controlled Trials, and SinoMed was performed, and a search was conducted for clinical trials on ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform, and StrokeCenter.org. Four independent reviewers conducted the study selection, data abstraction, and quality assessments.

Results: The literature review identified 17 trials including 3236 patients and 8 ongoing clinical trials. Sample sizes ranged from 7 to 656 participants. Intravenous thrombolysis (IVT) was the most common intervention, followed by IVT plus mechanical thrombectomy (MT), IVT plus intraarterial thrombolysis, intraarterial thrombolysis alone, and MT alone. In the pooled network meta-analysis, IVT+MT was associated with a higher rate of independent functioning. In contrast, IVT was ranked as the most ineffective treatment strategy with respect to neurological functions, while direct MT was ranked as the least safe intervention with respect to all-cause mortality. Also, irrespective of assessment tools, endovascular treatment plus IVT led to higher successful recanalization rate than thrombolysis alone.

Conclusions: Compared with other recanalization treatments, IVT+MT seems to be the most effective strategy, without increasing detrimental effects, for thrombolysis-eligible patients with large vessel occlusion-acute ischemic stroke. To improve the current evidentiary basis for recanalization treatment, future trials and real-world studies are warranted and should use unified definitions of symptomatic intracranial hemorrhage and recanalization.
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http://dx.doi.org/10.1161/STROKEAHA.119.028624DOI Listing
July 2020

The effects of DRGs-based payment compared with cost-based payment on inpatient healthcare utilization: A systematic review and meta-analysis.

Health Policy 2020 04 25;124(4):359-367. Epub 2020 Jan 25.

Department of Health Service Management, China Medical University, No. 77 Puhe Road, Shenyang, Liaoning, China. Electronic address:

Diagnosis related groups (DRGs)-based payment is increasingly used worldwide to control hospital costs instead of pre-existing cost-based payment, but the results of evaluations vary. A systematic analysis of the effects of DRGs-based payment is needed. This study aims to conduct a systematic review and meta-analysis to compare the effects of DRGs-based payment and cost-based payment on inpatient health utilization in terms of length of stay (LOS), total inpatient spending per admission and readmission rates. We included studies undertaken with designs approved by the Cochrane Effective Practice and Organisation of Care that reported associations between DRGs-based payment and one or more inpatient healthcare utilization outcomes. After a systematic search of eight electronic databases through October 2018, 18 studies were identified and included in the review. We extracted data and conducted quality assessment, systematic synthesis and meta-analyses on the included studies. Random-effects models were used to handle substantial heterogeneity between studies. Meta-analysis showed that DRGs-based payment was associated with lower LOS (pooled effect: -8.07 % [95 %CI -13.05 to -3.10], p = 0.001), and higher readmission rates (pooled effect: 1.36 % [95 %CI 0.45-2.27], p = 0.003). This meta-analysis revealed that DRGs-based payment may have cost-saving implications by lowering LOS, whereas hardly reduce the readmission rates. Policy-makers considering adopting DRGs-based payment should pay more attention to the hospital readmission rates compared with cost-based payment.
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http://dx.doi.org/10.1016/j.healthpol.2020.01.007DOI Listing
April 2020

Parental Experiences While Waiting For Children Undergoing Surgery in Singapore.

J Pediatr Nurs 2020 May - Jun;52:e42-e50. Epub 2020 Jan 24.

Alice Lee Centre for Nursing Studies, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; National University Health System, Singapore. Electronic address:

Purpose: To explore the experiences and needs of parents while waiting for their children undergoing surgery.

Designs And Methods: A descriptive qualitative study was conducted. A purposive sample of 11 parents who went through their first waiting experiences during their children's surgeries in a Singapore public hospital was recruited. Children younger than or equal to 16 years of age were included. A semi-structured interview guide facilitated the individual face-to-face interviews. Thematic analysis was used.

Results: Four themes were identified: "Care and care provision affecting waiting experiences", "Parental concerns and surgery affecting waiting experiences", "Coping strategies used during waiting periods" and "Recommendations to improve waiting experiences". Pre-operative instructions, the professionalism of medical teams, and a lack of timely updates affected parental experiences. Parents expressed their worries. The complexities and types of surgery influenced how they felt. Their concerns included potential complications, surgical outcomes, anesthesia-related side effects, and post-operative care including pain. They spent their waiting times eating, resting, using their smart devices, and coping with a support system. Environmental improvements, more updates, and mobile applications were recommended by the participants.

Conclusion: For a parent, the wait during his/her child's surgery can be unsettling. Our results give insights into parental waiting experiences and needs during their children's surgeries.

Practice Implications: These findings can guide the improvement of the current practise based on our evidence or the implementation of newer technology to provide better waiting experiences for parents during their children's surgeries and to enhance the quality of clients' experiences in the hospital.
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http://dx.doi.org/10.1016/j.pedn.2020.01.004DOI Listing
April 2021

Antidepressant Effect of Adjunct Repetitive Transcranial Magnetic Stimulation in Inpatients 60 Years and Older.

J ECT 2020 Sep;36(3):216-221

From the Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine, Shanghai Key Laboratory of Psychotic Disorders, Shanghai.

Background: Repetitive transcranial magnetic stimulation (rTMS) is now an established, safe, and effective treatment for adults with depression. However, specific research in rTMS for use in elderly patients with acute depression is scarce.

Objective: The aim of the present study was to investigate the efficacy of add-on rTMS in a clinical sample of older adults experiencing an acute phase of depression.

Method: This study examined 114 patients (54 elderly [aged ≥60] and 60 adults [aged 18-59]) with acute depression who were drug free at baseline. They were treated with at least 10 sessions of rTMS for 4 weeks along with 1 antidepressant. Symptoms of depression were measured using the Hamilton Rating Scale for Depression at baseline and after 2 and 4 weeks of treatment. Clinical improvement and rates of response and remission were compared across groups.

Results: Significant improvement was noted after 2 and 4 weeks of treatment in both adult and elderly groups. Higher remission rates were found in adult patients but with no differences in response. The stimulation intensity and course of illness were significant predictors of remission after 4 weeks of rTMS treatment in the elderly.

Conclusions: The add-on rTMS treatment for elderly depression patients is promising with respect to safety and feasibility. This preliminary evidence supports the application of rTMS to this group during acute episodes.
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http://dx.doi.org/10.1097/YCT.0000000000000648DOI Listing
September 2020

Up-regulation of miR-106a targets LIMK1 and contributes to cognitive impairment induced by isoflurane anesthesia in mice.

Genes Genomics 2020 04 13;42(4):405-412. Epub 2020 Jan 13.

Department of Anesthesia, Peking University International Hospital, No. 1, Life Garden Road, Zhongguancun Life Garden, Changping District, Beijing, China.

Background: Postoperative cognitive dysfunction (POCD) had a great relationship with anesthesia during surgery, and miRNAs have been found involved in anesthesia-induced cognitive impairment.

Objective: To explore the role and potential mechanism of miR-106a in isoflurane anesthesia-induced cognitive impairment.

Methods: Adult male mice were treated with isoflurane anesthesia; Morris water maze tests and fear conditioning tests were performed; and expression levels of miR-106a and LIMK1 were determined by quantitative real-time PCR (qRT-PCR) and western blot. Dual luciferase reporter assay was used to determine the binding of miR-106a and 3'UTR of LIMK1. To verify the role of miR-106a, antagomir of miR-106a were intrahippocampally injected. Finally, expression of BCL2 apoptosis regulator (Bcl-2), LIM domain kinase 1 (LIMK1), BCL2-associated X, apoptosis regulator (Bax) and cleaved caspase3 was determined by western blot.

Results: In isoflurane anesthesia-treated group (IS), the percentage of target quadrant dwell time was significantly lower and the escape latency was significantly higher than in the control group (sham), and the freezing behavior of IS was significantly less in contextual fear conditioning tests. Expression levels of miR-106a were increased and those of LIMK1 were decreased in response to IS. Dual luciferase reporter assay showed that miR-106a could bind with the 3'UTR of LIMK1. Decreased expression levels of miR-106a improved the cognitive impairment of the mice treated with isoflurane. Intrahippocampally injected antagomir of miR-106a also increased LIMK1 and Bcl-2 levels, decreased the BAX and cleaved caspase3 expression levels in the mice treated with isoflurane.

Conclusion: Decrease of LIMK1 expression by miR-106a played an important role in isoflurane anesthesia-induced cognitive impairment.
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http://dx.doi.org/10.1007/s13258-019-00913-8DOI Listing
April 2020