Publications by authors named "Lei Qi"

410 Publications

Study on the gene signature related to immune microenvironment on viral and nonviral infections of hepatocellular carcinoma.

Medicine (Baltimore) 2021 Apr;100(15):e25374

The First Hospital of Lanzhou University, Lanzhou.

Abstract: The pathogenesis of hepatocellular carcinoma (HCC) can be divided into viral infection (VIR) and nonviral (NVIR) infection. Two types of HCC performed different tumor immune microenvironment (TIME) which directly affected prognosis of HCC. This study aimed to identify an effective 2 types of HCC prognostic gene signature that related to immune TIME.The differential expression genes (DEGs) were analyzed by Limma R package from the Cancer Genome Atlas. Immune related genes getting from IMMport database were matched to DEGs for testing prognosis. Prognostic index (PI) consisted of prognostic immune related genes was calculated in different types of HCC by COX regression and the correlation with the abundance of immune infiltrates, including 6 type cells, via gene modules. Tumor immune estimation resource database was applied to analyze TIME. Finally, the correlations between PI of DEGs and TIICs were analyzed by the Spearman method.Results showed that PI consisted of 11 messenger RNAs in VIR and 12 messenger RNAs in NVIR groups. The PI related to HCC prognosis has different correlations with immune infiltrating cells in VIR and NVIR groups. The PI value of DEGs has significant correlations with neutrophils (R = 0.22, P-value = .029) and dendritic (R = 0.21, P-value = .036) infiltration levels in VIR group. However, in NVIR group, the result showed there were no significant correlations between PI and other 5 type cell infiltration levels (P-value > .05).The 11-gene signature in VIR and 12-gene signature in NVIR group selected based on data from the Cancer Genome Atlas database had a different correlation with immune infiltrating cells of HCC patients.
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http://dx.doi.org/10.1097/MD.0000000000025374DOI Listing
April 2021

Demethylated miR-216a Regulates High Mobility Group Box 3 Promoting Growth of Esophageal Cancer Cells Through Wnt/β-Catenin Pathway.

Front Oncol 2021 23;11:622073. Epub 2021 Mar 23.

Department of Thoracic Surgery, Cheeloo College of Medicine, Shandong University, Jinan, China.

Background: Esophageal cancer (EC) is the eighth most common cause of cancer-associated mortality in humans. Recent studies have revealed the important roles of microRNAs (miRs) in mediating tumor initiation and progression. miR-216a has been found to be involved in the progression of EC, but the underlying mechanisms remain largely unknown. The aim of this study is to explore the mechanism of miR-216a and the downstream molecules in esophageal cancer.

Materials And Methods: The degree of methylation of miR-216a promoter in EC tissues and cell lines was determined with methylation specific polymerase chain reaction (MSP). The levels of miR-216a and HMGB3 in EC cells were quantified by quantitative PCR (qPCR) and Western blot (WB). EC cell lines were treated with DNA methylation inhibitor 5-aza-2'-deoxycytidine (5-AZ), miR-216a mimics, and HMGB3 siRNA to explore the effects of miR-216a and HMGB3 on the proliferation, migration, invasion, and apoptosis of cells. Dual-luciferase reporter assay was employed to verify the binding of miR-216a to the 3'UTR of HMGB2 mRNA.

Results: The promoter of MiR-216a was hypermethylated and the expression of miR-216a was down-regulated in EC, while HMGB3 was up-regulated. Dual luciferase reporter assay confirmed the binding of miR-216a to the 3'UTR of HMGB3 mRNA. Demethylated miR-216a and miR-216a mimics elevated miR-216a expression and down-regulated HMGB3, as well as inhibited cell proliferation, migration, and invasion. Inhibiting the expression of HMGB3 played an important role in inducing apoptosis, suppressing cell expansion, and down-regulating the activity of Wnt/β-catenin pathway.

Conclusions: Hypermethylation in the promoter of miR-216a upregulated HMGB3 and the Wnt/β-catenin pathway, resulting in enhanced EC progression.
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http://dx.doi.org/10.3389/fonc.2021.622073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8025835PMC
March 2021

Bioinspired Cell Silicification: From Extracellular to Intracellular.

J Am Chem Soc 2021 Apr 7. Epub 2021 Apr 7.

Center for Micro-Engineered Materials, Department of Chemical and Biological Engineering, The University of New Mexico, Albuquerque, New Mexico 87131, United States.

In nature, biosilicification directs the formation of elaborate amorphous silica exoskeletons that provide diatoms mechanically strong, chemically inert, non-decomposable silica armor conferring chemical and thermal stability as well as resistance to microbial attack, without changing the optical transparency or adversely effecting nutrient and waste exchange required for growth. These extraordinary silica/cell biocomposites have inspired decades of biomimetic research aimed at replication of diatoms' hierarchically organized exoskeletons, immobilization of cells or living organisms within silica matrices and coatings to protect them against harmful external stresses, genetic re-programming of cellular functions by virtue of physico-chemical confinement within silica, cellular integration into devices, and endowment of cells with non-native, abiotic properties through facile silica functionalization. In this Perspective, we focus our discussions on the development and concomitant challenges of bioinspired cell silicification ranging from "cells encapsulated within 3D silica matrices" and "cells encapsulated within 2D silica shells" to extra- and intracellular silica replication, wherein all biomolecular interfaces are encased within nanoscopic layers of amorphous silica. We highlight notable examples of advances in the science and technology of biosilicification and consider challenges to advancing the field, where we propose cellular "mineralization" with arbitrary nanoparticle exoskeletons as a generalizable means to impart limitless abiotic properties and functions to cells, and, based on the interchangeability of water and silicic acid and analogies between amorphous ice and amorphous silica, we consider "freezing" cells within amorphous silica as an alternative to cryo-preservation.
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http://dx.doi.org/10.1021/jacs.1c00814DOI Listing
April 2021

The Archaeal Small Heat Shock Protein Hsp17.6 Protects Proteins from Oxidative Inactivation.

Int J Mol Sci 2021 Mar 4;22(5). Epub 2021 Mar 4.

State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.

Small heat shock proteins (sHsps) are widely distributed among various types of organisms and function in preventing the irreversible aggregation of thermal denaturing proteins. Here, we report that Hsp17.6 from exhibited protection of proteins from oxidation inactivation. The overexpression of Hsp17.6 in markedly increased the stationary phase cell density and survivability in HClO and HO. Treatments with 0.2 mM HClO or 10 mM HO reduced malate dehydrogenase (MDH) activity to 57% and 77%, whereas the addition of Hsp17.6 recovered the activity to 70-90% and 86-100%, respectively. A similar effect for superoxide dismutase oxidation was determined for Hsp17.6. Non-reducing sodium dodecyl sulfate polyacrylamide gel electrophoresis assays determined that the Hsp17.6 addition decreased HO-caused disulfide-linking protein contents and HClO-induced degradation of MDH; meanwhile, Hsp17.6 protein appeared to be oxidized with increased molecular weights. Mass spectrometry identified oxygen atoms introduced into the larger Hsp17.6 molecules, mainly at the aspartate and methionine residues. Substitution of some aspartate residues reduced Hsp17.6 in alleviating HO- and HClO-caused MDH inactivation and in enhancing the survivability in HO and HClO, suggesting that the archaeal Hsp17.6 oxidation protection might depend on an "oxidant sink" effect, i.e., to consume the oxidants in environments via aspartate oxidation.
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http://dx.doi.org/10.3390/ijms22052591DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7961418PMC
March 2021

A comprehensive analysis and resource to use CRISPR-Cas13 for broad-spectrum targeting of RNA viruses.

Cell Rep Med 2021 Mar 23:100245. Epub 2021 Mar 23.

Department of Bioengineering, Stanford University, Stanford, CA 94305, USA.

The COVID-19 pandemic caused by SARS-CoV-2 and variants has led to significant mortality. We recently reported that an RNA-targeting CRISPR-Cas13 system, termed prophylactic antiviral CRISPR in human (PAC-MAN), offered an antiviral strategy against SARS-CoV-2 and influenza A virus. Here, we expand in silico analysis to use PAC-MAN to target a broad spectrum of human- or livestock-infectious RNA viruses with high specificity, coverage, and predicted efficiency. Our analysis reveals that a minimal set of 14 crRNAs is able to target >90% of human-infectious viruses across 10 RNA virus families. We predict that a set of 5 experimentally validated crRNAs can target new SARS-CoV-2 variant sequences with zero mismatches. We also build an online resource (crispr-pacman.stanford.edu) to support community use of CRISPR-Cas13 for broad-spectrum RNA virus targeting. Our work provides a new bioinformatic resource for using CRISPR-Cas13 to target diverse RNA viruses in order to facilitate development of CRISPR-based antivirals.
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http://dx.doi.org/10.1016/j.xcrm.2021.100245DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985958PMC
March 2021

Efficacy of evoked potential monitoring for predicting postoperative motor status in internal carotid artery aneurysm surgeries.

J Clin Monit Comput 2021 Mar 23. Epub 2021 Mar 23.

Department of Neurophysiology, Beijing Neurosurgical Institute, Capital Medical University, 119 South Fourth Ring West Road, Fengtai District, Beijing, 100070, China.

This study aimed to investigate the efficacy of intraoperative motor evoked potential (MEP) and somatosensory evoked potential (SSEP) monitoring for predicting postoperative motor deficits (PMDs) in patients with internal carotid artery (ICA) aneurysms. The data for 138 patients with ICA aneurysms who underwent surgical clipping as well as their intraoperative neuromonitoring data were retrospectively reviewed. The efficacy of MEP/SSEP changes for predicting PMDs was assessed using binary logistic regression analysis. Subsequently, receiver operating characteristic curve analysis was used to obtain a supplementary critical value of the MEP/SSEP deterioration duration. The sensitivity and specificity of MEP changes for predicting PMDs were 0.824 and 0.843, respectively. For SSEP changes, the sensitivity and specificity were 0.529 and 0.959, respectively. MEP and SSEP changes were identified as independent predictors for short-term (p = 0.002 and 0.011, respectively) and long-term PMDs (p = 0.040 and 0.006, respectively). The supplementary critical value for MEP deterioration duration for predicting PMDs was 14 min (p = 0.007, AUC = 0.805). For SSEP, the value was 14.5 min (p = 0.042, AUC = 0.875). The MEP/SSEP changes adjusted by those optimal values were also identified as independent predictors for short-term (p < 0.001 and p = 0.005, respectively) and long-term PMDs (p = 0.019 and 0.003, respectively). Intraoperative MEP and SSEP deterioration durations are effective in predicting PMDs in patients with ICA aneurysms.
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http://dx.doi.org/10.1007/s10877-021-00693-1DOI Listing
March 2021

MicroRNA-10a suppresses cell metastasis by targeting BDNF and predicted patients survival in renal cell carcinoma.

J BUON 2021 Jan-Feb;26(1):250-258

Department of Urologic Surgery, Weifang People's Hospital, Weifang 261041, China.

Purpose: Renal cell carcinoma (RCC) is the most common renal neoplasm and accounts for 3% of all cancers. Increasing studies reported that miR-10a, acting as tumor suppressor, was downregulated in several cancers. It has been reported that the proteins encoded by Brain-Derived Neutrophic Factor (BDNF) were members of the nerve growth factor family, and could promote neuronal survival in the adult brain. The purpose of this study was to explore how miR-10a worked in RCC on the metastasis.

Methods: The expression level of miR-10a and BDNF were calculated using RT-PCR and western blot. Transwell assay was utilized to evaluate the invasive ability. Kaplan-Meier method along with log-rank test were applied to evaluate the 5-year overall survival of RCC patients.

Results: miR-10a was significantly downregulated and BDNF was upregulated in RCC tissues and cell lines A498 and 786-O. The expression of miR-10a had a reverse correlation with BDNF in RCC tissues. Overexpression of miR-10a or interference of BDNF inhibited the invasion and epithelial-mesenchymal transition (EMT) of A498 cells. What's more, BDNF was demonstrated to be a target gene of miR-10a and miR-10a could mediate the expression of BDNF in RCC. In addition, low expression of miR-10a or overexpression of BDNF predicted poor prognosis of RCC patients.

Conclusion: Our results indicated that miR-10a inhibited the invasion and EMT by regulating BDNF in RCC. The newly identified miR-10a/BDNF axis provides novel insight into the pathogenesis of RCC.
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March 2021

Comparison of the efficacy and safety of low-intensity extracorporeal shock wave therapy versus on-demand sildenafil for erectile dysfunction.

Transl Androl Urol 2021 Feb;10(2):860-868

Department of Urology, Peking Union Medical College Hospital, Beijing, China.

Background: Low-intensity extracorporeal shock wave therapy (Li-ESWT) is an effective therapy for erectile dysfunction (ED) but is not widely recognized and applied. This prospective nonrandomized study aimed to investigate the efficacy and safety of Li-ESWT.

Methods: After a 4-week washout period of past ED treatment, patients entered one of 2 active treatment groups, either 9-week Li-ESWT or 100 mg on-demand sildenafil. Patients were evaluated in the first- and third-month following initiation of treatment. The Li-ESWT protocol comprised 2 sessions per week for 3 weeks, which were repeated after a 3-week interval. Patients in the drug group took self-administered sildenafil at a dose of 100 mg before intercourse. The primary outcome was the effectiveness of Li-ESWT measured by the International Index of Erectile Function-5 (IIEF-5) scores. Other measurements included erection hardness score (EHS) and Self-Esteem And Relationship (SEAR).

Results: A total of 78 participants completed the study (46 in the Li-ESWT group and 32 in the sildenafil group). Overall, 26.9% of the participants (21/78) included were psychogenic. In the third month, the outcome measured by IIEF-5 was 21.52 in the Li-ESWT group and 21.26 in the sildenafil group (P>0.05). Proportion of improvement defined by minimal clinically important difference (MCID) criteria was 52.2% in the Li-ESWT group and 59.4% in the sildenafil group (P>0.05). The EHS and SEAR improvement was similar in the 2 groups (P>0.05 at baseline and third month). Transient and mild adverse events were observed in both groups.

Conclusions: In our study, a similar treatment efficacy and safety was shown by the application of Li-ESWT as on demand sildenafil.
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http://dx.doi.org/10.21037/tau-20-1069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947449PMC
February 2021

Tumor Growth and Spontaneous Metastasis Assays Using A549 Lung Cancer Cells.

Bio Protoc 2020 Apr 5;10(7):e3579. Epub 2020 Apr 5.

Markey Cancer Center, University of Kentucky, Lexington, 40536-0679, USA.

Metastasis accounts for the majority of cancer related deaths. The genetically engineered mouse (GEM) models and cell line-based subcutaneous and orthotopic mouse xenografts have been developed to study the metastatic process. By using lung cancer cell line A549 as an example, we present a modified protocol to establish the cell line-based xenograft. Our protocol ensures sufficient establishment of the mouse xenografts and allows us to monitor tumor growth and spontaneous metastasis. This protocol could be adapted to other types of established cancer cell lines or primary cancer cells to study the mechanism of metastatic process as well as to test the effect of the potential anti-cancer agents on tumor growth and metastatic capacity.
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http://dx.doi.org/10.21769/BioProtoc.3579DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7842773PMC
April 2020

Artificial Bioaugmentation of Biomacromolecules and Living Organisms for Biomedical Applications.

ACS Nano 2021 03 3;15(3):3900-3926. Epub 2021 Mar 3.

MOE International Joint Research Laboratory on Synthetic Biology and Medicines, School of Biology and Biological Engineering, South China University of Technology, Guangzhou 510006, China.

The synergistic union of nanomaterials with biomaterials has revolutionized synthetic chemistry, enabling the creation of nanomaterial-based biohybrids with distinct properties for biomedical applications. This class of materials has drawn significant scientific interest from the perspective of functional extension controllable coupling of synthetic and biomaterial components, resulting in enhancement of the chemical, physical, and biological properties of the obtained biohybrids. In this review, we highlight the forefront materials for the combination with biomacromolecules and living organisms and their advantageous properties as well as recent advances in the rational design and synthesis of artificial biohybrids. We further illustrate the incredible diversity of biomedical applications stemming from artificially bioaugmented characteristics of the nanomaterial-based biohybrids. Eventually, we aim to inspire scientists with the application horizons of the exciting field of synthetic augmented biohybrids.
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http://dx.doi.org/10.1021/acsnano.0c10144DOI Listing
March 2021

Oxygen content-related DNA damage of graphene oxide on human retinal pigment epithelium cells.

J Mater Sci Mater Med 2021 Feb 27;32(2):20. Epub 2021 Feb 27.

State Key Laboratory of Ophthalmology, Optometry and Visual Science, Institute of Advanced Materials for Nano-Bio Applications, School of Ophthalmology and Optometry, School of Biomedical Engineering, Wenzhou Medical University, Wenzhou, China.

Arguments regarding the biocompatibility of graphene-based materials (GBMs) have never ceased. Particularly, the genotoxicity (e.g., DNA damage) of GBMs has been considered the greatest risk to healthy cells. Detailed genotoxicity studies of GBMs are necessary and essential. Herein, we present our recent studies on the genotoxicity of most widely used GBMs such as graphene oxide (GO) and the chemically reduced graphene oxide (RGO) toward human retinal pigment epithelium (RPE) cells. The genotoxicity of GO and RGOs against ARPE-19 (a typical RPE cell line) cells was investigated using the alkaline comet assay, the expression level of phosphorylated p53 determined via Western blots, and the release level of reactive oxygen species (ROS). Our results suggested that both GO and RGOs induced ROS-dependent DNA damage. However, the DNA damage was enhanced following the reduction of the saturated C-O bonds in GO, suggesting that surface oxygen-containing groups played essential roles in the reduced genotoxicity of graphene and had the potential possibility to reduce the toxicity of GBMs via chemical modification.
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http://dx.doi.org/10.1007/s10856-021-06491-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914238PMC
February 2021

Structure and plasticity of silent synapses in developing hippocampal neurons visualized by super-resolution imaging.

Cell Discov 2020 Feb 25;6(1). Epub 2020 Feb 25.

Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, Anhui, 230027, China.

Excitatory synapses in the mammalian brain exhibit diverse functional properties in transmission and plasticity. Directly visualizing the structural correlates of such functional heterogeneity is often hindered by the diffraction-limited resolution of conventional optical imaging techniques. Here, we used super-resolution stochastic optical reconstruction microscopy (STORM) to resolve structurally distinct excitatory synapses formed on dendritic shafts and spines. The majority of these shaft synapses contained N-methyl-D-aspartate receptors (NMDARs) but not α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs), suggesting that they were functionally silent. During development, as more spine synapses formed with increasing sizes and expression of AMPARs and NMDARs, shaft synapses exhibited moderate reduction in density with largely unchanged sizes and receptor expression. Furthermore, upon glycine stimulation to induce chemical long-term potentiation (cLTP), the previously silent shaft synapses became functional shaft synapses by recruiting more AMPARs than did spine synapses. Thus, silent shaft synapse may represent a synaptic state in developing neurons with enhanced capacity of activity-dependent potentiation.
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http://dx.doi.org/10.1038/s41421-019-0139-1DOI Listing
February 2020

miR-21 inhibition reverses doxorubicin-resistance and inhibits PC3 human prostate cancer cells proliferation.

Andrologia 2021 Feb 17:e14016. Epub 2021 Feb 17.

Department of Urology Surgery, Central Hospital Affiliated to Shandong First Medical University, Jinan, Shandong Province, China.

Many approaches have been examined to reversing multidrug resistance (MDR), but sub-optimal target-based strategies have limited their efficacy. Herein, we investigate microRNA (miR-21) suppression on the doxorubicin (DOX)-sensitisation of the DOX-resistant (PC3/DOX) cell line in prostate cancer (PCa). Expression levels of miR-21, P-glycoprotein (P-gp), MDR-1 and PTEN evaluated in PC3/DOX cancer cells by qRT-PCR and western blot analyses. The cytotoxic effects of transfected of miR-21 were assessed by MTT assay for 72 hr. Rhodamine123 (Rh123) assay was employed to define the activity of P-gp. Apoptosis was detected by Flow cytometry. As expected, miR-21 was expressed highly in PC3/DOX cells (p < 0.05). It was shown that miRNA-21 suppression considerably hindered PC3/DOX cell viability. miR-21 suppression dramatically downregulated P-gp expression and activity in DOX-resistance cells and abolished MDR by an increment of intracellular accumulation of DOX in PC3/DOX cells (p < 0.05). PTEN is a key modulator of the PI3K/Akt/P-gp cascade, which miR-21 suppression led to the upregulation of PTEN and sequentially lower-expression of P-gp that reversed MDR. Also, miR-21 repression enhanced the apoptosis rate of PC3/DOX cells. The findings of this paper contribute to the current understanding of the functions of miR-21 in MDR-reversing in PCa.
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http://dx.doi.org/10.1111/and.14016DOI Listing
February 2021

Biocompatible nucleus-targeted graphene quantum dots for selective killing of cancer cells via DNA damage.

Commun Biol 2021 Feb 16;4(1):214. Epub 2021 Feb 16.

Australian Carbon Materials Centre (A-CMC), School of Chemical Engineering, University of New South Wales, Sydney, NSW, 2052, Australia.

Graphene quantum dots (GQDs) are nano-sized graphene slices. With their small size, lamellar and aromatic-ring structure, GQDs tend to enter into the cell nucleus and interfere with DNA activity. Thus, GQD alone is expected to be an anticancer reagent. Herein, we developed GQDs that suppress the growth of tumor by selectively damaging the DNA of cancer cells. The amine-functionalized GQDs were modified with nucleus targeting TAT peptides (TAT-NGs) and further grafted with cancer-cell-targeting folic acid (FA) modified PEG via disulfide linkage (FAPEG-TNGs). The resulting FAPEG-TNGs exhibited good biocompatibility, nucleus uptake, and cancer cell targeting. They adsorb on DNA via the π-π and electrostatic interactions, which induce the DNA damage, the upregulation of the cell apoptosis related proteins, and the suppression of cancer cell growth, ultimately. This work presents a rational design of GQDs that induce the DNA damage to realize high therapeutic performance, leading to a distinct chemotherapy strategy for targeted tumor therapy.
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http://dx.doi.org/10.1038/s42003-021-01713-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7886873PMC
February 2021

Calreticulin: a potential diagnostic and therapeutic biomarker in gallbladder cancer.

Aging (Albany NY) 2021 02 11;13(4):5607-5620. Epub 2021 Feb 11.

Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China.

Recent studies suggested that calreticulin (CRT) has an important role in the progression of various types of cancer. Our previous study suggested that CRT was upregulated and acted as an oncogene in hepatocellular carcinoma. However, the role of CRT in gallbladder cancer (GBC) remains unclear. The expression level of CRT was upregulated in GBC tissues in comparison with adjacent non-tumor tissues and chronic cholecystitis tissues. Moreover, CRT expression was found to be correlated with the tumor size. Knockdown of CRT inhibited cell proliferation, induced apoptosis, arrested cell cycle and resulted in decreased resistance to gemcitabine, which was mediated by the inactivation of the PI3K/Akt pathway. Collectively, the present results suggested a potential role of CRT in GBC progression and provided novel insights into the mechanism underlying the CRT-mediated chemosensitivity in GBC cells.
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http://dx.doi.org/10.18632/aging.202488DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7950265PMC
February 2021

A novel multiple instance learning framework for COVID-19 severity assessment via data augmentation and self-supervised learning.

Med Image Anal 2021 04 3;69:101978. Epub 2021 Feb 3.

Shanghai United Imaging Intelligence Co., Ltd., Shanghai, 201807, China; School of Biomedical Engineering, ShanghaiTech University, Shanghai, China; Department of Artificial Intelligence, Korea University, Seoul 02841, Republic of Korea. Electronic address:

How to fast and accurately assess the severity level of COVID-19 is an essential problem, when millions of people are suffering from the pandemic around the world. Currently, the chest CT is regarded as a popular and informative imaging tool for COVID-19 diagnosis. However, we observe that there are two issues - weak annotation and insufficient data that may obstruct automatic COVID-19 severity assessment with CT images. To address these challenges, we propose a novel three-component method, i.e., 1) a deep multiple instance learning component with instance-level attention to jointly classify the bag and also weigh the instances, 2) a bag-level data augmentation component to generate virtual bags by reorganizing high confidential instances, and 3) a self-supervised pretext component to aid the learning process. We have systematically evaluated our method on the CT images of 229 COVID-19 cases, including 50 severe and 179 non-severe cases. Our method could obtain an average accuracy of 95.8%, with 93.6% sensitivity and 96.4% specificity, which outperformed previous works.
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http://dx.doi.org/10.1016/j.media.2021.101978DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7857016PMC
April 2021

Engineering 3D genome organization.

Nat Rev Genet 2021 Feb 8. Epub 2021 Feb 8.

Department of Bioengineering, Stanford University, Stanford, CA, USA.

Cancers and developmental disorders are associated with alterations in the 3D genome architecture in space and time (the fourth dimension). Mammalian 3D genome organization is complex and dynamic and plays an essential role in regulating gene expression and cellular function. To study the causal relationship between genome function and its spatio-temporal organization in the nucleus, new technologies for engineering and manipulating the 3D organization of the genome have been developed. In particular, CRISPR-Cas technologies allow programmable manipulation at specific genomic loci, enabling unparalleled opportunities in this emerging field of 3D genome engineering. We review advances in mammalian 3D genome engineering with a focus on recent manipulative technologies using CRISPR-Cas and related technologies.
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http://dx.doi.org/10.1038/s41576-020-00325-5DOI Listing
February 2021

Post-transcriptional regulation is involved in the cold-active methanol-based methanogenic pathway of a psychrophilic methanogen.

Environ Microbiol 2021 Feb 4. Epub 2021 Feb 4.

State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China.

The methanol-derived methanogenetic pathway contributes to bulk methane production in cold regions, but the cold adaptation mechanisms are obscure. This work investigated the mechanisms using a psychrophilic methylotrophic methanogen Methanolobus psychrophilus R15. R15 possesses two mtaCB operon paralogues-encoding methanol:corrinoid methyltransferase that is key to methanol-based methanogenesis. Molecular combined methanogenic assays determined that MtaC1 is important in methanogenesis at the optimal temperature of 18°C, but MtaC2 can be a cold-adaptive paralogue by highly upregulated at 8°C. The 5'P-seq and 5'RACE all assayed that processing occurred at the 5' untranslated region (5'-UTR) of mtaC2; reporter genes detected higher protein expression, and RNA half-life experiments assayed prolonged lifespan of the processed transcript. Therefore, mtaC2 5'-UTR processing to move the bulged structure elevated both the translation efficiency and transcript stability. 5'P-seq, quantitative RT-PCR and northern blot all identified enhanced mtaC2 5'-UTR processing at 8°C, which could contribute to the upregulation of mtaC2 at cold. The R15 cell extract contains an endoribonuclease cleaving an identified 10 nt-processing motif and the native mtaC2 5'-UTR particularly folded at 8°C. Therefore, this study revealed a 5'-UTR processing mediated post-transcriptional regulation mechanism controlling the cold-adaptive methanol-supported methanogenetic pathway, which may be used by other methylotrophic methanogens.
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http://dx.doi.org/10.1111/1462-2920.15420DOI Listing
February 2021

Long-term results of concomitant atrioventricular valve intervention and the Fontan operation.

Eur J Cardiothorac Surg 2021 Feb 4. Epub 2021 Feb 4.

Pediatric Cardiac Surgery Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.

Objectives: The optimal timing for atrioventricular valve (AVV) repair in patients with a Fontan circulation remains controversial. Few studies have reported the long-term outcomes of AVV repair concomitant with a Fontan operation.

Methods: From January 2006 to December 2018, a total of 89 patients who developed moderate or severe AVV regurgitation before a Fontan operation were divided into 2 groups: group 1, including 37 patients who did not undergo concomitant AVV repair; and group 2, including 52 patients who received AVV repair concomitant with a Fontan operation.

Results: The mean age at the time of the Fontan operation was 6.74 years for group 1 and 8.96 years for group 2, respectively. Early death occurred in 3 patients [2 patients (5.4%) in group 2, patient 1 (1.9%) in group 1]. Freedom from long-term death, cardiac function reduction and protein-losing enteropathy were similar among the 2 groups. Common AVV function was apparently poorer than mitral valve function after repair [hazard ratio (HR) 3.83, 95% confidence interval (CI) 1.31-11.17; P = 0.014]. The occurrence of AVV valve failure in group 1 was lower than that in group 2 (HR 0.44, 95% CI 0.22-0.91; P = 0.026). AVV function became worse during the follow-up period than that at discharge in both groups (P = 0.03 in group 1 and P = 0.001 in group 2).

Conclusions: The long-term results of AVV repair concomitant with a Fontan operation are favourable.
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http://dx.doi.org/10.1093/ejcts/ezaa464DOI Listing
February 2021

Detecting High Frequency Oscillations for Stereoelectroencephalography in Epilepsy via Hypergraph Learning.

IEEE Trans Neural Syst Rehabil Eng 2021 8;29:587-596. Epub 2021 Mar 8.

Successful epilepsy surgeries depend highly on pre-operative localization of epileptogenic zones. Stereoelectroencephalography (SEEG) records interictal and ictal activities of the epilepsy in order to precisely find and localize epileptogenic zones in clinical practice. While it is difficult to find distinct ictal onset patterns generated the seizure onset zone from SEEG recordings in a confined region, high frequency oscillations are commonly considered as putative biomarkers for the identification of epileptogenic zones. Therefore, automatic and accurate detection of high frequency oscillations in SEEG signals is crucial for timely clinical evaluation. This work formulates the detection of high frequency oscillations as a signal segment classification problem and develops a hypergraph-based detector to automatically detect high frequency oscillations such that human experts can visually review SEEG signals. We evaluated our method on 4,000 signal segments from clinical SEEG recordings that contain both ictal and interictal data obtained from 19 patients who suffer from refractory focal epilepsy. The experimental results demonstrate the effectiveness of the proposed detector that can successfully localize interictal high frequency oscillations and outperforms multiple peer machine learning methods. In particular, the proposed detector achieved 90.7% in accuracy, 80.9% in sensitivity, and 96.9% in specificity.
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http://dx.doi.org/10.1109/TNSRE.2021.3056685DOI Listing
March 2021

A Spatial Ecological Study on Hair Selenium Level of Residents in Keshan Disease Endemic and Non-endemic Areas in Heilongjiang Province, China.

Biol Trace Elem Res 2021 Feb 3. Epub 2021 Feb 3.

Institute of Keshan Disease, Chinese Center for Endemic Disease Control, Harbin Medical University, 157 Baojian Road, Harbin, 150081, China.

This study was aimed to provide, by mapping the spatial distribution of hair selenium levels of residents, visualized evidence for assessment of KD elimination from a perspective of selenium nutrition of the residents living in the KD-endemic and non-endemic areas. Using a spatial ecological research design, 401 male permanent residents in KD-endemic and non-endemic areas participated in this study. Demographic information and hair samples were obtained through a questionnaire survey and sample collection, respectively. Hair selenium was measured using hydride generation atomic fluorescence spectrometry. Thematic maps were created, and spatial analysis was conducted using ArcGIS 9.0. The median of hair selenium of the participants was 0.30 (IQR, 0.23-0.34) mg/kg. The median hair selenium of the residents in the KD-endemic areas was significantly lower than that of the residents of the non-endemic areas. The hair selenium levels of residents were spatially clustered, with cold spots and hot spots located in northwest and southwest regions respectively. Residents living in KD-endemic areas may still have selenium deficiency. Measuring hair selenium levels of residents in KD-endemic areas as a molecular marker of selenium nutritional status as part of KD surveillance could provide visualized evidence for the evaluation of KD elimination from a perspective of selenium nutrition of the residents living in the KD endemic areas.
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http://dx.doi.org/10.1007/s12011-021-02609-1DOI Listing
February 2021

A new method for individual condylar osteotomy and repositioning guides used in patients with severe deformity secondary to condylar osteochondroma.

Orphanet J Rare Dis 2021 Jan 30;16(1):59. Epub 2021 Jan 30.

Department of Oral and Cranio-Maxillofacial Surgery, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China.

Background: Mandibular condylar osteochondroma (OC) could lead to facial morphologic and functional disturbances, such as facial asymmetry, malocclusion, and temporomandibular joint dysfunction. However, after condylar OC resection, the inaccurate reposition of the neocondyle still needs to be solved. The purpose of this study was to explore the feasibility of the condylar osteotomy and repositioning guide to reposition the neocondyle in the treatment of patients with severe deformity secondary to condylar OC.

Results: Three patients with severe deformity secondary to OC of the mandibular condyle were enrolled in this study. With the aid of condylar osteotomy and repositioning guide, condylar OC resection and repositioning were carried out, and the accuracy and stability of these guides were evaluated. All patients healed uneventfully, and no facial nerve injury and condylar ankylosis occurred. Compared with the computerized tomography scans in centric relation before surgery and 3 days after surgery, the results showed that the facial symmetry was greatly improved in all the patients. Also, after the superimposition of the condylar segments before surgery and 3 days after surgery, the postoperative reconstructed condyles had a high degree of similarity to the reconstruction of the virtual surgical planning. Observed from the sagittal and coronal directions, the measurements of condylar positions were very close to those of virtual surgical planning. Moreover, it also showed stable results after a 1-year follow-up.

Conclusions: For patients with severe deformity secondary to condylar OC, condylar osteotomy, and repositioning guide was expected to provide a new option for the improvement of facial symmetry and occlusal relationship.
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http://dx.doi.org/10.1186/s13023-021-01713-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7847561PMC
January 2021

Optimizing Surface Chemistry of PbS Colloidal Quantum Dot for Highly Efficient and Stable Solar Cells via Chemical Binding.

Adv Sci (Weinh) 2021 Jan 27;8(2):2003138. Epub 2020 Nov 27.

School of Engineering Macquarie University Sustainable Energy Research Centre Macquarie University Sydney NSW 2109 Australia.

The surface chemistry of colloidal quantum dots (CQD) play a crucial role in fabricating highly efficient and stable solar cells. However, as-synthesized PbS CQDs are significantly off-stoichiometric and contain inhomogeneously distributed S and Pb atoms at the surface, which results in undercharged Pb atoms, dangling bonds of S atoms and uncapped sites, thus causing surface trap states. Moreover, conventional ligand exchange processes cannot efficiently eliminate these undesired atom configurations and defect sites. Here, potassium triiodide (KI) additives are combined with conventional PbX matrix ligands to simultaneously eliminate the undercharged Pb species and dangling S sites via reacting with molecular I generated from the reversible reaction KI ⇌ I + KI. Meanwhile, high surface coverage shells on PbS CQDs are built via PbX and KI ligands. The implementation of KI additives remarkably suppresses the surface trap states and enhances the device stability due to the surface chemistry optimization. The resultant solar cells achieve the best power convention efficiency of 12.1% and retain 94% of its initial efficiency under 20 h continuous operation in air, while the control devices with KI additive deliver an efficiency of 11.0% and retains 87% of their initial efficiency under the same conditions.
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http://dx.doi.org/10.1002/advs.202003138DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7816699PMC
January 2021

Doubly committed subarterial ventricular septal defect closure through tricuspid approach: a clinical analysis.

Cardiol Young 2021 Jan 28:1-5. Epub 2021 Jan 28.

Department of Pediatric Center, Fuwai Hospital, Beijing, People's Republic of China.

Background: The research was to introduce the experience of doubly committed subarterial ventricular septal defect (DCVSD) repaired through tricuspid approach.

Methods: From January, 2015 to September, 2019, 86 consecutive DCVSD paediatrics underwent repair via right subaxillary vertical incision (RAVI) through tricuspid approach. Perioperative and follow-up data were collected.

Results: The age and weight at operation were 28.1 ± 18.5 (range: 7-101) months and 12.2 ± 4.2 (6-26.5) kg. There were two patients combined with discrete subaortic membrane, two patients with patent ductus arteriosus, one patient with atrial septal defect, and two patients with abnormal muscle bundle in right ventricular outflow tract. The mean size of ventricular septal defect was 7.0 ± 2.4 (3-13) mm. The defect was repaired with a piece of Dacron patch in 68 patients or directly with 1-2 pledgetted polypropylene sutures in 18 patients. The cardiopulmonary bypass time and aortic cross-clamp time were 46.2 ± 13.3 (23-101) minutes and 29.2 ± 11.5 (12-84) minutes. After 3.1 ± 2.4 (0-14) hours' ventilator assist and 23.2 ± 32.1 (0-264) hours' ICU stay, all patients were discharged safely. At the latest follow-up (27.9 ± 14.6 months), echocardiography showed trivial residual shunt in two patients. There was no malignant arrhythmia occurred and there was no chest deformity or asymmetrical development of the breast was found.

Conclusions: DCVSD repaired via right subaxillary vertical incision through tricuspid approach was safe and feasible, providing a feasible alternative to median sternotomy, and it can be performed with favourable cosmetic results.
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http://dx.doi.org/10.1017/S1047951120004643DOI Listing
January 2021

Flexible and efficient perovskite quantum dot solar cells via hybrid interfacial architecture.

Nat Commun 2021 Jan 20;12(1):466. Epub 2021 Jan 20.

School of Materials Science and Engineering, University of New South Wales (UNSW), Sydney, NSW, 2052, Australia.

All-inorganic CsPbI perovskite quantum dots have received substantial research interest for photovoltaic applications because of higher efficiency compared to solar cells using other quantum dots materials and the various exciting properties that perovskites have to offer. These quantum dot devices also exhibit good mechanical stability amongst various thin-film photovoltaic technologies. We demonstrate higher mechanical endurance of quantum dot films compared to bulk thin film and highlight the importance of further research on high-performance and flexible optoelectronic devices using nanoscale grains as an advantage. Specifically, we develop a hybrid interfacial architecture consisting of CsPbI quantum dot/PCBM heterojunction, enabling an energy cascade for efficient charge transfer and mechanical adhesion. The champion CsPbI quantum dot solar cell has an efficiency of 15.1% (stabilized power output of 14.61%), which is among the highest report to date. Building on this strategy, we further demonstrate a highest efficiency of 12.3% in flexible quantum dot photovoltaics.
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http://dx.doi.org/10.1038/s41467-020-20749-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817685PMC
January 2021

Origin, Regulation, and Fitness Effect of Chromosomal Rearrangements in the Yeast .

Int J Mol Sci 2021 Jan 14;22(2). Epub 2021 Jan 14.

Ocean College, Zhejiang University, Zhoushan 316021, China.

Chromosomal rearrangements comprise unbalanced structural variations resulting in gain or loss of DNA copy numbers, as well as balanced events including translocation and inversion that are copy number neutral, both of which contribute to phenotypic evolution in organisms. The exquisite genetic assay and gene editing tools available for the model organism facilitate deep exploration of the mechanisms underlying chromosomal rearrangements. We discuss here the pathways and influential factors of chromosomal rearrangements in . Several methods have been developed to generate on-demand chromosomal rearrangements and map the breakpoints of rearrangement events. Finally, we highlight the contributions of chromosomal rearrangements to drive phenotypic evolution in various strains. Given the evolutionary conservation of DNA replication and recombination in organisms, the knowledge gathered in the small genome of yeast can be extended to the genomes of higher eukaryotes.
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http://dx.doi.org/10.3390/ijms22020786DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7830279PMC
January 2021

Expression of MiR-608 in Nonsmall Cell Lung Cancer and Molecular Mechanism of Apoptosis and Migration of A549 Cells.

Biomed Res Int 2020 22;2020:8824519. Epub 2020 Dec 22.

Department of Thoracic Surgery, Laboratory of Basic Medical Sciences, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, China.

Objective: This Work is aimed at exploring the effect of microRNA (MiR)-608 on the function of nonsmall cell lung cancer (NSCLC) A549 cells and related mechanisms.

Methods: Blood samples of 106 NSCLC patients (experimental group) as well as 124 normal people (control group) were selected for relevant investigation. Polymerase chain reaction (PCR) as well as DNA sequencing was used to determine the genotyping of the MiR-608 rs4919510 polymorphism. MiR-608 expression in cells was detected by real-time PCR technology. Western blotting was used to detect changes in protein levels. NSCLC tissues as well as adjacent tissues were explored in 33 patients undergoing surgery.

Results: MiR-608 rs4919510 does not influence the incidence of NSCLC patients. In addition, MiR-608 expression was downregulated in the tumor tissue of NSCLC patients, while the transcription factor activating enhancer-binding protein 4 (TFAP4) expression was upregulated. MiR-608 promotes DOX- (Doxorubicin-) induced apoptosis by negatively regulating TFAP4 expression in NSCLC tissue. TFAP4 can significantly inhibit the migration of A549 cells.

Conclusion: The findings in this investigation can contribute to the effective treatment of NSCLC patients. Also, the investigation can provide some theoretical support for the application of new targets for NSCLC treatment.
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http://dx.doi.org/10.1155/2020/8824519DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7773458PMC
December 2020

CRISPR technologies for precise epigenome editing.

Nat Cell Biol 2021 01 8;23(1):11-22. Epub 2021 Jan 8.

Department of Bioengineering, Stanford University, Stanford, CA, USA.

The epigenome involves a complex set of cellular processes governing genomic activity. Dissecting this complexity necessitates the development of tools capable of specifically manipulating these processes. The repurposing of prokaryotic CRISPR systems has allowed for the development of diverse technologies for epigenome engineering. Here, we review the state of currently achievable epigenetic manipulations along with corresponding applications. With future optimization, CRISPR-based epigenomic editing stands as a set of powerful tools for understanding and controlling biological function.
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http://dx.doi.org/10.1038/s41556-020-00620-7DOI Listing
January 2021

Regenerating Urethral Striated Muscle by CRISPRi/dCas9-KRAB-Mediated Myostatin Silencing for Obesity-Associated Stress Urinary Incontinence.

CRISPR J 2020 12;3(6):562-572

Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California, San Francisco, California, USA; Department of Chemical and Systems Biology, ChEM-H, Stanford University, Stanford, California, USA.

Overweight females are prone to obesity-associated stress urinary incontinence (OA-SUI), and there are no definitive medical therapies for this common urologic condition. This study was designed to test the hypothesis that regenerative therapy to restore urethral striated muscle (stM) and pelvic floor muscles might represent a valuable therapeutic approach. For the experiment, single-guide RNAs targeting myostatin () were used for CRISPRi/dCas9-Kruppel associated box (KRAB)-mediated gene silencing. For the experiment, a total of 14 female lean ZUC-Lepr 186 and 14 fatty ZUC-Lepr 185 rats were used as control and CRISPRi-MSTN treated groups, respectively. The results indicated that lentivirus-mediated expression of MSTN CRISPRi/dCas9-KRAB caused sustained downregulation of MSTN in rat L6 myoblast cells and significantly enhanced myogenesis . , the urethral sphincter injection of lentiviral-MSTN sgRNA and lentiviral-dCas9-KRAB significantly increased the leak point pressure, the thickness of the stM layer, the ratio of stM to smooth muscle, and the number of neuromuscular junctions. Downregulation of with CRISPRi/dCas9-KRAB-mediated gene silencing significantly enhanced myogenesis and It also improved urethral continence in the OA-SUI rat model.
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http://dx.doi.org/10.1089/crispr.2020.0077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7757699PMC
December 2020