Publications by authors named "Qiang Liu"

2,323 Publications

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Anionic Polysaccharide-Modified Filter Papers for Rapid Isolation of Extracellular Vesicles from Diverse Samples in a Simple Bind-Wash-Elute Manner.

Anal Chem 2021 May 11. Epub 2021 May 11.

Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing 100084, China.

Extracellular vesicles (EVs) play a significant role in the pathophysiological process of many diseases, highlighting their values in medical diagnosis and disease monitoring. However, the current EV isolation methods are time-consuming, inconvenient to operate, and incompatible with downstream analyses. Here, we present a novel isolation method employing anionic polysaccharide-modified filter papers for the isolation of EVs (AppiEV) via electrostatic adsorption. A disc of glass fiber-based filter modified with sodium alginate was assembled into a spin column to function as the solid capture phase. In the acidic condition, EVs were induced to carry more positively charged ions, which enable the capture of EVs by the negatively charged filter paper. After a wash, the EVs were released from the spin column using an alkaline elution buffer, which induces the EVs to carry more negative charges. The EVs isolated by AppiEV from cell culture supernatants, plasma, and urine are similar to or even better than those isolated by ultracentrifugation in terms of EV size distribution, protein distribution, and nucleic acid contents. Due to the interference removal of the EV-free RNA and DNA attributed to the negatively charged capture medium, the eluate of AppiEV could be directly used for genetic analysis, including the stem-loop RT-PCR analysis of miR-21 and the allele-specific PCR analysis of mutation genes of p.L858R and p.T790M. We believe that AppiEV offers a simple and efficient approach for the isolation of high-quality EVs from various liquid specimens.
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http://dx.doi.org/10.1021/acs.analchem.0c02107DOI Listing
May 2021

[Identification techniques of small molecule drug target proteins without chemical modification and its applications: a review].

Authors:
Jie Ma Qiang Liu

Sheng Wu Gong Cheng Xue Bao 2021 Apr;37(4):1131-1138

Department of Histoembryology, Genetics and Developmental Biology, Basic Medical College, Shanghai Key Laboratory of Reproductive Medicine, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.

Identification of the target proteins of small molecule drugs is crucial for understanding the mechanisms of drug actions and its side effects. Conventional methods require chemical modification, which might alter the activities of the drugs. Various label-free techniques have been developed to identify drug target proteins without chemical modifications. This includes drug affinity responsive target stability (DARTS), stability of proteins from rates of oxidation (SPROX), cellular thermal shift assay (CETSA), thermal proteome profiling (TPP) and many others. Here we review the principles and applications of these label-free techniques, their advantages and limitations, as well as the most recent advances.
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http://dx.doi.org/10.13345/j.cjb.200426DOI Listing
April 2021

Lung cancer organoids analyzed on microwell arrays predict drug responses of patients within a week.

Nat Commun 2021 May 10;12(1):2581. Epub 2021 May 10.

Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing, China.

While the potential of patient-derived organoids (PDOs) to predict patients' responses to anti-cancer treatments has been well recognized, the lengthy time and the low efficiency in establishing PDOs hamper the implementation of PDO-based drug sensitivity tests in clinics. We first adapt a mechanical sample processing method to generate lung cancer organoids (LCOs) from surgically resected and biopsy tumor tissues. The LCOs recapitulate the histological and genetic features of the parental tumors and have the potential to expand indefinitely. By employing an integrated superhydrophobic microwell array chip (InSMAR-chip), we demonstrate hundreds of LCOs, a number that can be generated from most of the samples at passage 0, are sufficient to produce clinically meaningful drug responses within a week. The results prove our one-week drug tests are in good agreement with patient-derived xenografts, genetic mutations of tumors, and clinical outcomes. The LCO model coupled with the microwell device provides a technically feasible means for predicting patient-specific drug responses in clinical settings.
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http://dx.doi.org/10.1038/s41467-021-22676-1DOI Listing
May 2021

Recent Injury, Severe Radiographic Change and Lower Quadriceps Strength Increase Risk of Knee Pain Exacerbation During Walking: A Within-Person Knee-Matched Study.

J Orthop Sports Phys Ther 2021 May 10:1-28. Epub 2021 May 10.

Division of Rheumatology, Allergy, and Immunology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA.

Objective: To examine the association of knee injury, radiographic osteoarthritis severity and quadriceps strength with knee pain exacerbation during walking.

Design: Within-person knee-matched case-control study.

Methods: Participants from the Osteoarthritis Initiative who completed a 20-meter walking test at the 24-month visit were included. Pain exacerbation was defined as a pain intensity increase of ≥1 on a numeric rating scale (0=no pain, 10=worst imaginable pain) while completing the 20-meter walking test. We used conditional logistic regression to assess relation of recent knee injury, Kellgren and Lawrence (KL) grade and quadriceps strength to unilateral knee pain exacerbation during walking.

Results: We included 277 people who experienced unilateral knee pain exacerbation during the walking test. Recent knee injury was associated with pain exacerbation during walking with an odds ratio (OR) of 3.4 (95% confidence interval (CI):1.3, 9.2). Compared with knees with KL grade 0, the ORs (95% CI) of pain exacerbation during walking were 1.3 (0.7, 2.7), 3.3 (1.5, 7.1), and 8.1 (3.1, 21.1) for knees with KL grade 2, grade 3 and grade 4, respectively. Knees with ≥4% lower quadriceps strength had a 1.4-fold (95% CI: 1.0, 1.9) higher risk of pain exacerbation during walking than their counterparts.

Conclusion: Recent knee injury, more severe radiographic osteoarthritis and lower quadriceps strength were associated with an increased risk of knee pain exacerbation during walking. .
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http://dx.doi.org/10.2519/jospt.2021.9735DOI Listing
May 2021

Heterostructures between a tin-based intermetallic compound and a layered semiconductor for gas sensing.

Chem Commun (Camb) 2021 May 10. Epub 2021 May 10.

Institute of Advanced Materials (IAM), Nanjing Tech University (NanjingTech), 30 South Puzhu Road, Nanjing, 211816, China. and Frontiers Science Center for Flexible Electronics (FSCFE) & Shaanxi Institute of Flexible Electronics (SIFE), Northwestern Polytechnical University (NPU), 127 West Youyi Road, Xi'an 710072, China.

SnS2 nanoplates are used as sacrificial templates to facilitate the in situ growth of intermetallic compound Pt3Sn nanoparticles. The Pt3Sn/SnS2 heterostructures show promise for selective NO2 sensing due to the favored gas adsorption and gas-solid charge transfer on Pt3Sn, combined with the optimized film conductance and formation of ohmic-type Pt3Sn/SnS2 heterointerfaces.
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http://dx.doi.org/10.1039/d1cc00015bDOI Listing
May 2021

Screening of tumor grade-related mRNAs and lncRNAs for Esophagus Squamous Cell Carcinoma.

J Clin Lab Anal 2021 May 7:e23797. Epub 2021 May 7.

Department of Radiotherapy, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.

Background: The goal of our study was to screen tumor grade-related lncRNAs and mRNAs to reveal the underlying molecular mechanism of esophagus squamous cell carcinoma (ESCC).

Methods: The lncRNA and mRNA sequencing data were obtained from The Cancer Genome Atlas (TCGA). Tumor grade correlation analysis of lncRNAs and mRNAs was executed, followed by the functional enrichment analysis of all tumor grade-related mRNAs. The differentially expression mRNAs (DEmRNAs) and differentially expressed lncRNAs (DElncRNAs) were obtained. PPI network and DEmRNA-DElncRNA interaction analysis were constructed. The functional annotation of the DEmRNAs co-expressed with DElncRNAs was performed. The expression levels of the candidate genes were validated using qRT-PCR.

Results: A total of 1864 tumor grade-related mRNAs (846 positively related and 1018 negatively related) and 552 tumor grade-related lncRNAs (331 positively related and 221 negatively related) were obtained. The top 10 significantly grade-related mRNAs and lncRNAs included CA12, FABP4, DECR1, BAIAP2, IL1RAPL2, PPARD, LAD1, TSPAN10, LDOC1, ZNF853, RP11-25G10.2, RP11-557H15.3, RP11-521D12.5, CHKB-AS1, RP11-219B4.3, CH17-335B8.4, RP11-99 J16-A.2, CTB-111H14.1, ADNP-AS1, and JHDM1D-AS1. SFN, IL1RAPL2, and RP11-25G10.2 were overlapped from grade 1, grade 2, and grade 3. PPI network showed that top 10 proteins with higher degrees, including GNAI1, RAP2B, GNAZ, SHH, ADCY1, PRKAR2B, SH3GL1, GNA15, and ARRB1. A DElncRNAs-nearby DEmRNAs network was constructed to obtain hub lncRNAs including ADAMTS9-AS2, RP11-210 M15.2, RP11-13 K12.1, ZBED3-AS1, and RP11-25G10.2. Except for RP11-25G10.2, ADAMTS9-AS1, ZBED3-AS1, SFN, ATP1A2, and GNA15 were consistent with our TCGA analysis.

Conclusions: Alterations of DEmRNAs and DElncRNAs may provide key insights into the molecular mechanisms of ESCC.
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http://dx.doi.org/10.1002/jcla.23797DOI Listing
May 2021

Role of the ionic environment in enhancing the activity of reacting molecules in zeolite pores.

Science 2021 May 6. Epub 2021 May 6.

Department of Chemistry and Catalysis Research Center, Technical University of Munich, Lichtenbergstrasse 4, 85747 Garching, Germany.

Tailoring the molecular environment around catalytically active site allows to enhance catalytic reactivity via a hitherto unexplored pathway. In zeolites, the presence of water creates an ionic environment via formation of hydrated hydronium ions and the negatively charged framework Al tetrahedra. The high density of cation-anion pairs determined by the aluminum concentration of a zeolite induces a high local ionic strength that increases the excess chemical potential of sorbed and uncharged organic reactants. Charged transition states (carbocations for example) are stabilized, reducing the energy barrier and leading to higher reaction rates. Using the intramolecular dehydration of cyclohexanol on H-MFI in water, we show quantitatively the enhancement of the reaction rate by the presence of high ionic strength as well as potential limitations of this strategy.
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http://dx.doi.org/10.1126/science.abh3418DOI Listing
May 2021

Modeling and Dual Threshold Algorithm for Diffusion-based Molecular MIMO Communications.

IEEE Trans Nanobioscience 2021 May 4;PP. Epub 2021 May 4.

Molecular communication, as an emerging research direction, has emerged in the field of communication, which usually combined with nanotechnology and bio-related knowledge. In the direction of communication channel research, the most widespread model for a molecular communication channel is the diffusion-based channel, where the information-carrying molecules propagate randomly in the medium based on Brownian motion. Multi-input multi-output (MIMO) technology is often used to improve communication quality in the traditional communication field. Compared with the SISO model, which only has inter-symbol interference (ISI) as the interference source, the interference in MIMO communication model includes ISI as well as inter-link interference (ILI), which emerges when receiver receive other transmitters' molecules. In this paper, MIMO communication models are built, based on diffusion channel, CSK, probabilistic theory, considered with ISI and ILI, to establish the calculation formula of related bit error rate, And the influence of relevant parameters in the model on bit error rate is studied. Then, SISO and SIMO models will be built to compare with MIMO models. Last, self-adaptive dual threshold algorithm is proposed to reduce BER of the 2×2 MIMO system. Simulation results show that the proposed algorithm has better performance on reducing BER than other approaches.
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http://dx.doi.org/10.1109/TNB.2021.3077297DOI Listing
May 2021

Anatomic study of carpal tunnel in adults using monoenergetic reconstruction of dual-energy computed tomography.

J Pak Med Assoc 2021 Feb;71(2(B)):663-671

Department of Radiology, Shengjing Hospital of China Medical University, Heping, Shenyang, China.

Objective: To seek optimal keV settings for imaging carpal tunnel in adults by dual-energy computed tomography (DECT) monoenergetic technique; to describe anatomic characteristics of carpal tunnel and to observe correlation between carpal bony and soft tissue structures.

Methods: DECT images of 20 wrists (11 left and 9 right wrists; 14 men, mean age 26.93±1.38 years, range 23 to 28, and 6 women, mean age 24.17 ± 0.98 years, range 23 to 26) were evaluated. Monoenergetic images were reconstructed at 42, 62, 82, 102, 122, and 142 keV. Image quality was assessed along a 5-point Likert scale, and the highest-quality images were chosen for quantitative analysis. Two musculoskeletal radiologists performed both analyses independently.

Results: The optimal energy spectrum with the best contrast-to-noise ratio (CNR) for monoenergetic images were at 62 keV (19 wrists, 95%) and 61 keV (1 wrist, 5%). There was substantial interobserver agreement between the readers in the 5-point Likert scale analysis of image quality (k= 0.793). Bland-Altman plots also indicated good agreement between observers in quantitative analysis. Intra-category 1 and 2 correlation was mostly discovered at hamate hook level and middle level of pisiform (P < 0.05), while bony and soft tissue structures partly reached correlation (P < 0.05).

Conclusions: The optimal energy spectrum for monoenergetic DECT imaging of carpal tunnel structures was 62 keV. DECT monoenergetic imaging could predict changes in soft tissue structures and demonstrate carpal tunnel anatomic structures.
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http://dx.doi.org/10.47391/JPMA.1203DOI Listing
February 2021

cIAP1/2 are involved in the radiosensitizing effect of birinapant on NSCLC cell line in vitro.

J Cell Mol Med 2021 May 3. Epub 2021 May 3.

Institute of Radiation Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.

Tumour radioresistance is a major problem for cancer radiation therapy. To identify the underlying mechanisms of this resistance, we used human non-small cell lung cancer (NSCLC) cell lines and focused on the Inhibitor of Apoptosis Protein (IAP) family, which contributes to tumourigenesis and chemoresistance. We investigated the possible correlation between radioresistance in six NSCLC cell lines and IAP protein levels and tested the radiosensitizing effect of birinapant in vitro, a molecule that mimics the second mitochondria-derived activator of caspase. We found that birinapant-induced apoptosis and inhibited the proliferation of NSCLC cells after exposure to radiation. These effects were induced by birinapant downregulation of cIAP protein levels and changes of cIAP gene expression. Overall, birinapant can inhibit tumour growth of NSCLC cell lines to ironizing radiation and act as a promising strategy to overcome radioresistance in NSCLC.
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http://dx.doi.org/10.1111/jcmm.16526DOI Listing
May 2021

miR-376a Provokes Rectum Adenocarcinoma CTC1 Depletion-Induced Telomere Dysfunction.

Front Cell Dev Biol 2021 16;9:649328. Epub 2021 Apr 16.

Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences, Peking Union Medical College, Tianjin, China.

CTC1 is a component of the mammalian CST (CTC1-STN1-TEN1) complex which plays essential roles in resolving replication problems to facilitate telomeric DNA and genomic DNA replication. We previously reported that the depletion of CTC1 leads to stalled replication fork restart defects. Moreover, the mutation in CTC1 caused cancer-prone diseases including Coats plus (CP) or dyskeratosis congenita (DC). To better understand the CTC1 regulatory axis, the microRNAs (miRNAs) targeting to CTC1 were predicted by a bioinformatics tool, and the selected candidates were further confirmed by a dual-luciferase reporter assay. Here, our current results revealed that miR-376a significantly reduced CTC1 expression at the transcription level by recognizing CTC1 3'-UTR. In addition, the overexpression of miR-376a induced telomere replication defection and resulted in direct replicative telomere damage, which could be rescued by adding back CTC1. Telomere shortening was also observed upon miR-376a treatment. Furthermore, for the clinical patient samples, the high expression of miR-376a was associated with the deregulation of CTC1 and a poor outcome for the rectum adenocarcinoma patients. Together, our results uncovered a novel role of miR-376a in stimulating rectum adenocarcinoma progression CTC1 downregulating induced telomere dysfunction.
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http://dx.doi.org/10.3389/fcell.2021.649328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085492PMC
April 2021

Specimen number based diagnostic yields of suspicious axillary lymph nodes in core biopsy in breast cancer: clinical implications from a prospective exploratory study.

Quant Imaging Med Surg 2021 May;11(5):2151-2161

Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.

Background: Ultrasound (US)-guided core needle biopsy (CNB) is widely applied in the pathological diagnosis of suspicious axillary lymph nodes (ALNs) in breast cancer. However, the number of specimens removed during biopsy is currently based on the preference of the individual radiologist. This study aims to analyze the specimen number based diagnostic yields of US guided CNB of suspicious ALNs in breast cancer.

Methods: Core biopsy specimens of suspicious lymph nodes were prospectively obtained from breast cancer patients treated at our hospital between November, 2018, and July, 2019. Four specimens were obtained from each patient and labeled 1-4 in the order they were removed. Each specimen underwent pathological evaluation to determine whether metastasis had occurred. The diagnostic yields of the specimens were calculated and differences in diagnostic accuracy according to the number of specimens were evaluated by McNemar's test.

Results: A total of 167 patients were enrolled, and 139 (83.2%) cases were identified as metastasis by CNB. The diagnostic yields were: 74.2% (specimen 1), 87.8% (specimens 1-2), 91.2% (specimens 1-3), and 94.6% (specimens 1-4). The increases in diagnostic yield from specimen 1 to 1-2 and from specimens 1-2 to 1-4 were significant; however, no significant differences were detected between specimens 1-3 and the first two, or between specimens 1-4 and the first three in this sample size. The lower diagnostic abilities for the first two specimens were associated with shorter long- and short-axis lengths of lymph nodes on US.

Conclusions: Although the second specimen contributed significant diagnostic yield of suspicious axillary lymph nodes in core biopsy in breast cancer, a minimum number cannot be determined by this study. Additional specimens may improve diagnostic yield particularly in patients with small nodes.
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http://dx.doi.org/10.21037/qims-20-1030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8047355PMC
May 2021

Postoperative bisphosphonate do not significantly alter the fusion rate after lumbar spinal fusion: a meta-analysis.

J Orthop Surg Res 2021 Apr 29;16(1):284. Epub 2021 Apr 29.

Shanxi Bethune Hospital, Shanxi Academy of Medical Science, No. 99, Longcheng Street, Taiyuan, 030032, Shanxi Province, China.

Background: To evaluate the effect of postoperative BP treatment on improving the fusion rate after lumbar spinal fusion surgery by performing a meta-analysis of randomized controlled trials (RCTs) and other comparative cohort studies.

Methods: A comprehensive search of PubMed, EMBASE, the Web of Science, and the Cochrane Central Register of Controlled Trials was performed for RCTs and other comparative cohort studies on the effect of BP treatment on improving the fusion rate after lumbar spinal fusion surgery. The primary outcome measures were the number of patients with bone formation grades A, B, and C at 12 months of follow-up; fusion rates at 12 and 24 months of follow-up; vertebral compression fracture (VCF) at 12 and 24 months of follow-up; pedicle screw loosening at 24 months of follow-up; and cage subsidence, the Oswestry disability index (ODI), and the visual analogue score (VAS) at 12 months of follow-up. The final search was performed in July 2020.

Results: Seven studies with 401 patients were included. Compared with the placebo, BP treatment did not significantly alter the number of patients with bone formation grades A, B, and C, or the VAS at the 12-month follow-up or the fusion rates at the 12- and 24-month follow-ups. In addition, compared with the placebo, BPs significantly reduced the risks of VCF at the 12- and 24-month follow-ups, pedicle screw loosening at the 24-month follow-up, and cage subsidence and the ODI at the 12-month follow-up.

Conclusions: Postoperative BPs do not clearly improve bone formation and the fusion rate, but they reduce VCF, cage subsidence, and loosening of pedicle screws after lumbar fusion surgery compared with the control treatment.
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http://dx.doi.org/10.1186/s13018-021-02444-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082634PMC
April 2021

Impact of Fertilizer on Crop Yield and C:N:P Stoichiometry in Arid and Semi-Arid Soil.

Int J Environ Res Public Health 2021 Apr 20;18(8). Epub 2021 Apr 20.

State Key Laboratory of Soil Erosion and Dryland Farming on Loess Plateau, Institute of Soil and Water Conservation, Chinese Academy of Sciences and Ministry of Water Resources, Yangling 712100, China.

Fertilization can significantly affect the quality of crop and soil. To determine the effects of long-term fertilization on crop yield and carbon:nitrogen:phosphorus (C:N:P) stoichiometry in soil, a study was conducted on the terraced fields of the Loess Plateau from 2007 to 2019. Nine fertilization treatments were included: no fertilizer; organic fertilizer (O); organic and nitrogen fertilizers (ON); organic, nitrogen, and phosphorus fertilizers (ONP); organic and phosphorus fertilizers (OP); phosphorus and nitrogen fertilizers; potash and nitrogen fertilizers; potash, nitrogen, and phosphorus fertilizers; and potash and phosphorus fertilizers. Under these treatments except for CK and PK, crop yields initially decreased but later increased. The nutrient content and C:N:P stoichiometry increased in soil depth of 0-20 cm. The soil available nutrients did not change significantly with the duration of fertilization. The O, ON, ONP, and OP had the most evident effect on the enhancement of soil nutrient content, whereas O and ON had the most evident effect on the increase in soil organic carbon (SOC):total phosphorus (TP) and total nitrogen (TN):TP. In soil depth of 0-20 cm, crop yield, SOC:TN, SOC:TN, SOC:TP, and TN:TP significantly correlated with soil nutrients. This study indicated that long-term fertilization can effectively improve crop yield, soil fertility, and soil C:N:P stoichiometry. Meanwhile, the single application of an organic fertilizer or the combination of organic and nitrogen fertilizers can improve the condition of nitrogen limitation in arid and semi-arid areas.
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http://dx.doi.org/10.3390/ijerph18084341DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8072689PMC
April 2021

Rapid exploration of the epitope coverage produced by an Ebola survivor to guide the discovery of therapeutic antibody cocktails.

Antib Ther 2020 Jul 1;3(3):167-178. Epub 2020 Aug 1.

ImmunoPrecise Antibodies Ltd., Fargo, ND 58104, USA.

Background: Development of successful neutralizing antibodies is dependent upon broad epitope coverage to increase the likelihood of achieving therapeutic function. Recent advances in synthetic biology have allowed us to conduct an epitope binning study on a large panel of antibodies identified to bind to Ebola virus glycoprotein with only published sequences.

Methods And Results: A rapid, first-pass epitope binning experiment revealed seven distinct epitope families that overlapped with known structural epitopes from the literature. A focused set of antibodies was selected from representative clones per bin to guide a second-pass binning that revealed previously unassigned epitopes, confirmed epitopes known to be associated with neutralizing antibodies, and demonstrated asymmetric blocking of EBOV GP from allosteric effectors reported from literature.

Conclusions: Critically, this workflow allows us to probe the epitope landscape of EBOV GP without any prior structural knowledge of the antigen or structural benchmark clones. Incorporating epitope binning on hundreds of antibodies during early stage antibody characterization ensures access to a library's full epitope coverage, aids in the identification of high quality reagents within the library that recapitulate this diversity for use in other studies, and ultimately enables the rational development of therapeutic cocktails that take advantage of multiple mechanisms of action such as cooperative synergistic effects to enhance neutralization function and minimize the risk of mutagenic escape. The use of high-throughput epitope binning during new outbreaks such as the current COVID-19 pandemic is particularly useful in accelerating timelines due to the large amount of information gained in a single experiment.
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http://dx.doi.org/10.1093/abt/tbaa016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7454256PMC
July 2020

Characteristics of TCM Constitution and Related Biomarkers for Mild Cognitive Impairment.

Neuropsychiatr Dis Treat 2021 20;17:1115-1124. Epub 2021 Apr 20.

Department of Acupuncture and Moxibustion, The First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning, 530023, People's Republic of China.

Introduction: The incidence of Alzheimer's disease is on the rise, early detection of cognitive impairment of the elderly is very important. In traditional Chinese medicine, constitution is related to the susceptibility of the human body to diseases. Based on the theory of constitution of traditional Chinese medicine (TCM), the human population can be classified into 9 constitutions. However, little is known about the characteristics of medical constitution and related biomarkers in subjects with mild cognitive impairment (MCI).

Methods: We measured the TCM Constitution of 214 subjects by using the Constitution in Chinese Medicine Questionnaire (CCMQ). MMSE and MoCA were used to assess cognitive function. The subjects were divided into mild cognitive impairment group (MCI, n = 152) and normal control group (NC, n = 62). The levels of serum Hcy and serum/urine 8-iso-PGF 2α were determined.

Results: 1) It was found that there was a significant difference in constitution types between MCI and NC. There were significant differences in MMSE and MoCA score, serum Hcy and serum/urine 8-iso-PGF 2a levels between the two groups. 2) In logistic regression analysis, the variables with statistical significance were TCM Constitution of Yang-Deficient, Phlegm-Dampness, Blood-Stasis and abnormal increase of Hcy (OR>1). 3) The MoCA scores had a positive correlation with the MMSE. A statistically significant inverse association was found between serum Hcy, blood and urine 8-iso-PGF 2a and scores of cognitive assessment in MCI.

Conclusion: Constitution types (Yang-Deficient, Phlegm-Dampness and Blood-Stasis) and abnormal serum Hcy elevation can be used as risk factors for MCI. MoCA scores can serve to detect MCI at early stage. Serum/urine 8-iso-PGF 2α has a certain relationship with MCI. Higher levels of serum/urine 8-iso-PGF 2α are more likely to be associated with MCI risk.
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http://dx.doi.org/10.2147/NDT.S290692DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8068505PMC
April 2021

A Frailty Assessment Tool to Predict In-Hospital Mortality in Patients with Acute Exacerbations of Chronic Obstructive Pulmonary Disease.

Int J Chron Obstruct Pulmon Dis 2021 20;16:1093-1100. Epub 2021 Apr 20.

Department of Laboratory Medicine,The Affiliated People's Hospital of Jiangsu University, Zhejiang, 212002, People's Republic of China.

Background: The exacerbation of chronic obstructive pulmonary disease (AECOPD) is a chronic, frequent, and life-threatening lung disease. In 2014, a frailty index (FI) based on deficits in commonly used laboratory tests (FI-Lab) was suggested to identify older adults at increased risk of death.

Objective: We aim to study the prognostic value of the FI-Lab in older Chinese patients who were admitted because of AECOPD.

Methods: We screened 1932 older patients hospitalized with AECOPD from September 2016 to June 2019 at Zhenjiang First People's Hospital, China. A multivariate logistic regression analysis was used to identify prognostic factors for in-hospital mortality.

Results: A total of 77 survivors and 77 non-survivors were finally included in the study. Both the mean DECAF (including dyspnea, eosinopenia, consolidation, acidemia, and atrial fibrillation) score and the mean FI-Lab value of non-survivors were statistically higher than those of survivors (4.45 ± 0.80 versus 3.03 ± 0.90, =0.000; 0.51 ± 0.13 versus 0.29 ± 0.10, =0.000, respectively). Logistic regression analysis suggested that DECAF Rank and FI-Lab Rank were strongly related factors of death in AECOPD patients. The areas under the receiver-operating characteristic (ROC) curves were 0.906 for FI-Lab and 0.870 for DECAF (=0.2991).

Conclusion: FI-Lab is a simple, efficient, and objective tool to stratify the risk of in-hospital mortality of AECOPD.
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http://dx.doi.org/10.2147/COPD.S300980DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8068494PMC
April 2021

Inhibition of the transient receptor potential vanilloid 3 channel attenuates carbon tetrachloride-induced hepatic fibrosis.

Biochem Biophys Res Commun 2021 Jun 24;558:86-93. Epub 2021 Apr 24.

Hunan Provincial Key Laboratory of Hepatobiliary Disease Research, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China; Department of General Surgery. Pinghu Hospital, Health Science Center, Shenzhen University, Shenzhen, 518116, China. Electronic address:

Transient receptor potential vanilloid 3 (TRPV3) is a member of the TRP superfamily. Previous studies have demonstrated that TRPV3 is associated with myocardial fibrosis. However, the role of TRPV3 in hepatic fibrosis and its underlying mechanisms are still unclear. This study aimed to elucidate the underlying effects of TRPV3 on hepatic fibrosis at multiple biological levels. First, immunohistochemical staining was performed to examine TRPV3 expression in human hepatic cirrhosis tissues. Then, we established a CCl-induced hepatic fibrosis mouse model. The TRPV3 selective agonist drofenine and its inhibitor, forsythoside B, were intraperitoneally injected to investigate the relationship between TRPV3 and liver fibrosis progression. Finally, in vitro studies were performed using hepatic stellate cells (HSCs) to discover the potential molecular biological mechanisms. Immunohistochemistry revealed TRPV3 overexpression in liver cirrhosis. In the liver fibrosis groups, TRPV3 inhibitor treatment significantly reduced liver fibrosis, while TRPV3 agonist exacerbated its progression. In HSCs, knocking down TRPV3 with siRNA impaired DNA synthesis and cell proliferation and increased cell apoptosis. Furthermore, we found that knockdown of TRPV3 could reduce the lectin like oxidized lowdensity lipoprotein receptor-1 (LOX-1) protein levels. Our research suggests that lower expression or functional levels of TRPV3 can ameliorate the inflammatory response and fibrotic tissue proliferation.
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http://dx.doi.org/10.1016/j.bbrc.2021.04.065DOI Listing
June 2021

Improvement of phosphorus release from sludge by combined electrochemical-EDTA treatment.

Water Sci Technol 2021 Apr;83(8):1824-1833

School of Environmental and Chemical Engineering, Shanghai University, No. 99, Shangda Rd, Shanghai 200444, China E-mail:

In this paper, combined with the addition of ethylenediaminetetraacetic acid (EDTA), the electrochemical treatment of waste activated sludge (WAS) was investigated to explore its effect on the release of phosphorus (P) from WAS. The results showed that during the electrochemical treatment, the addition of EDTA could significantly promote the release of P from the WAS to the supernatant, the optimal amount of EDTA was 0.4 g/g total suspended solids (TSS), when the release of total dissolved phosphorus (TDP), organic phosphorus (OP) and molybdate reactive phosphorus (PO-P) were 187.30, 173.84 and 13.46 mg/L, respectively. OP was the most likely form of P to be released during this process. Moreover, combined electrochemical-EDTA treatment could promote the release of P and metal ions from extracellular polymeric substances (EPSs) to the supernatant, and increase the solubility and disintegration of sludge. EDTA chelated the metal ions of sludge flocs and phosphate precipitates to cause sludge floc decomposition, thereby promoting the release of P from WAS.
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http://dx.doi.org/10.2166/wst.2021.107DOI Listing
April 2021

Analysis of drought and salt-alkali tolerance in tobacco by overexpressing gene from .

Plant Signal Behav 2021 Apr 27:1918885. Epub 2021 Apr 27.

Key Laboratory of Saline-alkali Vegetation Ecology Restoration, Ministry of Education, College of Life Sciences, Northeast Forestry University, Harbin, Heilongjiang, China.

WRKY is one of the largest families of transcription factors in plants. It not only regulates plant growth and development but also participates in the regulation of plant defense against biological and abiotic stresses. In this study, research was aimed to overexpress gene of () and to identify its important role played in drought and saline-alkali tolerance in tobacco model plant. Under the control of CaMV35S promoter, the overexpression of gene was increased to more than 10 times in T3 generation of transgenic tobacco plant. The drought resistance and saline-alkali tolerance were evidenced in overexpressed transgenic lines at germination/seedling stage. The overall germination rate, fresh weight, and chlorophyll contents of overexpressed lines were significantly higher while the level of malondialdehyde was significantly lower in transgenic lines than that of wild type (WT) lines. The content of HO in leaves was detected by the 3, 3-Diaminobenzidine method showed that the overexpression of gene could reduce the accumulation of ROS (mainly HO) and enhance salt-alkali tolerance. Phenotypic analysis at 7-leaf pot transgenic seedlings stage treated with the saline-alkali soil extract and salt NaCl under root irrigation stress, revealed growth of the transgenic line was significantly higher than that of WT. This work concludes that overexpression of gene can improve the regulation of drought resistance and saline-alkali tolerance of transgenic plants during seed germination and vegetative growth.
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http://dx.doi.org/10.1080/15592324.2021.1918885DOI Listing
April 2021

Synergistic Effects of Chronic Restraint-Induced Stress and Low-Dose 56Fe-particle Irradiation on Induction of Chromosomal Aberrations in Trp53-Heterozygous Mice.

Radiat Res 2021 Apr 26. Epub 2021 Apr 26.

National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba.

Astronauts can develop psychological stress (PS) during space flights due to the enclosed environment, microgravity, altered light-dark cycles, and risks of equipment failure or fatal mishaps. At the same time, they are exposed to cosmic rays including high atomic number and energy (HZE) particles such as iron-56 (Fe) ions. Psychological stress or radiation exposure can cause detrimental effects in humans. An earlier published pioneering study showed that chronic restraint-induced psychological stress (CRIPS) could attenuate Trp53 functions and increase carcinogenesis induced by low-linear energy transfer (LET) g rays in Trp53-heterozygous (Trp53+/-) mice. To elucidate possible modification effects from CRIPS on high-LET HZE particle-induced health consequences, Trp53+/- mice were received both CRIPS and accelerated Fe ion irradiation. Six-week-old Trp53+/- C57BL/6N male mice were restrained 6 h per day for 28 consecutive days. On day 8, they received total-body Fe-particle irradiation (Fe-TBI, 0.1 or 2 Gy). Metaphase chromosome spreads prepared from splenocytes at the end of the 28-day restraint regimen were painted with the fluorescence in situ hybridization (FISH) probes for chromosomes 1 (green), 2 (red) and 3 (yellow). Induction of psychological stress in our experimental model was confirmed by increase in urinary corticosterone level on day 7 of restraint regimen. Regardless of Fe-TBI, CRIPS reduced splenocyte number per spleen at the end of the 28-day restraint regimen. At 2 Gy, Fe-TBI alone induced many aberrant chromosomes and no modifying effect was detected from CRIPS on induction of aberrant chromosomes. Notably, neither Fe-TBI at 0.1 Gy nor CRIPS alone induced any increase in the frequency of aberrant chromosomes, while simultaneous exposure resulted in a significant increase in the frequency of chromosomal exchanges. These findings clearly showed that CRIPS could enhance the frequency of chromosomal exchanges induced by Fe-TBI at a low dose of 0.1 Gy.
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http://dx.doi.org/10.1667/RADE-20-00218.1DOI Listing
April 2021

Comparative evaluation and design of a G-triplex/thioflavin T-based molecular beacon.

Analyst 2021 Apr;146(8):2567-2573

Key Laboratory of Applied Surface and Colloid Chemistry, Ministry of Education; Key Laboratory of Analytical Chemistry for Life Science of Shaanxi Province, School of Chemistry and Chemical Engineering, Shaanxi Normal University, Xi'an 710062, China.

Both G-quadruplex (G4) and G-triplex (G3) can bind thioflavin T (ThT) to light up the fluorescence of ThT. G4/ThT and G3/ThT can be used as fluorescent indicators to construct a label-free molecular beacon (MB). In this work, we present a comparative perspective of G3/ThT-based MB and G4/ThT-based MB. The results showed that the G3/ThT-based MB had higher sensitivity and faster response speed than the G4/ThT-based MB. Furthermore, we systematically studied the effect of stem length and varying pairs on the response of the G3/ThT-based MB, and then proposed one rational design of the G3/ThT-based MB. This work demonstrates that the shorter G3 is more suitable for constructing the MB stem. This present work opens a promising way to develop a sensitive, simple and homogeneous biosensing method.
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http://dx.doi.org/10.1039/d1an00252jDOI Listing
April 2021

FOXO3a regulates lipid accumulation and adipocyte inflammation in adipocytes through autophagy : Role of FOXO3a in obesity.

Inflamm Res 2021 May 23;70(5):591-603. Epub 2021 Apr 23.

Department of Endocrinology, Yangpu Hospital, Tongji University School of Medicine, 450 Tengyue Road, Yangpu, Shanghai, 200090, China.

Background: FOXO3a is a widely studied transcription factor and plays an important role in a variety of biology. The purpose of this study was to explore the role and potential mechanism of FOXO3a on lipid accumulation and adipocyte inflammation in adipocytes through regulation of autophagy.

Methods: The obese mouse model was successfully induced by high-fat diet. SiRNA targeting FOXO3a was transfected into differentiation of 3T3-L1 adipocytes to reduce the expression of FOXO3a. The culture medium of RAW264.7 cells was added to the differentiated 3T3-L1 adipocytes to form a co-culture system. Subsequently, ELISA or AdipoRed assay was performed to measure the expression of triglyceride (TG) and cholesterol (TC) in mouse adipose tissue or differentiation of 3T3-L1 adipocytes. Adipocyte differentiation was detected by Oil Red O-staining. Ad-mCherry-GFP-LC3II was used to detect the level of autophagy in differentiation of 3T3-L1 adipocytes. Western blotting or qRT-PCR was used to detect the expression of FOXO3a, autophagy-related proteins (beclin 1, CEBPβ, PPARγ, ACC1 and KLF4), inflammatory cytokines (TNF-α, IL-1β, IL-6 and MCP1), NF-κB signal pathway-related proteins or adipokines (Adiponectin, AdipoR1 and resistin) in differentiated 3T3-L1 or RAW264.7 cells.

Results: The expression of FOXO3a and autophagy levels were significantly increased in visceral adipose tissue of obese mice and differentiation of 3T3-L1 adipocytes. Downregulation of FOXO3a significantly inhibited the autophagy and lipid accumulation in differentiation of 3T3-L1 adipocytes. In addition, FOXO3a knockdown significantly reduced Lipopolysaccharide (LPS)-induced inflammation and adipokines release in RAW264.7 cells treated with the culture medium of 3T3-L1 adipocytes. These above activity changes could be reversed by autophagy inducer rapamycin.

Conclusion: FOXO3a could promote lipid accumulation and inflammation in differentiated 3T3-L1 adipocytes by targeting autophagy. Our results provide a new theoretical basis for FOXO3a to regulate obesity.
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http://dx.doi.org/10.1007/s00011-021-01463-0DOI Listing
May 2021

Primary Cutaneous Nocardiosis Due to Nocardia Farcinica: A Case Report of an Often Overlooked Infection.

Infect Drug Resist 2021 15;14:1435-1440. Epub 2021 Apr 15.

Yichang Central People's Hospital, The First College of Clinical Medical Science, China Three Gorges University, Yichang, Hubei, People's Republic of China.

Primary cutaneous nocardiosis by is exceedingly rare. Only six cases have been reported from PubMed in the past 15 years. We encounter such a case in a 55-year-old man receiving long-term steroid and cyclophosphamide. Owing to no characteristic symptoms, the disease can be so easily overlooked and causes fatal consequences. Therefore, we herein discuss common features of primary cutaneous nocardiosis by that remind clinicians considering it.
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http://dx.doi.org/10.2147/IDR.S306161DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8055275PMC
April 2021

Directing photocatalytic pathway to exceedingly high antibacterial activity in water by functionalizing holey ultrathin nanosheets of graphitic carbon nitride.

Water Res 2021 Apr 8;198:117125. Epub 2021 Apr 8.

Shenyang National Laboratory for Materials Science, Institute of Metal Research, Chinese Academy of Sciences, Shenyang, 110016, China; University of Illinois at Urbana-Champaign, Urbana, IL 61801 United States. Electronic address:

Metal-free polymeric carbon nitride (CN) photocatalysts offer attractive technological advantages over the conventional transition metal oxides or sulfides -based photocatalysts in water disinfection, but their antimicrobial activities are limited by their rapid charge carrier recombination and low specific surface areas. By controlling photocatalytic pathways, we obtained in amino-rich holey ultrathin g-CN nanosheets (AHUCN) a highly efficient inactivation rate against E-coli, which is the highest among the monolithic g-CN and exceeds the antibacterial performance of the most of the previously reported g-CN-based photocatalysts. Both the experiments and theoretical calculations demonstrated that the high photocatalytic disinfection performance of AHUCN was derived from the synergistic advantages of their unique holey ultrathin structure and the amino - rich surface in controlling the charge separation and transfer, and most importantly in increasing the photo-production of the dominant antibacterial species, HO. From the analysis of the reactive oxygen species and rotating disk electrode (RDE) measurements, it was found that the presence of abundant surface amino groups enabled the switch of the oxygen-reduction pathway from the two-step single-electron indirect reduction on holey ultrathin g-CN nanosheets (HUCN) to the one-step two-electron direct reduction on AHUCN. The switch of the HO production pathway not only facilitated the separation of photogenerated electron-hole pairs but also promoted the generation of reactive oxygen species, greatly enhancing photocatalytic disinfection efficiency.
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http://dx.doi.org/10.1016/j.watres.2021.117125DOI Listing
April 2021

Controlling the Lewis Acidity and Polymerizing Effectively Prevent Frustrated Lewis Pairs from Deactivation in the Hydrogenation of Terminal Alkynes.

Org Lett 2021 May 20;23(9):3685-3690. Epub 2021 Apr 20.

School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, China.

Two strategies were reported to prevent the deactivation of Frustrated Lewis pairs (FLPs) in the hydrogenation of terminal alkynes: reducing the Lewis acidity and polymerizing the Lewis acid. A polymeric Lewis acid (P-BPh) with high stability was designed and synthesized. Excellent conversion (up to 99%) and selectivity can be achieved in the hydrogenation of terminal alkynes catalyzed by P-BPh. This catalytic system works quite well for different substrates. In addition, the P-BPh can be easily recycled.
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http://dx.doi.org/10.1021/acs.orglett.1c01073DOI Listing
May 2021

Increased Accumulation of α-Synuclein in Inflamed Appendices of Parkinson's Disease Patients.

Mov Disord 2021 Apr 20. Epub 2021 Apr 20.

Department of Neurology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.

Background: The accumulation of α-synuclein (α-Syn) aggregates that leads to the onset of Parkinson's disease (PD) has been postulated to begin in the gastrointestinal tract. The normal human appendix contains pathogenic forms of α-Syn, and appendectomy has been reported to affect the incidence of PD.

Objective: This study investigated appendix abnormality in patients with PD.

Methods: We assessed appendix morphology in 100 patients with PD and 50 control subjects by multislice spiral computed tomography. We analyzed the clinical characteristics of patients with PD with diseased appendices, which was confirmed in seven patients by histopathological analysis.

Results: Chronic appendicitis-like lesions were detected in 53% of patients with PD, but these were not associated with the duration of motor symptoms. Appendicitis-like lesions, impaired olfaction, and rapid eye movement sleep behavior disorder were risk factors for PD. The following clinical symptoms could be used to identify patients with PD with appendicitis-like lesions: first motor symptoms were bradykinesia/rigidity, onset of motor symptoms in the central axis or left limb, prodromal constipation, high ratio of Unified Parkinson's Disease Rating Scale Part III score to symptom duration, low Montreal Cognitive Assessment score, and high Epworth Sleepiness Scale score. The seven patients with PD who were diagnosed with chronic appendicitis underwent appendectomy, and histopathological analysis revealed structural changes associated with chronic appendicitis and α-Syn aggregation.

Conclusions: These results indicate an association between chronic appendicitis-like lesions and PD, and suggest that α-Syn accumulation in the diseased appendix occurs in PD. © 2021 International Parkinson and Movement Disorder Society.
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http://dx.doi.org/10.1002/mds.28553DOI Listing
April 2021

Therapeutic inhibition of keratinocyte TRPV3 sensory channel by local anesthetic dyclonine.

Elife 2021 Apr 20;10. Epub 2021 Apr 20.

State Key Laboratory of Virology, Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Frontier Science Center for Immunology and Metabolism, Wuhan University, Wuhan, China.

The multimodal sensory channel transient receptor potential vanilloid-3 (TRPV3) is expressed in epidermal keratinocytes and implicated in chronic pruritus, allergy, and inflammation-related skin disorders. Gain-of-function mutations of TRPV3 cause hair growth disorders in mice and Olmsted syndrome in humans. Nevertheless, whether and how TRPV3 could be therapeutically targeted remains to be elucidated. We here report that mouse and human TRPV3 channel is targeted by the clinical medication dyclonine that exerts a potent inhibitory effect. Accordingly, dyclonine rescued cell death caused by gain-of-function TRPV3 mutations and suppressed pruritus symptoms in vivo in mouse model. At the single-channel level, dyclonine inhibited TRPV3 open probability but not the unitary conductance. By molecular simulations and mutagenesis, we further uncovered key residues in TRPV3 pore region that could toggle the inhibitory efficiency of dyclonine. The functional and mechanistic insights obtained on dyclonine-TRPV3 interaction will help to conceive therapeutics for skin inflammation.
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http://dx.doi.org/10.7554/eLife.68128DOI Listing
April 2021

Corrigendum: Role of HK2 in the Enzootic Cycle of .

Front Med (Lausanne) 2021 31;8:668709. Epub 2021 Mar 31.

Wenzhou Key Laboratory of Sanitary Microbiology, Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, China.

[This corrects the article DOI: 10.3389/fmed.2020.573648.].
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http://dx.doi.org/10.3389/fmed.2021.668709DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8045412PMC
March 2021

Molecular and Clinical Characterization of CCT2 Expression and Prognosis Large-Scale Transcriptome Profile of Breast Cancer.

Front Oncol 2021 2;11:614497. Epub 2021 Apr 2.

Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Molecular chaperones play important roles in regulating various cellular processes and malignant transformation. Expression of some subunits of molecular chaperone CCT/TRiC complex have been reported to be correlated with cancer development and patient survival. However, little is known about the expression and prognostic significance of Chaperonin Containing TCP1 Subunit 2 (CCT2). CCT2 is a gene encoding a molecular chaperone that is a member of the chaperonin containing TCP1 complex (CCT), also known as the TCP1 ring complex (TRiC). Through the Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) databases, we systematically reviewed a total of 2,994 cases with transcriptome data and analyzed the functional annotation of CCT2 by Gene ontology and KEGG analysis. Univariate and multivariate survival analysis were performed to investigate the prognostic value of CCT2 in breast cancer. We found CCT2 was significantly upregulated in various tumors. In breast cancer, CCT2 expression was significantly upregulated in HER2-positive (HER2+) group, and more malignant group. In addition, we investigated correlations between CCT2 and other CCT members. Interestingly, almost all CCTs expression were positively correlated with each other, but not CCT6B. Survival analysis suggested that CCT2 overexpression was independently associated with worse prognosis of patients with breast cancer, especially in luminal A subtype. In summary, our results revealed that CCT2 might be involved in regulating cell cycle pathway, and independently predicted worse prognosis in breast cancer patients. These findings may expand understanding of potential anti-CCT2 treatments. To our knowledge, this is the largest and most comprehensive study characterizing the expression pattern of CCT2 together with its prognostic values in breast cancer.
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http://dx.doi.org/10.3389/fonc.2021.614497DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8050343PMC
April 2021