Publications by authors named "Long Wu"

229 Publications

Nanozyme Applications: A Glimpse of Insight in Food Safety.

Front Bioeng Biotechnol 2021 24;9:727886. Epub 2021 Aug 24.

College of Food Science and Engineering, Hainan University, Haikou, China.

Nanozymes own striking merits, including high enzyme-mimicking activity, good stability, and low cost. Due to the powerful and distinguished functions, nanozymes exhibit widespread applications in the field of biosensing and immunoassay, attracting researchers in various fields to design and engineer nanozymes. Recently, nanozymes have been innovatively used to bridge nanotechnology with analytical techniques to achieve the high sensitivity, specificity, and reproducibility. However, the applications of nanozymes in food applications are seldom reviewed. In this review, we summarize several typical nanozymes and provide a comprehensive description of the history, principles, designs, and applications of nanozyme-based analytical techniques in food contaminants detection. Based on engineering and modification of nanozymes, the food contaminants are classified and then discussed in detail via discriminating the roles of nanozymes in various analytical methods, including fluorescence, colorimetric and electrochemical assay, surface-enhanced Raman scattering, magnetic relaxing sensing, and electrochemiluminescence. Further, representative examples of nanozymes-based methods are highlighted for contaminants analysis and inhibition. Finally, the current challenges and prospects of nanozymes are discussed.
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http://dx.doi.org/10.3389/fbioe.2021.727886DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8421533PMC
August 2021

A Modified Hypothermic Circulatory Arrest Technique Improves Early and Near-Midterm Results in Patients with Acute Type A Aortic Dissection.

Heart Surg Forum 2021 Jul 29;24(4):E675-E679. Epub 2021 Jul 29.

Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.

Background: The hypothermic circulatory arrest (HCA) is an indispensable step in the surgical treatment of an acute type A aortic dissection (ATAAD), which could greatly affect the postoperative outcome. We modified the HCA technique and validated the feasibility and superiority of the new approach relative to the conventional method.

Methods And Results: Eighty-eight patients with ATAAD were enrolled in this study between May 2016 and April 2018. Of those, 36 patients in the Conventional treatment group had circulatory arrest at 25°C for about 16-28 minutes, while 52 patients in the Modification group underwent a circulatory arrest at 28°C for only 1-3 minutes. The preoperative clinical data and postoperative clinical outcomes were compared between the two groups. No intraoperative mortality occurred in any of the cases. No significant differences were observed in the aortic cross-clamp times during the cardiopulmonary bypass (CPB) between the two groups. In the Modification group, several indicators, such as mechanical ventilation time, postoperative 48-h drainage volume, blood transfusion volume, the ICU-stay time and postoperative hospital stay, were reduced significantly as compared with those in the Conventional group. Whereas three postoperative deaths in the hospital occurred in the Conventional treatment group, all the patients in the Modification group were cured. There is no difference in the incidence of postoperative complications between the two groups. The patients had a 100% follow up with a mean of 17 ± 6 months.

Conclusions: A moderate hypothermia with a short circulatory arrest is a safe and effective HCA approach that provides satisfactory early and near-midterm results in the patients who received ATAAD treatment.
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http://dx.doi.org/10.1532/hsf.3879DOI Listing
July 2021

Comparative proteomic investigation of multiple methicillin-resistant strains generated through adaptive laboratory evolution.

iScience 2021 Sep 6;24(9):102950. Epub 2021 Aug 6.

Department of Chemical and Biological Engineering, The Hong Kong University of Science & Technology, Clear Water Bay, Kowloon, Hong Kong.

Recent discoveries indicate that tolerance and resistance could rapidly evolve in bacterial populations under intermittent antibiotic treatment. In the present study, we applied antibiotic combinations in laboratory experiments to generate novel methicillin-resistant strains with distinct phenotypes (tolerance, resistance, and suppressed tolerance), and compared their proteome profiles to uncover the adaptation mechanisms. While the tolerant strains have very different proteomes than the susceptible ancestral strain, the resistant strain largely resembles the ancestral in terms of their proteomes. Our proteomics data and other assays support the connection between the detected mutations to the observed phenotypes, confirming the general understanding of tolerance and resistance mechanisms. While resistance directly counteracts the action mechanism of the antibiotic, tolerance involves complex substantial changes in the cells' biological process to achieve survival advantages. Overall, this study provides insights into the existence of diverse evolutionary pathways for tolerance and resistance development under different treatment scenarios.
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http://dx.doi.org/10.1016/j.isci.2021.102950DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8377494PMC
September 2021

Highly sensitive magnetic relaxation sensing method for aflatoxin B1 detection based on Au NP-assisted triple self-assembly cascade signal amplification.

Biosens Bioelectron 2021 Nov 9;192:113489. Epub 2021 Jul 9.

Institute of Quality Standard and Testing Technology for Agro-Products, Chinese Academy of Agricultural Science/Key Laboratory of Agro-Products Quality and Safety of MOA, Beijing, 100081, PR China. Electronic address:

Highly sensitive detection of aflatoxin B (AFB) is of great significance because of its high toxicity and carcinogenesis. We propose a magnetic relaxation sensing method based on gold nanoparticles (Au NPs)-assisted triple self-assembly cascade signal amplification for highly sensitive detection of AFB. Both AFB antibody and initiator DNA (iDNA) are labeled on Au NPs to form Ab-Au-iDNA probe. iDNA is enriched by Au NPs to achieve first signal amplification. Different amounts of Ab-Au-iDNA were bound with AFB antigen by indirect competitive immunoassay, and then hybridization chain reaction event was initiated by iDNA to produce long hybridization chain reaction products to enrich more horseradish peroxidase-streptavidin for the second signal amplification. Dopamine could be rapidly converted to polydopamine by HRP catalysis, which is used as the third signal amplification. The Fe solution, providing paramagnetic ions with a strong magnetic signal, could be adsorbed by the polydopamine due to the formation of coordination bonds of phenolic hydroxyl groups with Fe. This effective interaction between polydopamine and Fe significantly changes the transverse relaxation time signal of Fe supernatant solution, which can be used as a magnetic probe for highly sensitive detection of AFB. The sensor exhibited high specificity and sensitivity with a detection limit of 0.453 pg/mL owing to the Au NP-assisted triple self-assembly cascade signal amplification strategy. It has been successfully employed for AFB detection in animal feed samples with consistent results of enzyme linked immune sorbent assay and high-performance liquid chromatography.
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http://dx.doi.org/10.1016/j.bios.2021.113489DOI Listing
November 2021

Combinatory strategy using nanoscale proteomics and machine learning for T cell subtyping in peripheral blood of single multiple myeloma patients.

Anal Chim Acta 2021 Aug 29;1173:338672. Epub 2021 May 29.

Department of Chemistry, Southern University of Science and Technology, Shenzhen, 518055, China. Electronic address:

T cells play crucial roles in our immunity against hematological tumors by inducing sustained immune responses. Flow cytometry-based detection of a limited number of specific protein markers has been routinely applied for basic research and clinical investigation in this area. In this study, we combined flow cytometry with the simple integrated spintip-based proteomics technology (SISPROT) to characterize the proteome of primary T cell subtypes in the peripheral blood (PB) from single multiple myeloma (MM) patients. Taking advantage of the integrated high pH reversed-phase fractionation in the SISPROT device, the global proteomes of CD3, CD4 and CD8 T cells were firstly profiled with a depth of >7 000 protein groups for each cell type. The sensitivity of single-shot proteomic analysis was dramatically improved by optimizing the SISPROT and data-dependent acquisition parameters for nanogram-level samples. Eight subtypes of T cells were sorted from about 4 mL PB of single MM patients, and the individual subtype-specific proteomes with coverage among 1 702 and 3 699 protein groups were obtained from as low as 70 ng and up to 500 ng of cell lysates. In addition, we developed a two-step machine learning-based subtyping strategy for proof-of-concept classifying eight T cell subtypes, independent of their cell numbers and individual differences. Our strategy demonstrates an easy-to-use proteomic analysis on immune cells with the potential to discover novel subtype-specific protein biomarkers from limited clinical samples in future large scale clinical studies.
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http://dx.doi.org/10.1016/j.aca.2021.338672DOI Listing
August 2021

Circular RNA mmu_circ_0005019 inhibits fibrosis of cardiac fibroblasts and reverses electrical remodeling of cardiomyocytes.

BMC Cardiovasc Disord 2021 06 21;21(1):308. Epub 2021 Jun 21.

Department of Epidemiology, College of Preventive Medicine, Army Medical University (Third Military Medical University), NO. 30 Gaotanyan Street, Chongqing, 400038, People's Republic of China.

Background: Circular RNA (circRNA) have been reported to play important roles in cardiovascular diseases including myocardial infarction and heart failure. However, the role of circRNA in atrial fibrillation (AF) has rarely been investigated. We recently found a circRNA hsa_circ_0099734 was significantly differentially expressed in the AF patients atrial tissues compared to paired control. We aim to investigate the functional role and molecular mechanisms of mmu_circ_0005019 which is the homologous circRNA in mice of hsa_circ_0099734 in AF.

Methods: In order to investigate the effect of mmu_circ_0005019 on the proliferation, migration, differentiation into myofibroblasts and expression of collagen of cardiac fibroblasts, and the effect of mmu_circ_0005019 on the apoptosis and expression of I, I and SK3 of cardiomyocytes, gain- and loss-of-function of cell models were established in mice cardiac fibroblasts and HL-1 atrial myocytes. Dual-luciferase reporter assays and RIP were performed to verify the binding effects between mmu_circ_0005019 and its target microRNA (miRNA).

Results: In cardiac fibroblasts, mmu_circ_0005019 showed inhibitory effects on cell proliferation and migration. In cardiomyocytes, overexpression of mmu_circ_0005019 promoted Kcnd1, Scn5a and Kcnn3 expression. Knockdown of mmu_circ_0005019 inhibited the expression of Kcnd1, Kcnd3, Scn5a and Kcnn3. Mechanistically, mmu_circ_0005019 exerted biological functions by acting as a miR-499-5p sponge to regulate the expression of its target gene Kcnn3.

Conclusions: Our findings highlight mmu_circ_0005019 played a protective role in AF development and might serve as an attractive candidate target for AF treatment.
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http://dx.doi.org/10.1186/s12872-021-02128-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8215745PMC
June 2021

OPG/TRAIL ratio as a predictive biomarker of mortality in patients with type A acute aortic dissection.

Nat Commun 2021 06 7;12(1):3401. Epub 2021 Jun 7.

Beijing Anzhen Hospital of Capital Medical University and Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing, China.

Following hospital discharge, patients with type A acute aortic dissection (TA-AAD) may present an increase in mortality risk. However, little is known about specific biomarkers associated with post-discharge survival, and there is a paucity of prognostic markers associated with TA-AAD. Here, we identify nine candidate proteins specific for patietns with TA-AAD in a cross-sectional dataset by unbiased protein screening and in-depth bioinformatic analyses. In addition, we explore their association with short-term and long-term mortality in a derivation cohort of patients with TA-AAD, including an internal (n = 300) and external (n = 236) dataset. An elevated osteoprotegerin (OPG)/tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) ratio was the strongest predictor of overall, 30-day, post-30-day mortality in both datasets and was confirmed to be a strong predictor of mortality in an independent validation cohort (n = 400). Based on OPG/TRAIL ratio-guided risk stratification, patients at high risk (>33) had a higher 1-year mortality (55.6% vs. 4.3%; 68.2% vs. 2.6%) than patients at low risk (<4) in both cohorts. In Conclusion, we show that an elevated OPG/TRAIL ratio is associated with a significant increase in short-term and long-term mortality in patients with TA-AAD.
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http://dx.doi.org/10.1038/s41467-021-23787-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8185077PMC
June 2021

Food additives: From functions to analytical methods.

Crit Rev Food Sci Nutr 2021 Jun 1:1-21. Epub 2021 Jun 1.

School of Life and Health Sciences, The Chinese University of Hong Kong, Shenzhen, P.R. China.

Food additives refer to all kinds of trace substances used in food or food processing to preserve flavor or enhance food taste, appearance, or other qualities. At present, artificial synthetic food additives have gradually replaced the natural food additives and many problems related to food additives, involving the abuse of food additives, excessive additives or even toxic additives. Obviously, food additives can bring people great sensory enjoyment and commercial convenience, but they may also cause potential risks to human health. So, it is of high significance to conduct quantitative analysis on the content of food additives. According to their functions and the regulatory requirements of food additives, this review starts from the classification and structures of various food additives involving colorants, preservatives, antioxidants, sweeteners, emulsifiers, stabilizers, thickeners, gelling agents. It then summarizes and discusses analytical methods for quantification of food additives including modern immunoassays and other biotechnological methods. The proposed review aspires to fill in the knowledge gap of food additives between academia and industry by covering all kinds of analytical methods for quantifying food additives.
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http://dx.doi.org/10.1080/10408398.2021.1929823DOI Listing
June 2021

The efficient enrichment of marine peptides from the protein hydrolysate of the marine worm Urechis unicinctus by using mesoporous materials MCM-41, SBA-15 and CMK-3.

Anal Methods 2021 06 17;13(21):2405-2414. Epub 2021 May 17.

College of Food Science and Engineering, Dalian Ocean University, Dalian, Liaoning 116023, China.

Peptides found in marine life have various specific activities due to their special growth environment, and there is increasing interest in the isolation and concentration of these biofunctional compounds. In this study, the protein hydrolysate of the marine worm Urechis unicinctus was prepared by enzymolysis and enriched by using mesoporous materials of silica MCM-41 and SBA-15 and carbon CMK-3. The differences in pore structures and elemental composition of these materials lead to differences in surface area and hydrophobicity. The adsorption capacities of peptides were 459.5 mg g, 431.3 mg g, and 626.3 mg g for MCM-41, SBA-15 and CMK-3, respectively. Adsorption kinetics studies showed that the pseudo-second-order model fit the adsorption process better, where both external mass transfer and intraparticle diffusion affected the adsorption, while the Langmuir model better fit the adsorption of peptides on MCM-41 and SBA-15 and the Freundlich model was more suitable for CMK-3. Aqueous acetonitrile (ACN, 50/50, v/v) yielded the most extracted peptides. MALDI-TOF mass spectrometry of the extracted peptides showed that the three mesoporous materials, especially the CMK-3, gave good enrichment results. This study demonstrates the great potential of mesoporous materials in the enrichment of marine biofunctional peptides.
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http://dx.doi.org/10.1039/d1ay00616aDOI Listing
June 2021

α-synuclein aggregates induce c-Abl activation and dopaminergic neuronal loss by a feed-forward redox stress mechanism.

Prog Neurobiol 2021 Jul 2;202:102070. Epub 2021 May 2.

Department of Neurology, University of California San Francisco, United States; Neurology Service, San Francisco Veterans Affairs Health Care System, United States. Electronic address:

Oxidative stress and α-synuclein aggregation both drive neurodegeneration in Parkinson's disease, and the protein kinase c-Abl provides a potential amplifying link between these pathogenic factors. Suppressing interactions between these factors may thus be a viable therapeutic approach for this disorder. To evaluate this possibility, pre-formed α-synuclein fibrils (PFFs) were used to induce α-synuclein aggregation in neuronal cultures. Exposure to PFFs induced oxidative stress and c-Abl activation in wild-type neurons. By contrast, α-synuclein - deficient neurons, which cannot form α-synuclein aggregates, failed to exhibit either oxidative stress or c-Abl activation. N-acetyl cysteine, a thiol repletion agent that supports neuronal glutathione metabolism, suppressed the PFF - induced redox stress and c-Abl activation in the wild-type neurons, and likewise suppressed α-synuclein aggregation. Parallel findings were observed in mouse brain: PFF-induced α-synuclein aggregation in the substantia nigra was associated with redox stress, c-Abl activation, and dopaminergic neuronal loss, along with microglial activation and motor impairment, all of which were attenuated with oral N-acetyl cysteine. Similar results were obtained using AAV-mediated α-synuclein overexpression as an alternative means of driving α-synuclein aggregation in vivo. These findings show that α-synuclein aggregates induce c-Abl activation by a redox stress mechanism. c-Abl activation in turn promotes α-synuclein aggregation, in a feed-forward interaction. The capacity of N-acetyl cysteine to interrupt this interaction adds mechanistic support its consideration as a therapeutic in Parkinson's disease.
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http://dx.doi.org/10.1016/j.pneurobio.2021.102070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8210833PMC
July 2021

The application of acupuncture in obstetrics and gynecology: a bibliometric analysis based on Web of Science.

Ann Palliat Med 2021 Mar;10(3):3194-3204

Department of Obstetrics and Gynecology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.

Background: Acupuncture therapy has a wide range of applications in obstetrics and gynecology, especially for patients with reproductive issues, irregular menstruation, dysmenorrhea, and pelvic inflammatory disease. In recent decades, acupuncture therapy has gradually attracted the attention of professionals in China and overseas due to its beneficial effects, and has been the focus of many studies. This study aimed to conduct a statistical analysis of the relevant literature to understand the current application and research status of acupuncture in obstetric and gynecologic diseases.

Methods: A search of the SCI-EXPANDED database in the Web of Science Core Collection (WOSCC) was performed. Search strategy included two formulas: #1 WC=Obstetrics & Gynecology, limited: index =SCI-EXPANDED time span=all years; #2 subject: (ACUPUNCTURE-MOXIBUSTION) OR subject: (ACUPUNCTURE) OR subject: (MOXIBUSTION), limited: index=SCI-EXPANDED time span=all years. The final result was acquired by searching #1 AND #2. CiteSpace software was used to analyze and visualize the annual distribution of articles, and the distributions of disciplines, countries/institutions, journals, and authors. Keywords were used to infer the application of acupuncture in obstetrics and gynecology.

Results: A total of 593 research literatures, including 323 original articles, were retrieved. Since 1972, the number of literatures has shown a general increase. Studies on reproductive medicine accounted for the highest proportion of the retrieved literatures (139, 23.44%). The United States (25.5%), China (14.0%), Germany (7.6%), Australia (7.3%), and Sweden (7.1%) were the main contributors. The centrality index showed that the United States (0.19), the United Kingdom (0.19), and Germany (0.16) had the closest cooperation. The retrieved literatures covered 15 subdivision areas, including menstruation, embryo transfer, production, and pelvic pain. Obstetrics & Gynecology, Cochrane Database of Systematic Reviews, and American Journal of Obstetrics and Gynecology were found to be the most influential journals. The most frequently cited keywords were acupuncture (intensity =5.5326), low back pain (intensity =5.0506), and pregnancy (intensity =4.7016).

Conclusions: Acupuncture is receiving an increasing amount of attention in obstetrics and gynecology, and international cooperation in research in this field is also increasing.
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http://dx.doi.org/10.21037/apm-21-477DOI Listing
March 2021

Food Safety in Post-COVID-19 Pandemic: Challenges and Countermeasures.

Biosensors (Basel) 2021 Mar 4;11(3). Epub 2021 Mar 4.

Key Laboratory of Food Nutrition and Functional Food of Hainan Province, College of Food Science and Engineering, Hainan University, Haikou 570228, China.

Understanding food safety hazard risks is essential to avoid potential negative heath impacts in the food supply chain in a post-COVID-19 pandemic era. Development of strategies for virus direction in foods plays an important role in food safety and verification. Early warning, tracing, and detection should be implemented as an integrated system in order to mitigate thecoronavirus disease 2019 (COVID-19) outbreak, in which the detection of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is critical as it not only concerns screening of populations but also monitoring of possible contaminated sources such as the food supply chain. In this review, we point out the consequences in different aspects of our daily life in the post-COVID-19 pandemic from the perspective of the food supply chain and the food industry. We summarize the possible transmission routes of COVID-19 in the food supply chain before exploring the development of corresponding detection tools of SARS-CoV-2. Accordingly, we compare different detection methods for the virus in foods, including different pretreatments of food matrices in the virus detection. Finally, the future perspectives are proposed.
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http://dx.doi.org/10.3390/bios11030071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8000942PMC
March 2021

Reoperation after Implanting a Triple-Branched Stent Graft: Case Report.

Heart Surg Forum 2021 02 19;24(1):E191-E193. Epub 2021 Feb 19.

Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Acute type A aortic dissection (ATAAD) is an aortic catastrophe with high mortality, requiring immediate surgical intervention. Recently, placement of a triple-branch stent graft has emerged as an effective technique for total arch reconstruction. Indications for this approach, however, are limited by various complications, such as endoleak, stent graft migration or kinking, and spontaneous thrombosis. Here, we report a case of Marfan syndrome in which the patient underwent a reoperation owing to frame fractures (or degradation of graft material) in a triple-branched stent graft implanted 5 years earlier.
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http://dx.doi.org/10.1532/hsf.3345DOI Listing
February 2021

Short-term outcomes of a novel modified Bentall procedure in acute type A aortic dissection.

J Cardiovasc Surg (Torino) 2021 Aug 22;62(4):385-390. Epub 2021 Feb 22.

Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China -

Background: The Bentall procedure is a common surgical treatment for aortic root replacement in acute type A aortic dissection (ATAAD) with some complications which affect postoperative efficacy. We innovatively modified the Bentall procedure and investigated its short-term efficacy.

Methods: From March 2017 to March 2019, 77 cases with ATAAD in our department underwent total arch replacement and frozen elephant trunk technique following prior Bentall procedure. They were divided into three groups. In modified-Bentall group, 20 patients underwent a modified Bentall surgery. In Bentall-inclusion group, coronary ostia inclusion anastomosis and Cabrol shunt were performed in 32 patients. In Bentall-button group, coronary ostia button anastomosis was used to 25 cases.

Results: No intraoperative deaths occurred in three groups. Operation time, CPB time, and aortic cross-clamp time in modified-Bentall group was longer than those in Bentall-inclusion group (P<0.05), but the number of RBC transfusion and postoperative drainage volume decreased compared with Bentall-button group (P<0.05). One patient with mesenteric malperfusion syndrome died after surgery in modified-Bentall group, 2 patients died in Bentall-inclusion group, and 1 patient died in Bentall-button group. No coronary anastomotic leak and vena cava-right atrium shunt signal occurred in modified-Bentall group, and there was no contrast extravasation and no pseudoaneurysm formation in the aortic root. The cardiac function of patients was grade I-II.

Conclusions: This novel modified procedure is feasible and can significantly reduce postoperative complications with satisfactory short-term efficacy in ATAAD.
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http://dx.doi.org/10.23736/S0021-9509.21.11522-8DOI Listing
August 2021

Enzyme-induced Cu/Cu conversion as the electrochemical signal for sensitive detection of ethyl carbamate.

Anal Chim Acta 2021 Mar 28;1151:338256. Epub 2021 Jan 28.

National "111" Center for Cellular Regulation and Molecular Pharmaceutics, Key Laboratory of Fermentation Engineering (Ministry of Education), College of Bioengineering and Food, Hubei University of Technology, Wuhan, Hubei, 430068, PR China. Electronic address:

Traditional enzyme-linked immunosorbent assay (t-ELISA) method suffers from its relatively low sensitivity or accuracy in the detection of trace level of analyte in complicated samples. In this work, to extend the application of ELISA in practical samples, a newly electrochemical immunoassay (ECIA) was developed based on an enzyme-induced Cu/Cu conversion for the determination of ethyl carbamate (EC). Wherein, three rounds of signal transformation-the catalysis of ALP enzyme, the conversion of Cu/Cu and signal output of square wave voltammetry (SWV), can be realized to obtain higher sensitivity as compared to t-ELISA. The ECIA method combines the advantages of electrochemistry and ELISA, behaving superior detection performance, such as good selectivity, high sensitivity, and low background signal. For the wine samples, the method showed a linear detection range from 2.5 nM to 2.5 × 10 nM with a limit of detection of 2.28 nM (S/N = 3), which reveals that the ECIA sensor is a promising platform for the detection of trace level of EC in practical samples.
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http://dx.doi.org/10.1016/j.aca.2021.338256DOI Listing
March 2021

Circulating Long Noncoding RNAs Act as Diagnostic Biomarkers in Non-Small Cell Lung Cancer.

Front Oncol 2020 7;10:537120. Epub 2020 Dec 7.

Department of Epidemiology, College of Preventive Medicine, Army Medical University (Third Military Medical University), Chongqing, China.

Identification of novel effective early diagnostic biomarkers may provide alternative strategies to reduce the mortality for non-small cell lung cancer (NSCLC) patients. Circulating long non-coding RNAs (lncRNAs) have emerged as a new class of promising cancer biomarkers. Our study aimed to identify circulating lncRNAs for diagnosing NSCLC. A total 528 plasma samples were continuously collected and allocated to four progressive phases: discovery, training, verification, and expansion phases. The expression of candidate lung cancer related lncRNAs were detected using quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR). We identified a 4-lncRNA panel (RMRP, NEAT1, TUG1, and MALAT1) that provided a high diagnostic value in NSCLC (AUC = 0.86 and 0.89 for training and verification phase, respectively). Subgroup analyses showed that the 4-lncRNA panel had a sensitivity of 78.95% [95% confidence interval (CI) = 62.22%-89.86%] in stage I-II patients and 75.00% (95% CI = 52.95%-89.40%) in patients with small tumor size (≤3cm). Notably, the sensitivity of 4-lncRNA panel was significantly higher than that of routine protein panels in adenocarcinoma (CEA, CA125, and CYFRA21-1, 86.30% vs. 73.96%). Adding 4-lncRNA to protein markers significantly improved the diagnostic capacity in both adenocarcinoma (AUC=0.85, 95% CI = 0.78-0.91) and squamous cell carcinoma (AUC=0.93, 95% CI = 0.86-0.97). In conclusion, we identified a plasma 4-lncRNA panel that has considerable clinical value in diagnosing NSCLC. The 4-lncRNA panel could improve the diagnostic values of routine tumor protein markers in diagnosing NSCLC. Circulating lncRNAs could be used as promising candidates for NSCLC diagnosis.
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http://dx.doi.org/10.3389/fonc.2020.537120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7793881PMC
December 2020

MyD88 Costimulation in Donor CD8 T Cells Enhances the Graft-versus-Tumor Effect in Murine Hematopoietic Cell Transplantation.

J Immunol 2021 02 6;206(4):892-903. Epub 2021 Jan 6.

Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland Baltimore, Baltimore, MD 21201;

Donor-derived lymphocytes from allogeneic hematopoietic cell transplantation (allo-HCT) or donor lymphocyte infusion can mediate eradication of host tumor cells in a process labeled the graft-versus-tumor (GVT) effect. Unfortunately, these treatments have produced limited results in various types of leukemia because of an insufficient GVT effect. In this context, molecular engineering of donor lymphocytes to increase the GVT effect may benefit cancer patients. Activating MyD88 signaling in CD8 T cells via TLR enhances T cell activation and cytotoxicity. However, systemic administration of TLR ligands to stimulate MyD88 could induce hyperinflammation or elicit protumor effects. To circumvent this problem, we devised a synthetic molecule consisting of MyD88 linked to the ectopic domain of CD8a (CD8α:MyD88). We used this construct to test the hypothesis that MyD88 costimulation in donor CD8 T cells increases tumor control following allo-HCT in mice by increasing T cell activation, function, and direct tumor cytotoxicity. Indeed, an increase in both in vitro and in vivo tumor control was observed with CD8α:MyD88 T cells. This increase in the GVT response was associated with increased T cell expansion, increased functional capacity, and an increase in direct cytotoxic killing of the tumor cells. However, MyD88 costimulation in donor CD8 T cells was linked to increased yet nonlethal graft-versus-host disease in mice treated with these engineered CD8 T cells. Given these observations, synthetic CD8α:MyD88 donor T cells may represent a unique and versatile approach to enhance the GVT response that merits further refinement to improve the effectiveness of allo-HCT.
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http://dx.doi.org/10.4049/jimmunol.2000479DOI Listing
February 2021

Long intergenic non-coding RNA Linc00485 promotes lung cancer progression by modulating miR-298/c-Myc axis.

J Cell Mol Med 2021 01 25;25(1):309-322. Epub 2020 Nov 25.

Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China.

Long non-coding RNAs (lncRNAs), which are non-protein-coding transcripts, are emerging as novel biomarkers for cancer diagnosis. Their dysregulation is increasingly recognized to contribute to the development and progression of human cancers, including lung cancer. Linc00485 is a newly discovered cancer-related lncRNA; however, little is known about its role in lung cancer progression. In this study, we found that the expression of Linc00485 was significantly increased in human lung cancer tissue and associated with malignant phenotypes, including tumour-node-metastasis (TNM) stage, metastasis and relapse. Furthermore, the proliferative, migratory and invasive abilities of lung cancer cells in vitro were significantly enhanced by overexpression of Linc00485 but inhibited by its silencing. Mechanistically, Linc00485 regulated the expression of c-Myc by directly binding to miR-298; the effects of Linc00485 overexpression could be significantly reversed by a c-Myc inhibitor or small interfering RNA. Xenotransplantation experiments showed that Linc00485 silencing significantly weakened the proliferation potential of A549 cells in vivo. Overall, these findings indicate that Linc00485 overexpression down-regulates miR-298, resulting in the up-regulation of c-Myc and thereby promoting the development of lung cancer.
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http://dx.doi.org/10.1111/jcmm.16036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7810966PMC
January 2021

Eupafolin alleviates cerebral ischemia/reperfusion injury in rats via blocking the TLR4/NF‑κB signaling pathway.

Mol Med Rep 2020 Dec 26;22(6):5135-5144. Epub 2020 Oct 26.

Department of Intensive Care Unit, Shenzhen Hospital of Integrated Traditional Chinese and Western Medicine, Shenzhen, Guangdong 518104, P.R. China.

Eupatorium perfoliatum L. (E. perfoliatium) has been used traditionally for treating fever, malaria and inflammation‑associated diseases. Eupafolin, the extract of E. perfoliatium, was also reported to suppress inflammation. The present study aimed to investigate the protective effects of eupafolin on cerebral ischemia/reperfusion (I/R) injury in rats and its possible underlying mechanisms. Cerebral I/R injury was induced in rats by middle cerebral artery occlusion (MCAO) for 1.5 h, followed by reperfusion. The rats were randomly assigned into six groups: Control, model, 10 mg/kg eupafolin, 20 mg/kg eupafolin, 50 mg/kg eupafolin and 20 mg/kg nimodipine. Eupafolin and nimodipine were intragastrically administrated to the rats 1 week before MCAO induction. Following reperfusion for 24 h, the neurological deficit was scored, and brain samples were harvested for evaluating encephaledema, infarct volume, oxidative stress, apoptosis, inflammation and the expression of TLR4/NF‑κB signaling. The results revealed that eupafolin decreased the neurological score, relieved encephaledema and decreased infarct volume. Eupafolin also attenuated oxidative stress, neuronal apoptosis and inflammation, with decreases in lactate dehydrogenase, malondialdehyde, TUNEL‑positive cells, Bax and caspase‑3, along with TNF‑α, IL‑1β and IL‑6, but increases in superoxide dismutase and Bcl‑2 levels. Furthermore, eupafolin may decrease the expression of TLR4 downstream proteins and proteins involved in the NF‑κB pathway. Treatment with TLR4 agonist‑LPS significantly blunted the protective effect of eupafolin on encephaledema and cerebral infarct. Meanwhile, 20 mg/kg eupafolin showed nearly equivalent effects to the positive‑control drug nimodipine. In conclusion, eupafolin protected against cerebral I/R injury in rats and the underlying mechanism may be associated with the suppression of apoptosis and inflammation via inhibiting the TLR4/ NF‑κB signaling pathway.
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http://dx.doi.org/10.3892/mmr.2020.11637DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7646971PMC
December 2020

A risk nomogram of COVID-19 infection in cancer patients.

Curr Probl Cancer 2021 Apr 27;45(2):100645. Epub 2020 Aug 27.

Department of Oncology, Renmin Hospital of Wuhan University, Wuhan, China. Electronic address:

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http://dx.doi.org/10.1016/j.currproblcancer.2020.100645DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7451093PMC
April 2021

Early outcomes of Stanford type A aortic dissection under the coronavirus disease 2019 (COVID-19) pandemic: a multicentre study from Hubei province.

Interact Cardiovasc Thorac Surg 2020 12;31(6):834-840

Department of Cardiovascular Surgery, Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Objectives: Our goal was to compare the short-term outcomes of Stanford type A aortic dissection (TAAD), during the coronavirus disease 2019 (COVID-19) pandemic with those during normal times and summarize our perioperative management experience of patients with TAAD in the context of COVID-19.

Methods: From 17 January 2020 to 8 March 2020, a total of 27 patients with TAAD were operated on in 8 cardiovascular surgery centres in Hubei Province (COVID-19 group). The data from 91 patients with TAAD from the same centres during the same period last year were extracted from the Hubei Cardiac Surgery Registration System (control group). A propensity score matched subgroup of 26 pairs (1:2) was identified. Perioperative data and short-term outcomes were assessed.

Results: Nine patients in the COVID-19 group were categorized as suspicious for the disease (9/27, 33.3%), and others were excluded (18/27, 66.7%). No one was laboratory confirmed preoperatively. The average waiting, cross-clamp and circulatory arrest times were longer in the COVID-19 group (22.9 ± 8.3 vs 9.7 ± 4.0 h, P < 0.001; 135 ± 36 vs 103 ± 45 min, P = 0.003; 24 ± 9 vs 17 ± 8 min, P < 0.001, respectively). The 30-day or in-hospital deaths were 3.8% in both groups (P = 1.0). The COVID-19 group was associated with longer ventilation and intensive care unit times (81 ± 71 vs 45 ± 19 h, P < 0.001; 7.4 ± 3.8 vs 4.5 ± 2.7 days; P < 0.001, respectively). There were no statistical differences between the 2 groups in the incidence of complications such as stroke, neurological deficit, acute kidney injury, pulmonary infection and reoperation. Serum antibody tests for those patients showed 7 out of 9 suspected cases were Immunoglobulin G positive. No cross-infection occurred in other patients or associated medical staff.

Conclusions: With adequate preparation and appropriate protection, satisfactory early outcomes can be achieved after emergency operations for patients with TAAD during the COVID-19 pandemic.
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http://dx.doi.org/10.1093/icvts/ivaa209DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7665539PMC
December 2020

Association of Polymorphism in IL-18 Gene with Periodontitis in Uyghur Adults in Xinjiang and Evidence from Six Case-Control Studies with a Comprehensive Analysis.

Immunol Invest 2020 Nov 4:1-20. Epub 2020 Nov 4.

Department of dentistry, Xinjiang Medical University, Ürümqi, China.

Aim: The aim of the study was to evaluate the association of IL-18 137 G > C, 607 C > A gene polymorphism in Uyghur population with chronic periodontitis (CP) and combine the results with the meta-analysis.

Methods: In a case-control study, 200 cases with CP and 100 healthy controls were recruited; IL-18 137 G > C, 607 C > A genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). In the meta-analysis, we used electronic databases, including CNKI, Wan Fang, PubMed, EMBASE databases etc.to obtain relevant research published through June 2020. Studies were considered eligible if odds ratios (ORs) and 95% confidence intervals (95% CI) were provided or calculated from the given data. The size of the combined effect was calculated using STATA 15.0.

Results: Our study revealed significant association between CP and IL-18 137 G > C ( = .045, OR = 1.67), 607 C > A ( = .045, OR = 1.67). The overall meta-analysis revealed significant associations between IL-18 137 G > C polymorphism and CP risk in Allele, dominant, co-dominant and recessive genetic models. The subgroup analysis also showed a significant association between the IL-18 137 G > C and risk for periodontitis and aggressive periodontitis in the Asian (GC+ CC VS. GG: = .047, OR = 1.64,95%CI = 1.01-2.68).

Conclusions: IL-18 137 G > C, 607 C > A could be associated with susceptibility to periodontitis in Uyghur population. Further case-control of candidate genes studies targeting larger sample sizes and different ethnic groups are needed to arrive more accurate conclusions.
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http://dx.doi.org/10.1080/08820139.2020.1841222DOI Listing
November 2020

Serum lipid levels correlate to the progression of gastric cancer with neuroendocrine immunophenotypes: A multicenter retrospective study.

Transl Oncol 2021 Jan 1;14(1):100925. Epub 2020 Nov 1.

Department of Medical Oncology, Second Affiliated Hospital of Zhejiang University, School of Medicine, No. 88 Jiefang Road, Shangcheng District, Hangzhou, Zhejiang 310000, China. Electronic address:

Purpose: Dyslipidemia was associated with gastric adenocarcinoma or neuroendocrine tumors, but its role in a more malignant entity, gastric cancer with neuroendocrine immunophenotypes (GCNEI), was unclarified. This study sought to explore the relationship between serum lipid levels and the biological behaviors of gastric cancer with neuroendocrine immunophenotypes (GCNEI).

Methods: Patients with neuroendocrine carcinoma (NEC), GC with NEC components (GC-NEC), or GC expressing NE marker(s) but no NE morphology (GC-NENM) were enrolled from three centers. Their preoperative serum lipid levels, demographic, and clinicopathological information were analyzed and compared with those of patients with pure adenocarcinoma (PAC) or a background population selected from 10,061 health-check people by propensity-score matching.

Results: A total of 342 GCNEI patients were enrolled. Compared with the background population, total cholesterol (TCHO) and high-density lipoprotein cholesterol (HDL-C) levels were lower in GCNEI. Compared with PAC, GC-NENM and GC-NEC showed lower triglyceride (TG) levels, while, carcinoma with NE morphology showed higher low-density lipoprotein cholesterol (LDL-C) levels. Among GCNEI subtypes, GC-NEC differed from the others by higher LDL-C and non-HDL-C levels. A higher LDL-C level and(or) lower TG, HDL-C levels correlated to higher stages or large tumor sizes in GC-NENM, and a lower HDL-C level correlated to large tumor sizes in GC-NEC. A higher LDL-C level, lower TG, HDL-C, and non-HDL levels increased the risk of GC-NEC, and lower TG, and HDL-C levels increased the risk of GC-NENM and NEC.

Conclusion: GCNEI had distinct and heterogeneous serum lipid patterns, which correlated to tumor development and progression.
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http://dx.doi.org/10.1016/j.tranon.2020.100925DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7644677PMC
January 2021

Single-nucleotide polymorphism rs4142441 and MYC co-modulated long non-coding RNA OSER1-AS1 suppresses non-small cell lung cancer by sequestering ELAVL1.

Cancer Sci 2021 Jun 2;112(6):2272-2286. Epub 2021 May 2.

Department of Epidemiology, College of Preventive Medicine, Army Medical University, Third Military Medical University), Chongqing, China.

Single-nucleotide polymorphisms (SNP) and long non-coding RNAs (lncRNAs) have been involved in the process of lung cancer. Following clues given by lung cancer risk-associated SNP, we aimed to find novel functional lncRNAs as candidate targets in lung cancer. We identified a lncRNA Oxidative Stress Responsive Serine Rich 1 Antisense RNA 1 (OSER1-AS1) through a lung cancer risk-associated SNP rs4142441. OSER1-AS1 was down-regulated in tumor tissue and its low expression was significantly associated with poor overall survival among non-smokers in non-small cell lung cancer (NSCLC) patients. Gain- and loss-of-function studies showed that OSER1-AS1 acted as a tumor suppressor by inhibiting lung cancer cell growth, migration and invasion in vitro. Xenograft tumor assays and a metastasis mouse model confirmed that OSER1-AS1 suppressed tumor growth and metastasis in vivo. The promoter of OSER1-AS1 was repressed by MYC, and the 3'-end of OSER1-AS1 was competitively targeted by microRNA hsa-miR-17-5p and RNA-binding protein ELAVL1. Our results indicated that OSER1-AS1 exerted tumor-suppressive functions by acting as an ELAVL1 decoy to keep it away from its target mRNAs. Our findings characterized OSER1-AS1 as a new tumor-suppressive lncRNA in NSCLC, suggesting that OSER1-AS1 may be suitable as a potential biomarker for prognosis, and a potential target for treatment.
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http://dx.doi.org/10.1111/cas.14713DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8177763PMC
June 2021

Nanozyme and aptamer- based immunosorbent assay for aflatoxin B1.

J Hazard Mater 2020 11 11;399:123154. Epub 2020 Jun 11.

National "111" Center for Cellular Regulation and Molecular Pharmaceutics, Key Laboratory of Fermentation Engineering (Ministry of Education), College of Bioengineering and Food, Hubei University of Technology, Wuhan, Hubei 430068, PR China.

Traditional enzyme-linked immunosorbent assay (ELISA) suffers from the limitations of relatively low sensitivity and stability, and enzyme-labelled antibodies are hard to be prepared and purified. Based on a nanozyme, an aptamer and FeO magnetic nanoparticles (MNP), a nanozyme and aptamer-based immunosorbent assay (NAISA) was developed for aflatoxin B1 (AFB1) detection with simpler operation and separation. In this work, mesoporous SiO/Au-Pt (m-SAP) were prepared to act as signal labels, which showed high catalase-like activity and was denoted as nanozyme. Aptamer was adopted to specifically recognize with AFB1, and MNP facilitated to realize magnetic separation. To verify the performance of NAISA, traditional ELISA (t-ELISA) and enhanced ELISA (e-ELISA) using MNP and m-SAP nanozyme were applied in AFB1 detection. The NAISA method showed the lowest limit of detection (LOD) with 5 pg mL (n = 3, ±4.2 %), 600 and 12-fold lower than that of t-ELISA (3 ng mL) and e-ELISA (0.06 ng mL), respectively. In the interference tests, AFB1 can be identified among six different interfering substances. The NAISA method, thus, can be of great importance as it allows selective and sensitive AFB1 detection, while providing the simplicity of use and need for screening hazardous materials.
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http://dx.doi.org/10.1016/j.jhazmat.2020.123154DOI Listing
November 2020

Double-enzymes-mediated Fe/Fe conversion as magnetic relaxation switch for pesticide residues sensing.

J Hazard Mater 2021 02 11;403:123619. Epub 2020 Aug 11.

College of Food Science and Technology, Huazhong Agricultural University, Wuhan, 430070, PR China. Electronic address:

It is a great challenge to develop a newly rapid and accurate detection method for pesticide residues. In this work, based on acetylcholinesterase (AChE) and choline oxidase (CHO), a double-enzymes-mediated Fe/Fe conversion as magnetic relaxation switch was explored for the measurement of acetamiprid residue. In the double-enzymes reactions, acetylcholine chloride (ACh) can be catalyzed to produce choline by AChE, which is successively hydrolyzed to betaine and hydrogen peroxide (HO) by CHO. According to the enzyme inhibition principle, AChE activity will be inactivated in the presence of acetamiprid, thus leading to the less production of HO. Wherein, Fe, ACh, AChE and CHO were optimized as the reaction substrates. In the reaction system, acetamiprid can be reflected by the transverse relaxation time (T) that related with HO mediated Fe variations, which was further developed as an enzyme cascade amplification method. The detection linear range is 0.01∼1000 μg mL (R = 0.99), and the limit of detection (LOD) is 2.66 ng mL (S/N = 3, n = 3), behaving a 335-fold improvement in LOD than that of traditional enzyme inhibition method (0.89 μg mL). This method can realize "one-step mixing" detection of acetamiprid, which makes it a promising analytical tool for monitoring pesticide residue in complicated samples.
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http://dx.doi.org/10.1016/j.jhazmat.2020.123619DOI Listing
February 2021

The C/D box small nucleolar RNA SNORD52 regulated by Upf1 facilitates Hepatocarcinogenesis by stabilizing CDK1.

Theranostics 2020 23;10(20):9348-9363. Epub 2020 Jul 23.

Department of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, P.R. China.

Understanding the roles of small nucleolar RNAs (snoRNAs) in hepatocarcinogenesis will provide new avenues to identify diagnostic and therapeutic targets for hepatocellular carcinoma (HCC). Our previous research confirmed the tumor-suppressive effect of Up-frameshift 1 (Upf1) in HCC. Herein, we examined the expression profiles of snoRNAs regulated by Upf1 in hepatoma cells. We examined the expression profiles of snoRNAs regulated by Upf1 in hepatoma cells using RNA-sequencing analysis and then investigated the expression and significance of SNORD52 in HCC tissue and different cell lines. The protumorigenic effects of SNORD52 on HCC cells were confirmed both and by gain-of-function and loss-of-function assays. RNA pull-down assays and mass spectrometry were used to identify the RNA-binding protein that binds to SNORD52. Many snoRNAs were identified; one of which, the human C/D box small nucleolar RNA SNORD52, was upregulated in HCC tissues and negatively correlated with Upf1 expression, and patients with higher SNORD52 expression had a poor clinical prognosis. SNORD52 promoted HCC tumorigenesis both and . Mechanistically, KEGG analysis showed that SNORD52 upregulated a series of cell cycle genes in HCC cells. We further confirmed that SNORD52 upregulated CDK1 by enhancing the stability of CDK1 proteins and that the function of SNORD52 depends on the presence of CDK1. Overall, the present study indicates that SNORD52 could be a potential biomarker for HCC. Targeting the Upf1/SNORD52/CDK1 pathway might have therapeutic potential for HCC.
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http://dx.doi.org/10.7150/thno.47677DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7415794PMC
May 2021

Cellular heterogeneity map of diverse immune and stromal phenotypes within breast tumor microenvironment.

PeerJ 2020 10;8:e9478. Epub 2020 Jul 10.

Department of Oncology, Renmin Hospital of Wuhan University, Wuhan, China.

Background: Cellular heterogeneity within the tumor microenvironment is essential to tumorigenesis and tumor development. A high-resolution global view of the tumor-infiltrating immune and stromal cells in breast tumors is needed.

Methods: xCell was used to create a cellular heterogeneity map of 64 cell types in 1,092 breast tumor and adjacent normal tissues. xCell digitally dissects tissue cellular heterogeneity based on gene expression. Integrated statistical analyses were then performed.

Results: There were noticeable differences between the cell fractions in tumor tissues and normal tissues. Tumors displayed higher proportions of immune cells, including CD4+ Tem, CD8+ naïve T cells, and CD8+ Tcm compared with normal tissues. Immune inhibitory receptors (PD1, CTLA4, LAG3 and TIM3) were co-expressed on certain subtypes of T cells in breast tumors, and PD1 and CTLA4 were both positively correlated with CD8+ Tcm and CD8+ T cells. 28 cell types were significantly associated with overall survival in univariate analysis. CD4+ Tem, CD8+ Tcm, CD8+ T-cells, CD8+ naive T-cells, and B cells were positive prognostic factors but CD4+ naive T-cells were negative prognostic factors for breast cancer patients. TDRD6 and TTK are promising T cell and B cell targets for tumor vaccines. Endothelial cells and fibroblasts were significantly less prevalent in tumor tissues; astrocytes and mesangial cells were negatively correlated with the T stage. Mesangial cells and keratinocytes were found to be favorable prognostic factors and myocytes were negative prognostic factors. Five cell types were found to be independent prognostic factors and we used these to create a reliable prognostic model for breast cancer patients. Cellular heterogeneity was discovered among different breast cancer subtypes by Her2, ER, and PR status. Tri-negative patients had the highest fraction of immune cells while luminal type patients had the lowest. The various cells may have diverse or opposing roles in the prognosis of breast cancer patients.

Conclusions: We created a uniquecellular map for the diverse heterogeneity of immune and stromal phenotypes within the breast tumor microenvironment. This map may lead to potential therapeutic targets and biomarkers with prognostic utility.
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http://dx.doi.org/10.7717/peerj.9478DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7357563PMC
July 2020

Detection of chromosomal abnormalities in spontaneous miscarriage by low‑coverage next‑generation sequencing.

Mol Med Rep 2020 Aug 3;22(2):1269-1276. Epub 2020 Jun 3.

Institute of Antibody Engineering, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.

Chromosomal abnormalities (CAs) can cause spontaneous miscarriage and increase the incidence of subsequent pregnancy loss and other complications. Presently, CAs are detected mainly by array comparative genomic hybridization (CGH) and single nucleotide polymorphism microarrays. The present study developed a low‑coverage next‑generation sequencing method to detect CAs in spontaneous miscarriage and assess its clinical performance. In total, 1,401 patients who had experienced an abortion were enrolled in the present study and divided into two groups. In group I, 437 samples that had been previously validated by array CGH were used to establish a method to detect CAs using a semiconductor sequencing platform. In group II, 964 samples, which were not verified, were assessed using established methods with respect to clinical significance. Copy number variant (CNV)‑positive and euploidy samples were verified by array CGH and short tandem repeat profiling, respectively, based on quantitative fluorescent PCR. The low‑coverage sequencing method detected CNVs >1 Mb in length and a total of 3.5 million unique reads. Similar results to array CGH were obtained in group I, except for six CNVs <1 Mb long. In group II, there were 341 aneuploidies, 195 CNVs, 25 mosaicisms and 403 euploidies. Overall, among the 1,401 abortion samples, there were 536 aneuploidies, 263 CNVs, 34 mosaicisms, and 568 euploidies. Trisomies were present in all autosomal chromosomes. The most common aneuploidies were T16, monosomy X, T22, T15, T21 and T13. Furthermore, one tetrasomy 21, one CNV associated with Wolf‑Hirschhorn syndrome, one associated with DiGeorge syndrome and one associated with both Prader‑Willi and Angelman syndromes were identified. These four cases were confirmed by short tandem repeat profiling and array CGH. Quantitative fluorescent PCR revealed nine polyploidy samples. The present method demonstrated equivalent efficacy to that of array CGH in detecting CNVs >1 Mb, with advantages of requiring less input DNA and lower cost.
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http://dx.doi.org/10.3892/mmr.2020.11208DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7339674PMC
August 2020

Prognostic value of chemokines in patients with newly diagnosed atrial fibrillation.

Int J Cardiol 2020 Dec 27;320:83-89. Epub 2020 Jun 27.

Department of Epidemiology, College of Preventive Medicine, Army Medical University (Third Military Medical University), Chongqing 400038, People's Republic of China; Evidence-based Medicine and Clinical Epidemiology Center, Army Medical University (Third Military Medical University), Chongqing 400038, People's Republic of China. Electronic address:

Background: Chemokines play an important role in inflammation and atherosclerosis. However, little is known about the relationship between chemokines and the prognosis of atrial fibrillation (AF). This "real-world" cohort study was designed to observe the prognostic value of plasma CC motif chemokine ligand (CCL) 18, CCL23, CCL28, CXC motif chemokine ligand (CXCL) 14, CXCL16 in newly diagnosed AF patients.

Methods: Baseline plasma levels of chemokines were measured in a cohort with 299 AF patients using Bio-plex Pro™ xMAP arrays. A Cox proportional hazard model was used to evaluate the associations of chemokines with AF outcomes. Net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were calculated to evaluate the improvement of chemokines to CHADS-VASc score.

Results: High CCL18 (hazard ratio [HR] 2.65, 95% confidence interval [CI] 1.18-5.98, P = 0.019) and CCL23 levels (HR 2.78, 95%CI 1.07-7.22, P = 0.036) were associated with stroke in AF patient. Patients with low CXCL14 (HR 0.39, 95%CI 0.15-0.97, P = 0.042) and high CXCL16 levels (HR 3.02, 95%CI 1.39-6.58, P = 0.005) have increased risk of all-cause mortality. High CCL16 levels (HR 5.41, 95%CI 2.32-12.63, P < 0.001) were associated with cardiovascular death. However, CCL28 had no significant association with outcomes. Adding chemokines to CHADS-VASc score increased the reclassification and clinical net benefit.

Conclusions: Plasma levels of CCL18, CCL23, CXCL14, and CXCL16 were independently associated with AF outcomes. Chemokines added to CHADS-VASc score significantly enhanced risk assessment for the outcomes. Incorporation of chemokines into clinical decisions may help the management of AF treatment.
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http://dx.doi.org/10.1016/j.ijcard.2020.06.030DOI Listing
December 2020
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