Publications by authors named "Ling Fei"

168 Publications

Epitope screening of the major capsid protein within grouper iridovirus of Taiwan and the immunoprotective effect with SWCNTs as the vaccine carrier.

Fish Shellfish Immunol 2021 Jul 16;117:17-23. Epub 2021 Jul 16.

College of Animal Science and Technology, Northwest A & F University, Yangling, 712100, China. Electronic address:

Iridovirus can cause a mass of death in grouper, leading to huge economic loss in recent years. At present, practical vaccine is still the best way to control the outbreak of this virus. Many researches had indicated that the major capsid protein (MCP) of grouper iridovirus of Taiwan (TGIV) is an effective antigen to induce a specific immune response in grouper. However, these traditional vaccines that based on large proteins or whole organisms are faced with challenges because of the unnecessary antigenic load. Thus, in this study, we screened the dominant linear epitope within the MCP of TGIV and then, a new peptide vaccine (P2) was developed via prokaryotic expression system. Furthermore, SWCNTs was used as a vaccine carrier to enhance the immunoprotective effect. To evaluate the immunoprotective effect of this vaccine, a total of 245 fish were vaccinated with P2 (5, 10, 20 mg L) and SWCNTs-P2 (5, 10, 20 mg L) via immersion before being challenged with live TGIV at 28 days post immunization (d.p.i.). Results showed that the serum antibody titer, enzymatic activity, expression level of some immune-related genes (CC chemokine, IgM and TNF-α) and survival rate were significantly increased (SWCNTs-P2, 20 mg L, 100%) compared to the control group (0%). These results indicated that this peptide vaccine could effectively induce specific immune response in vaccinated groupers. Functionalized SWCNTs could serve as a carrier of the peptide vaccine to enhance the immunoprotective effect via immersion. To sum up, epitope screening might be a potential way to develop an effective vaccine nowadays, and SWCNTs might provide a practical method that can be used in large-scale vaccination, especially for juvenile fish, to fight against diseases in aquaculture industry.
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http://dx.doi.org/10.1016/j.fsi.2021.07.013DOI Listing
July 2021

New genetic variants associated with major adverse cardiovascular events in patients with acute coronary syndromes and treated with clopidogrel and aspirin.

Pharmacogenomics J 2021 Jun 22. Epub 2021 Jun 22.

Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.

Although a few studies have reported the effects of several polymorphisms on major adverse cardiovascular events (MACE) in patients with acute coronary syndromes (ACS) and those undergoing percutaneous coronary intervention (PCI), these genotypes account for only a small fraction of the variation and evidence is insufficient. This study aims to identify new genetic variants associated with MACE end point during the 18-month follow-up period by a two-stage large-scale sequencing data, including high-depth whole exome sequencing of 168 patients in the discovery cohort and high-depth targeted sequencing of 1793 patients in the replication cohort. We discovered eight new genotypes and their genes associated with MACE in patients with ACS, including MYOM2 (rs17064642), WDR24 (rs11640115), NECAB1 (rs74569896), EFR3A (rs4736529), AGAP3 (rs75750968), ZDHHC3 (rs3749187), ECHS1 (rs140410716), and KRTAP10-4 (rs201441480). Notably, the expressions of MYOM2 and ECHS1 are downregulated in both animal models and patients with phenotypes related to MACE. Importantly, we developed the first superior classifier for predicting 18-month MACE and achieved high predictive performance (AUC ranged between 0.92 and 0.94 for three machine-learning methods). Our findings shed light on the pathogenesis of cardiovascular outcomes and may help the clinician to make a decision on the therapeutic intervention for ACS patients.
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http://dx.doi.org/10.1038/s41397-021-00245-5DOI Listing
June 2021

Synergistic adsorption and degradation of sulfamethoxazole from synthetic urine by hickory-sawdust-derived biochar: The critical role of the aromatic structure.

J Hazard Mater 2021 Jun 9;418:126366. Epub 2021 Jun 9.

Department of Civil Engineering, University of Louisiana at Lafayette, Lafayette, LA, 70504, USA; Energy Institute of Louisiana, University of Louisiana at Lafayette, Lafayette, LA, 70504, USA. Electronic address:

This study investigated the adsorptive removal and subsequent degradation of sulfamethoxazole (SMX) from a synthetic urine by biochar (BC). The BCs used in this study were prepared using two different feedstocks with different temperatures. Element analysis and Fourier transform infrared spectroscopy (FTIR) results suggested that the aromaticity of one of the BCs, 700HSBC was significantly different from the 700PSBC although both of them were prepared at the same temperature (700 °C) with similar pore size distributions and specific surface areas. Due to the presence of abundant aromatic structures, 700HSBC showed a higher SMX uptake than 700PSBC, suggesting that the π-π interaction was the main adsorption mechanism. The removal of SMX from the urine was significantly enhanced by adding hydrogen peroxide to the 700HSBC. The carbonate radicals degradation of SMX mechanism was proposed and verified. With 700HSBC having abundant aromatic structures acting as π-electron donors, it could be an efficient activator for peroxymonocarbonate (HCO) to generate carbonate radicals. Hence, it could be concluded that the aromatic structures on BCs play a key role in both of the adsorption and hydrogen peroxide degradation of the SMX resulting in its removal from urine.
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http://dx.doi.org/10.1016/j.jhazmat.2021.126366DOI Listing
June 2021

A Novel Prediction Model of COVID-19 Progression: A Retrospective Cohort Study.

Infect Dis Ther 2021 Sep 14;10(3):1491-1504. Epub 2021 Jun 14.

Department of Liver Diseases, Shanghai Public Health Clinical Center, Fudan University, Shanghai, 201508, China.

Introduction: Estimating the risk of disease progression is of utmost importance for planning appropriate setting of care and treatment for patients with coronavirus disease 2019 (COVID-19). This study aimed to develop and validate a novel prediction model of COVID-19 progression.

Methods: In total, 814 patients in the training set were included to develop a novel scoring system; and 420 patients in the validation set were included to validate the model.

Results: A prediction score, called ACCCDL, was developed on the basis of six risk factors associated with COVID-19 progression: age, comorbidity, CD4 T cell count, C-reactive protein (CRP), D-dimer, and lactate dehydrogenase (LDH). For predicting COVID-19 progression, the ACCCDL score yielded a significantly higher area under the receiver operating characteristic curve (AUROC) compared with the CALL score, CoLACD score, PH-COVID-19 score, neutrophil-lymphocyte ratio, and lymphocyte-monocyte ratio both in the training set (0.92, 0.84, 0.83, 0.83, 0.76, and 0.65, respectively) and in the validation set (0.97, 0.83, 0.83, 0.78, 0.74, and 0.60, respectively). Over 99% of patients with the ACCCDL score < 12 points will not progress to severe cases, and over 30% of patients with the ACCCDL score > 20 points will progress to severe cases.

Conclusion: The ACCCDL score could stratify patients with at risk of COVID-19 progression, and was useful in regulating the large flow of patients with COVID-19 between primary health care and tertiary centers.
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http://dx.doi.org/10.1007/s40121-021-00460-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8202540PMC
September 2021

Dynamic changes in coagulation parameters and correlation with disease severity and mortality in patients with COVID-19.

Aging (Albany NY) 2021 05 24;13(10):13393-13404. Epub 2021 May 24.

Department of Liver Diseases, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China.

Objective: This study aimed to describe the dynamic changes of coagulation parameters and evaluate the relationship between longitudinal coagulation parameters abnormalities and prognosis of COVID-19 patients.

Methods: We performed a retrospective study of 1131 COVID-19 patients. Longitudinal coagulation parameters and clinical outcomes were analyzed.

Results: Abnormal coagulation parameters were observed in patients with COVID-19, both at hospital admission (INR 2.3%, PT 7.9%, APTT 15.4%, TT 0.9%, FDP 2.3%, D-dimer 19.7%) and peak hospitalization (INR 4.8%, PT 13.4%, APTT 25.6%, TT 2.7%, FDP 10.4%, D-dimer 31.5%). Compared with non-severe patients with COVID-19, severe patients had a slightly higher INR, PT, APTT, whereas remarkably higher FDP and D-dimer ( < 0.05). On multivariate analysis, age > 60 years, male, obesity, comorbidity, abnormal D-dimer on hospital admission, and abnormal peak hospitalization PT, APTT, FDP and D-dimer were associated with COVID-19 severity. The extreme coagulation parameters abnormalities (PT > 16s, FDP > 50 ug/ml, and D-dimer > 5 ug/ml) were associated with a significantly higher mortality.

Conclusion: Longitudinal coagulation parameters abnormalities are common in patients with COVID-19, and associated with disease severity and mortality. Monitoring coagulation parameters is advisable to improve the management of patients with COVID-19.
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http://dx.doi.org/10.18632/aging.203052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8202864PMC
May 2021

Dietary supplementation of Bacillus velezensis B8 enhances immune response and resistance against Aeromonas veronii in grass carp.

Fish Shellfish Immunol 2021 Aug 17;115:14-21. Epub 2021 May 17.

College of Animal Science and Technology, Northwest A&F University, Xinong Road 22nd, Yangling, Shaanxi, 712100, China. Electronic address:

The heavy use of prophylactic antibiotics in aquaculture leads to elevated antibiotic residues, posing a huge hidden danger in aquaculture products and other natural aquatic environments. Therefore, this study aims to isolate probiotics that can replace antibiotics from the gut of grass carp for disease control. Bacillus velezensis B8 was isolated from the gut of grass carp and showed broad-spectrum antimicrobial activity against several fish pathogenic bacteria, including Aeromonas hydrophilis, Aeromonas veronii, Vibrio parahaemolyticus, Escherichia coli, Edwardsiella tarda and Vibrio mimicus. The safety evaluation showed that the strain B8 was non-toxic to grass carp, had no hemolytic activity, and was sensitive to most antibiotics. In vitro study indicated that strain B8 was viable at pH 2-7, had weak tolerance to 0.1% (w/v) bile salt, and could grow at 10°C-40 °C. The grass carps were fed with diets containing 0 (control), 10, and 10 cfu/g of strain B8 for 4 weeks. Various immune parameters were measured at 1, 2, 3, and 4 weeks of post-feeding. The results of non-specific immunoassay showed that diets supplemented with B8 significantly increased alkaline phosphatase (AKP) and superoxide dismutase (SOD) activity in serum samples (p < 0.05). The expression levels of immune-related genes in the kidney and spleen of grass carp were measured. Among them, the expression levels of IgM and TNF-α both in spleen and kidney were significantly increased after 3 and 4 weeks of post-feeding (p < 0.05). The expression of IgD and MHCI in kidney was significantly upregulated in high-dose groups after 2 and 3 weeks of feeding, respectively (p < 0.05). In addition, after 7 days of challenging with A. veronii, the high-dose group and low-dose group had 48% and 53% survival compared to 25% survival for the control group. These results suggest that B. velezensis B8 has the potential to be developed into a microecological preparation for the alternatives of antibiotics in aquaculture.
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http://dx.doi.org/10.1016/j.fsi.2021.05.012DOI Listing
August 2021

Enantioselective synthesis of functionalized 1,4-dihydropyrazolo-[4',3':5,6]pyrano[2,3-]quinolines through ferrocenyl-phosphine-catalyzed annulation of modified MBH carbonates and pyrazolones.

Chem Commun (Camb) 2021 May;57(38):4690-4693

College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou 310014, People's Republic of China.

An enantioselective synthesis of highly functionalized 1,4-dihydropyrazolo[4',3':5,6]pyrano[2,3-b]quinolines from modified MBH carbonates and pyrazolones via a chiral phosphine-mediated alkylation/annulation sequence has been realized. The chiral dihydropyrano[2,3-c]pyrazoles bearing bio-active condensed heterocycles were facilely formed in good chemical yields and with high to excellent enantioselectivity by utilizing low catalyst loading.
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http://dx.doi.org/10.1039/d1cc00989cDOI Listing
May 2021

Efficacy Evaluation of Thymosin Alpha 1 in Non-severe Patients With COVID-19: A Retrospective Cohort Study Based on Propensity Score Matching.

Front Med (Lausanne) 2021 23;8:664776. Epub 2021 Apr 23.

Department of Liver Diseases, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.

Thymosin alpha 1 (Thymosin-α1) is a potential treatment for patients with COVID-19. We aimed to determine the effect of Thymosin-α1 in non-severe patients with COVID-19. We retrospectively enrolled 1,388 non-severe patients with COVID-19. The primary and secondary clinical outcomes were evaluated with comparisons between patients treated with or without Thymosin-α1 therapy. Among 1,388 enrolled patients, 232 patients (16.7%) received both Thymosin-α1 therapy and standard therapy (Thymosin-α1 group), and 1,156 patients (83.3%) received standard therapy (control group). After propensity score matching (1:1 ratio), baseline characteristics were well-balanced between the Thymosin-α1 group and control group. The proportion of patients that progressed to severe COVID-19 is 2.17% for the Thymosin-α1 group and 2.71% for the control group ( = 0.736). The COVID-19-related mortality is 0.54% for the Thymosin-α1 group and 0 for the control group ( = 0.317). Compared with the control group, the Thymosin-α1 group had significantly shorter SARS-CoV-2 RNA shedding duration (13 vs. 16 days, = 0.025) and hospital stay (14 vs. 18 days, < 0.001). No statistically significant difference was found between the Thymosin-α1 group and control group in duration of symptoms (median, 4 vs. 3 days, = 0.843) and antibiotic utilization rate (14.1% vs. 15.2%, = 0.768). For non-severe patients with COVID-19, Thymosin-α1 can shorten viral RNA shedding duration and hospital stay but did not prevent COVID-19 progression and reduce COVID-19-related mortality rate.
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http://dx.doi.org/10.3389/fmed.2021.664776DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102900PMC
April 2021

Immune Gene Expression Covaries with Gut Microbiome Composition in Stickleback.

mBio 2021 05 4;12(3). Epub 2021 May 4.

University of Connecticut, Department of Ecology and Evolutionary Biology, Storrs, Connecticut, USA.

Commensal microbial communities have immense effects on their vertebrate hosts, contributing to a number of physiological functions, as well as host fitness. In particular, host immunity is strongly linked to microbiota composition through poorly understood bi-directional links. Gene expression may be a potential mediator of these links between microbial communities and host function. However, few studies have investigated connections between microbiota composition and expression of host immune genes in complex systems. Here, we leverage a large study of laboratory-raised fish from the species (three-spined stickleback) to document correlations between gene expression and microbiome composition. First, we examined correlations between microbiome alpha diversity and gene expression. Our results demonstrate robust positive associations between microbial alpha diversity and expression of host immune genes. Next, we examined correlations between host gene expression and abundance of microbial taxa. We identified 15 microbial families that were highly correlated with host gene expression. These families were all tightly correlated with host expression of immune genes and processes, falling into one of three categories-those positively correlated, negatively correlated, and neutrally related to immune processes. Furthermore, we highlight several important immune processes that are commonly associated with the abundance of these taxa, including both macrophage and B cell functions. Further functional characterization of microbial taxa will help disentangle the mechanisms of the correlations described here. In sum, our study supports prevailing hypotheses of intimate links between host immunity and gut microbiome composition. Here, we document associations between host gene expression and gut microbiome composition in a nonmammalian vertebrate species. We highlight associations between expression of immune genes and both microbiome diversity and abundance of specific microbial taxa. These findings support other findings from model systems which have suggested that gut microbiome composition and host immunity are intimately linked. Furthermore, we demonstrate that these correlations are truly systemic; the gene expression detailed here was collected from an important fish immune organ (the head kidney) that is anatomically distant from the gut. This emphasizes the systemic impact of connections between gut microbiota and host immune function. Our work is a significant advancement in the understanding of immune-microbiome links in nonmodel, natural systems.
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http://dx.doi.org/10.1128/mBio.00145-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8262870PMC
May 2021

Correction: Enantioselective synthesis of functionalized 1,4-dihydropyrazolo-[4',3':5,6]pyrano[2,3-b]quinolines through ferrocenyl-phosphine-catalyzed annulation of modified MBH carbonates and pyrazolones.

Chem Commun (Camb) 2021 May 21;57(35):4331. Epub 2021 Apr 21.

Institute of Pharmaceutical Science and Technology, Zhejiang University of Technology, Hangzhou 310014, People's Republic of China.

Correction for 'Enantioselective synthesis of functionalized 1,4-dihydropyrazolo-[4',3':5,6]pyrano[2,3-b]quinolines through ferrocenyl-phosphine-catalyzed annulation of modified MBH carbonates and pyrazolones' by Xiao Xiao et al., Chem. Commun., 2021, DOI: .
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http://dx.doi.org/10.1039/d1cc90146jDOI Listing
May 2021

Dynamic Changes in Liver Function Tests and Their Correlation with Illness Severity and Mortality in Patients with COVID-19: A Retrospective Cohort Study.

Clin Interv Aging 2021 21;16:675-685. Epub 2021 Apr 21.

Department of Liver Diseases, Shanghai Public Health Clinical Center, Fudan University, Shanghai, 201508, People's Republic of China.

Objective: To describe the longitudinal changes in liver function tests, and their association with illness severity and mortality in patients with COVID-19.

Methods: A retrospective cohort study of 1003 hospitalized patients with COVID-19 was conducted. Longitudinal liver function tests and clinical outcomes were analyzed.

Results: Abnormal liver function parameters were observed, both at admission (ALT 13.2%, AST 8.5%, ALP 2.0%, GGT 7.4%, LDH 37.6%, TBIL 4.0%, DBIL 7.8%, Albumin 10.1%) and peak hospitalization (ALT 29.4%, AST 17.5%, ALP 2.6%, GGT 13.4%, LDH 49.4%, TBIL 10.1%, DBIL 18.0%, Albumin 30.6%) in patients with COVID-19. Compared with non-severe patients, severe patients had markedly higher liver function parameters from baseline to 30 days after hospital admission. Abnormal ALT and LDH at hospital admission and some medications use (Hydroxychloroquine, Lopinavir/Ritonavir, and Traditional Chinese medicines) were associated with peak hospitalization ALT > 5× the upper limit unit of normal (ULN). On multivariate analysis, age >60 years, male, obesity, comorbidity, abnormal LDH and albumin at hospital admission and peak hospitalization were associated with progression to severe COVID-19 (OR > 1; < 0.05). COX analysis revealed that ALT > 2 ULN (HR=7.0, =0.011), AST > 2 ULN (HR=34.7, < 0.001), and TBIL > 2 ULN (HR=54.6, < 0.001) were associated with a higher mortality.

Conclusion: Dynamic abnormalities of liver function parameters are common in hospitalized patients with COVID-19, and associated with illness severity and mortality.
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http://dx.doi.org/10.2147/CIA.S303629DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8071705PMC
May 2021

A Novel Prediction Model for Long-Term SARS-CoV-2 RNA Shedding in Non-Severe Adult Hospitalized Patients with COVID-19: A Retrospective Cohort Study.

Infect Dis Ther 2021 Jun 31;10(2):897-909. Epub 2021 Mar 31.

Department of Liver Diseases, Shanghai Public Health Clinical Center, Fudan University, Shanghai, 201508, China.

Introduction: Due to the lack of clear direction (evidence) on the duration of viral shedding and thus potential for transmission, this retrospective study aimed to come up with a prediction model of prolonged coronavirus disease-19 (COVID-19) transmission or infection-spreading potential.

Methods: A total of 1211 non-severe patients with COVID-19 were retrospectively enrolled. Multivariate Cox regression was performed to identify the risk factors associated with long-term SARS-CoV-2 RNA shedding, and a prediction model was established.

Results: In the training set, 796 patients were divided into the long-term (> 21 days) group (n = 116, 14.6%) and the short-term (≤ 21 days) group (n = 680, 85.4%) based on their viral shedding duration. Multivariate analysis identified that age > 50 years, comorbidity, CD4-positive T-lymphocytes count (CD4 + T cell) ≤ 410 cells/ul, C-reactive protein (CRP) > 10 mg/L, and the corticosteroid use were independent risk factors for long-term SARS-CoV-2 RNA shedding. Incorporating the five risk factors, a prediction model, named as the CCCCA score, was established, and its area under the receiver operator characteristic curve (AUROC) was 0.87 in the training set and 0.83 in the validation set, respectively. In the validation set, using a cut-off of 8 points, we found sensitivity, specificity, positive predictive value, and negative predictive value of 51.7%, 92.2%, 33.3%, and 96.2%, respectively. Long-term SARS-CoV-2 RNA shedding increased from 14/370 (3.8%) in patients with CCCCA < 8 points to 15/45 (33.3%) in patients with CCCCA ≥ 8 points.

Conclusion: Using the CCCCA score, clinicians can identify patients with long-term SARS-CoV-2 RNA shedding.
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http://dx.doi.org/10.1007/s40121-021-00437-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8011066PMC
June 2021

Comparative proteomic analysis provides insight into the key proteins as potential targets underlying the effect of malachite green against Ichthyophthirius multifiliis.

J Fish Dis 2021 Jul 9;44(7):881-892. Epub 2021 Feb 9.

Northwest A&F University, Yangling, Shaanxi, China.

Target identification is important for drug discovery. Unfortunately, no drug targets have been found in Ichthyophthirius multifiliis until now and further limited development of the novel drug for Ichthyophthiriasis. In this study, an iTRAQ-based quantitative proteomic analysis was used to find the target of malachite green (MG), exhibiting greater efficacy than the existing drugs, against I. multifiliis trophonts in situ. We also verified the proteomic results by RT-qPCR, TEM and cell apoptosis assay. Our results showed that major variations in protein abundance were found among many of the ribosome proteins, indicating ribosome might be a candidate target. Furthermore, GO and KEGG pathway analyses of differentially expressed proteins (DEPs) revealed that ribosome and PI3K-Akt signalling pathway were remarkably enriched. Taken together, the above DEPs were also verified by RT-qPCR and morphological observations. This study provides insights into the key proteins enriched in PI3K-Akt signal pathway and ribosome pathway as potential targets of MG killing I. multifiliis, which could be served as targets for other less toxic drugs and be tested as potential treatments for I. multifiliis.
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http://dx.doi.org/10.1111/jfd.13346DOI Listing
July 2021

Multiregion single-cell sequencing reveals the transcriptional landscape of the immune microenvironment of colorectal cancer.

Clin Transl Med 2021 01;11(1):e253

Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, School of Medicine, South China University of Technology, Guangzhou, Guangdong, China.

The tumor microenvironment is a complex ecosystem formed by distinct and interacting cell populations, and its composition is related to cancer prognosis and response to clinical treatment. In this study, we have taken the advantage of two single-cell RNA sequencing technologies (Smart-seq2 and DNBelab C4) to generate an atlas of 15,115 immune and nonimmune cells from primary tumors and hepatic metastases of 18 colorectal cancer (CRC) patients. We observed extensive changes in the proportions and functional states of T cells and B cells in tumor tissues, compared to those of paired non-tumor tissues. Importantly, we found that B cells from early CRC tumor were identified to be pre-B like expressing tumor suppressors, whereas B cells from advanced CRC tumors tended to be developed into plasma cells. We also identified the association of IgA IGLC2 plasma cells with poor CRC prognosis, and demonstrated a significant interaction between B-cell and myeloid-cell signaling, and found CCL8 cycling B cells/CCR5 T-cell interactions as a potential antitumoral mechanism in advanced CRC tumors. Our results provide deeper insights into the immune infiltration within CRC, and a new perspective for the future research in immunotherapies for CRC.
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http://dx.doi.org/10.1002/ctm2.253DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7775989PMC
January 2021

Efficacy evaluation of intravenous immunoglobulin in non-severe patients with COVID-19: A retrospective cohort study based on propensity score matching.

Int J Infect Dis 2021 Apr 9;105:525-531. Epub 2021 Jan 9.

Department of Liver Disease, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China. Electronic address:

Objectives: At the present time, there is an absence of any proven effective antiviral therapy for patients with coronavirus disease 2019 (COVID-19). The aim of this study was to assess the efficacy of intravenous immunoglobulin (IVIG) in non-severe patients with COVID-19.

Methods: A retrospective study based on propensity score matching (PSM) was designed. Primary outcomes included the severity and mortality rates. Secondary outcomes included the duration of fever, virus clearance time, length of hospital stay, and use of antibiotics.

Results: A total of 639 non-severe patients with COVID-19 were enrolled. Forty-five patients received IVIG therapy and 594 received non-IVIG therapy. After PSM (1:2 ratio), the baseline characteristics were well balanced between the IVIG group (n = 45) and control group (n = 90). No statistically significant difference was found between the IVIG group and control group in the duration of fever (median 3 vs 3 days, p = 0.667), virus clearance time (median 11 vs 10 days, p = 0.288), length of hospital stay (median 14 vs 13 days, p = 0.469), or use of antibiotics (40% vs 38.9%, p = 0.901). Meanwhile, compared to the IVIG group, no more patients in the control group progressed to severe disease (3.3% vs 6.6%, p = 0.376) or died (0 vs 2.2%, p = 0.156).

Conclusions: In non-severe patients with COVID-19, no benefit was observed with IVIG therapy beyond standard therapy.
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http://dx.doi.org/10.1016/j.ijid.2021.01.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7833031PMC
April 2021

Leptin Receptor (LEPR) promotes proliferation, migration, and invasion and inhibits apoptosis in hepatocellular carcinoma by regulating ANXA7.

Cancer Cell Int 2021 Jan 4;21(1). Epub 2021 Jan 4.

Department of Pathology, College of Basic Medical Sciences, Dalian Medical University, 9 W. Lushun South Road, Dalian, 116044, Liaoning, China.

Background: Leptin Receptor (LEPR) has been suggested to have several roles in cancer metastasis. However, the role of LEPR and its underlying mechanisms in lymphatic metastasis of hepatocarcinoma have not yet been studied.

Methods: We performed bioinformatics analysis, qRT-PCR, western blotting, immunohistochemistry, immunofluorescence, enzyme-linked immunosorbent, coimmunoprecipitation assays and a series of functional assays to investigate the roles of LEPR in hepatocellular carcinoma.

Results: We discovered that LEPR was highly expressed in liver cancer tissues, and the expression of LEPR in Hca-F cells was higher than that in Hca-P cells. Furthermore, LEPR promotes the proliferation, migration and invasion and inhibits the apoptosis of hepatocarcinoma lymphatic metastatic cells. Further studies indicated that LEPR interacts with ANXA7. Mechanistically, LEPR regulated ERK1/2 and JAK2/STAT3 expression via ANXA7 regulation.

Conclusions: These findings unveiled a previously unappreciated role of LEPR in the regulation of lymphatic metastatic hepatocellular carcinoma, assigning ANXA7-LEPR as a promising therapeutic target for liver cancer treatments.
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http://dx.doi.org/10.1186/s12935-020-01641-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7784271PMC
January 2021

Atorvastatin Reduces Accumulation of Vascular Smooth Muscle Cells to Inhibit Intimal Hyperplasia via p38 MAPK Pathway Inhibition in a Rat Model of Vein Graft.

Arq Bras Cardiol 2020 10;115(4):630-636

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

Background: The rate of saphenous vein graft failure one year after coronary artery bypass grafting ranges from 10% to 25%. The aim of this study was to explore whether atorvastatin can reduce accumulation of vascular smooth muscle cells to inhibit intimal hyperplasia via p38 MAPK pathway inhibition.

Methods: Forty-five Sprague-Dawley rats were randomized to three groups. Thirty rats received a vein graft operation, and they were randomized to be treated with vehicle or atorvastatin; fifteen rats received a sham operation. We detected intimal hyperplasia by hematoxylin-eosin staining and related protein expression by immunohistochemical and Western blot analysis. Comparisons were analyzed by single-factor analysis of variance and Fisher's least significant difference test, with p < 0.05 considered significant.

Results: The intima analyzed by hematoxylin-eosin staining was dramatically thicker in the control group than in the atorvastatin group and sham group (p < 0.01). The outcomes of immunohistochemical staining of α-SMA demonstrated that the percentage of α-SMA-positive cells in the control group was higher than in the atorvastatin group (p < 0.01). We also evaluated α-SMA, PCNA, p38 MAPK, and phosphorylation of p38 MAPK after statin treatment by Western blot analysis, and the results indicated that atorvastatin did not lead to p38 MAPK reduction (p < 0.05); it did, however, result in inhibition of p38 MAPK phosphorylation (p < 0.01), and it significantly reduced α-SMA and PCNA levels, in comparison with the control group (p < 0.01).

Conclusion: We have demonstrated that atorvastatin can inhibit accumulation of vascular smooth muscle cells by inhibiting the p38 MAPK pathway, and it is capable of inhibiting intimal hyperplasia in a rat vein graft model.
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http://dx.doi.org/10.36660/abc.20190231DOI Listing
October 2020

Single Cobalt Sites Dispersed in Hierarchically Porous Nanofiber Networks for Durable and High-Power PGM-Free Cathodes in Fuel Cells.

Adv Mater 2020 Nov 15;32(46):e2003577. Epub 2020 Oct 15.

Department of Chemical and Biological Engineering, University at Buffalo, The State University of New York, Buffalo, NY, 14260, USA.

Increasing catalytic activity and durability of atomically dispersed metal-nitrogen-carbon (M-N-C) catalysts for the oxygen reduction reaction (ORR) cathode in proton-exchange-membrane fuel cells remains a grand challenge. Here, a high-power and durable Co-N-C nanofiber catalyst synthesized through electrospinning cobalt-doped zeolitic imidazolate frameworks into selected polyacrylonitrile and poly(vinylpyrrolidone) polymers is reported. The distinct porous fibrous morphology and hierarchical structures play a vital role in boosting electrode performance by exposing more accessible active sites, providing facile electron conductivity, and facilitating the mass transport of reactant. The enhanced intrinsic activity is attributed to the extra graphitic N dopants surrounding the CoN moieties. The highly graphitized carbon matrix in the catalyst is beneficial for enhancing the carbon corrosion resistance, thereby promoting catalyst stability. The unique nanoscale X-ray computed tomography verifies the well-distributed ionomer coverage throughout the fibrous carbon network in the catalyst. The membrane electrode assembly achieves a power density of 0.40 W cm in a practical H /air cell (1.0 bar) and demonstrates significantly enhanced durability under accelerated stability tests. The combination of the intrinsic activity and stability of single Co sites, along with unique catalyst architecture, provide new insight into designing efficient PGM-free electrodes with improved performance and durability.
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http://dx.doi.org/10.1002/adma.202003577DOI Listing
November 2020

Ruthenium-Catalyzed Electrochemical Synthesis of Indolines through Dehydrogenative [3 + 2] Annulation with H Evolution.

J Org Chem 2020 Nov 13;85(21):13735-13746. Epub 2020 Oct 13.

Key Laboratory for Green Pharmaceutical Technologies and Related Equipment of Ministry of Education, College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou 310014, People's Republic of China.

A dehydrogenative [3 + 2] annulation reaction of aniline derivatives and alkenes has been developed via the ruthenium-electron catalytic systems for the synthesis of versatile indolines. Electricity is used as a sustainable oxidant to regenerate the active Ru(II) catalyst and promote H evolution. This protocol is ecofriendly and easy to handle as it uses a simple undivided cell in mild conditions without the employment of metal oxidants.
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http://dx.doi.org/10.1021/acs.joc.0c01879DOI Listing
November 2020

A Mini Review on Superhydrophobic and Transparent Surfaces.

Chem Rec 2020 Nov 21;20(11):1257-1268. Epub 2020 Sep 21.

School of Chemistry and Chemical Engineering, Anhui University, Jiulong Road 111, Anhui, 23003, China.

In recent years, self-cleaning and transparent surfaces have been widely studied for application on smart windows, solar panels, camera lenses, and other optoelectronic devices. The self-cleaning properties can possibly extend the lifetime of these products and decrease, even eliminate, the requirement of chemical detergents and high labor costs of cleaning. It can also promote the overall efficiency of outdoor optoelectronic devices (e. g. solar cell panels) since dirt accumulation and bacteria growth can be slowed down, even inhibited on such surfaces. In this mini review, the fundamentals and conditions that govern superhydrophobicity and transparency are introduced, followed by the discussion of roughness as the competing factor for superhydrophobicity and transparency. Representative examples of the surface design and fabrication are introduced and future perspectives are shared. This mini review can help the research community better understand such surfaces and further accelerate its development for innovative practical applications.
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http://dx.doi.org/10.1002/tcr.202000075DOI Listing
November 2020

The potential mechanism of action of Sorcin and its interacting proteins.

Clin Chim Acta 2020 Nov 15;510:741-745. Epub 2020 Sep 15.

Department of Pathology, Dalian Medical University, Dalian 116044, China. Electronic address:

Sorcin (Soluble resistance-related calcium binding protein) is a calcium binding oncoprotein. Sorcin is overexpressed in several human tumors and cancer cells lines which confers multidrug resistance (MDR) to these cells. This review summarizes the biochemical functions of Sorcin which includes modulation of calcium homeostasis, apoptosis, and cancer metastasis. Sorcin is involved in various biological processes by interacting with other proteins, such as p-glycoprotein, programmed cell death protein 6, tumor necrosis factor receptor-associated protein 1, Annexin A7, polo-like kinase 1, HCV nonstructural 5A, signal transducer and activator of transcription 3, presenilin 2, α-synuclein, Ca-release channel and others. A deeper look into the function and interacting partners of Sorcin sheds more light on the possible effects of its physical activity and more elaborately, exploring the role of Sorcin in future research prospects.
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http://dx.doi.org/10.1016/j.cca.2020.09.011DOI Listing
November 2020

Investigating the Effects of Lithium Phosphorous Oxynitride Coating on Blended Solid Polymer Electrolytes.

ACS Appl Mater Interfaces 2020 Sep 27;12(36):40749-40758. Epub 2020 Aug 27.

National Renewable Energy Laboratory, Materials Science Center, Golden, Colorado 80401, United States.

Solid-state electrolytes are very promising to enhance the safety of lithium-ion batteries. Two classes of solid electrolytes, polymer and ceramic, can be combined to yield a hybrid electrolyte that can synergistically combine the properties of both materials. Chemical stability, thermal stability, and high mechanical modulus of ceramic electrolytes against dendrite penetration can be combined with the flexibility and ease of processing of polymer electrolytes. By coating a polymer electrolyte with a ceramic electrolyte, the stability of the solid electrolyte is expected to improve against lithium metal, and the ionic conductivity could remain close to the value of the original polymer electrolyte, as long as an appropriate thickness of the ceramic electrolyte is applied. Here, we report a bilayered lithium-ion conducting hybrid solid electrolyte consisting of a blended polymer electrolyte (BPE) coated with a thin layer of the inorganic solid electrolyte lithium phosphorous oxynitride (LiPON). The hybrid system was thoroughly studied. First, we investigated the influence of the polymer chain length and lithium salt ratio on the ionic conductivity of the BPE based on poly(ethylene oxide) (PEO) and poly(propylene carbonate) (PPC) with the salt lithium bis(trifluoromethanesulfonyl)imide (LiTFSI). The optimized BPE consisted of 100 k molecular weight PEO, 50 k molecular weight PPC, and 25(w/w)% LiTFSI, (denoted as PEO100PPC50LiTFSI25), which exhibited an ionic conductivity of 2.11 × 10 S/cm, and the ionic conductivity showed no thermal memory effects as the PEO crystallites were well disrupted by PPC and LiTFSI. Second, the effects of LiPON coating on the BPE were evaluated as a function of thickness down to 20 nm. The resulting bilayer structure showed an increase in the voltage window from 5.2 to 5.5 V (vs Li/Li+) and thermal activation energies that approached the activation energy of the BPE when thinner LiPON layers were used, resulting in similar ionic conductivities for 30 nm LiPON coatings on PEO100PPC50LiTFSI25. Coating BPEs with a thin layer of LiPON is shown to be an effective strategy to improve the long-term stability against lithium.
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http://dx.doi.org/10.1021/acsami.0c09113DOI Listing
September 2020

Single-Sample Node Entropy for Molecular Transition in Pre-deterioration Stage of Cancer.

Front Bioeng Biotechnol 2020 14;8:809. Epub 2020 Jul 14.

School of Biology and Biological Engineering, South China University of Technology, Guangzhou, China.

A complex disease, especially cancer, always has pre-deterioration stage during its progression, which is difficult to identify but crucial to drug research and clinical intervention. However, using a few samples to find mechanisms that propel cancer crossing the pre-deterioration stage is still a complex problem. In this study, we successfully developed a novel single-sample model based on node entropy with established protein interaction network. Using this model, critical stages were successfully detected in simulation data and four TCGA datasets, indicating its sensitivity and robustness. Besides, compared with the results of the differential analysis, our results showed that most of dynamic network biomarkers identified by node entropy, such as or , located in upstream in many important cancer-related signaling pathways regulated intergenic signaling within pathways. We also identified some novel prognostic biomarkers such as , , and using node entropy rather than expression level. More importantly, we found the switch of non-specific pathways related to DNA damage repairing was the main driven force for cancer progression. In conclusion, we have successfully developed a dynamic node entropy model based on single case data to find out tipping point and possible mechanism for cancer progression. These findings may provide new target genes in therapeutic intervention tactics.
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http://dx.doi.org/10.3389/fbioe.2020.00809DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7381145PMC
July 2020

Dietary supplementation of salidroside increases immune response and disease resistance of crucian carp (Carassius auratus) against Aeromonas hydrophila.

Fish Shellfish Immunol 2020 Nov 28;106:1-7. Epub 2020 Jul 28.

Northwest A&F University, Xinong Road 22nd, Yangling, Shaanxi, 712100, China. Electronic address:

Some medicinal plants have been known as immunostimulants, and the medicinal plants extract has been used to control the outbreak of the disease in aquaculture for many years. In this study, a total of 270 crucian carp (30 ± 5 g) were randomly distributed in 9 aquaria (55 cm l × 40 cm w × 50 cm h) and divided into three feeding groups including 0 (Control), 50 mg kg (Diet A) and 100 mg kg (Diet B) of salidroside. The expression of immune-related genes (IL-1β, TNFα, MYD88, CXCL-8, TGF-β, and IL-11) in the kidney had a significant increase when the crucian carp fed with Diet B for 4 weeks (P < 0.05). Meanwhile, the expression of IL-1β, TNFα, and CXCL-8 in the spleen was significantly up-regulated when the fish fed with Diet B (P < 0.05). Higher serum alkaline phosphatase (AKP) activity, catalase (CAT) activity, superoxide dismutase (SOD) activity, and complement C3 content were found in the fish which fed with salidroside-supplemented diet. Our results also proved that fish fed with salidroside-supplemented diet for four weeks, especially at a concentration of 100 mg kg diet, improved the protection of crucian carp against A. hydrophila. The amount of A. hydrophila in the kidney and spleen was significantly decreased in salidroside-supplemented diet groups (P < 0.05). In conclusion, the present results demonstrate that the addition of salidroside for four weeks can improve the immune response of crucian carp and increase the protection against the pathogen, especially at the concentration of 100 mg kg diet. The protective effect of the salidroside to the crucian carp could be used as alternatives to antibiotics for controlling fish diseases in aquaculture.
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http://dx.doi.org/10.1016/j.fsi.2020.07.054DOI Listing
November 2020

Characterization of a pathogenic variant in GBA for Parkinson's disease with mild cognitive impairment patients.

Mol Brain 2020 07 8;13(1):102. Epub 2020 Jul 8.

School of Biology and Biological Engineering, South China University of Technology, Guangzhou, China.

Parkinson's disease (PD) is the second most common neurodegenerative disease, and mild cognitive impairment (MCI) is a well-established risk factor for the development of dementia in PD. A growing body of evidence suggests that low expression of glucocerebrosidase (GBA) promotes the transmission of α-synuclein (α-Syn) interpolymers and the progression of PD. However, how GBA mutations affect the pathogenesis of PD via abnormal aggregation of α-Syn is unclear, and no clinically valid PD-MCI genetic markers have been identified. Here, we first located a GBA eQTL, rs12411216, by analysing DHS, eQTL SNP, and transcription factor binding site data using the UCSC database. Subsequently, we found that rs12411216 was significantly associated with PD-MCI (P < 0.05) in 306 PD patients by genotyping. In exploring the relationship between rs12411216 and GBA expression, the SNP was found to be associated with GBA expression in 50 PD patients through qPCR verification. In a further CRISPR/Cas9-mediated genome editing module, the SNP was identified to cause a decrease in GBA expression, weaken enzymatic activity and enhance the abnormal aggregation of α-Syn in SH-SY5Y cells. Additionally, using an electrophoretic mobility shift assay, we confirmed that the binding efficiency of transcription factor E2F4 was affected by the rs12411216 SNP. In conclusion, our results showed that rs12411216 regulated GBA expression, supporting its potential role as a PD-MCI genetic biomarker and highlighting novel mechanisms underlying Parkinson's disease.
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http://dx.doi.org/10.1186/s13041-020-00637-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7346430PMC
July 2020

Comparative transcriptome analysis of a taxol-producing endophytic fungus, Aspergillus aculeatinus Tax-6, and its mutant strain.

Sci Rep 2020 06 29;10(1):10558. Epub 2020 Jun 29.

Department of Environmental Engineering, College of Biology and the Environment, Nanjing Forestry University, Nanjing, 210037, Jiangsu Province, China.

Taxol is a rare but extremely effective antitumor agent extracted from Taxus yew barks. Taxus plants are valuable and rare species, and the production of taxol from them is a complex process. Therefore, taxol-producing endophytic fungi seem to be a promising alternative because of their high practical value and convenient progress. In this study, the transcriptome of an endophytic fungus, Aspergillus aculeatinus Tax-6 was analyzed in order to understand the molecular mechanisms of producing fungal taxol. The results showed that genes involved in the mevalonate (MVA) pathway and non-mevalonate (MEP) pathway were expressed, including isopentenyl pyrophosphate transferase, geranyl pyrophosphate transferase, and geranylgeranyl pyrophosphate synthetase. However, those downstream genes involved in the conversion of taxa-4(5)-11(12)-diene from geranylgeranyl pyrophosphate were not expressed except for taxane 10-beta-hydroxylase. Additionally, a mutant strain, A. aculeatinus BT-2 was obtained from the original strain, A. aculeatinus Tax-6, using fungicidin as the mutagenic agent. The taxol yield of BT-2 was 560 µg L, which was higher than that of Tax-6. To identify the mechanism of the difference in taxol production, we compared the transcriptomes of the two fungi and explored the changes in the gene expression between them. When compared with the original strain, Tax-6, most genes related to the MVA pathway in the mutant strain BT-2 showed upregulation, including GGPPS. Moreover, most of the downstream genes were not expressed in the mutant fungi as well. Overall, the results revealed the pathway and mechanism of taxol synthesis in endophytic fungi and the potential for the construction of taxol-producing genetic engineering strains.
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http://dx.doi.org/10.1038/s41598-020-67614-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7324598PMC
June 2020

Transcriptome Analysis of the Acid Stress Response of Desulfovibrio vulgaris ATCC 7757.

Curr Microbiol 2020 Oct 1;77(10):2702-2712. Epub 2020 Jun 1.

School of Environment and Energy, South China University of Technology, Guangzhou, 510006, People's Republic of China.

The application of sulfate-reducing bacteria (SRB) shows great potential in the anaerobic biological treatment of acid mine wastewater; therefore, it has attracted much attention. The low pH in acidic wastewater affects the growth and reducing power of SRB. To uncover the mechanism underlying the reduction efficiency of SRB under acidic conditions, in this study, transcriptomic analysis was performed with Desulfovibrio vulgaris ATCC 7757 under three different pH conditions (pH 4.0, 5.5 and 7.0) and in the initial inoculation, logarithmic growth and plateau phases. Our results showed that ATCC 7757 still had biological activity at pH 4.0 and exhibited gene expression patterns at pH 4.0 that were different from those at pH 5.5 and pH 7. Importantly, the gene expression pattern was similar between pH 5.5 and pH 7. Transcriptomic analysis identified differentially expressed genes that affected the growth of ATCC 7757 under pH 7.0 at 22 h compared to 15 h; 196 of these genes were upregulated and 575 were downregulated. These differentially expressed genes were mainly enriched in genetic information processing and metabolism. Additionally, we identified 57 candidate genes associated with low-pH tolerance. Adaptation to low pH was reflected by an increase in the expression of genes involved in cell membrane structure and proton transport. The expression of genes involved in the reduction process decreased, including the genes DVU0499 and sat, which encode proteins that affect the sulfate reduction process. Both gene activities were validated by qPCR. Our results will contribute to further promoting the reducing power of SRB in acid mine wastewater and the development of successful bioremediation strategies.
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http://dx.doi.org/10.1007/s00284-020-02051-xDOI Listing
October 2020

Driving force to detect Alzheimer's disease biomarkers: application of a thioflavine [email protected] ratiometric fluorescent sensor for smart detection of presenilin 1, amyloid β-protein and acetylcholine.

Analyst 2020 Jul 27;145(13):4646-4663. Epub 2020 May 27.

Key Laboratory of Inorganic-Organic Hybrid Functional Material Chemistry (Tianjin Normal University), Ministry of Education, Tianjin Key Laboratory of Structure and Performance for Functional Molecule, College of Chemistry, Tianjin Normal University, 393 Binshui West Road, Tianjin 300387, PR China.

Currently, the highly sensitive detection of Alzheimer's Disease (AD) biomarkers, namely presenilin 1, amyloid β-protein (Aβ), and acetylcholine (ACh), is vital to helping us prevent and diagnose AD. In this work, a novel metal-organic framework [Er(L)(DMF)] (Er-MOF) (HL = terphenyl-3,4'',5-tricarboxylic acid) has been synthesized by solvothermal and ultrasonic methods. Further, through the post-synthesis assembly strategy, the fluorescent dye thioflavine T (ThT) has been introduced into Er-MOF to construct a dual-emission [email protected] ratiometric fluorescent sensor. This is the first time that [email protected] has been successfully applied in the highly sensitive detection of three main Alzheimer's disease biomarkers in the cerebrospinal fluid through three different low cost and facile detection strategies. Firstly, with the spilted DNA strategy, this is the first time that [email protected] can be applied in the label-free detection of SSODN (part of the presenilin 1 gene). Secondly, for the detection of Aβ, because ThT can be specifically combined with Aβ and has an excellent characteristic fluorescence band, the dual-emission [email protected] sensor can be selectively applied to detect Aβ over the analog protein, which shows far more sensitivity than other Aβ sensors. Thirdly, through the acetylcholine esterase (AchE) enzymatic cleavage and release strategy, [email protected] enhances the detection of acetylcholine (ACh) with a low limit of detection (LOD) value (0.03226 nM). It should be noticed that the three different detection methods are low cost and facile. This study also provides the first example of utilizing laser scanning confocal microscopy (LSCM) to investigate the fluorescence resonance energy transfer (FRET) detection mechanism by [email protected] in more detail. The location of FRET occurrence and FRET efficiency can also be investigated by LSCM, which can be helpful to understand the FRET detection process by these unique MOF-based hybrid materials.
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http://dx.doi.org/10.1039/d0an00440eDOI Listing
July 2020

Meta-analysis of 16S rRNA Microbial Data Identified Distinctive and Predictive Microbiota Dysbiosis in Colorectal Carcinoma Adjacent Tissue.

mSystems 2020 Apr 14;5(2). Epub 2020 Apr 14.

BGI Genomics, BGI-Shenzhen, Shenzhen, China

As research focusing on the colorectal cancer fecal microbiome using shotgun sequencing continues, increasing evidence has supported correlations between colorectal carcinomas (CRCs) and fecal microbiome dysbiosis. However, large-scale on-site and off-site (surrounding adjacent) tissue microbiome characterization of CRC was underrepresented. Here, considering each taxon as a feature, we demonstrate a machine learning-based method to investigate tissue microbial differences among CRC, colorectal adenoma (CRA), and healthy control groups using 16S rRNA data sets retrieved from 15 studies. A total of 2,099 samples were included and analyzed in case-control comparisons. Multiple methods, including differential abundance analysis, random forest classification, cooccurrence network analysis, and Dirichlet multinomial mixture analysis, were conducted to investigate the microbial signatures. We showed that the dysbiosis of the off-site tissue of colonic cancer was distinctive and predictive. The AUCs (areas under the curve) were 80.7%, 96.0%, and 95.8% for CRC versus healthy control random forest models using stool, tissue, and adjacent tissue samples and 69.9%, 91.5%, and 89.5% for the corresponding CRA models, respectively. We also found that the microbiota ecologies of the surrounding adjacent tissues of CRC and CRA were similar to their on-site counterparts according to network analysis. Furthermore, based on the enterotyping of tissue samples, the cohort-specific microbial signature might be the crux in addressing classification generalization problems. Despite cohort heterogeneity, the dysbiosis of lesion-adjacent tissues might provide us with further perspectives in demonstrating the role of the microbiota in colorectal cancer tumorigenesis. Turbulent fecal and tissue microbiome dysbiosis of colorectal carcinoma and adenoma has been identified, and some taxa have been proven to be carcinogenic. However, the microbiomes of surrounding adjacent tissues of colonic cancerous tissues were seldom investigated uniformly on a large scale. Here, we characterize the microbiome signatures and dysbiosis of various colonic cancer sample groups. We found a high correlation between colorectal carcinoma adjacent tissue microbiomes and their on-site counterparts. We also discovered that the microbiome dysbiosis in adjacent tissues could discriminate colorectal carcinomas from healthy controls effectively. These results extend our knowledge on the microbial profile of colorectal cancer tissues and highlight microbiota dysbiosis in the surrounding tissues. They also suggest that microbial feature variations of cancerous lesion-adjacent tissues might help to reveal the microbial etiology of colonic cancer and could ultimately be applied for diagnostic and screening purposes.
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http://dx.doi.org/10.1128/mSystems.00138-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7159898PMC
April 2020

Proteome interrogation using gold nanoprobes to identify targets of arctigenin in fish parasites.

J Nanobiotechnology 2020 Feb 18;18(1):32. Epub 2020 Feb 18.

College of Animal Science and Technology, Northwest A&F University, Yangling, 712100, People's Republic of China.

Gold nanoparticles (GNPs) are one of the most widely used nanomaterials in various fields. Especially, the unique chemical and physical properties make them as the promising candidates in drug target identification, unfortunately, little is known about their application in parasites. In this paper, GNPs were employed as new solid support to identify drug targets of natural bioactive compound arctigenin (ARG) against fish monogenean parasite Gyrodactylus kobayashi. Before target identification, GNPs with ARG on the surface showed the ability to enter the live parasites even the nucleus or mitochondria, which made the bound compounds capable of contacting directly with target proteins located anywhere of the parasites. At the same time, chemically modified compound remained the anthelminthic efficacy against G. kobayashii. The above results both provide assurance on the reliability of using GNPs for drug target-binding specificity. Subsequently, by interrogating the cellular proteome in parasite lysate, myosin-2 and UNC-89 were identified as the potential direct target proteins of ARG in G. kobayashii. Moreover, results of RNA-seq transcriptomics and iTRAQ proteomics indicated that myosin-2 expressions were down-regulated after ARG bath treatment both in transcript and protein levels, but for UNC-89, only in mRNA level. Myosin-2 is an important structural muscle protein expressed in helminth tegument and its identification as our target will enable further inhibitor optimization towards future drug discovery. Furthermore, our findings demonstrate the power of GNPs to be readily applied to other parasite drugs of unknown targets, facilitating more broadly therapeutic drug design in any pathogen or disease model.
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http://dx.doi.org/10.1186/s12951-020-00591-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7027246PMC
February 2020
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