Publications by authors named "Zhimin Zhang"

224 Publications

Recurrence Plot-Based Approach for Cardiac Arrhythmia Classification Using Inception-ResNet-v2.

Front Physiol 2021 17;12:648950. Epub 2021 May 17.

School of Information Technology and Electrical Engineering, University of Queensland, Brisbane, QLD, Australia.

The present study addresses the cardiac arrhythmia (CA) classification problem using the deep learning (DL)-based method for electrocardiography (ECG) data analysis. Recently, various DL techniques have been utilized to classify arrhythmias, with one typical approach to developing a one-dimensional (1D) convolutional neural network (CNN) model to handle the ECG signals in the time domain. Although the CA classification in the time domain is very prevalent, current methods' performances are still not robust or satisfactory. This study aims to develop a solution for CA classification in two dimensions by introducing the recurrence plot (RP) combined with an Inception-ResNet-v2 network. The proposed method for nine types of CA classification was tested on the 1st China Physiological Signal Challenge 2018 dataset. During implementation, the optimal leads (lead II and lead aVR) were selected, and then 1D ECG segments were transformed into 2D texture images by the RP approach. These RP-based images as input signals were passed into the Inception-ResNet-v2 for CA classification. In the CPSC, Georgia, and the PTB_XL ECG databases of the PhysioNet/Computing in Cardiology Challenge 2020, the RP-based method achieved an average F1-score of 0.8521, 0.8529, and 0.8862, respectively. The results suggested the excellent generalization ability of the proposed method. To further assess the performance of the proposed method, we compared the 2D RP-image-based solution with the published 1D ECG-based works on the same dataset. Also, it was compared with two traditional ECG transform into 2D image methods, including the time waveform of the ECG recordings and time-frequency images based on continuous wavelet transform (CWT). The proposed method achieved the highest average F1-score of 0.844, with only two leads of the 12-lead ECG original data, which outperformed other works. Therefore, the promising results indicate that the 2D RP-based method has a high clinical potential for CA classification using fewer lead ECG signals.
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http://dx.doi.org/10.3389/fphys.2021.648950DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165394PMC
May 2021

Pure Ion Chromatograms Combined with Advanced Machine Learning Methods Improve Accuracy of Discriminant Models in LC-MS-Based Untargeted Metabolomics.

Molecules 2021 May 5;26(9). Epub 2021 May 5.

Yunnan Academy of Tobacco Agricultural Sciences, Kunming 650021, China.

Untargeted metabolomics based on liquid chromatography coupled with mass spectrometry (LC-MS) can detect thousands of features in samples and produce highly complex datasets. The accurate extraction of meaningful features and the building of discriminant models are two crucial steps in the data analysis pipeline of untargeted metabolomics. In this study, pure ion chromatograms were extracted from a liquor dataset and left-sided colon cancer (LCC) dataset by K-means-clustering-based Pure Ion Chromatogram extraction method version 2.0 (KPIC2). Then, the nonlinear low-dimensional embedding by uniform manifold approximation and projection (UMAP) showed the separation of samples from different groups in reduced dimensions. The discriminant models were established by extreme gradient boosting (XGBoost) based on the features extracted by KPIC2. Results showed that features extracted by KPIC2 achieved 100% classification accuracy on the test sets of the liquor dataset and the LCC dataset, which demonstrated the rationality of the XGBoost model based on KPIC2 compared with the results of XCMS (92% and 96% for liquor and LCC datasets respectively). Finally, XGBoost can achieve better performance than the linear method and traditional nonlinear modeling methods on these datasets. UMAP and XGBoost are integrated into KPIC2 package to extend its performance in complex situations, which are not only able to effectively process nonlinear dataset but also can greatly improve the accuracy of data analysis in non-target metabolomics.
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http://dx.doi.org/10.3390/molecules26092715DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8125400PMC
May 2021

Effect of proximal box elevation on fracture resistance and microleakage of premolars restored with ceramic endocrowns.

PLoS One 2021 26;16(5):e0252269. Epub 2021 May 26.

Hospital of Stomatology, Jilin University, Changchun, P.R China.

Background: Restoration of endodontically treated premolar is in high risk for biomechanical failure, and often presents with subgingival margins. Proximal box elevation (PBE) has been used to relocate subgingival cavity outlines.

Objective: To evaluate the influence of PBE on fracture resistance and gingival microleakage of premolars with endodontic access cavities following ceramic endocrown.

Methods: Eighty sound maxillary premolars with standardized Class II cavities on mesial surfaces were randomly assigned to four groups (n = 20 in each group). Groups E1, E2 and E3, with proximal margins located in dentin/cementum, 2 mm below the cemento-enamel junction (CEJ), simulated subgingival location. Group E4 (supragingival group), with proximal margins located in enamel, 1 mm above the CEJ, was used as the positive control. For margin elevation of the proximal cavities, bulk-fill Smart Dentin Replacement (SDR), a visible light cured resin composite, was applied in group E1, and conventional resin composite (3M Z350 XT, a light-activated composite) was placed in group E2. Group E3 was only treated with a ceramic crown and served as the negative control. In all groups, computer-aided design (CAD) ceramic endocrowns were adhesively inserted, and fracture resistance, failure mode and microleakage were evaluated.

Results: A higher fracture resistance value was observed in PBE groups E1 and E2, regardless of the materials used (P = 0.038, and 0.010, respectively, vs E3), and fracture resistance in group E1 was higher than that in group E2. In teeth without PBE, the percentage of catastrophic failures reached 70%. Compared to group E3, a lower frequency distribution of microleakage was detected in supragingival group E4 (P = 0.031). No increased percentage of microleakage was observed in groups treated with PBE.

Conclusion: For endodontically treated maxillary premolars restored with ceramic endocrowns, PBE increases fracture resistance but not microleakage.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0252269PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8153463PMC
May 2021

Cytosolic protein delivery metabolic glycoengineering and bioorthogonal click reactions.

Biomater Sci 2021 May 26. Epub 2021 May 26.

Institute of Functional Nano and Soft Materials (FUNSOM), Jiangsu Key Laboratory of Carbon-Based Functional Materials and Devices, Collaborative Innovation Center of Suzhou Nano Science & Technology, Soochow University, Suzhou 215123, China.

Cytosolic protein delivery holds great potential for the development of protein-based biotechnologies and therapeutics. Currently, cytosolic protein delivery is mainly achieved with the assistance of various carriers. Herein, we present a universal and effective strategy for carrier-free cytosolic protein delivery via metabolic glycoengineering and bioorthogonal click reactions. Ac4ManNAz (AAM), an azido-modified N-acetylmannosamine analogue, was first employed to label tumor cell surfaces with abundant azido groups via glycometabolism. Then, proteins including RNase A, cytochrome C (Cyt C), and bovine serum albumin (BSA) were covalently modified with dibenzocyclooctyne (DBCO). Based on the highly efficient bioorthogonal click reactions between DBCO and azido, DBCO-modified proteins could be efficiently internalized by azido-labeled cancer cells. RNase A-DBCO could largely maintain its enzymatic activity and, thus, led to notable anti-tumor efficacy in HeLa and B16F10 cells in vitro and in B16F10 xenograft tumors in vivo. This study therefore provides a simple and powerful approach for carrier-free protein delivery and would have broad applicability in anti-tumor protein therapy.
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http://dx.doi.org/10.1039/d1bm00548kDOI Listing
May 2021

Tianlongkechuanling Inhibits Pulmonary Fibrosis Through Down-Regulation of Arginase-Ornithine Pathway.

Front Pharmacol 2021 22;12:661129. Epub 2021 Apr 22.

Traditional Chinese Medicine, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

Pulmonary Fibrosis (PF) is an interstitial lung disease characterized by excessive accumulation of extracellular matrix in the lungs, which disrupts the structure and gas exchange of the alveoli. There are only two approved therapies for PF, nintedanib (Nib) and pirfenidone. Therefore, the use of Chinese medicine for PF is attracting attention. Tianlongkechuanling (TL) is an effective Chinese formula that has been applied clinically to alleviate PF, which can enhance lung function and quality of life. The potential effects and specific mechanisms of TL have not been fully explored, yet. In the present study, proteomics was performed to explore the therapeutic protein targets of TL on Bleomycin (BLM)-induced Pulmonary Fibrosis. BLM-induced PF mice models were established. Hematoxylineosin staining and Masson staining were used to analyze histopathological changes and collagen deposition. To screen the differential proteins expression between the Control, BLM, BLM + TL and BLM + Nib (BLM + nintedanib) groups, quantitative proteomics was performed using tandem mass tag (TMT) labeling with nanoLC-MS/MS [nano liquid chromatographymass spectrometry]). Changes in the profiles of the expressed proteins were analyzed using the bioinformatics tools Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). The protein-protein interactions (PPI) were established by STRING. Expressions of α-smooth muscle actin (α-SMA), (), () and enzymes in arginase-ornithine pathway were detected by Western blot or RT-PCR. TL treatments significantly ameliorated BLM-induced collagen deposition in lung tissues. Moreover, TL can inhibit the protein expressions of α-SMA and the mRNA expressions of and . Using TMT technology, we observed 253 differentially expressed proteins related to PPI networks and involved different KEGG pathways. Arginase-ornithine pathway is highly significant. The expression of Arg was significantly decreased after TL treatments. Administration of TL in BLM-induced mice resulted in decreasing pulmonary fibrosis. Our findings propose that the down regulation of arginase-ornithine pathway expression with the reduction of arginase biosynthesis is a central mechanism and potential treatment for pulmonary fibrosis with the prevention of TL.
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http://dx.doi.org/10.3389/fphar.2021.661129DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8114272PMC
April 2021

Dynamic analysis of peripheral blood TCR β-chain CDR3 repertoire in occupational medicamentosa-like dermatitis due to trichloroethylene.

Sci Rep 2021 May 11;11(1):9971. Epub 2021 May 11.

Medical Laboratory, Shenzhen Prevention and Treatment Center for Occupational Diseases, 2019 Buxin Rd., Luohu district, Shenzhen, 518020, China.

Previously, we had cross-sectionally explored the characteristics of T cell receptor (TCR) repertoires from occupational medicamentosa-like dermatitis due to trichloroethylene (OMDT) patients, now we further analyzed the dynamic features of OMDT TCR repertoires. Peripheral blood TCR β-chain complementarity-determining region 3 (CDR3) genes were detected with the high throughput sequencing in 24 OMDT cases in their acute, chronic and recovery stages, respectively, and in 24 trichloroethylene-exposed healthy controls. The TCR repertoire diversity, TRBV/TRBD/TRBJ gene usage and combination, frequencies of CDR3 nucleotide (nt) and amino acid (aa) sequences in the cases in different stages and in the controls were analyzed. TRBV6-4 and TRBV7-9 frequencies significantly differed between the cases and controls (both P < 6.1 × 10). TRBV6-4 combination with TRBJ2-1, TRBJ2-2, TRBJ2-3, and TRBJ2-6, and TRBV7-9 combination with TRBJ2-1 were associated with the stage by OMDT severity (all P < 0.001). Ten CDR3-nt and 7 CDR3-aa sequences in TRBV7-9-TRBJ2-1 combination and 1 CDR3-nt and 1 CDR3-aa sequences in TRBV6-4-TRBJ2-1 combination were identified as associated with the severity of OMDT (all P < 0.001). We revealed further how TCR repertoires vary with the severity in the development of OMDT, and severity-related TCRs may provide important therapeutic targets for OMDT in clinical practice.
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http://dx.doi.org/10.1038/s41598-021-89431-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113444PMC
May 2021

Co-Occurring Alteration of NOTCH and DDR Pathways Serves as Novel Predictor to Efficacious Immunotherapy in NSCLC.

Front Oncol 2021 22;11:659321. Epub 2021 Apr 22.

Cancer Center, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China.

Although immune checkpoint inhibitors (ICIs) have shown remarkable benefit for treatment of advanced non-small lung cancer (NSCLC), only a minority of patients can achieve durable responses and the most patients produce an ultra-rapid progressive disease. Here, we collected the availably published datasets and mined the determinants of response to immunotherapy on pathway levels. One hundred six NSCLC patients treated with immunotherapy were combined from Rizvi et al. and Hellman et al. studies (whole exon sequencing). Two independent validation datasets consisted of the MSKCC cohort (targeted sequencing) and data by Anagnostou and colleagues (whole exon sequencing). The Cancer Genome Atlas (TCGA) somatic mutation and gene expression data were applied to explore the immunobiology features. In the first combined cohort, we detected NOTCH pathway altered in 71% patients with durable clinical benefit (DCB) while only 36% among no durable benefit (NDB) (p = 0.005). Compared to NDB group, co-occurrence of NOTCH and at least two DDR (co-DDR) pathway was discovered in DCB group and contributed to a prolonged progression-free survival (PFS) [22.1 3.6 months, p < 0.0001, HR, 0.34, 95% confidence interval (CI), 0.2-0.59]. In two independent datasets, co-occurrence of NOTCH+/co-DDR+ was also validated to be a better immunotherapy efficacy [Cohort 2: 13 6 months, p = 0.034, HR, 0.55, 95% CI, 0.31-0.96; Cohort 3: 21 11 months, p = 0.067, HR, 0.45, 95% CI, 0.18-1.1]. By analyzing TCGA cohort, we found patients with coexisting NOTCH+/co-DDR+ pathway had a higher TMB, more infiltration of CD4+T cells. Overall, co-occurrence of NOTCH and co-DDR pathway reflect a better immunotherapy efficacy in advanced NSCLC. This genomic predictor show promise in stratifying patients that suit for immunotherapy for future clinical practice.
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http://dx.doi.org/10.3389/fonc.2021.659321DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100434PMC
April 2021

Long Non-Coding RNA LINC01929 Accelerates Progression of Oral Squamous Cell Carcinoma by Targeting the miR-137-3p/FOXC1 Axis.

Front Oncol 2021 21;11:657876. Epub 2021 Apr 21.

Department of General Dentistry, Hospital of Stomatology, Jilin University, Changchun, China.

Recently, additional long noncoding RNAs (lncRNAs) have been identified and their possible roles were investigated in a variety of human tumors. One of these lncRNAs, LINC01929, promoted the progression of some cancers, whereas its expression and biological function in human oral squamous cell carcinoma (OSCC) remains still mostly uncertain. The LINC01929 expression in OSCC tissues or cell lines was identified quantitative real-time polymerase chain reaction. The cell counting kit-8, transwell migration, wound-healing, and flow cytometry assays were utilized to characterize the functions of LINC01929 in OSCC cells. The interactive relationships between LINC01929 and miR-137-3p, miR-137-3p and Forkhead box C1 (FOXC1) were investigated by the dual-luciferase activity assay. Our findings demonstrated that LINC01929 was highly expressed in OSCC tissue samples and cell lines, whereas miR-137-3p expression was downregulated. LINC01929 acted as a carcinogenic lncRNA with accelerated OSCC cell proliferation, migration and invasion, and suppression of apoptosis. We further indicated that LINC01929 facilitated tumor growth in xenograft mouse models. Mechanistically, LINC01929 acted as a sponge for miR-137-3p to elevate FOXC1 expression, which is the target of miR-137-3p. In addition, downregulated miR-137-3p expression rescued the suppressive behaviors of LINC01929 knockdown on the biological behaviors of OSCC cells. Taken together, LINC01929 functioned as a tumor-promoting lncRNA the miR-137-3p/FOXC1 axis in OSCC, suggesting novel targets for OSCC therapy.
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http://dx.doi.org/10.3389/fonc.2021.657876DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097103PMC
April 2021

Ligustilide Prevents Radiation Enteritis by Targeting Gch1/BH/eNOS to Improve Intestinal Ischemia.

Front Pharmacol 2021 22;12:629125. Epub 2021 Apr 22.

Department of Pharmacy, The Second Affiliated Hospital of Air Force Medical University, Xi'an, China.

There is a high incidence of radiation enteritis (RE) after abdominal radiotherapy. The occurrence of RE seriously affects the treatment and quality of life of patients; however, its pathogenesis is complex and there are no effective drugs for its prevention or treatment. Intestinal ischemia plays an important role in the occurrence of enteritis. Previous studies have shown that targeting GTP-cyclohydrolase 1 (Gch1) to improve intestinal ischemia could be a new strategy to prevent and treat RE. A high content of the naturally occurring phthalide derivative ligustilide (LIG) has been found in the plant drug Rhizoma Ligustici Chuanxiong for the treatment of cardiovascular diseases. The purpose of this study was to evaluate the protective effects of LIG on RE. Ionizing radiation (IR) rat and endothelial cell models were used to observe and record rat body weights and stool morphologies, measure intestinal blood perfusion by laser Doppler blood flow imaging, determine the diastolic functions of mesenteric arteries, detect the levels of Gch1/BH/eNOS pathway-related proteins and regulatory molecules in the mesenteric arteries and endothelial cells, and predict affinity by molecular docking technology. The results showed that LIG significantly improved the body weights, loose stools, intestinal villi lengths, intestinal perfusion and vasodilatory functions of IR rats. LIG also significantly improved Gch1 protein and BH levels in the mesenteric arteries and endothelial cells after IR, increased the NO content, reduced superoxide accumulation, and improved p-eNOS (Ser1177) levels in endothelial cells. LIG has good affinity for Gch1, which significantly improves its activity. These results indicate that LIG is the preferred compound for the prevention and treatment of RE by improving intestinal ischemia through the Gch1/BH/eNOS pathway. This study provides a theoretical basis and new research ideas for the development of new drugs for RE.
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http://dx.doi.org/10.3389/fphar.2021.629125DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100595PMC
April 2021

Correlation between GPR, MHR and elderly essential hypertension with unstable angina pectoris.

Zhong Nan Da Xue Xue Bao Yi Xue Ban 2021 Apr;46(4):373-378

Department of Cardiac Electrophysiology, Affiliated Hospital of Chengde Medical College, Chengde Hebei 067000.

Objectives: To investigate the level and significance of serum γ-glutamyl transferase-to-platelet ratio (GPR) and monocyte count to high-density lipoprotein ratio (MHR) in patients with essential hypertension (EH) and unstable angina (UA).

Methods: A total of 218 patients with coronary angiography aged ≥60 years, who were admitted to the EH hospital of the Department of Cardiac Medicine, Affiliated Hospital of Chengde Medical College, were selected from September 2018 to September 2019. They were divided into an EH+UA group (=113) and an EH group (=105). In addition, 106 patients with normal coronary angiography who were diagnosed with coronary heart disease were selected as a control group. The general data, blood biochemical indicators, GPR and MHR in each group were compared, and partial correlation analysis and receiver operator characteristic (ROC) curve analysis were performed.

Results: Compared with the control group, patients in the EH+UA group and the EH group had higher body mass index (BMI), tyiglyceride (TG), GPR, and MHR, and lower high-density lipoprotein-cholesterol (HDL-C) (all <0.05); and patients in the EH+UA group had higher white blood cell counts, alanine aminotransferase (ALT), and uric acid (all <0.05). Compared with the EH group, patients in the EH+UA group had higher GPR and MHR (both <0.05). Partial correlation analysis showed that after controlling the antihypertensive drugs and lipid-lowering drugs, GPR was found to be positively correlated with BMI, white blood cell count, ALT, TG, and uric acid (=0.160, 0.111, 0.205, 0.250, 0.154, respectively, all <0.05), which was negatively correlated with HDL-C (=-0.238, <0.05); MHR was positively correlated with BMI, ALT, TG, uric acid, and GPR (=0.186, 0.307, 0.157, 0.141, 0.223, respectively, all <0.05), and negatively correlated with HDL-C (=-0.610, <0.001). ROC curve analysis showed that GPR had higher specificity and positive predictive value, while MHR had higher sensitivity. When the two indicators were combined, the sensitivity and positive predictive value were higher.

Conclusions: There is a correlation between GPR, MHR and EH combined with UA pectoris, and the combined detection of the two indicators has adjuvant diagnostic value for elderly EH combined with UA.
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http://dx.doi.org/10.11817/j.issn.1672-7347.2021.200222DOI Listing
April 2021

Characterization of dicarboxylic acids, oxoacids, and α-dicarbonyls in PM within the urban boundary layer in southern China: Sources and formation pathways.

Environ Pollut 2021 Apr 19;285:117185. Epub 2021 Apr 19.

Institute of Surface-Earth System Science, School of Earth System Science, Tianjin University, Tianjin, 300072, PR China.

Low-molecular-weight dicarboxylic acids, which are important components of secondary organic aerosols, have been extensively studied in recent years. Many studies have focused on ground-level observations and literature reports on the vertical distribution of the organic aerosols within the urban boundary layer are limited. In this study, the vertical profiles of dicarboxylic acids and related organic compounds (DCRCs) in PM were investigated at altitudinal levels (ground level and 488 m above the ground level) at the Canton Tower in Guangzhou, southern China, to elucidate their primary sources and secondary formation processes. The concentrations of DCRCs at ground level were generally higher than those at 488 m. Oxalic acid (C) was the most abundant species, followed by succinic acid (C) and malonic acid (C) at both heights. The higher ratio of DCRCs-bound carbon to organic carbon (i.e., DCRCs-C/OC) at 488 m (4.8 ± 1.2%) relative to that at ground level (2.7 ± 0.5%) indicated a higher degree of aerosol aging at 488 m. The abundance of C was increased and the conversion of C to C was enhanced due to the photochemical oxidation of its homologues during long-range transport periods. The increase in C was associated with in-cloud processes during pollution periods. Principal component analysis showed that DCRCs were mainly derived from atmospheric secondary processing and biomass burning was also an important source of long-chain carboxylic acids during autumn in Guangzhou. Our results illustrate that secondary processing and biomass burning play prominent roles in controlling the abundance of DCRCs. Furthermore, DCRCs are affected by air masses from regional areas, oxidation of their precursors via vertical transport and in-cloud processes.
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http://dx.doi.org/10.1016/j.envpol.2021.117185DOI Listing
April 2021

Neutrophil-derived TNF drives fungal acute lung injury in chronic granulomatous disease.

J Infect Dis 2021 Apr 5. Epub 2021 Apr 5.

Division of Pulmonary, Critical Care, and Sleep Medicine, University of Florida, Gainesville, FL, USA.

Chronic granulomatous disease (CGD) results from NADPH oxidase deficiency and impaired reactive oxygen species (ROS) generation. This results in impaired killing of Aspergillus and, independently, a pathologic hyperinflammatory response to the organism. We hypothesized that neutrophil-derived ROS inhibit the inflammatory response to Aspergillus, and acute lung injury in CGD is due to failure of this regulation. Mice with gp91phox-deficiency, the most common CGD mutation, had more severe lung injury, neutrophil infiltration, and lung TNF after Aspergillus challenge compared to wildtypes. Neutrophils were surprisingly the predominant source of TNF in gp91phox-deficient lungs. TNF neutralization inhibited neutrophil recruitment in gp91phox-deficient mice and protected from lung injury. We propose that, in normal hosts, Aspergillus stimulates TNF-dependent neutrophil recruitment to the lungs and neutrophil-derived ROS limit inflammation. In CGD, in contrast, recruited neutrophils are the dominant source of TNF, promoting further neutrophil recruitment in a pathologic positive-feedback cycle, resulting in progressive lung injury.
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http://dx.doi.org/10.1093/infdis/jiab188DOI Listing
April 2021

Tumor suppressor role of sFRP‑4 in hepatocellular carcinoma via the Wnt/β‑catenin signaling pathway.

Mol Med Rep 2021 May 24;23(5). Epub 2021 Mar 24.

Department of Oncology, General Hospital of The Central Theater Command of The People's Liberation Army, Wuhan, Hubei 430070, P.R. China.

Hepatocellular carcinoma (HCC) is a malignant tumor located in the liver. Secreted frizzled‑related protein 4 (sFRP‑4) is associated with cancer occurrence, but the relationship between sFRP‑4 and HCC is not completely understood. The present study aimed to investigate the role and mechanism underlying sFRP‑4 in HCC. sFRP‑4 mRNA expression levels were determined via reverse transcription‑quantitative PCR and immunohistochemistry. The Cell Counting Kit‑8 assay was performed to evaluate HCCLM3 and Huh7 cell viability. Moreover, HCCLM3 and Huh7 cell proliferation were assessed using the BrdU ELISA assay kit, and cell apoptosis was measured via flow cytometry. Western blotting was conducted to measure β‑catenin and GSK‑3β protein expression levels. The results demonstrated that sFRP‑4 expression was significantly downregulated in HCC tissues and cells compared with adjacent healthy tissues and MIHA cells, respectively. Moreover, the results indicated that compared with the control group, sFRP‑4 overexpression inhibited HCC cell viability and proliferation, and accelerated HCC cell apoptosis. Furthermore, the results suggested that sFRP‑4 inhibited the Wnt/β‑catenin signaling pathway by upregulating GSK‑3β expression and downregulating β‑catenin expression, thus restraining the malignant behavior of HCC cells. In conclusion, the present study indicated that sFRP‑4 served a tumor suppressor role in HCC cells by restraining the Wnt/β‑catenin signaling pathway.
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http://dx.doi.org/10.3892/mmr.2021.11975DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7974405PMC
May 2021

Convalescent plasma to treat COVID-19: clinical experience and efficacy.

Aging (Albany NY) 2021 03 18;13(6):7758-7766. Epub 2021 Mar 18.

Hunan Engineering Research Center of Obstetrics and Gynecological Disease, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China.

The recent outbreak of COVID-19 in the world is currently a big threat to global health and economy. Convalescent plasma has been confirmed effective against the novel corona virus in preliminary studies. In this paper, we first described the therapeutic schedule, antibody detection method, indications, contraindications of the convalescent plasmas and reported the effectiveness of convalescent plasma therapy by a retrospective cohort study.
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http://dx.doi.org/10.18632/aging.202795DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034927PMC
March 2021

Patterns of Sediment Fungal Community Dependent on Farming Practices in Aquaculture Ponds.

Front Microbiol 2021 19;12:542064. Epub 2021 Feb 19.

Key Laboratory of Algal Biology, State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China.

Despite fungi playing an important role in nutrient decomposition in aquatic ecosystems and being considered as vital actors in the ecological processes, they received limited attention regarding the community in aquaculture pond sediments which are extremely important and typically disturbed habitats. Using an ITS1 region of fungal rDNA, this study aimed to investigate sediment fungal communities in fish, crab, and crayfish ponds for decades of farming practices at representative aquaculture regions in the middle Yangtze River basin, China. We then aimed to explore the community patterns associated with species-based farming practices in the ponds at 18 farms. The results showed that the pond sediments harbored more than 9,000 operational taxonomic units. The sediments had significantly higher alpha diversity in crab ponds compared to that in fish and crayfish ponds. The fungal phyla largely belonged to and , and the dominance of over and was observed. The majority of sediment fungal members were ascribed to unclassified fungi, with higher proportions in fish ponds than crab and crayfish ponds. Further, the fungal communities were markedly distinct among the three types of ponds, suggesting divergent patterns of fungal community assemblages caused by farming practices in aquaculture ponds. The community diversity and structure were closely correlated to sediment properties, especially sediment carbon content and pH. Thus, the distribution and pattern of fungal communities in the sediments appear to primarily depend on species-based farming practices responsible for the resulting sediment carbon content and pH in aquaculture ponds. This study provides a detailed snapshot and extension of understanding fungal community structure and variability in pond ecosystems, highlighting the impacts of farming practices on the assembly and succession of sediment fungal communities in aquaculture ponds.
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http://dx.doi.org/10.3389/fmicb.2021.542064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7933557PMC
February 2021

Bacterial Communities and Enzymatic Activities in Sediments of Long-Term Fish and Crab Aquaculture Ponds.

Microorganisms 2021 Feb 26;9(3). Epub 2021 Feb 26.

Key Laboratory of Algal Biology, State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China.

Aquaculture is among the most important and fastest growing agriculture sectors worldwide; however, it generates environmental impacts by introducing nutrient accumulations in ponds, which are possibly different and further result in complex biological processes in the sediments based on diverse farming practices. In this study, we investigated the effects of long-term farming practices of representative aquatic animals dominated by grass carp (GC, ) or Chinese mitten crab (CMC, ) on the bacterial community and enzyme activity of sediments from more than 15 years of aquaculture ponds, and the differences associated with sediment properties were explored in the two farming practices. Compared to CMC ponds, GC ponds had lower contents of TC, TN, and TP in sediments, and similar trends for sediment pH and moisture content. Sediment bacterial communities were significantly different between GC and CMC ponds, with higher bacterial richness and diversity in GC ponds. The bacterial communities among the pond sediments were closely associated with sediment pH, TC, and TN. Additionally, the results showed profoundly lower activities of β-1,4-glucosidase, leucine aminopeptidase, and phosphatase in the sediments of GC ponds than CMC ponds. Pearson's correlation analysis further revealed strong positive correlations between the hydrolytic enzyme activities and nutrient concentrations among the aquaculture ponds, indicating microbial enzyme regulation response to sediment nutrient dynamics. Our study herein reveals that farming practices of fish and crab differently affect bacterial communities and enzymatic activities in pond sediments, suggesting nutrient-driven sediment biological processes in aquaculture ponds for different farming practices.
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http://dx.doi.org/10.3390/microorganisms9030501DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7996777PMC
February 2021

Guanidine-rich helical polypeptides bearing hydrophobic amino acid pendants for efficient gene delivery.

Biomater Sci 2021 Apr 19;9(7):2670-2678. Epub 2021 Feb 19.

Institute of Functional Nano & Soft Materials (FUNSOM), Collaborative Innovation Center of Suzhou Nano Science and Technology, Soochow University, Suzhou 215123, China.

Non-viral gene delivery vectors with high transfection efficiency both in vitro and in vivo and low cytotoxicity are highly desirable for clinical applications. Herein, a series of guanidine-rich polypeptides bearing hydrophobic amino acid pendants was efficiently prepared via the 1,3-dipolar cycloaddition between azido decorated polypeptide and propargyl functionalized guanidinium and N-acetylamino acids. CD analysis indicated α-helical conformations of all resulting polypeptides in aqueous solution. The guanidine-rich polypeptide/DNA complexes showed significantly enhanced cellular internalization and high cell viability (>90%) in different mammalian cell lines (i.e., HeLa and RAW 264.7) at concentrations of the best performance. The top-performing guanidine-rich polypeptide containing 10% N-acetyl-l-valine pendants outperformed the commercial transfection reagent PEI by 400 times in vitro and 6 times in vivo. This study provides a new guidance for future molecular design of non-viral gene vectors with high delivery efficiency and low cytotoxicity.
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http://dx.doi.org/10.1039/d0bm02188aDOI Listing
April 2021

Serum and Tissue Levels of Advanced Glycation End Products and Risk of Mortality in Patients on Maintenance Hemodialysis.

Am J Nephrol 2021 17;52(1):8-16. Epub 2021 Feb 17.

Division of Nephrology, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, China,

Background: The relation of tissue and circulating advanced glycation end products (AGEs) with mortality in hemodialysis (HD) patients remains inconclusive. We aimed to investigate the association of serum AGEs (CML) and tissue AGEs estimated by skin autofluorescence (SAF) with all-cause and cardiovascular disease (CVD) mortality, and examine the possible modifiers for the association in HD patients with by far the largest sample size in any similar studies.

Methods: A total of 1,634 HD patients were included from the China Cooperative Study on Dialysis (CCSD), a multicenter prospective cohort study. The primary and secondary outcomes were all-cause mortality and CVD mortality, respectively.

Results: The median follow-up duration was 5.2 years. Overall, there was a positive relation of baseline SAF levels with the risk of all-cause mortality (per 1 AU increment, adjusted hazard ratio (HR), 1.30; 95% confidence interval (CI): 1.12, 1.50) and CVD mortality (per 1 AU increment, adjusted HR, 1.36; 95% CI: 1.14, 1.62). Moreover, a stronger positive association between baseline SAF (per 1 AU increment) and all-cause mortality was found in participants with shorter dialysis vintage, or lower C-reactive protein levels (Both p interactions <0.05). Nevertheless, there was no significant association between serum CML and the risk of mortality.

Conclusions: In patients undergoing long-term HD, baseline SAF, but not serum CML, was significantly associated with the risk of all-cause and CVD death.
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http://dx.doi.org/10.1159/000512385DOI Listing
February 2021

A Labeling Strategy for Living Specimens in Long-Term/Super-Resolution Fluorescence Imaging.

Front Chem 2020 15;8:601436. Epub 2021 Jan 15.

State Key Laboratory of Modern Optical Instrumentation, College of Optical Science and Engineering, Zhejiang University, Hangzhou, China.

Despite the urgent need to image living specimens for cutting-edge biological research, most existing fluorescent labeling methods suffer from either poor optical properties or complicated operations required to realize cell-permeability and specificity. In this study, we introduce a method to overcome these limits-taking advantage of the intrinsic affinity of bright and photostable fluorophores, no matter if they are supposed to be live-cell incompatible or not. Incubated with living cells and tissues in particular conditions (concentration and temperature), some Atto and BODIPY dyes show live-cell labeling capability for specific organelles without physical cell-penetration or chemical modifications. Notably, by using Atto 647N as a live-cell mitochondrial marker, we obtain 2.5-time enhancement of brightness and photostability compared with the most commonly used SiR dye in long-term imaging. Our strategy has expanded the scientist's toolbox for understanding the dynamics and interactions of subcellular structures in living specimens.
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http://dx.doi.org/10.3389/fchem.2020.601436DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7843436PMC
January 2021

Genomic analysis of mutations in platelet mitochondria in a case of benzene-induced leukaemia: A case report.

Medicine (Baltimore) 2021 Jan;100(1):e24014

Shenzhen Prevention and Treatment Center for Occupational Diseases, Shenzhen, Guangdong.

Introduction: As a hematopoietic carcinogen, benzene induces human leukemia through its active metabolites such as benzoquinone, which may cause oxidative damage to cancer-related nuclear genes by increasing reactive oxygen species (ROS). Mitochondrion is the main regulatory organelle of ROS, genetic abnormality of mitochondrion can impede its regulation of ROS, leading to more severe oxidative damage. Mutations have been related to certain types of cancer in several mitochondrial genes, but they have never been completely analyzed genome-wide in leukemia.

Patient Concerns: The patient was a 52-year-old female who had chronic exposure to benzene for several years. Her symptoms mainly included recurrent dizziness, fatigue, and they had lasted for nearly 8 years and exacerbated in recent weeks before diagnosis.

Diagnosis: Samples of peripheral blood were taken from the patient using evacuated tubes with EDTA anticoagulant on the second day of her hospitalization. At the same time blood routine and BCR/ABL genes of leukemic phenotype were tested. Platelets were isolated for mitochondrial DNA (mtDNA) extraction. The genetic analysis of ATP synthase Fo subunit 8 (complex V), ATP synthase Fo subunit 6 (complex V), cytochrome c oxidase subunit 1 (complex IV), cytochrome c oxidase subunit 2 (complex IV), cytochrome c oxidase subunit 3, Cytb, NADH dehydrogenase subunit 1 (complex I) (ND) 1, ND2, ND3, ND4, ND5, ND6, 12S-RNA, 16S-RNA, tRNA-Cysteine, A, N, tRNA-Leucine, E, displacement loop in platelet mtDNA were performed. All the detected gene mutations were validated using the conventional Sanger sequencing method.

Interventions: The patient received imatinib, a small molecule kinase inhibitor, and symptomatic treatments.

Outcomes: After 3 months treatment her blood routine test indicators were restored to normal.

Conclusion: A total of 98 mutations were found, and 25 mutations were frame shift. The ND6 gene mutation rate was the highest among all mutation points. Frame shifts were identified in benzene-induced leukemia for the first time. Many mutations in the platelet mitochondrial genome were identified and considered to be potentially pathogenic in the female patient with benzene-induced leukemia. The mutation rate of platelet mitochondrial genome in the benzene-induced leukemia patient is relatively high, and the complete genome analysis is helpful to fully comprehend the disease characteristics.
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http://dx.doi.org/10.1097/MD.0000000000024014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7793417PMC
January 2021

Prediction of Liquid Chromatographic Retention Time with Graph Neural Networks to Assist in Small Molecule Identification.

Anal Chem 2021 02 7;93(4):2200-2206. Epub 2021 Jan 7.

College of Chemistry and Chemical Engineering, Central South University, Changsha 410083, China.

The predicted liquid chromatographic retention times (RTs) of small molecules are not accurate enough for wide adoption in structural identification. In this study, we used the graph neural network to predict the retention time (GNN-RT) from structures of small molecules directly without the requirement of molecular descriptors. The predicted accuracy of GNN-RT was compared with random forests (RFs), Bayesian ridge regression, convolutional neural network (CNN), and a deep-learning regression model (DLM) on a METLIN small molecule retention time (SMRT) dataset. GNN-RT achieved the highest predicting accuracy with a mean relative error of 4.9% and a median relative error of 3.2%. Furthermore, the SMRT-trained GNN-RT model can be transferred to the same type of chromatographic systems easily. The predicted RT is valuable for structural identification in complementary to tandem mass spectra and can be used to assist in the identification of compounds. The results indicate that GNN-RT is a promising method to predict the RT for liquid chromatography and improve the accuracy of structural identification for small molecules.
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http://dx.doi.org/10.1021/acs.analchem.0c04071DOI Listing
February 2021

Impacts of land use at multiple buffer scales on seasonal water quality in a reticular river network area.

PLoS One 2021 6;16(1):e0244606. Epub 2021 Jan 6.

College of Geography Science and Geomatics Engineering, Suzhou University of Science and Technology, Suzhou, Jiangsu, China.

The assessment and prediction of regional water quality are fundamental inputs to environmental planning and watershed ecological management. This paper explored spatiotemporal changes in the correlation of water quality parameters (WQPs) and land-use types (LUTs) in a reticular river network area. Water samples of 44 sampling sites were collected every quarter from 2016 to 2018 and evaluated for dissolved oxygen (DO), total phosphorus (TP), ammonia nitrogen (NH3-N), and permanganate index (CODMn). A redundancy analysis (RDA) and stepwise multiple linear regression (SMLR) were applied to analyze the land-use type impacts on seasonal WQPs at five buffer scales (100, 200, 500, 800, and 1000 m). The Kruskal-Wallis test results revealed significant seasonal differences in NH3-N, TP, CODMn, and DO. The area percentages of farmland, water area and built-up land in the study area were 38.96%, 22.75% and16.20%, respectively, for a combined total area percentage of nearly 80%. Our study showed that orchard land had an especially favorable influence on WQPs. Land-use type impacts on WQPs were more significant during the dry season than the wet season. The total variation explained by LUTs regarding WQPs at the 1 km buffer scale was slightly stronger than at smaller buffer scales. Built-up land had a negative effect on WQPs, but orchard and forest-grassland had a positive effect on WQPs. The effects of water area and farmland on WQPs were complex on different buffer scales. These findings are helpful for improving regional water resource management and environmental planning.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0244606PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7787537PMC
May 2021

Cancer cell-targeted cisplatin prodrug delivery metabolic labeling and bioorthogonal click reaction.

Biomater Sci 2021 Feb;9(4):1301-1312

Institute of Functional Nano and Soft Materials (FUNSOM), Jiangsu Key Laboratory of Carbon-Based Functional Materials and Devices, Collaborative Innovation Center of Suzhou Nano Science & Technology, Soochow University, Suzhou 215123, China.

The discrepancy of surface receptors on cancerous and non-cancerous cells has been regarded as the mainstay of cancer-targeted therapy. However, due to the heterogeneity of tumor cells and the insufficient levels of receptors on the tumor cell surface, the success of cancer cell-targeted therapies is largely limited. Histone deacetylase/cathepsin l-responsive acetylated azidomannose (DCL-AAM) was previously developed to effectively and selectively label cancer cell surfaces with reactive azido groups via sugar metabolism. Herein, the labeling kinetics and generality of DCL-AAM were systematically investigated in varieties of tumor cells in vitro and in SKOV3 xenograft tumors in vivo. Based on this, dibenzocyclooctyne-cisplatin (DBCO-Pt) prodrug was developed, and DCL-AAM-mediated metabolic labeling of SKOV3 cells enhanced the tumor accumulation of DBCO-Pt ∼2 fold via bioorthogonal click chemistry, potentiating the anti-tumor efficacy of cisplatin yet alleviating the systemic toxicity. This work, therefore, provides the experimental and theoretical support for the future design of sugar metabolism-based targeted delivery systems and may provide a promising candidate for the treatment of cancers lacking appropriate biomarkers.
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http://dx.doi.org/10.1039/d0bm01709dDOI Listing
February 2021

The efficacy of a nursing care and follow-up program for patients with heart failure: Study protocol for a randomized controlled trial.

Medicine (Baltimore) 2020 Dec;99(49):e23380

Department of Nursing, Changshan County People's Hospital, Zhejiang, China.

Background: Heart failure (HF) is one of the primary causes of the increasing public health costs, incidence rate and mortality of heart disease. As treatment options for the HF have evolved, people have a better understanding of overall burden of HF, resulting a more centralized method for the treatment of these patients with chronic diseases. At present, with the rapid progress of medical technology, the nursing mode must be updated accordingly. The objective of this trial is to investigate the effects of the program of nursing care and follow-up on life quality, self-care, and the rehospitalization of patients with HF.

Method: This is a randomized controlled study to be carried out from November 2020 to March 2021 and was granted through the Ethics Committee of Changshan County People's Hospital (CCPH002376). The patients meet the following criteria will be included: the age of the patients is 18 years and above, and the functional classification is NYHA II or NYHA III. The patients with the following criteria will be excluded: patients who have received the by-pass surgery in the last 6 months; cancer patients are given radiotherapy or chemotherapy; patients with severe renal failure requiring dialysis; patients with chronic obstructive pulmonary disease who need ventilation; and patients with hearing or visual impairment. In our experiment, patient information scale, the life quality scale (The Left Ventricular Dysfunction Scale) and Self-Care of HF Index are utilized for the assessment. All the analyses are implemented with SPSS for Windows Version 20.0.

Results: Impact of experimental programs on outcomes will be illustrated in the Table.

Conclusion: We hypothesize that the nursing care conducted for the HF patients may improve the life quality and self-care.

Trial Registration Number: researchregistry 6129.
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http://dx.doi.org/10.1097/MD.0000000000023380DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7717929PMC
December 2020

Role of the stromal cell derived factor-1 in the biological functions of endothelial progenitor cells and its underlying mechanisms.

Exp Ther Med 2021 Jan 17;21(1):39. Epub 2020 Nov 17.

Department of Oncology, General Hospital of Central Theater Command, Wuhan, Hubei 430070, P.R. China.

Stromal cell derived factor-1 (SDF-1) is a chemokine that plays a critical role in the homing of stem and progenitor cells, including endothelial progenitor cells (EPCs). However, little research has been undertaken to evaluate the roles of SDF-1 in the biological functions of EPCs and related signaling pathways. The present study aimed to investigate the biological functions of EPCs in response to SDF-1, as well as the underlying mechanisms. The effects of SDF-1 treatment on EPC proliferation, migration and tube formation were assessed by performing MTS, Transwell and tube formation assays, respectively. The phosphorylation status of Akt and ERK was evaluated by western blotting. The present results indicated that SDF-1 treatment enhanced EPC proliferation, migration and tube formation compared with the control group. Furthermore, SDF-1-induced EPC proliferation was significantly reduced following treatment with a C-X-C Motif Chemokine Receptor 4 antagonist (AMD3100), a PI3K inhibitor (LY294002) and the mitogen-activated protein kinase kinase inhibitor (MEK; PD98059). SDF-1-induced migration and angiogenesis were significantly suppressed by the PI3K inhibitor, but not the MEK inhibitor. Moreover, SDF-1 significantly increased the protein expression levels of phosphorylated (p)-Akt and p-ERK; however, SDF-1-induced effects on protein expression were suppressed by AMD3100, LY294002 and PD98059. Thus, SDF-1-induced EPC proliferation was mediated by activation of the Akt and ERK signaling pathways, whereas SDF-1-mediated EPC migration and tube formation only involved activation of the Akt signaling pathway.
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http://dx.doi.org/10.3892/etm.2020.9471DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7706408PMC
January 2021

Role of PARP1-mediated autophagy in EGFR-TKI resistance in non-small cell lung cancer.

Sci Rep 2020 12 1;10(1):20924. Epub 2020 Dec 1.

Cancer Center, Daping Hospital, Army Medical University, #10 Changjiang Zhilu, Daping, Yuzhong District, Chongqing, 400042, China.

Resistance to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) has become the main clinical challenge of advanced lung cancer. This research aimed to explore the role of PARP1-mediated autophagy in the progression of TKI therapy. PARP1-mediated autophagy was evaluated in vitro by CCK-8 assay, clonogenic assay, immunofluorescence, and western blot in the HCC-827, H1975, and H1299 cells treated with icotinib (Ico), rapamycin, and AZD2281 (olaparib) alone or in combination. Our results and GEO dataset analysis confirmed that PARP1 is expressed at lower levels in TKI-sensitive cells than in TKI-resistant cells. Low PARP1 expression and high p62 expression were associated with good outcomes among patients with NSCLC after TKI therapy. AZD2281 and a lysosomal inhibitor reversed resistance to Ico by decreasing PARP1 and LC3 in cells, but an mTOR inhibitor did not decrease Ico resistance. The combination of AZD2281 and Ico exerted a markedly enhanced antitumor effect by reducing PARP1 expression and autophagy in vivo. Knockdown of PARP1 expression reversed the resistance to TKI by the mTOR/Akt/autophagy pathway in HCC-827IR, H1975, and H1299 cells. PARP1-mediated autophagy is a key pathway for TKI resistance in NSCLC cells that participates in the resistance to TKIs. Olaparib may serve as a novel method to overcome the resistance to TKIs.
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http://dx.doi.org/10.1038/s41598-020-77908-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7708842PMC
December 2020

Pyrido[2, 3-d]pyrimidin-7(8H)-ones as new selective orally bioavailable Threonine Tyrosine Kinase (TTK) inhibitors.

Eur J Med Chem 2021 Feb 16;211:113023. Epub 2020 Nov 16.

International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Discovery of Chinese Ministry of Education (MOE), Guangzhou City Key Laboratory of Precision Chemical Drug Development, School of Pharmacy, Jinan University, 601 Huangpu Avenue West, Guangzhou 510632, China. Electronic address:

A series of pyrido [2, 3-d]pyrimidin-7(8H)-ones were designed and synthesized as new selective orally bioavailable Threonine Tyrosine Kinase (TTK) inhibitors. One of the representative compounds, 5o, exhibited strong binding affinity with a K value of 0.15 nM, but was significantly less potent against a panel of 402 wild-type kinases at 100 nM. The compound also potently inhibited the kinase activity of TTK with an IC value of 23 nM, induced chromosome missegregation and aneuploidy, and suppressed proliferation of a panel of human cancer cell lines with low μM IC values. Compound 5o demonstrated good oral pharmacokinetic properties with a bioavailability value of 45.3% when administered at a dose of 25 mg/kg in rats. Moreover, a combination therapy of 5o with paclitaxel displayed promising in vivo efficacy against the HCT-116 human colon cancer xenograft model in nude mice with a Tumor Growth Inhibition (TGI) value of 78%. Inhibitor 5o may provide a new research tool for further validating therapeutic potential of TTK inhibition.
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http://dx.doi.org/10.1016/j.ejmech.2020.113023DOI Listing
February 2021

Deep-Learning-Assisted multivariate curve resolution.

J Chromatogr A 2021 Jan 13;1635:461713. Epub 2020 Nov 13.

College of Chemistry and Chemical Engineering, Central South University, Changsha, 410083, P. R. China. Electronic address:

Gas chromatography-mass spectrometry (GC-MS) is one of the major platforms for analyzing volatile compounds in complex samples. However, automatic and accurate extraction of qualitative and quantitative information is still challenging when analyzing complex GC-MS data, especially for the components incompletely separated by chromatography. Deep-Learning-Assisted Multivariate Curve Resolution (DeepResolution) was proposed in this study. It essentially consists of convolutional neural networks (CNN) models to determine the number of components of each overlapped peak and the elution region of each compound. With the assistance of the predicted elution regions, the informative regions (such as selective region and zero-concentration region) of each compound can be located precisely. Then, full rank resolution (FRR), multivariate curve resolution-alternating least squares (MCR-ALS) or iterative target transformation factor analysis (ITTFA) can be chosen adaptively to resolve the overlapped components without manual intervention. The results showed that DeepResolution has superior compound identification capability and better quantitative performances when comparing with MS-DIAL, ADAP-GC and AMDIS. It was also found that baseline levels, interferents, component concentrations and peak tailing have little influences on resolution result. Besides, DeepResolution can be extended easily when encountering unknown component(s), due to the independence of each CNN model. All procedures of DeepResolution can be performed automatically, and adaptive selection of resolution methods ensures the balance between resolution power and consumed time. It is implemented in Python and available at https://github.com/XiaqiongFan/DeepResolution.
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http://dx.doi.org/10.1016/j.chroma.2020.461713DOI Listing
January 2021

LncRNA LUADT1 sponges miR-195 to prevent cardiac endothelial cell apoptosis in sepsis.

Mol Med 2020 11 23;26(1):112. Epub 2020 Nov 23.

Department of Clinical Laboratory, Affliated Dongfeng Hospital, Hubei University of Medicine, Shiyan, 442008, Hubei, People's Republic of China.

Background: The oncogenic role of the newly identified lncRNA LUADT1 has been revealed in lung adenocarcinoma. It was reported that LUADT1 plays a critical role in multiple human diseases. This study was carried out to investigate the role of LUADT1 in sepsis.

Methods: Sixty patients with sepsis and sixty healthy volunteers were recruited for this study. Plasma samples were collected from all participants. Human primary coronary artery endothelial cells were also used in this study. The expression of Pim-1, miR-195 and LUADT1 were detected by RT-qPCR. The interaction between miR-195 and LUADT1 was determined by overexpression experiments and luciferase activity assay. Cell apoptosis was detected by flow cytometry. The expression of apoptosis-related protein was detected by Western blotting.

Results: Bioinformatics analysis revealed the potential interaction between LUADT1 and miR-195, which was confirmed by dual luciferase reporter assay. LUADT1 was downregulated in patients with sepsis. Moreover, LPS treatment downregulated the expression of LUADT1 in primary cardiac endothelial cells. Overexpression of LUADT1 and miR-195 did not affect the expression of each other in primary cardiac endothelial cells. Interestingly, overexpression of LUADT1 was found to upregulate the expression of Pim-1, a target of miR-195. In addition, it was found that overexpression of LUADT1 and Pim-1 reduced the enhancement effects of miR-195 on LPS-induced cardiac endothelial cell apoptosis.

Conclusion: In summary, LUADT1 may protect cardiac endothelial cells against apoptosis in sepsis by regulating the miR-195/Pim-1 axis.
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http://dx.doi.org/10.1186/s10020-020-00228-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7682058PMC
November 2020

Proteolysis targeting chimera (PROTAC) in drug discovery paradigm: Recent progress and future challenges.

Eur J Med Chem 2021 Jan 31;210:112981. Epub 2020 Oct 31.

Key Laboratory of Neuropsychiatric Drug Research of Zhejiang Province, Institute of Materia Medica, Hangzhou Medical College, Hangzhou, 310013, PR China; School of Pharmacy, Hangzhou Medical College, Hangzhou, 310013, PR China. Electronic address:

Proteolysis targeting chimera (PROTAC), hijacking protein of interest (POI) and recruiting E3 ligase for target degradation via the ubiquitin-proteasome pathway, is a novel drug discovery paradigm which has been widely used as biological tools and medicinal molecules with the potential of clinical application value. Currently, ARV-110, an orally small molecule PROTAC was designed to specifically target Androgen receptor (AR), firstly enters clinical phase I trials for the treatment of metastatic castration-resistant prostate cancer, which turns a new avenue for the development of PROTAC. We herein provide a detail summary on the latest one year progress of PROTAC target various proteins and elucidate the advantages of PROTAC technology. Finally, the potential challenges of this vibrant field are also discussed.
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http://dx.doi.org/10.1016/j.ejmech.2020.112981DOI Listing
January 2021