Publications by authors named "Haoyang Zhang"

46 Publications

High-efficiency dynamic sensing of biothiols in cancer cells with a fluorescent β-cyclodextrin supramolecular assembly.

Chem Sci 2020 Apr 22;11(18):4791-4800. Epub 2020 Apr 22.

State Key Laboratory of Elemento-Organic Chemistry, College of Chemistry, Nankai University Tianjin 300071 P. R. China

A unique fluorescent supramolecular assembly was constructed using coumarin-modified β-cyclodextrin as a reversible ratiometric probe and an adamantane-modified cyclic arginine-glycine-aspartate peptide as a cancer-targeting agent host-guest inclusion complexation. Importantly, the coumarin-modified β-cyclodextrin not only showed higher sensitivity than the parent coumarin derivatives owing to the presence of numerous hydroxyl groups on the cyclodextrin but also provided a hydrophobic cavity for encapsulation of a cancer-targeting agent. The assembly showed a reversible and fast response to biothiols with a micromolar dissociation constant, as well as outstanding cancer cell permeability, which can be used for high-efficiency real-time monitoring of biothiols in cancer cells. This supramolecular assembly strategy endows the fluorescent probe with superior performance for dynamic sensing of biothiols.
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http://dx.doi.org/10.1039/d0sc00414fDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8159256PMC
April 2020

Discovery of novel tripeptide propylene oxide proteasome inhibitors for the treatment of multiple myeloma.

Bioorg Med Chem 2021 Jun 1;40:116182. Epub 2021 May 1.

College of Life Science, Nanjing Normal University, No. 1 Wenyuan Road, Nanjing 210037, PR China; Jiangsu Chia Tai Fenghai Pharmaceutical Co. Ltd., No. 9 Weidi Road, Nanjing 210046, PR China. Electronic address:

The ubiquitin proteasome pathway (UPP) plays a critical role in the maintenance of cell homeostasis and the development of diseases, such as cancer and neurodegenerative disease. A series of novel tripeptide propylene oxide compounds as proteasome inhibitors were designed, synthesized and biologically investigated in this manuscript. The enzymatic activities of final compounds against 20S human proteasome were investigated and structure-activity relationship (SAR) was summarized. Some potent compounds were further evaluated to inhibit the proliferation of multiple myeloma (MM) cancer cell lines RPMI8226 and U266B. The results showed that some compounds were active against MM cancer cell lines with IC values of less than 50 nM. The microsomal metabolic stabilities in human, rat and mice species were carried out and the results showed that compounds 30 and 31 were stable enough to be in vivo investigated. The in vivo pharmacokinetic results showed that compounds 30 and 31 had acceptable biological parameters for both ig and iv administrations. In vivo antitumor activities of compounds 30 and 31 with the doses of 100 mg/kg and 50 mg/kg BIW were performed by using RPMI8226 xenograft nude mouse model. Toxicities of compounds 30 and 31 were not observed during the experiment and dose dependent effect was obvious and the tumor volume was greatly inhibited.
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http://dx.doi.org/10.1016/j.bmc.2021.116182DOI Listing
June 2021

Anti-tumor activity of a novel proteasome inhibitor D395 against multiple myeloma and its lower cardiotoxicity compared with carfilzomib.

Cell Death Dis 2021 Apr 30;12(5):429. Epub 2021 Apr 30.

Department of Hematology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing, 210029, China.

Carfilzomib, a second-generation proteasome inhibitor, has significantly improved the survival rate of multiple myeloma (MM) patients, but its clinical application is still restricted by drug resistance and cardiotoxicity. Here, we identified a novel proteasome inhibitor, D395, and assessed its efficacy in treating MM as well as its cardiotoxicity at the preclinical level. The activities of purified and intracellular proteasomes were measured to determine the effect of D395 on the proteasome. CCK-8 and flow cytometry experiments were designed to evaluate the effects of D395 on cell growth and apoptosis. The effects of D395 and carfilzomib on serum enzyme activity, echocardiography features, cardiomyocyte morphology, and hERG channels were also compared. In our study, D395 was highly cytotoxic to MM cell lines and primary MM cells but not normal cells, and it was well tolerated in vivo. Similar to carfilzomib, D395 inhibited osteoclast differentiation in a dose-dependent manner. In particular, D395 exhibited lower cardiotoxicity than carfilzomib in all experiments. In conclusion, D395 is a novel irreversible proteasome inhibitor that has remarkable anti-MM activity and mild cardiotoxicity in vitro and in vivo.
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http://dx.doi.org/10.1038/s41419-021-03701-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087809PMC
April 2021

Risk factors for bronchiectasis in patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis.

Clinics (Sao Paulo) 2021 16;76:e2420. Epub 2021 Apr 16.

Liaoning University of Traditional Chinese Medicine, Shenyang, China.

The risk factors of bronchiectasis in patients with chronic obstructive pulmonary disease have not yet been established. This systematic review and meta-analysis aimed to investigate and identify potential risk factors for patients with chronic obstructive pulmonary disease accompanied by bronchiectasis. We reviewed eight electronic journal databases from their inception to November 2019 for observational studies with no language restrictions. The Newcastle-Ottawa Scale was applied to evaluate the quality of the literature. Binary variables were pooled using odds ratios and continuous variables using the standardized mean difference with 95% confidence intervals. The confidence of evidence was assessed according to the grading of the recommendations assessment, development, and evaluation method. Eight case-control studies met the inclusion criteria. Tuberculosis history, smoking history, hospitalization stays, admissions in the past year, and duration of symptoms were considered risk factors. In addition, the ratio between the forced expiratory volume in 1s and forced vital capacity, the percentage of forced expiratory volume in 1s, the forced expiratory volume in 1s as a percentage of the predicted value, purulent sputum, purulent mucus sputum, positive sputum culture, Pseudomonas aeruginosa infection, arterial oxygen pressure, daily dyspnea, C-reactive protein, leukocytes, and the percentage of neutrophils were found to be closely related to bronchiectasis. However, these were not considered risk factors. The evidence of all outcomes was judged as "low" or "very low." Additional prospective studies are required to elucidate the underlying risk factors and identify effective preventive interventions.
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http://dx.doi.org/10.6061/clinics/2021/e2420DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024924PMC
April 2021

Resin Transfer Moldable Fluorinated Phenylethynyl-Terminated Imide Oligomers with High T: Structure-Melt Stability Relationship.

Polymers (Basel) 2021 Mar 15;13(6). Epub 2021 Mar 15.

Key Laboratory of Engineering Plastics and Beijing National Laboratory for Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China.

Phenylethynyl-terminated aromatic polyimides meet requirements of resin transfer molding (RTM) and exhibits high glass transition temperature (T) were prepared. Moreover, the relationship between the polyimide backbones structure and their melting stability was investigated. The phenylethynyl-terminated polyimides were based on 4,4'-(hexafluorosiopropylidene)-diphthalic anhydride (6FDA) and different diamines of 3,4'-oxydianiline (3,4'-ODA), m-phenylenediamine (m-PDA) and 2,2'-bis(trifluoromethyl)benzidine (TFDB) were prepared. These oligoimides exhibit excellent melting flowability with wide processing temperature window and low minimum melt viscosities (<1 Pa·s). Two of the oligoimides display good melting stability at 280-290 °C, which meet the requirements of resin transfer molding (RTM) process. After thermally cured, all resins show high glass transition temperatures (Ts, 363-391 °C) and good tensile strength (51-66 MPa). The cure kinetics studied by the differential scanning calorimetry (DSC), C nuclear magnetic resonance (C NMR) characterization and density functional theory (DFT) definitely confirmed that the electron-withdrawing ability of oligoimide backbone can tremendously affect the curing reactivity of terminated phenylethynyl groups. The replacement of 3,4'-ODA units by m-PDA or TFDB units increase the electron-withdrawing ability of the backbone, which increase the curing rate of terminated phenylethynyl groups at processing temperatures, hence results in the worse melting stability.
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http://dx.doi.org/10.3390/polym13060903DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7999610PMC
March 2021

Supramolecular Pins with Ultralong Efficient Phosphorescence.

Adv Mater 2021 Apr 3;33(14):e2007476. Epub 2021 Mar 3.

Department College of Chemistry, Nankai University, Tianjin, 300071, P. R. China.

Constructing ultralong organic phosphorescent materials possessing a high quantum yield is challenging. Herein, assemblies of purely organic supramolecular pins composed of alkyl-bridged phenylpyridinium salts and cucurbit[8]uril (CB[8]) are reported. Different from "one host with two guests" and "head-to-tail" binding, the binding formation of supramolecular pins is "one host with one guest" and "head-to-head," which overcomes electrostatic repulsion and promotes intramolecular charge transfer. The supramolecular pin 1/CB[8] displays afterglow with high phosphorescence quantum yield (99.38%) after incorporation into a rigid matrix, which is the highest yield reported to date for phosphorescent materials. Moreover, multicolor photoluminescence can be obtained by different excitation wavelengths and ratios of host to guest. Owing to the redshift of the absorption, the supramolecular pins are applied for targeted phosphorescence imaging of mitochondria. This work will provide a reasonable supramolecular strategy to achieve redshifted and efficient phosphorescence both in the solid state and in aqueous solution.
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http://dx.doi.org/10.1002/adma.202007476DOI Listing
April 2021

Performance Evaluation of and Methylation for the Aid in Diagnosis of Lung Cancer Based on the Analysis of FFPE Specimen.

Front Oncol 2020 14;10:565780. Epub 2020 Dec 14.

Department of Pathology, Tongji Hospital, Tongji University, Shianghai, China.

Emerging molecular diagnostic methods are more sensitive and objective, which can overcome the intrinsic failings of morphological diagnosis. Here, a RT-PCR-based diagnostic test kit (LungMe) was developed and characterized to simultaneously quantify the DNA methylation of and in FFPE tissue specimens. The clinical manifestations were evaluated in 251 FFPE samples with specificity and sensitivity of 90.4 and 89.8%, respectively. Furthermore, the quantitative analysis shows that the degree of methylation was correlated with the stages of lung cancer, but not in the case of . Our observation indicated that the DNA methylation of and may play different roles in cancer development. Comparison of the methylation levels of and between cancer and cancer-adjacent specimens (n = 30), showed they have "epigenetic field defect". As additional clinical validation, the hypermethylation of and was detected not only in surgical operative specimens, but also in histopathological negative puncture biopsies. and methylation detection can be used to increase sensitivity and NPV, which provide us with a more accurate method of differential diagnosis and are likely to be rapidly applied in clinical examinations.
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http://dx.doi.org/10.3389/fonc.2020.565780DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7793934PMC
December 2020

A twin-axial pseudorotaxane for phosphorescence cell imaging.

Chem Commun (Camb) 2021 Feb;57(10):1214-1217

College of Chemistry, State Key Laboratory of Elemento-Organic Chemistry, Nankai University, Tianjin 300071, P. R. China.

A twin-axial pseudorotaxane is constructed using a phenylpyridine salt with diethanolamine (DA-PY) and cucurbit[8]uril (CB[8]), and it not only displays phosphorescence in aqueous solution but it can also be used for targeted cell-imaging.
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http://dx.doi.org/10.1039/d0cc06717bDOI Listing
February 2021

Primary Clear Cell Sarcoma of the Ileum: A Case Report With Next-Generation Sequencing Analysis.

Int J Surg Pathol 2021 Jan 7:1066896920985311. Epub 2021 Jan 7.

Department of Pathology, Tongji Hospital, Tongji University School of Medicine, Shanghai, China.

As the concept of clear cell sarcoma-like tumor or malignant gastrointestinal neuroectodermal tumor (CCS-LT/MGNET) has been widely accepted, primary CCS of the gastrointestinal tract (CCS-GI) is becoming a rare entity. In this article, we describe a case of primary CCS-GI that occurred in the ileum of a 65-year-old male to further illustrate its rare occurrence. Similar to CCS of soft tissue (CCS-ST), the tumor was composed of spindled to epithelioid cells displaying fascicular, nested, or pseudopapillary arrangement. The tumor cells had large round to ovoid nuclei with vesicular chromatin and prominent nucleoli, containing eosinophilic to pale cytoplasm. In contrast to CCS-LT/MGNET, immunohistochemical study also showed variable positivity of HMB45, melan A, and MiTF besides the strong and diffuse staining of S100 protein and SOX10. Fluorescence in situ hybridization (FISH) using fusion probes identified and genes rearrangement. Next-generation sequencing (NGS) analysis further revealed exons9/8- exon4 and exon3- exon11 fusion genes. CCS-GI and CCS-LT/MGNET possibly represent 2 related entities of the same spectrum, which differentiate along 2 different pathways.
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http://dx.doi.org/10.1177/1066896920985311DOI Listing
January 2021

A data-driven integrative platform for computational prediction of toxin biotransformation with a case study.

J Hazard Mater 2021 04 11;408:124810. Epub 2020 Dec 11.

CAS Key Laboratory of Computational Biology, CAS Key Laboratory of Nutrition, Metabolism and Food Safety, CAS-MPG Partner Institute for Computational Biology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, PR China. Electronic address:

Recently, biogenic toxins have received increasing attention owing to their high contamination levels in feed and food as well as in the environment. However, there is a lack of an integrative platform for seamless linking of data-driven computational methods with 'wet' experimental validations. To this end, we constructed a novel platform that integrates the technical aspects of toxin biotransformation methods. First, a biogenic toxin database termed ToxinDB (http://www.rxnfinder.org/toxindb/), containing multifaceted data on more than 4836 toxins, was built. Next, more than 8000 biotransformation reaction rules were extracted from over 300,000 biochemical reactions extracted from ~580,000 literature reports curated by more than 100 people over the past decade. Based on these reaction rules, a toxin biotransformation prediction model was constructed. Finally, the global chemical space of biogenic toxins was constructed, comprising ~550,000 toxins and putative toxin metabolites, of which 94.7% of the metabolites have not been previously reported. Additionally, we performed a case study to investigate citrinin metabolism in Trichoderma, and a novel metabolite was identified with the assistance of the biotransformation prediction tool of ToxinDB. This unique integrative platform will assist exploration of the 'dark matter' of a toxin's metabolome and promote the discovery of detoxification enzymes.
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http://dx.doi.org/10.1016/j.jhazmat.2020.124810DOI Listing
April 2021

and efficacy of the novel oral proteasome inhibitor NNU546 in multiple myeloma.

Aging (Albany NY) 2020 11 16;12(22):22949-22974. Epub 2020 Nov 16.

College of Life Science, Nanjing Normal University, Nanjing 210046, PR China.

Proteasome inhibition demonstrates highly effective impact on multiple myeloma (MM) treatment. Here, we aimed to examine anti-tumor efficiency and underlying mechanisms of a novel well tolerated orally applicable proteasome inhibitor NNU546 and its hydrolyzed pharmacologically active form NNU219. NNU219 showed more selective inhibition to proteasome catalytic subunits and less off-target effect than bortezomib . Moreover, intravenous and oral administration of either NNU219 or NNU546 led to more sustained pharmacodynamic inhibitions of proteasome activities compared with bortezomib. Importantly, NNU219 exhibited potential anti-MM activity in both MM cell lines and primary samples . The anti-MM activity of NNU219 was associated with induction of G2/M-phase arrest and apoptosis via activation of the caspase cascade and endoplasmic reticulum stress response. Significant growth-inhibitory effects of NNU219 and NNU546 were observed in 3 different human MM xenograft mouse models. Furthermore, such observation was even found in the presence of a bone marrow microenvironment. Taken together, these findings provided the basis for clinical trial of NNU546 to determine its potential as a candidate for MM treatment.
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http://dx.doi.org/10.18632/aging.104023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746380PMC
November 2020

Effectiveness of Traditional Chinese Exercise for Symptoms of Knee Osteoarthritis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Int J Environ Res Public Health 2020 10 27;17(21). Epub 2020 Oct 27.

Department of Physical Education, Sun Yat-Sen University, Guangzhou 510000, China.

Growing evidences have advocated the potential benefits of traditional Chinese exercise (TCE) on symptomatic improvement of knee osteoarthritis (KOA). However, most of them have been derived from cross-sectional studies or case reports; the effectiveness of TCE therapies has not been fully assessed with a randomized control trial (RCT). In order to evaluate the combined clinical effectiveness of TCE for KOA, we conducted a systematic review and meta-analysis on the existing RCTs on KOA. A systematic search was performed in four electronic databases: PubMed, Web of Science, Cochrane Library, and EMBASE from the time of their inception to February 2020. All eligible RCTs were included in which TCE was utilized for treating KOA as compared to a control group. Two reviewers independently extracted the data and evaluated the risk of bias following the Cochrane Risk of Bias Tool for RCT. The symptoms of KOA evaluated by the Western Ontario and McMaster Universities Arthritis Index (WOMAC) and the Knee Injury and Osteoarthritis Outcome Score (KOOS) were regarded as the primary outcomes in this study. Each outcome measure was pooled by a standardized mean difference (SMD) with 95% confidence intervals (CI). A meta-analysis was applied with a random or fixed effect model for the collected data to calculate the summary SMD with 95% CI based on different statistical heterogeneity. In addition, subgroup analyses were used to investigate heterogeneity and sensitivity analysis was carried out for the results of the meta-analysis. Egger's test and the funnel plots were used to examine the potential bias in the RCTs. A total of 14 RCTs involving 815 patients with KOA were included. Compared with a control group; the synthesized data of TCE showed a significant improvement in WOMAC/KOOS pain score (SMD = -0.61; 95% CI: -0.86 to -0.37; < 0.001), stiffness score (SMD = -0.75; 95% CI: -1.09 to -0.41; < 0.001), and physical function score (SMD = -0.67; 95% CI: -0.82 to -0.53; < 0.001). Conclusions: Our meta-analysis suggested that TCE may be effective in alleviating pain; relieving stiffness and improving the physical function for patients with KOA. Yet; given the methodological limitations of included RCTs in this meta-analysis; more high-quality RCTs with large sample size and long-term intervention are required to further confirm the effectiveness and underlying mechanisms of TCE for treating KOA.
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http://dx.doi.org/10.3390/ijerph17217873DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7662219PMC
October 2020

Ultralong purely organic aqueous phosphorescence supramolecular polymer for targeted tumor cell imaging.

Nat Commun 2020 09 16;11(1):4655. Epub 2020 Sep 16.

College of Chemistry, State Key Laboratory of Elemento-Organic Chemistry, Nankai University, Tianjin, 300071, P. R. China.

Purely organic room-temperature phosphorescence has attracted attention for bioimaging but can be quenched in aqueous systems. Here we report a water-soluble ultralong organic room-temperature phosphorescent supramolecular polymer by combining cucurbit[n]uril (CB[7], CB[8]) and hyaluronic acid (HA) as a tumor-targeting ligand conjugated to a 4-(4-bromophenyl)pyridin-1-ium bromide (BrBP) phosphor. The result shows that CB[7] mediated pseudorotaxane polymer CB[7]/HA-BrBP changes from small spherical aggregates to a linear array, whereas complexation with CB[8] results in biaxial pseudorotaxane polymer CB[8]/HA-BrBP which transforms to relatively large aggregates. Owing to the more stable 1:2 inclusion complex between CB[8] and BrBP and the multiple hydrogen bonds, this supramolecular polymer has ultralong purely organic RTP lifetime in water up to 4.33 ms with a quantum yield of 7.58%. Benefiting from the targeting property of HA, this supramolecular polymer is successfully applied for cancer cell targeted phosphorescence imaging of mitochondria.
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http://dx.doi.org/10.1038/s41467-020-18520-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7494876PMC
September 2020

GPRC5A reduction contributes to pollutant benzo[a]pyrene injury via aggravating murine fibrosis, leading to poor prognosis of IIP patients.

Sci Total Environ 2020 Oct 3;739:139923. Epub 2020 Jun 3.

Department of Pathology, Tongji University Affiliated Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China; Tongji University School of Medicine, Tongji University, Shanghai 200092, China. Electronic address:

Air pollution exposure is recently reported to be one of the drivers of exacerbation in idiopathic pulmonary fibrosis (IPF). But there was a lack of direct evidence between pollution and lung fibrosis. Here, our data show effects of pollutant benzo[a]pyrene (BaP) and protein G-protein-coupled receptor family C group 5 type A (GPRC5A) on pulmonary fibrosis, which might help limit potential pollutant injury and disease progression. We cross-referenced epithelial differentially-expressed-genes (DEGs) from pollutant injury and published experimental fibrosis and IPF patients' data, top common-DEG (CO-DEG) GPRC5A was identified as a potential link between exposure-damage and fibrogenesis. The role of GPRC5A was evaluated under BaP exposure, in idiopathic interstitial pneumonia (IIP) tissue-array and via CRISPR/Cas9 knockout mice (Gprc5a). BaP exposure enhanced bleomycin (BLM)-induced murine pulmonary fibrosis with increased Fibronectin and α-SMA expression in primary fibroblasts, thickened respiratory membrane and damaged alveolar type II cell, combined with Gprc5a decline in fibrotic mass. GPRC5A mRNA reduced after 10-14 days' BaP exposure in human epithelial cell A549. GPRC5A protein was further found to decrease in IIP epithelium, especially hyperplastic regions. A high epithelial GPRC5A expression score was positively associated with long survival time (R = 0.34) while negatively with high age (R = -0.4) and IIP type IPF (R = -0.5). Low GPRC5A expression predicts poor prognosis (HR = 4.5). Gprc5a depletion aggravated mortality rate (50%) with increased collagen deposition and myofibroblast activation under BLM treatment and exacerbated BaP injury in lung remodeling. Vitamin metabolic imbalance and Mitofusion2 (Mfn2) or Opa1-regulated mitochondrial dynamics were deduced to contribute to Gprc5a depletion and fibrogenesis. Pollutant BaP exposure worsens murine fibrosis and myofibroblast activation via GPRC5A reduction in the damaged epithelium. GPRC5A deficiency was first confirmed to contribute to both poor prognosis of IIP patients and fibrogenesis in murine model; thus, GPRC5A could serve as a novel therapeutic target in pollutant injury and pulmonary fibrosis.
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http://dx.doi.org/10.1016/j.scitotenv.2020.139923DOI Listing
October 2020

Preventive and therapeutic effectiveness of Sanfu acupoint herbal patching for chronic obstructive pulmonary disease at stable stages: a systematic review and Meta-analysis.

J Tradit Chin Med 2020 08;40(4):530-549

Liaoning University of Traditional Chinese Medicine, Shenyang 110033, China.

Objective: To evaluate the preventive and therapeutic effects of Sanfu acupoint herbal patching (SAHP) in adjuvant treatment in patients with stable chronic obstructive pulmonary disease (COPD).

Methods: We had searched eight electronic databases and six major trial registries from their inception to July 2017 for randomized controlled trials (RCTs). We utilized RevMan 5.3 to evaluate the methodological quality and to perform data analyses.

Results: A total of 28 RCTs involving 1615 records were included in the descriptive analysis, and 25 RCTs were performed for Meta-analysis. Lung function such as forced vital capacity rate of one second FEV1/predicted%, forced vital capacity (FVC) % found no significant difference. The results of Meta-analysis showed that SAHP plus conventional therapy (CT) in the treatment of stable COPD were better than CT, in second sessions' data of FEV1, in third sessions' data of FEV1/FVC, in three sessions' data of SGRQ, in third session's data of Modified Medical Research Council and 6MWT. The symptoms of SAHP's adverse reactions seem to be mild and the incidence of that seems to be low. Descriptive analysis shows that SAHP with CT seems to improve clinical effective rate and had a certain preventive effect on acute exacerbation of COPD, which the curative effect may be better with the increase of treatment course.

Conclusion: SAHP with CT appears to be more effective than CT or CT plus placebo only on improving the quality of life, but the effect on lung function is not obvious. Improve clinical effective rate and preventive effect is uncertainty. SAHP with CT may be used in any Grade to safely treat patients with stable COPD. The more exactly clinical effect still needs to be proved by more high-quality, large sampling, multilingual RCTs.
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http://dx.doi.org/10.19852/j.cnki.jtcm.2020.04.003DOI Listing
August 2020

FADB-China: A molecular-level food adulteration database in China based on molecular fingerprints and similarity algorithms prediction expansion.

Food Chem 2020 Oct 8;327:127010. Epub 2020 May 8.

CAS Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, PR China. Electronic address:

Food adulteration is a growing concern worldwide. The collation and analysis of food adulteration cases is of immense significance for food safety regulation and research. We collected 961 cases of food adulteration between 1998 and 2019 from the literature reports and announcements released by the Chinese government. Critical molecules were manually annotated in food adulteration substances as determined by food chemists, to build the first food adulteration database in China (http://www.rxnfinder.org/FADB-China/). This database is also the first molecular-level food adulteration database worldwide. Additionally, we herein propose an in silico method for predicting potentially illegal food additives on the basis of molecular fingerprints and similarity algorithms. Using this algorithm, we predict 1919 chemicals that may be illegally added to food; these predictions can effectively assist in the discovery and prevention of emerging food adulteration.
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http://dx.doi.org/10.1016/j.foodchem.2020.127010DOI Listing
October 2020

Development of an electrochemical biosensor for phylogenetic analysis of Amaryllidaceae based on the enhanced electrochemical fingerprint recorded from plant tissue.

Biosens Bioelectron 2020 Jul 15;159:112212. Epub 2020 Apr 15.

Key Laboratory of Marine New Materials and Related Technology, Zhejiang Key Laboratory of Marine Materials and Protection Technology, Ningbo Institute of Material Technology and Engineering, Chinese Academy of Sciences, Ningbo, 315201, PR China. Electronic address:

A biosensor has been developed based on disposable screen-printed electrode for recording the electrochemical fingerprint of plant leaf tissue. A thin layer of polydopamine functionalized graphene sheets was coated on the plant tissue modified electrode for signal enhancement. The voltammetric data recorded under different buffer solutions can be derived as patterns for species identification. As the distribution of electrochemical active compounds in plants is controlled by genes, these fingerprints can reflect differences at the genetic level between species. Therefore, the electrochemical fingerprint of plant tissues can be used for phylogenetic research without qualitative analysis. 19 species of Amaryllidaceae including A. africanus, Clivia miniata, Clivia nobilis, Crinum firmifolium, Crinum latifolium, Crinum moorei, Curculiga gracilis, Cyrtanthus breviflorus, Habranthus robustus, Haemanthus albiflos, Haemathus multiflorus, Hippeastrum rutilum, Hymenocallis littoralis, Leucojum aestivum, Sprekelia formosissima, Tulbaghia violacea, Zephyranthes grandiflora, Zephyranthes macrosiphon and Zephyranthes minima have been selected deliberately. The dendrogram deduced from the electrochemical fingerprint was compared with the molecular phylogenetics. The results indicate the electrochemical fingerprint-based phylogenetic study is a persuasive methodology for plant phylogenetic analysis.
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http://dx.doi.org/10.1016/j.bios.2020.112212DOI Listing
July 2020

Coexistence of the bla-carrying plasmid pWLK-NDM and the bla-carrying plasmid pWLK-KPC in a Raoultella ornithinolytica isolate.

Sci Rep 2020 02 11;10(1):2360. Epub 2020 Feb 11.

College of Tobacco Science, Henan Agricultural University, Zhengzhou, 450002, China.

To date, bla and bla genes have been found predominantly in clinical settings around the world. In contrast, bacteria harbouring these two genes from natural environments are relatively less well studied compared to those found in clinical settings. In this study, a carbapenem-resistant Raoultella ornithinolytica strain, WLK218, was isolated from urban river sediment in Zhengzhou City, Henan Province, China. This isolate was subjected to PCR and antimicrobial susceptibility testing. PCR results showed that this isolate was positive for both the bla and bla genes. The antimicrobial susceptibility testing results showed that this isolate exhibited resistance or intermediate resistance to all the antibiotics tested except for streptomycin (susceptible) and cefepime (susceptible-dose dependent). The complete genome sequence of the WLK218 isolate was then determined by using a combination of the PacBio and Illumina sequencing technologies. The de novo assembly of the genome generated one chromosome and six plasmids. Among the six plasmids, the bla gene was carried on the IncX3 plasmid pWLK-NDM, while the bla gene was located on the untypeable plasmid pWLK-KPC. This is the first report of an environmental Raoultella ornithinolytica isolate co-harbouring the bla and bla genes.
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http://dx.doi.org/10.1038/s41598-020-59341-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7012882PMC
February 2020

The Association between Meteorological Factors and the Prevalence of Acute-on-chronic Liver Failure: A Population-based Study, 2007-2016.

J Clin Transl Hepatol 2019 Dec 19;7(4):341-345. Epub 2019 Dec 19.

Liver Research Center of the First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China.

The aim of this study was to investigate the effect(s) of meteorological factors on the prevalence of acute-on-chronic liver failure (ACLF) based on 10-years' worth of population data. We retrospectively collected ACLF case data from January 2007 to December 2016 from three major hospitals in Fuzhou City, China. Climatic data, including rainfall, mean temperature, differences in temperature (delta temperature) and mean humidity for each month were downloaded from the China Climatic Data Service Center. Following data collection, Poisson regression analysis was used to estimate the effect(s) of climatic factors on the risk of the prevalence of ACLF. The population consisted of a total of 3510 cases, with a mean age of 44.7 ± 14.8 years-old and with 79.8% being male. Upon analyzing the population data, we found a growing trend and seasonal pattern of monthly counts of ACLF-related hospitalization throughout the past decade. Specifically, the primary peak of ACLF prevalence was in January and the secondary peak was in July. Poisson regression showed mean temperature (risk ratio = 0.991, 95%CI = 0.986-0.996) and mean humidity (risk ratio = 1.011, 95%CI = 1.006-1.017) to be independently correlated with the monthly cases of ACLF. The results suggest that every unit increase of mean temperature (1°C) and mean humidity (1%) are associated with 0.991- and 1.011-fold changes of ACLF cases, respectively. Rainfall and delta temperature did not appear to affect the prevalence of this disease. The hospitalization for ACLF peaks in January and July. Low temperature and high humidity appear to function as factors contributing to this seasonal pattern.
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http://dx.doi.org/10.14218/JCTH.2019.00044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6943211PMC
December 2019

The effects of daily meteorological perturbation on pregnancy outcome: follow-up of a cohort of young women undergoing IVF treatment.

Environ Health 2019 11 28;18(1):103. Epub 2019 Nov 28.

Assisted Reproductive Technology Unit, Department of Obstetrics and Gynaecology, Faculty of Medicine, The Chinese University of Hong Kong, Block E, 9F, Special Block, Prince of Wales Hospital, 30-32 Ngan Shing Street, Hong Kong, China.

Background: Human reproduction follows a seasonal pattern with respect to spontaneous conception, a phenomenon wherein the effect of meteorological fluctuations might not be unique. However, the effect of seasonal variations on patients who underwent in vitro fertilization (IVF) treatment is unclear. We aimed to evaluate the effects of meteorological variation on the pregnancy rate in a cohort undergoing IVF treatment by performing multivariable analyses.

Methods: We conducted a cohort study in a sub-tropical region with prominent seasonal variations (2005-2016). Women aged < 35 years who were treated with a long ovarian stimulation protocol and underwent fresh embryo transfer (ER) were included. Data on gonadotropin administration (CYCL), oocyte retrieval (OR), ER, and pregnancy outcomes were prospectively recorded. For each patient, the daily average of meteorological data (temperature, humidity, sunlight duration, solar radiation) was recorded from the date of CYCL to ER. Multiple logistic regression analysis adjusted for age, fertilization method, year of the cycle, gonadotropin dose, and transferred embryo grade was performed to determine the relationship between the meteorological parameters and clinical pregnancy. Patients with one successful cycle and one failed cycle were subtracted for a case-control subgroup analysis through mixed effect logistics regressions. Time-series analysis of data in the epidemic level was conducted using the distributed lag linear and non-linear models (DLNMs).

Results: There were 1029 fresh cycles in 860 women (mean age 31.9 ± 2.0 years). Higher mean temperature from CYCL to OR (adjusted odds ratio [aOR] 1.04; 95% confidence interval [CI] 1.01-1.07, P = 0.01) increased the odds of pregnancy, while OR to ER did not show any statistical significance. Compared to that in winter, the odds of becoming pregnant were higher during higher temperature seasons, summer and autumn (aOR 1.47, 95%CI 0.97-2.23, P = 0.07 (marginally significant) and aOR 1.73, 95%CI 1.12-2.68, P = 0.02, respectively). Humidity, sunlight duration, and solar radiation had no effect on the outcome. The subgroup analysis confirmed this finding. The time-series analysis revealed a positive association between temperature and relative risk for pregnancy.

Conclusions: In IVF treatment, the ambient temperature variation alters the pregnancy rates; this aspect must be considered when obtaining patient consent for assisted conception.
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http://dx.doi.org/10.1186/s12940-019-0538-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6883622PMC
November 2019

Robust Visual Tracking Using Structural Patch Response Map Fusion Based on Complementary Correlation Filter and Color Histogram.

Sensors (Basel) 2019 Sep 26;19(19). Epub 2019 Sep 26.

School of Mechano-Electronic Engineering, Xidian University, Xi'an 710071, Shaanxi, China.

A part-based strategy has been applied to visual tracking with demonstrated success in recent years. Different from most existing part-based methods that only employ one type of tracking representation model, in this paper, we propose an effective complementary tracker based on structural patch response fusion under correlation filter and color histogram models. The proposed method includes two component trackers with complementary merits to adaptively handle illumination variation and deformation. To identify and take full advantage of reliable patches, we present an adaptive hedge algorithm to hedge the responses of patches into a more credible one in each component tracker. In addition, we design different loss metrics of tracked patches in two components to be applied in the proposed hedge algorithm. Finally, we selectively combine the two component trackers at the response maps level with different merging factors according to the confidence of each component tracker. Extensive experimental evaluations on OTB2013, OTB2015, and VOT2016 datasets show outstanding performance of the proposed algorithm contrasted with some state-of-the-art trackers.
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http://dx.doi.org/10.3390/s19194178DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6806098PMC
September 2019

Association between Vitamin D Status and Non-Alcoholic Fatty Liver Disease: A Population-Based Study.

J Nutr Sci Vitaminol (Tokyo) 2019 ;65(4):303-308

Liver Research Center, the First Affiliated Hospital of Fujian Medical University.

The relationship between vitamin D levels and non-alcoholic fatty liver disease (NAFLD) remains unestablished. In this study, we aimed to explore the relationship between vitamin D levels and NAFLD based on population survey data. This cross-sectional study was conducted based on data from the National Health and Nutrition Examination Survey. Liver steatosis was diagnosed by ultrasonography. Binary logistic regression analyses were performed to determine the relationship between vitamin D status and NAFLD. A total of 9,782 participants were identified in this analysis, with 46.8% male and an average age of 44.41±0.16 y old. Among them, 6,047 (61.8%) cases were without NAFLD, 1,357 (13.9%) had mild NAFLD, 1,594 (16.3%) had moderate and 784 (8.0%) had severe NAFLD. Compared to those with non-NAFLD or mild NAFLD, patients in the moderate to severe NAFLD group had higher vitamin D deficiency or insufficiency rates (12.4% vs 11.5% and 36.8% vs 33.2%, respectively). After adjustment for male gender, older age, race, BMI, history of diabetes and vitamin D intake, vitamin D levels were independently associated with the severity of NAFLD (vitamin D deficiency group OR: 1.314, 95% CI: 1.129 to 1.529, vitamin D insufficiency group OR: 1.203, 95% CI: 1.090 to 1.328). Besides that, cold season was also found to be an independent factor for NAFLD (OR: 0.896, 95% CI: 0.820 to 0.979). Lower vitamin D level is an independent risk factor for NAFLD. Vitamin D levels are inversely associated with the severity of NAFLD. Cold season increases the risk of NAFLD independently.
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http://dx.doi.org/10.3177/jnsv.65.303DOI Listing
February 2020

Detection of the three-dimensional trajectory of an object based on a curved bionic compound eye.

Opt Lett 2019 Sep;44(17):4143-4146

Biological compound-eye systems have unique advantages in three-dimensional (3D) positioning based on light energy distribution. A curved compound eye was designed and manufactured to imitate a biological compound eye. To overcome the nonuniform off-axis response and enlarge the aperture of the eyelet, a novel dome light cone was designed. The dome light cone was designed as a conical structure, which consisted of a lot of fiber wires with a diameter of 6 μm. Additionally, based on the proposed biological compound-eye systems, an algorithm was proposed to obtain the 3D position of the object by analyzing the light location and intensity distribution. The effect of the illumination intensity, the position of the target's center, and the non-repeatability were evaluated. The relative standard uncertainty in the 3D position was estimated to be 8.6%. Low uncertainty verified the validity of the 3D localization algorithm.
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http://dx.doi.org/10.1364/OL.44.004143DOI Listing
September 2019

Preparation and biological evaluation of soluble tetrapeptide epoxyketone proteasome inhibitors.

Bioorg Med Chem 2019 09 30;27(18):4151-4162. Epub 2019 Jul 30.

College of Life Science, Nanjing Normal University, No. 1 Wenyuan Road, Nanjing 210046, PR China; Jiangsu Chia Tai Fenghai Pharmaceutical Co. Ltd., No. 9 Weidi Road, Nanjing 210046, PR China. Electronic address:

A series of novel tetrapeptidyl epoxyketone inhibitors of 20S proteasome was designed and synthesized. To fully understand the SAR, various groups at R, R, R, R and R positions, including aromatic and aliphatic substituents were designed, synthesized and biologically assayed. Based on the enzymatic results, seven compounds were selected to evaluate their cellular activities and soluble compound 36 showed strong potency against human multiple myeloma (MM) cell lines. Microsomal stability results indicated that compound 36 was more stable in mice, rat and human microsomes than marketed carfilzomib. The in vivo activities of this compound were evaluated with the xenograft mice models of MM cell lines ARH77 and RPMI-8226 with luciferase expression and the T/C value of the two models were 49.5% and 37.6%, respectively. To evaluate the potential cardiovascular toxicity, inhibition of hERG ion channel in HEK293 cells by compound 36 and carfilzomib was carried out. The results indicated that 36 had no binding affinity for the hERG ion channel while carfilzomib could bind it with IC of 92.1 μM.
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http://dx.doi.org/10.1016/j.bmc.2019.07.044DOI Listing
September 2019

The epidemiological trend of acute promyelocytic leukemia over past four decades: a population-based analysis.

Leuk Lymphoma 2019 12 15;60(14):3470-3481. Epub 2019 Jul 15.

Theragnostic Laboratory, Department of Imaging and Pathology, Biomedical Sciences Group, KU Leuven, Leuven, Belgium.

The treatment regimens for acute promyelocytic leukemia (APL) dramatically changed over time. However, its survival trend, based on a large sample size has not been reported. Patients diagnosed with APL were accessed from the Surveillance, Epidemiology, and End Results database. Their incidence and survival trend were evaluated in overall and subgroup levels. The overall incidence of APL increased with an annual percentage change of 5.5% from 1992 to 2006 and remained stable thereafter. In addition, the 5-year relative survival rates of APL improved significantly, from 12.3 to 32.2% to 59.5 to 72.1% over past four decades ( < .0001), sharing similar trend with different subgroups. Importantly, survival disparities exist among races and different socioeconomic status groups, with superior survival in whites and patients in low-poverty regions. Increasing incidence urges for increased awareness of clinicians over diagnosis of APL. In addition, a wider insurance coverage may help balance survival gap.
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http://dx.doi.org/10.1080/10428194.2019.1639164DOI Listing
December 2019

An electrochemical method for plant species determination and classification based on fingerprinting petal tissue.

Bioelectrochemistry 2019 Oct 5;129:199-205. Epub 2019 Jun 5.

Key Laboratory of Marine Materials and Related Technologies, Zhejiang Key Laboratory of Marine Materials and Protective Technologies, Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo 315201, PR China.

The identification of plant species not only is a hobby but also has important application value in plant resources science. Traditional plant identification often relies on the experience of botanists. The infrageneric identification of plants is easily mistaken due to similarities in organ features. In this work, we propose an electrochemical method to obtain fingerprints of plant petal tissue. Fourteen species of Lycoris were used as a model for validating this methodology. Pattern and color recognition were established for visualization of electrochemical fingerprints recorded after various solvent extractions. In addition, the infrageneric relationships of these Lycoris species were deduced from the electrochemical fingerprints since the type and content of electroactive compounds in plants are controlled by genes. The results indicate that the electrochemical fingerprints of Lycoris petals are correlated with the infrageneric relationships of native Lycoris species.
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http://dx.doi.org/10.1016/j.bioelechem.2019.06.001DOI Listing
October 2019

Enhanced K-ion kinetics in a layered cathode for potassium ion batteries.

Chem Commun (Camb) 2019 Jul;55(55):7910-7913

Center of Energy Storage Materials & Technology, College of Engineering and Applied Sciences, Jiangsu Key Laboratory of Artificial Functional Materials, National Laboratory of Solid State Microstructures, Collaborative Innovation Center of Advanced Microstructures, Nanjing University, Nanjing 210093, China.

A layered cathode for K-ion storage was achieved using electrochemical ion-exchange. It delivers a large specific capacity, superior rate performance and excellent cycling performance. Interestingly, it was found from the GITT results that the K ion diffusion coefficients were above 10-12 cm2 s-1, comparable with that of Na-ion in the layered structure.
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http://dx.doi.org/10.1039/c9cc03156aDOI Listing
July 2019

Time-dependence of NIHSS in predicting functional outcome of patients with acute ischemic stroke treated with intravenous thrombolysis.

Postgrad Med J 2019 Apr 11;95(1122):181-186. Epub 2019 Apr 11.

Department of Neurology, Peking University Shenzhen Hospital, Shenzhen, China

Objectives: The National Institute of Health Stroke Scale (NIHSS) is a predictor for the prognosis of acute ischaemic stroke (AIS) and its prediction is time-dependent. We examined the performance of NIHSS at different timepoints in predicting functional outcome of patients with thrombolysed AIS.

Methods: This prospective study included 269 patients with AIS treated with recombinant tissue plasminogen activator (rt-PA). Unfavourable functional outcome was defined as modified Rankin Scale score 4-6 at 3 months after rt-PA treatment. Receiver operating characteristic curves were used to examine the predictive power of NIHSS score at admission and 2 hours/24 hours/7 days/10 days after rt-PA treatment. Youden's index was used to select the threshold of NIHSS score. Logistic regression was used to estimate the ORs of unfavourable functional outcome for patients with NIHSS score higher than the selected thresholds.

Results: The threshold of NIHSS score at admission was 12 (sensitivity: 0.51, specificity: 0.84) with an acceptable predictive power (area under curve [AUC] 0.74) for unfavourable functional outcome. The threshold changed to 5 at 24 hours after rt-PA treatment (sensitivity: 0.83, specificity: 0.65) and remained unchanged afterwards. The predictive power and sensitivity sequentially increased over time and peaked at 10 days after rt-PA treatment (AUC 0.92, sensitivity: 0.85, specificity: 0.80). NIHSS scores higher than the thresholds were associated with elevated risk of unfavourable functional outcome at all timepoints (all p<0.001).

Conclusions: NIHSS is time-dependent in predicting AIS prognosis with increasing predictive power over time. Since patients whose NIHSS score ≥ 12 are likely to have unfavourable functional outcome with rt-PA treatment only, mechanical thrombectomy should be largely taken into consideration for these patients.
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http://dx.doi.org/10.1136/postgradmedj-2019-136398DOI Listing
April 2019

Discovery of a new class of valosine containing protein (VCP/P97) inhibitors for the treatment of non-small cell lung cancer.

Bioorg Med Chem 2019 02 28;27(3):533-544. Epub 2018 Dec 28.

College of Life Science, Nanjing Normal University, No. 1 Wenyuan Road, Nanjing 210037, PR China. Electronic address:

Valosine containing protein (VCP/p97) is a member of the AAA ATPase family involved in several essential cellular functions and plays an important role in the ubiquitin-mediated degradation of misfolded proteins. P97 has a significant role in maintaining the cellular protein homeostasis for tumor cell growth and survival and has been found overexpressed in many tumor types. No new molecule entities based on p97 target were approved in clinic. Herein, a series of novel pyrimidine structures as p97 inhibitors were designed and synthesized. After enzymatic evaluations, structure-activity relationships (SAR) were discussed in detailed. Among the screened compounds, derivative 35 showed excellent enzymatic inhibitory activity (IC, 36 nM). The cellular inhibition results showed that compound 35 had good antiproliferative activity against the non-small cell lung cancer A549 cells (IC, 1.61 μM). Liver microsome stability showed that the half-life of compound 35 in human liver microsome was 42.3 min, which was more stable than the control CB-5083 (25.8 min). The in vivo pharmacokinetic results showed that the elimination phase half-lives of compound 35 were 4.57 h for ig and 3.64 h for iv, respectively and the oral bioavailability was only 4.5%. These results indicated that compound 35 could be effective for intravenous treatment of non-small cell lung cancer.
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http://dx.doi.org/10.1016/j.bmc.2018.12.036DOI Listing
February 2019

Discovery of a novel dipeptidyl boronic acid proteasome inhibitor for the treatment of multiple myeloma and triple-negative breast cancer.

Org Biomol Chem 2019 01;17(3):683-691

College of Science, Nanjing Forestry University, No. 159 Longpan Road, Nanjing 210037, PR China.

A series of novel dipeptidyl boronic acid compounds were designed, synthesized and biologically investigated for the inhibition of the β5 subunit of 20S proteasome and several compounds showed high activities with IC50 values of less than 10 nM. Some of these compounds potently inhibited the multiple myeloma (MM) cancer cell lines with IC50 values of less than 10 nM. It was reported that the inhibition of both β2 and β5 subunits strongly increased the cytotoxicity of proteasome inhibitors in solid tumor cells, so some of the compounds were evaluated for the inhibition of the β2 subunit and the solid tumor triple-negative breast cancer cell line MDA-MB-231. The results showed that three compounds were active for both the β2 subunit and the triple-negative breast cancer cell line MDA-MB-231. The in vivo pharmacokinetic results showed that compound 8t had good biological parameters for both ig and iv administrations. An in vivo pharmacodynamic experiment showed that compound 8t inhibited the β5 subunit in whole blood more greatly than the marketed MLN9708 with the same dose at different time periods. A pathological analysis indicated that the injection of compound 8t in the tumor of a triple-negative breast cancer xenograft mice model led to tumor cell necrosis, nucleus condensation, deep staining, cell fragmentation, dissolution and neutrophil infiltration compared with the control group. The data in hand showed that compound 8t might be an effective candidate for the treatment of both MM and triple-negative breast cancer.
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http://dx.doi.org/10.1039/c8ob02668hDOI Listing
January 2019