Publications by authors named "Weiyang Chen"

56 Publications

Anti-seizure activity of African medicinal plants: The identification of bioactive alkaloids from the stem bark of Rauvolfia caffra using an in vivo zebrafish model.

J Ethnopharmacol 2021 Jun 10;279:114282. Epub 2021 Jun 10.

Department of Pharmaceutical Sciences, Tshwane University of Technology, Pretoria, 0001, South Africa. Electronic address:

Ethnopharmacological Relevance: Epilepsy is one of the major chronic diseases that does not have a cure to date. Adverse drug reactions have been reported from the use of available anti-epileptic drugs (AEDs) which are also effective in only two-thirds of the patients. Accordingly, the identification of scaffolds with promising anti-seizure activity remains an important first step towards the development of new anti-epileptic therapies, with improved efficacy and reduced adverse effects. Herbal medicines are widely used in developing countries, including in the treatment of epilepsy but with little scientific evidence to validate this use. In the search for new epilepsy treatment options, the zebrafish has emerged as a chemoconvulsant-based model for epilepsy, mainly because of the many advantages that zebrafish larvae offer making them highly suitable for high-throughput drug screening.

Aim Of The Study: In this study, 20 medicinal plants traditionally used in South Africa to treat epilepsy were screened for anti-epileptic activity using a zebrafish larvae model.

Materials And Methods: Toxicity triaging was conducted on 120 crude extracts, 44 fractions and three isolated compounds to determine the maximum tolerated concentration (MTC) of each extract, fraction or compound. MTC values were used to guide the concentration range selection in bioactivity studies. The effectiveness of crude extracts, fractions and isolated compounds from Rauvolfia caffra Sond. in suppression of pentylenetetrazole (PTZ) induced seizure-like behaviour in a 6-dpf zebrafish larvae model was measured using the PTZ assay.

Results: Following a preliminary toxicity triage and bioactivity screen of crude extracts from 20 African plants used traditionally for the treatment and management of epilepsy, the methanolic extract of Rauvolfia caffra Sond. was identified as the most promising at suppressing PTZ induced seizure-like behaviour in a zebrafish larvae model. Subsequent bioactivity-guided fractionation and spectroscopic structural elucidation resulted in the isolation and identification of two tryptoline derivatives; a previously unreported alkaloid to which we assigned the trivial name rauverine H (1) and the known alkaloid pleiocarpamine (2). Pleiocarpamine was found to reduce PTZ-induced seizures in a dose-dependent manner.

Conclusions: Accordingly, pleiocarpamine represents a promising scaffold for the development of new anti-seizure therapeutic compounds. Furthermore, the results of this study provide preliminary evidence to support the traditional use of Rauvolfia caffra Sond. in the treatment and management of epilepsy. These findings warrant further studies on the anti-epileptic potential of Rauvolfia caffra Sond. using other models.
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http://dx.doi.org/10.1016/j.jep.2021.114282DOI Listing
June 2021

Age prediction based on a small number of facial landmarks and texture features.

Technol Health Care 2021 ;29(S1):497-507

Background: Age is an essential feature of people, so the study of facial aging should have particular significance.

Objective: The purpose of this study is to improve the performance of age prediction by combining facial landmarks and texture features.

Methods: We first measure the distribution of each texture feature. From a geometric point of view, facial feature points will change with age, so it is essential to study facial feature points. We annotate the facial feature points, label the corresponding feature point coordinates, and then use the coordinates of feature points and texture features to predict the age.

Results: We use the Support Vector Machine regression prediction method to predict the age based on the extracted texture features and landmarks. Compared with facial texture features, the prediction results based on facial landmarks are better. This suggests that the facial morphological features contained in facial landmarks can reflect facial age better than facial texture features. Combined with facial landmarks and texture features, the performance of age prediction can be improved.

Conclusions: According to the experimental results, we can conclude that texture features combined with facial landmarks are useful for age prediction.
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http://dx.doi.org/10.3233/THC-218047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8150531PMC
January 2021

Automatic Detection of Scattered Garbage Regions Using Small Unmanned Aerial Vehicle Low-Altitude Remote Sensing Images for High-Altitude Natural Reserve Environmental Protection.

Environ Sci Technol 2021 03 1;55(6):3604-3611. Epub 2021 Mar 1.

The Engineering Research Center of GIS Technology in Western China of Ministry of Education, Kunming 650500, China.

Recently, some famous high-altitude nature reserves have been shut down due to tourist garbage pollution. In order to clean up such garbage more conveniently and quickly, a novel detection framework is proposed to automatically detect scattered garbage regions using low-altitude remote sensing of small unmanned aerial vehicles (SUAVs), and it contains the following steps. First, high-resolution, low-altitude, multitemporal remote sensing images containing scattered garbage regions are collected by SUAVs, and two data augmentation methods are proposed to expand the training samples. Second, low-altitude remote sensing image registration and target-level image change detection are used to extract the candidate regions of garbage. Finally, a deep learning detection network is adopted to classify the scattered garbage regions. Experimental results show that the proposed detection framework achieves a mean accuracy of 96.94% and provides better performances on the real dataset compared with state-of-the-art methods.
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http://dx.doi.org/10.1021/acs.est.0c04068DOI Listing
March 2021

Phytochemical Profiling and Quality Control of Burch. ex DC. Using HPTLC Metabolomics.

Molecules 2021 Jan 15;26(2). Epub 2021 Jan 15.

Department of Pharmaceutical Sciences, Faculty of Science, Tshwane University of Technology, Private Bag X680, Pretoria 0001, South Africa.

is used throughout Africa for the treatment of a variety of conditions and has been identified as a potential commercial plant. The study was aimed at establishing a high-performance thin layer chromatography (HPTLC) chemical fingerprint for root bark as a reference for quality control and exploring chemical variation within the species using HPTLC metabo3lomics. Forty-two root bark samples were collected from ten populations in South Africa and extracted with dichloromethane: methanol (1:1). An HPTLC method was optimized to resolve the major compounds from other sample components. Dichloromethane: ethyl acetate: methanol: formic acid (90:10:30:1) was used as the developing solvent and the plates were visualized using 10% sulfuric acid in methanol as derivatizing agent. The concentrations of three major bioactive compounds, sericic acid, sericoside and resveratrol-3---rutinoside, in the extracts were determined using a validated ultra-performance liquid chromatography-photodiode array (UPLC-PDA) detection method. The rTLC software (written in the R-programming language) was used to select the most informative retardation factor (R) ranges from the images of the analysed sample extracts. Further chemometric models, including principal component analysis (PCA) and hierarchical cluster analysis (HCA), were constructed using the web-based high throughput metabolomic software. The rTLC chemometric models were compared with the models previously obtained from ultra-performance liquid chromatography coupled with mass spectrometry (UPLC-MS). A characteristic fingerprint containing clear bands for the three bioactive compounds was established. All three bioactive compounds were present in all the samples, although their corresponding band intensities varied. The intensities correlated with the UPLC-PDA results, in that samples containing a high concentration of a particular compound, displayed a more intense band. Chemometric analysis using HCA revealed two chemotypes, and the subsequent construction of a loadings plot indicated that sericic acid and sericoside were responsible for the chemotypic variation; with sericoside concentrated in Chemotype 1, while sericic acid was more abundant in Chemotype 2. A characteristic chemical fingerprint with clearly distinguishable features was established for root bark that can be used for species authentication, and to select samples with high concentrations of a particular marker compound(s). Different chemotypes, potentially differing in their therapeutic potency towards a particular target, could be distinguished. The models revealed the three analytes as biomarkers, corresponding to results reported for UPLC-MS profiling and thereby indicating that HPTLC is a suitable technique for the quality control of root bark.
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http://dx.doi.org/10.3390/molecules26020432DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7830210PMC
January 2021

Anti-tyrosinase activity of South African Aloe species and isolated compounds plicataloside and aloesin.

Fitoterapia 2021 Apr 9;150:104828. Epub 2021 Jan 9.

Department of Pharmaceutical Sciences, Faculty of Science, Tshwane University of Technology, Private Bag X680, Pretoria 0001, South Africa; SAMRC Herbal Drugs Research Unit, Faculty of Science, Tshwane University of Technology, Private Bag X680, Pretoria 0001, South Africa. Electronic address:

Tyrosinase is the key enzyme in the production of melanin. Tyrosinase inhibitors have gained interest in the cosmetics industry to prevent hyperpigmentation and skin-related disorders by inhibiting melanin production. It has been reported that several Aloe species exhibit anti-tyrosinase efficacy in vitro. In this study, the exudates of thirty-nine South African Aloe species were screened to identify species and compounds with anti-tyrosinase activity. Qualitative screening revealed that twenty-nine Aloe species exhibited tyrosinase inhibition activity with one to three active bands. Quantitative screening was performed for 29 species and expressed as IC values. Three species were further analysed and subsequently, aloesin and aloeresin A was isolated from A. ferox and plicataloside from A. plicatilis and A. chabaudii. Aloeresin A was determined to be a substrate of mushroom tyrosinase. Dose-response assays showed that aloesin (IC = 31.5 μM) and plicataloside (IC = 84.1 μM) exhibited moderate to weak activity. Molecular docking scores for plicataloside were considerably lower than for aloesin (P < 0.01), confirming its lower IC. Several Aloe species may have potential for the management of hyperpigmentation or as a skin lightening agent. This is the first report showing that plicataloside, present in A. plicatilis and A. chabaudii, exhibits anti-tyrosinase activity.
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http://dx.doi.org/10.1016/j.fitote.2021.104828DOI Listing
April 2021

Investigating antimicrobial compounds in South African Combretaceae species using a biochemometric approach.

J Ethnopharmacol 2021 Apr 9;269:113681. Epub 2020 Dec 9.

Department of Pharmaceutical Sciences, Faculty of Science, Tshwane University of Technology, Private Bag X680, Pretoria, 0001, South Africa; SAMRC Herbal Drug Research Unit, Faculty of Science, Tshwane University of Technology, Private Bag X680, Pretoria, 0001, South Africa. Electronic address:

Ethnopharmacological Relevance: Many species within the family Combretaceae are popular medicinal plants that are used traditionally to treat various conditions, of which many are related to bacterial infections. Global concerns regarding the increasing resistance of pathogens towards currently available antibiotics have encouraged researchers to find new drugs with antibacterial activity, particularly from plant sources.

Aim Of The Study: This study was aimed at exploring the broad-spectrum antibacterial potential of methanol extracts of species representing four genera of Combretaceae (Combretum, Pteleopsis, Quisqualis, Terminalia), indigenous to South Africa, using a biochemometric approach.

Materials And Methods: The microdilution assay was used to determine the antibacterial activities, measured as minimum inhibitory concentrations (MICs), of the 51 methanol extracts representing 35 Combretaceae species, against nine species of pathogenic bacteria. Integrative biochemometric analysis was performed, thereby correlating the MIC values with the metabolomic data obtained from ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) analysis. Orthogonal projections to latent structures-discriminant analysis (OPLS-DA) models were constructed for six pathogens displaying variation in their susceptibility towards the extracts.

Results: Evaluation of the overall MIC values obtained indicated that extracts of species from the four genera displayed the highest activity towards Bacillus cereus ATCC 11778 (average MIC 0.52 mg/mL) and Salmonella typhimurium ATCC 14028 (average MIC 0.63 mg/mL). These bacteria were the most sensitive Gram-positive and Gram-negative bacteria, respectively. Extracts from Combretum acutifolium, Combretum imberbe and Combretum elaeagnoides were the most active, with average MIC values of 0.70 mg/mL, 0.52 mg/mL and 0.45 mg/mL, respectively. Five triterpenoid compounds were tentatively identified as biomarkers from the biochemometric analysis.

Conclusion: Correlation of the phytochemistry of species from four genera in the Combretaceae family with antibacterial activity revealed that triterpenoids are responsible for the broad-spectrum antibacterial activity observed.
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http://dx.doi.org/10.1016/j.jep.2020.113681DOI Listing
April 2021

Chemotypic variation of non-volatile constituents of Artemisia afra (African wormwood) from South Africa.

Fitoterapia 2020 Nov 9;147:104740. Epub 2020 Oct 9.

Department of Pharmaceutical Sciences, Faculty of Science, Tshwane University of Technology, Pretoria 0001, South Africa; SAMRC Herbal Drugs Research Unit, Faculty of Science, Tshwane University of Technology, Pretoria 0001, South Africa. Electronic address:

Artemisia afra (African wormwood) is a popular medicinal plant of southern Africa and is an excellent candidate for commercialisation. This current study was aimed at exploring the phytochemistry and chemical variation of non-volatile compounds within wild populations of A. afra, and developing chromatographic quality control protocols for raw materials based on the identification of marker compounds. Chromatographic data, from samples representing 12 distinct populations, were obtained using liquid chromatography-mass spectrometry. An untargeted chemometric approach revealed three clusters. Marker compounds for each cluster, revealed through discriminant analysis, were isolated and identified using NMR spectroscopy, as acacetin (1) (Group 1), chrysoeriol (2) (Group 2), and 3,5-di-O-caffeoylquinic acid (3) and scopoletin (4) (Group 3). In addition, (3) and rutin (5), (both reported for the first time from A. afra), and (1), (2), (4) and 4-caffeoylquinic acid (6) were established as reliable markers for species identification, since they were abundant in most samples. Quantitative analysis using a validated method established (4) as the dominant compound in the samples (1080-19,600 μg/g dry weight (d.w.)), followed by (5) (49.5-2490 μg/g d.w.). A high performance thin layer chromatography (HPTLC) method was developed. The Rf values and colours of the bands corresponding to the marker compounds were recorded so that these compounds could be easily identified for quality control purposes. Multivariate analysis of the data using the rTLC online application confirmed the presence of different chemical groupings within the samples. It was deduced that quantitative, rather than qualitative differences, characterised the samples. Future research should focus on comparing the efficacy of the various chemical clusters in multi-target biological assays aligned to the traditional use of the plant.
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http://dx.doi.org/10.1016/j.fitote.2020.104740DOI Listing
November 2020

Three-dimensional facial-image analysis to predict heterogeneity of the human ageing rate and the impact of lifestyle.

Nat Metab 2020 09 7;2(9):946-957. Epub 2020 Sep 7.

CAS Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences Center for Excellence in Molecular Cell Science, Collaborative Innovation Center for Genetics and Developmental Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.

Not all individuals age at the same rate. Methods such as the 'methylation clock' are invasive, rely on expensive assays of tissue samples and infer the ageing rate by training on chronological age, which is used as a reference for prediction errors. Here, we develop models based on convoluted neural networks through training on non-invasive three-dimensional (3D) facial images of approximately 5,000 Han Chinese individuals that achieve an average difference between chronological or perceived age and predicted age of ±2.8 and 2.9 yr, respectively. We further profile blood transcriptomes from 280 individuals and infer the molecular regulators mediating the impact of lifestyle on the facial-ageing rate through a causal-inference model. These relationships have been deposited and visualized in the Human Blood Gene Expression-3D Facial Image (HuB-Fi) database. Overall, we find that humans age at different rates both in the blood and in the face, but do so coherently and with heterogeneity peaking at middle age. Our study provides an example of how artificial intelligence can be leveraged to determine the perceived age of humans as a marker of biological age, while no longer relying on prediction errors of chronological age, and to estimate the heterogeneity of ageing rates within a population.
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http://dx.doi.org/10.1038/s42255-020-00270-xDOI Listing
September 2020

Isolation, in vitro evaluation and molecular docking of acetylcholinesterase inhibitors from South African Amaryllidaceae.

Fitoterapia 2020 Oct 30;146:104650. Epub 2020 May 30.

Department of Pharmacognosy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; SAMRC Herbal Drugs Research Unit, Faculty of Science, Tshwane University of Technology, Pretoria, South Africa. Electronic address:

Inhibition of acetylcholinesterase (AChE) is considered a promising strategy for the treatment of Alzheimer's disease (AD) and dementia. Members of the Amaryllidaceae family are well known for their pharmacologically active alkaloids, including galanthamine, which is used to treat AD. The aim of this study was to evaluate the potential of South African Amaryllidaceae species to inhibit AChE, to isolate the active compounds, and probe their ability to bind the enzyme using molecular docking. The AChE inhibitory activity of extracts of 41 samples, representing 14 genera and 28 species, as well as isolated compounds, were evaluated in vitro using a qualitative thin layer chromatography (TLC) bio-autography assay and Ellman's method in a quantitative 96-well microplate assay. Targeted isolation of compounds was achieved with the aid of preparative-high perfomance liquid chromatography-mass spectrometry. The structures of the isolates were elucidated using nuclear magnetic resonance spectrocopy, and were docked into the active site of AChE to rationalise their biological activities. The most active species were found to be Amaryllis belladonna L (IC 14.3 ± 2.6 μg/mL), Nerine huttoniae Schönland (IC 45.3 ± 0.4 μg/mL) and Nerine undulata (L.) Herb. (IC 52.8 ± 0.5 μg/mL), while TLC bio-autography indicated the presence of several active compounds in the methanol extracts. Four compounds, isolated from A. belladonna, were identified as belladine, undulatine, buphanidrine and acetylcaranine. Acetylcaranine and undulatine were previously isolated from A. belladonna, while belladine and buphanidrine were reported from other South African Amaryllidaceae species. Using Ellman's method, acetylcaranine was found to be the most active of the isolates towards AChE, with an IC of 11.7 ± 0.7 μM, comparable to that of galanthamine (IC = 6.19 ± 2.60 μM). Molecular docking successfully predicted the binding modes of ligands within receptor binding sites. Acetylcaranine was predicted by the docking workflow to have the highest activity, which corresponds to the in vitro results. Both qualitative and quantitative assays indicate that several South African Amaryllidaceae species are notable AChE inhibitors.
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http://dx.doi.org/10.1016/j.fitote.2020.104650DOI Listing
October 2020

CCS52 and DEL1 function in root-knot nematode giant cell development in Xinjiang wild myrobalan plum (Prunus sogdiana Vassilcz).

Protoplasma 2020 Sep 5;257(5):1333-1344. Epub 2020 May 5.

College of Horticulture, China Agricultural University, Beijing, 100193, China.

Root-knot nematodes (RKNs) are highly invasive plant parasites that establish permanent feeding sites within the roots of the host plant. Successful establishment of the feeding site is essential for the survival of RKN. The formation and development of the feeding cell, also called giant cell, involve both cell division and endoreduplication. Here, we examined giant cell development and endoreduplication in Prunus sogdiana infected with the RKN. We found that feeding sites were established 3-5 days post inoculation (dpi) and matured at 21-28 dpi. The giant cells began to form 5 dpi and continued to increase in size from 7 to 21 dpi. The large numbers of dividing nuclei were observed in giant cells from 7 to 14 dpi. However, nuclear division was rarely observed after 28 days. RT-PCR and in situ hybridization analyses revealed that PsoCCS52A was abundantly expressed at 7-21 dpi and the PsoCCS52A signal observed in giant cell nucleus at 7-14 dpi. The PsoCCS52B is highly expressed at 14 dpi, and the hybridization signal was mainly in the cytoplasm of giant cells. The PsoDEL1 expression was lowest 7-21 dip, with negligible transcript detected in the giant cells. This indicates that the PsoCCS52A plays a role in the process of cell division, while the CCS52B plays a role in the development of giant cells. The PsoDEL1 plays a negative regulatory role in megakaryocyte nuclear replication. These data suggest that an increased expression of PsoCCS52A promotes nuclear division and produces a large number of polyploid nuclei, the area of giant cells and feeding sites increase, ultimately leading to the formation of galls in Prunus sogdiana.
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http://dx.doi.org/10.1007/s00709-020-01505-0DOI Listing
September 2020

Definition and Usage of Texture Feature for Biological Sequence.

IEEE/ACM Trans Comput Biol Bioinform 2021 Mar-Apr;18(2):773-776. Epub 2021 Apr 8.

In recent years, sequencing technology has developed rapidly. This produces a large number of biological sequence data. Because of its importance, there have been many studies on biological sequences. However, there is still a lack of an effective quantitative method for defining and calculating texture features of biological sequences. Texture is an important visual feature. It is generally used to describe the spatial arrangement of intensities of images. Here we defined the texture features of biological sequence. Combining the digital coding of biological sequence with the calculation method of image texture features, we defined the texture features of biological sequence and designed the calculation method. We applied this method to DNA sequence features quantification and analysis. Using these quantified features, we can compute the similarity distance matrix of DNA sequences and construct the phylogenetic relationships based on the clustering of the quantified features. This method can be applied to analyze any biological sequence, and all biological sequences can be digitally coded and texture features can be calculated by this method. This is a novel study of biological sequence texture features. This will usher in a new era of quantitative and mathematical calculation of biological sequence features.
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http://dx.doi.org/10.1109/TCBB.2020.2973084DOI Listing
April 2021

Salvianolic acid B exerts anti-liver fibrosis effects via inhibition of MAPK-mediated phospho-Smad2/3 at linker regions in vivo and in vitro.

Life Sci 2019 Dec 31;239:116881. Epub 2019 Oct 31.

Department of Pharmacology, Anhui Medical University, Key Laboratory of Anti-inflammatory and Immunopharmacology, Ministry of Education, 81 Meishan Road, Hefei, 230032, China. Electronic address:

Aim: To investigate anti-liver fibrosis effects of Salvianolic acid B (Sal B) from Salvia miltiorrhiza Bunge involved mitogen-activated protein kinase (MAPK)-mediated transforming growth factor-beta (TGF-β) signaling.

Main Methods: Diethylnitrosamine (DEN)-induced liver fibrosis in mice and TGF-β-activated hepatic stellate cells (HSCs) were established and treated with dosage/concentration-graded Sal B and/or MAPK activator (Vacquinol-1: MKK4-specific activator)/inhibitors (PD98059: ERK-specific inhibitor; SP600125: JNK-specific inhibitor; SB203580: p38-specific inhibitor). Histopathological characteristics and cell migration were assessed, α-SMA, Collagen I and members of TGF-β/MAPK/Smad signal transduction pathway were measured.

Key Findings: Results in vivo showed that Sal B alleviated DEN-caused liver fibrosis embodied in ameliorative histopathological characteristics and decreased protein levels of hepatic fibrosis related markers (α-SMA, Collagen I, TGF-β), its molecular mechanisms of action were correlative with inhibited activation of MAPK and phosphorylation of Smad2/3 at linker regions (P-Smad2/3L) and Smad2 at C-terminal (P-Smad2C) while increased phosphorylation of Smad3 at C-terminal (P-Smad3C). Results in vitro showed that Sal B restrained TGF-β-induced HSCs activation, Collagen I production and cell migration; Sal B inhibited activation of MAPK and markedly decreased protein levels of P-Smad2/3L and P-Smad2C while slightly increased P-Smad3C in TGF-β-stimulated HSCs, the expression of PAI-1 was inhibited by Sal B; activating MAPK receded inhibitory effects of Sal B on α-SMA, Collagen I, P-Smad2L and P-Smad3L expression while inhibited activation of MAPK reinforced those.

Significance: Sal B attenuates liver fibrosis via mediation of TGF-β/Smad and MAPK pathways, especially inhibition of MAPK-mediated P-Smad2/3L signaling, which maybe provides theoretical foundation of Sal B for treating clinically liver fibrosis.
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http://dx.doi.org/10.1016/j.lfs.2019.116881DOI Listing
December 2019

The Use of Texture Features to Extract and Analyze Useful Information from Retinal Images.

Comb Chem High Throughput Screen 2020 ;23(4):313-318

College of Computer Science and Technology, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250353, China.

Background: The analysis of retinal images can help to detect retinal abnormalities that are caused by cardiovascular and retinal disorders.

Objective: In this paper, we propose methods based on texture features for mining and analyzing information from retinal images.

Methods: The recognition of the retinal mask region is a prerequisite for retinal image processing. However, there is no way to automatically recognize the retinal region. By quantifying and analyzing texture features, a method is proposed to automatically identify the retinal region. The boundary of the circular retinal region is detected based on the image texture contrast feature, followed by the filling of the closed circular area, and then the detected circular retinal mask region can be obtained.

Results: The experimental results show that the method based on the image contrast feature can be used to detect the retinal region automatically. The average accuracy of retinal mask region detection of images from the Digital Retinal Images for Vessel Extraction (DRIVE) database was 99.34%.

Conclusion: This is the first time these texture features of retinal images are analyzed, and texture features are used to recognize the circular retinal region automatically.
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http://dx.doi.org/10.2174/1386207322666191022123445DOI Listing
April 2021

Exploring Common Culinary Herbs and Spices as Potential Anti-Quorum Sensing Agents.

Nutrients 2019 Mar 29;11(4). Epub 2019 Mar 29.

Department of Pharmaceutical Sciences, Tshwane University of Technology, Private Bag X680, Pretoria 0001, South Africa.

Quorum sensing controls bacterial pathogenesis and virulence; hence, interrupting this system renders pathogenic bacteria non-virulent, and presents a novel treatment for various bacterial infections. In the search for novel anti-quorum sensing (AQS) compounds, 14 common culinary herbs and spices were screened for potential antipathogenicity activity against ATCC 12472. Extracts of (liquorice), (celery), (cayenne pepper) and (aniseed) demonstrated good AQS potential, yielding opaque halo zones ranging from 12⁻19 mm diameter at sub-minimum inhibitory concentrations (0.350⁻4.00 mg/mL). For the same species, the percentage reduction in violacein production ranged from 56.4 to 97.3%. Zones with violacein inhibitory effects were evident in a celery extract analysed using high performance thin layer chromatography-bio-autography. The major active compound was isolated from celery using preparative-high performance liquid chromatography-mass spectrometry and identified using gas chromatography-mass spectrometry (GC-MS) as 3--butyl-4,5-dihydrophthalide (sedanenolide). Potent opaque zones of inhibition observed on the HPTLC-bio-autography plate seeded with confirmed that sedanenolide was probably largely responsible for the AQS activity of celery. The bacteriocidal properties of many herbs and spices are reported. This study, however, was focussed on AQS activity, and may serve as initial scientific validation for the anti-infective properties ascribed to several culinary herbs and spices.
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http://dx.doi.org/10.3390/nu11040739DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6521156PMC
March 2019

A High-throughput Assay for the Prediction of Chemical Toxicity by Automated Phenotypic Profiling of Caenorhabditis elegans.

J Vis Exp 2019 03 14(145). Epub 2019 Mar 14.

Beijing Key Laboratory of Diagnostic and Traceability Technologies for Food Poisoning, Beijing Center for Disease Prevention and Control/Beijing Center of Preventive Medicine Research, China; Beijing Key Laboratory of Environmental Toxicology, School of Public Health, Capital Medical University, China;

Applying toxicity testing of chemicals in higher order organisms, such as mice or rats, is time-consuming and expensive, due to their long lifespan and maintenance issues. On the contrary, the nematode Caenorhabditis elegans (C. elegans) has advantages to make it an ideal choice for toxicity testing: a short lifespan, easy cultivation, and efficient reproduction. Here, we describe a protocol for the automatic phenotypic profiling of C. elegans in a 384-well plate. The nematode worms are cultured in a 384-well plate with liquid medium and chemical treatment, and videos are taken of each well to quantify the chemical influence on 33 worm features. Experimental results demonstrate that the quantified phenotype features can classify and predict the acute toxicity for different chemical compounds and establish a priority list for further traditional chemical toxicity assessment tests in a rodent model.
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http://dx.doi.org/10.3791/59082DOI Listing
March 2019

Compound Astragalus and Salvia miltiorrhiza extract inhibits hepatocellular carcinoma progression via miR-145/miR-21 mediated Smad3 phosphorylation.

J Ethnopharmacol 2019 Mar 6;231:98-112. Epub 2018 Nov 6.

Department of Pharmacology, Anhui Medical University, Key Laboratory of Anti-inflammatory and Immunopharmacology, Ministry of Education, Hefei 230032, China. Electronic address:

Ethnopharmacological Relevance: Compound Astragalus and Salvia miltiorrhiza extract (CASE), containing astragalosides, astragalus polysaccharide extracted from Astragalus membranaceus (Fisch.) Bge. and salvianolic acids from Salvia miltiorhiza Bge., has been found to inhibit hepatocarcinogenesis via mediating transforming growth factor-β (TGF-β)/Smad signaling, especially Smad3 phosphorylation. The crucial interaction between microRNA-145/microRNA-21 (miR-145/miR-21) and Smad3 phosphorylation is implicated in the pathogenesis and progression of hepatocellular carcinoma (HCC). However, effects of CASE on HCC progression involved in the expression of miR-145/miR-21 and their interaction with Smad3 phosphorylation downstream of TGF-β/MAPK/Smad pathway remain unclear. This study addressed above questions using in vitro (HepG2 cells) and in vivo (Xenografts of nude mice) models of HCC.

Materials And Methods: In vivo [Diethylnitrosamine (DEN)-induced HCC in rats] and in vitro [TGF-β-stimulated HepG2 cells] models of HCC were established and co-administrated using graded doses/concentrations CASE (60, 120, 240 mg/kg used in rats; 20, 40, 80 µg/ml used in HepG2 cells), miR-145 and miR-21 were measured. HepG2 cells were transfected with miR-145 antagomir, miR-21 agomir and Smad3C/L plasmids (Smad3 EPSM, Smad3 3S-A and Smad3 WT related to up-regulated expression of pSmad3C, pSmad3L and pSmad3C/3L respectively) and then treated by CASE (80 µg/ml). Similarly, HepG2 cell xenografted nude mice were administered with miR-145 antagomir, miR-21 agomir and CASE (310 mg/kg); Smad3 WT, Smad3 EPSM and Smad3 3S-A plasmids stably transfected HepG2 cell lines were constructed respectively and their xenografted nude mice were established, and then treated by CASE (310 mg/kg). Cell proliferation, migration, apoptosis, tumor growth and histopathologic characteristics of xenografts were assessed; also, domain-specific Smad3 phosphorylation isoforms (pSmad3C/pSmad3L), activated MAPKs (pERK1/2, pJNK1/2, pp38) and miR-145, miR-21 were measured.

Results: CASE up-regulated miR-145 while down-regulated miR-21 expression in both rats with DEN-induced HCC and TGF-β-stimulated HepG2 cells; CASE inhibited cell migration, proliferation and tumor growth while facilitated cell apoptosis in TGF-β-stimulated HepG2 cells and xenografts of nude mice with miR-145 antagomir/miR-21 agomir treatment via increasing miR-145 and facilitating miR-145 modulated pSmad3L→pSmad3C signaling switch while decreasing miR-21 and inhibiting miR-21 modulated MAPK-dependent Smad3L phosphorylation. Also, up-regulated pSmad3C enhanced inhibited effect of CASE on tumor growth and facilitated effect of CASE on cell apoptosis involved in increased miR-145 while decreased miR-21 expression, however, inverse phenomena were observed when up-regulated pSmad3L.

Conclusion: Our results suggest that CASE inhibits HCC progression via mediating the interaction of miR-145/miR-21 and Smad3 phosphorylation, especially miR-145/miR-21 mediated Smad3 phosphorylation, which maybe provides an important theoretical foundation for CASE's anti-HCC therapy used for patients in a near future.
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http://dx.doi.org/10.1016/j.jep.2018.11.007DOI Listing
March 2019

Activation of the Oxidative Pentose Phosphate Pathway is Critical for Photomixotrophic Growth of a hik33-Deletion Mutant of Synechocystis sp. PCC 6803.

Proteomics 2018 10 25;18(20):e1800046. Epub 2018 Sep 25.

State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100101, China.

The histidine kinase Hik33 plays a central role in acclimation to changing environments in cyanobacteria. Deletion of hik33 induces a strong stress-like response in Synechocystis sp. PCC 6803 (Synechocystis) as represented by repressed photoautotrophic growth and photosynthesis, and differential expression of stress-responsive proteins. In contrast, the photomixotrophic growth of the hik33-deletion mutant (Δhik33) with glucose as the exogenous carbon source is only marginally repressed. To investigate how glucose rescues the growth of Δhik33, the proteomes of the photomixotrophically growing wild-type (WT) and the mutant strains of Synechocystis are quantitatively analyzed. It is found that glucose induces upregulation of the oxidative pentose phosphate (OPP) pathway. Depletion of glucose-6-phosphate dehydrogenase (G6PDH), which catalyzes the first and the rate-limiting step of the OPP pathway, significantly inhibits the photomixotrophic growth of Δhik33 but not of the WT. The result suggests that the OPP pathway, which is usually nonfunctional in the photomixotrophically growing WT, plays a major role in the photomixotrophic growth of Δhik33.
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http://dx.doi.org/10.1002/pmic.201800046DOI Listing
October 2018

Use of image texture analysis to find DNA sequence similarities.

J Theor Biol 2018 10 4;455:1-6. Epub 2018 Jul 4.

College of Information, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250353, China.

Sequence similarity analysis is a basic method in computational biological studies. Determining the similarity of biological sequences is a vital step in much research, such as exploring the evolutionary relationship among species, gene function analysis, protein structure prediction, and sequence retrieving. This paper introduces a method that uses the theory of the gray-level co-occurrence matrix, which is important in image texture analysis, to define and calculate the features of a DNA sequence. The proposed method can make a quantitative analysis and compute the defined texture features of a DNA sequence. Using these quantified sequence features, a similarity distance matrix can be computed and phylogenetic relationships also can be inferred. From the quantified features, we found that the DNA sequence of humans has the highest entropy and lowest energy. From human to chimpanzee, orangutan, gorilla, and other species, the entropy decreases and energy increases. The advantage of the proposed method is that it can compute multiple features inherent in each sequence. Furthermore, the defined features can be the key values or tags for each sequence for sequence retrieval and similarity analysis.
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http://dx.doi.org/10.1016/j.jtbi.2018.07.001DOI Listing
October 2018

H-NMR and UPLC-MS metabolomics: Functional tools for exploring chemotypic variation in Sceletium tortuosum from two provinces in South Africa.

Phytochemistry 2018 Aug 21;152:191-203. Epub 2018 May 21.

Department of Pharmaceutical Sciences, Tshwane University of Technology, Private Bag X680, Pretoria 0001, South Africa; SAMRC Herbal Drugs Unit, Tshwane University of Technology, Private Bag X680, Pretoria 0001, South Africa. Electronic address:

Sceletium tortuosum (Aizoaceae) is widely recognised for the treatment of stress, anxiety and depression, as well as for obsessive compulsive disorders. A comprehensive intraspecies chemotypic variation study, using samples harvested from two distinct regions of South Africa, was done using both proton nuclear magnetic resonance (H-NMR) spectroscopy of methanol extracts (N = 145) and ultra performance liquid chromatography-mass spectrometry (UPLC-MS) of acid/base extracts (N = 289). Chemometric analysis of the H-NMR data indicated two main clusters that were region-specific (Northern Cape and Western Cape provinces). Two dimensional (2D) NMR was used to identify analytes that contributed to the clustering as revealed by the S-plot. The sceletium alkaloids, pinitol and two alkylamines, herein reported for the first time from S. tortuosum, were identified as markers that distinguished the two groups. Relative quantification of the marker analytes conducted by qNMR indicated that samples from the Northern Cape generally contained higher concentrations of all the markers than samples from the Western Cape. Quantitative analysis of the four mesembrine alkaloids using a validated UPLC-photo diode array (PDA) detection method confirmed the results of qNMR with regard to the total alkaloid concentrations. Samples from the Northern Cape Province were found to contain, on average, very high total alkaloids, ranging from 4938.0 to 9376.8 mg/kg dry w. Regarding the Western Cape samples, the total yields of the four mesembrine alkaloids were substantially lower (averages 16.4-4143.2 mg/kg). Hierarchical cluster analysis of the UPLC-MS data, based on the alkaloid chemistry, revealed three branches, with one branch comprising samples primarily from the Northern Cape that seemed somewhat chemically conserved, while the other two branches represented mainly samples from the Western Cape. The construction of an orthogonal projections to latent structures-discriminant analysis model and subsequent loadings plot, allowed alkaloid markers to be identified for each cluster. The diverse sceletium alkaloid chemistry of samples from the three clusters may facilitate the recognition of alkaloid profiles, rather than individual compounds, that exert targeted effects on various brain receptors involved in stress, anxiety or depression.
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http://dx.doi.org/10.1016/j.phytochem.2018.03.013DOI Listing
August 2018

Classification and prediction of toxicity of chemicals using an automated phenotypic profiling of Caenorhabditis elegans.

BMC Pharmacol Toxicol 2018 04 18;19(1):18. Epub 2018 Apr 18.

Beijing Key Laboratory of Diagnostic and Traceability Technologies for Food Poisoning, Beijing Center for Disease Prevention and Control/Beijing Center of Preventive Medicine Research, Beijing, 100013, China.

Background: Traditional toxicological studies have relied heavily on various animal models to understand the effect of various compounds in a biological context. Considering the great cost, complexity and time involved in experiments using higher order organisms. Researchers have been exploring alternative models that avoid these disadvantages. One example of such a model is the nematode Caenorhabditis elegans. There are some advantages of C. elegans, such as small size, short life cycle, well defined genome, ease of maintenance and efficient reproduction.

Methods: As these benefits allow large scale studies to be initiated with relative ease, the problem of how to efficiently capture, organize and analyze the resulting large volumes of data must be addressed. We have developed a new method for quantitative screening of chemicals using C. elegans. 33 features were identified for each chemical treatment.

Results: The compounds with different toxicities were shown to alter the phenotypes of C. elegans in distinct and detectable patterns. We found that phenotypic profiling revealed conserved functions to classify and predict the toxicity of different chemicals.

Conclusions: Our results demonstrate the power of phenotypic profiling in C. elegans under different chemical environments.
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http://dx.doi.org/10.1186/s40360-018-0208-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5907177PMC
April 2018

Identification, Isolation and Determination of Biomarkers for Quality Control of Bush Tea (Athrixia phyllicoides).

Planta Med 2018 Aug 13;84(12-13):902-912. Epub 2018 Apr 13.

Department of Pharmaceutical Sciences, Faculty of Science, Tshwane University of Technology, Pretoria, South Africa.

, known as "bush tea", grows abundantly in South Africa. An infusion of the leaves is used as a beverage and to treat a multitude of health conditions. The aim of this study was to investigate the chemical variation within and to identify characteristic compounds for quality control. Samples from 12 locations in South Africa were analysed using ultra-performance liquid chromatography. Hierarchical cluster analysis of the aligned ultra-performance liquid chromatography-time-of-flight mass spectrometry data indicated two groups on the resulting dendrogram, representing 48 samples. Five marker compounds, identified through visual inspection and the construction of a discriminant analysis model, were evident on the ultra-performance liquid chromatography-MS profiles. Four of these compounds were isolated and identified, three as hydroxy methoxyflavones and the fourth as a coumarate, using nuclear magnetic resonance spectroscopy. An ultra-performance liquid chromatography-photodiode array method was developed and validated for the determination of the marker compounds using the isolates as standards. The limits of detection for the four compounds ranged from 0.92 - 2.50 µg/mL. Their recoveries at three concentration levels (1.00, 10.0, and 100 µg/mL) were between 97.0 and 101%, while acceptable intra- and inter-day precision was obtained as reflected by percentage relative standard deviation values below 2.24%. The concentrations of all the marker compounds were found to be higher in samples corresponding to Group 1 of the dendrogram than in those from Group 2. This may be attributable to differences in altitude, climate, and some edaphic factors. Identification of these marker compounds will make a valuable contribution towards the quality control and sustainable commercialisation of bush tea.
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http://dx.doi.org/10.1055/a-0594-9527DOI Listing
August 2018

Potential Herb-Drug Pharmacokinetic Interactions between African Wild Olive Leaf Extract and Selected Antihypertensive Drugs.

Planta Med 2018 Aug 19;84(12-13):886-894. Epub 2018 Mar 19.

Department of Pharmaceutical Sciences, Tshwane University of Technology, Pretoria, South Africa.

The African wild olive ( subsp. ) is traditionally used as a hypotensive agent. Herb-drug interactions may result from the concurrent use of herbal medicines and conventional prescription drugs. This aspect was investigated by determining the effect of the extract on the intestinal epithelial permeation of selected hypotensive drugs using the Caco-2 cell culture model. The phytochemical profiles of leaf extracts of African wild olive from different localities in South Africa were compared, since efficacy is determined by the chemical composition. Extracts were analysed using ultra-performance liquid chromatography. The oleuropein concentration varied considerably from below the detection limit (4.94 µg/mL) to 59.4 mg/g dry weight. Chemometric models constructed from the aligned chromatographic data indicated only quantitative differences between the profiles. The leaf extract was found to increase the permeability of propranolol in the absorptive direction (P = 8.93 × 10 cm/s) across Caco-2 cell monolayers, but considerably decreased transport in the secretory direction (P = 3.68 × 10 cm/s). The permeation of diltiazem was enhanced by the extract in both the absorptive (P = 7.33 × 10 cm/s) as well as in the secretory direction (P = 7.16 × 10 cm/s), but a decrease in the efflux ratio was observed. The extract therefore caused a net increase in the transport of both drugs in the absorptive direction due to an inhibition effect on their efflux. This suggests a potential increase in the blood levels of these drugs when taken simultaneously with African wild olive leaf extract, indicating potential adverse effects that must be verified .
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http://dx.doi.org/10.1055/a-0583-0543DOI Listing
August 2018

Systematic identification of light-regulated cold-responsive proteome in a model cyanobacterium.

J Proteomics 2018 05 13;179:100-109. Epub 2018 Mar 13.

State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, No.1 West Beichen Rd., Beijing 100101, China; University of Chinese Academy of Sciences, No.19(A) Yuquan Road, Beijing 100049, China. Electronic address:

Differential expression of cold-responsive proteins is necessary for cyanobacteria to acclimate to cold stress frequently occurring in their natural habitats. Accumulating evidence indicates that cold-induced expression of certain proteins is dependent on light illumination, but a systematic identification of light-dependent and/or light-independent cold-responsive proteins in cyanobacteria is still lacking. Herein, we comprehensively identified cold-responsive proteins in a model cyanobacterium Synechocystis sp. PCC 6803 (Hereafter Synechocystis) that was cold-stressed in light or in dark. In total, 72 proteins were identified as cold-responsive, including 19 and 17 proteins whose cold-responsiveness are light-dependent and light-independent, respectively. Bioinformatic analysis revealed that outer membrane proteins, proteins involved in translation, and proteins involved in divergent types of stress responses were highly enriched in the cold-responsive proteins. Moreover, a protein network responsible for nitrogen assimilation and amino acid biosynthesis, transcription, and translation were upregulated in response to the cold stress. The network contains both light-dependent and light-independent cold-responsive proteins, probably for fine tuning its activity to endow Synechocystis the flexibility necessary for cold adaptation in their natural habitats, where days and nights are alternating. Together, our results should serve as an important resource for future study toward understanding the mechanism of cold acclimation in cyanobacteria.

Significance: Photosynthetic cyanobacteria need to acclimate to frequently occurring abiotic stresses such as cold in their natural habitats, and the acclimation process has to be coordinated with photosynthesis, the light-dependent process that provides carbon and energy for propagation of cyanobacteria. It is conceivable that cold-induced differential protein expression can also be regulated by light. Hence it is important to systematically identify cold responsive proteins that are regulated or not regulated by light to better understand the mechanism of cold acclimation in cyanobacteria. In this manuscript, we identified a network involved in protein synthesis that were upregulated by cold. The network contains both light-dependent and light-independent cold-inducible proteins, presumably for fine tuning the activity of the network in natural habitats of cyanobacteria where days and nights are alternating. This finding underscores the significance of proteome reprograming toward enhancing protein synthesis in cold adaptation.
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http://dx.doi.org/10.1016/j.jprot.2018.03.006DOI Listing
May 2018

Inference of differentiation time for single cell transcriptomes using cell population reference data.

Nat Commun 2017 11 30;8(1):1856. Epub 2017 Nov 30.

Chinese Academy of Sciences Key Laboratory of Computational Biology, Chinese Academy of Sciences-Max Planck Partner Institute for Computational Biology, CAS Center for Excellence in Molecular Cell Science, Collaborative Innovation Center for Genetics and Developmental Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.

Single-cell RNA sequencing (scRNA-seq) is a powerful method for dissecting intercellular heterogeneity during development. Conventional trajectory analysis provides only a pseudotime of development, and often discards cell-cycle events as confounding factors. Here using matched cell population RNA-seq (cpRNA-seq) as a reference, we developed an "iCpSc" package for integrative analysis of cpRNA-seq and scRNA-seq data. By generating a computational model for reference "biological differentiation time" using cell population data and applying it to single-cell data, we unbiasedly associated cell-cycle checkpoints to the internal molecular timer of single cells. Through inferring a network flow from cpRNA-seq to scRNA-seq data, we predicted a role of M phase in controlling the speed of neural differentiation of mouse embryonic stem cells, and validated it through gene knockout (KO) experiments. By linking temporally matched cpRNA-seq and scRNA-seq data, our approach provides an effective and unbiased approach for identifying developmental trajectory and timing-related regulatory events.
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http://dx.doi.org/10.1038/s41467-017-01860-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5707349PMC
November 2017

Hyperspectral Imaging and Support Vector Machine: A Powerful Combination to Differentiate Black Cohosh (Actaea racemosa) from Other Cohosh Species.

Planta Med 2018 Apr 6;84(6-07):407-419. Epub 2017 Oct 6.

Department of Pharmaceutical Sciences, Faculty of Science, Tshwane University of Technology, Pretoria, South Africa.

(black cohosh) has a history of traditional use in the treatment of general gynecological problems. However, the plant is known to be vulnerable to adulteration with other cohosh species. This study evaluated the use of shortwave infrared hyperspectral imaging (SWIR-HSI) in tandem with chemometric data analysis as a fast alternative method for the discrimination of four cohosh species () and 36 commercial products labelled as black cohosh. The raw material and commercial products were analyzed using SWIR-HSI and ultra-high-performance liquid chromatography coupled to mass spectrometry (UHPLC-MS) followed by chemometric modeling. From SWIR-HSI data (920 - 2514 nm), the range containing the discriminating information of the four species was identified as 1204 - 1480 nm using Matlab software. After reduction of the data set range, partial least squares discriminant analysis (PLS-DA) and support vector machine discriminant analysis (SVM-DA) models with coefficients of determination ( ) of ≥ 0.8 were created. The novel SVM-DA model showed better predictions and was used to predict the commercial product content. Seven out of 36 commercial products were recognized by the SVM-DA model as being true black cohosh while 29 products indicated adulteration. Analysis of the UHPLC-MS data demonstrated that six commercial products could be authentic black cohosh. This was confirmed using the fragmentation patterns of three black cohosh markers (cimiracemoside C; 12-,21-dihydroxycimigenol-3--L-arabinoside; and 24--acetylhydroshengmanol-3---D-xylopyranoside). SWIR-HSI in conjunction with chemometric tools (SVM-DA) could identify 80% adulteration of commercial products labelled as black cohosh.
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http://dx.doi.org/10.1055/s-0043-119887DOI Listing
April 2018

Segmenting Microscopy Images of Multi-Well Plates Based on Image Contrast.

Microsc Microanal 2017 10 17;23(5):932-937. Epub 2017 Jul 17.

Key Laboratory of Computational Biology, CAS Center for Excellence in Molecular Cell Science, Collaborative Innovation Center for Genetics and Developmental Biology, Chinese Academy of Sciences-Max Planck Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, China.

Image segmentation is a key process in analyzing biological images. However, it is difficult to detect the differences between foreground and background when the image is unevenly illuminated. The unambiguous segmenting of multi-well plate microscopy images with various uneven illuminations is a challenging problem. Currently, no publicly available method adequately solves these various problems in bright-field multi-well plate images. Here, we propose a new method based on contrast values which removes the need for illumination correction. The presented method is effective enough to distinguish foreground and therefore a model organism (Caenorhabditis elegans) from an unevenly illuminated microscope image. In addition, the method also can solve a variety of problems caused by different uneven illumination scenarios. By applying this methodology across a wide range of multi-well plate microscopy images, we show that our approach can consistently analyze images with uneven illuminations with unparalleled accuracy and successfully solve various problems associated with uneven illumination. It can be used to process the microscopy images captured from multi-well plates and detect experimental subjects from an unevenly illuminated background.
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http://dx.doi.org/10.1017/S1431927617012375DOI Listing
October 2017

Translating Divergent Environmental Stresses into a Common Proteome Response through the Histidine Kinase 33 (Hik33) in a Model Cyanobacterium.

Mol Cell Proteomics 2017 07;16(7):1258-1274

§State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, No.1 West Beichen Rd., Beijing 100101, China;

The histidine kinase Hik33 plays important roles in mediating cyanobacterial response to divergent types of abiotic stresses including cold, salt, high light (HL), and osmotic stresses. However, how these functions are regulated by Hik33 remains to be addressed. Using a hik33-deficient strain (Δhik33) of sp. PCC 6803 () and quantitative proteomics, we found that Hik33 depletion induces differential protein expression highly like that induced by divergent types of stresses. This typically includes downregulation of proteins in photosynthesis and carbon assimilation that are necessary for cell propagation, and upregulation of heat shock proteins, chaperons, and proteases that are important for cell survival. This observation indicates that depletion of Hik33 alone mimics divergent types of abiotic stresses, and that Hik33 could be important for preventing abnormal stress response in the normal condition. Moreover, we found most proteins of plasmid origin were significantly upregulated in Δhik33, though their biological significance remains to be addressed. Together, the systematically characterized Hik33-regulated cyanobacterial proteome, which is largely involved in stress responses, builds the molecular basis for Hik33 as a general regulator of stress responses.
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http://dx.doi.org/10.1074/mcp.M116.068080DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5500759PMC
July 2017

Molecular and phenotypic biomarkers of aging.

F1000Res 2017 9;6:860. Epub 2017 Jun 9.

Key Laboratory of Computational Biology, CAS Center for Excellence in Molecular Cell Science, Collaborative Innovation Center for Genetics and Developmental Biology, Chinese Academy of Sciences-Max Planck Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.

Individuals of the same age may not age at the same rate. Quantitative biomarkers of aging are valuable tools to measure physiological age, assess the extent of 'healthy aging', and potentially predict health span and life span for an individual. Given the complex nature of the aging process, the biomarkers of aging are multilayered and multifaceted. Here, we review the phenotypic and molecular biomarkers of aging. Identifying and using biomarkers of aging to improve human health, prevent age-associated diseases, and extend healthy life span are now facilitated by the fast-growing capacity of multilevel cross-sectional and longitudinal data acquisition, storage, and analysis, particularly for data related to general human populations. Combined with artificial intelligence and machine learning techniques, reliable panels of biomarkers of aging will have tremendous potential to improve human health in aging societies.
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http://dx.doi.org/10.12688/f1000research.10692.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5473407PMC
June 2017

Translating Divergent Environmental Stresses into a Common Proteome Response through Hik33 in a Model Cyanobacterium.

Mol Cell Proteomics 2017 May 12. Epub 2017 May 12.

Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, China;

The histidine kinase Hik33 plays important roles in mediating cyanobacterial response to divergent types of abiotic stresses including cold, salt, high light (HL), and osmotic stresses. However, how these functions are regulated by Hik33 remains to be addressed. Using a hik33-deficient strain (Δhik33) of Synechocystis sp. PCC 6803 (Synechocystis) and quantitative proteomics, we found that Hik33 depletion induces differential protein expression highly similar to that induced by divergent types of stresses. This typically includes downregulation of proteins in photosynthesis and carbon assimilation that are necessary for cell propagation, and upregulation of heat shock proteins, chaperons, and proteases that are important for cell survival. This observation indicates that depletion of Hik33 alone mimics divergent types of abiotic stresses, and that Hik33 could be important for preventing abnormal stress response in the normal condition. Moreover, we found the majority of proteins of plasmid origin were significantly upregulated in Δhik33, though their biological significance remains to be addressed. Together, the systematically characterized Hik33-regulated cyanobacterial proteome, which is largely involved in stress responses, builds the molecular basis for Hik33 as a general regulator of stress responses.
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http://dx.doi.org/10.1074/mcp.M117.068080DOI Listing
May 2017
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