Syndrome Differentiation Analysis on Mars500 Data of Traditional Chinese Medicine.

Mars500 study was a psychological and physiological isolation experiment conducted by Russia, the European Space Agency, and China, in preparation for an unspecified future manned spaceflight to the planet Mars. Its intention was to yield valuable psychological and medical data on the effects of the planned long-term deep space mission. In this paper, we present data mining methods to mine medical data collected from the crew consisting of six spaceman volunteers. The synthesis of the four diagnostic methods of TCM, inspection, listening, inquiry, and palpation, is used in our syndrome differentiation. We adopt statistics method to describe the syndrome factor regular pattern of spaceman volunteers. Hybrid optimization based multilabel (HOML) is used as feature selection method and multilabel k-nearest neighbors (ML-KNN) is applied. According to the syndrome factor statistical result, we find that qi deficiency is a base syndrome pattern throughout the entire experiment process and, at the same time, there are different associated syndromes such as liver depression, spleen deficiency, dampness stagnancy, and yin deficiency, due to differences of individual situation. With feature selection, we screen out ten key factors which are essential to syndrome differentiation in TCM. The average precision of multilabel classification model reaches 80%.

Discovery of novel aromatase inhibitors using a homogeneous time-resolved fluorescence assay.

AIM: Aromatase is an important target for drugs to treat hormone-dependent diseases, including breast cancer. The aim of this study was to develop a homogeneous time-resolved fluorescence (HTRF) aromatase assay suitable for high-throughput screening (HTS). METHODS: A 384-well aromatase HTRF assay was established, and used to screen about 7000 compounds from a compound library. Anti-proliferation activity of the hit was evaluated using alamarBlue(R) assay in a hormone-dependent breast cancer cell line T47D. Molecular docking was conducted to elucidate the binding mode of the hit using the Discovery Studio program. RESULTS: The Z' value and signal to background (S/B) ratio were 0.74 and 5.4, respectively. Among the 7000 compounds, 4 hits (XHN22, XHN26, XHN27 and triptoquinone A) were found to inhibit aromatase with IC50 values of 1.60±0.07, 2.76±0.24, 0.81±0.08 and 45.8±11.3 µmol /L, respectively. The hits XHN22, XHN26 and XHN27 shared the same chemical scaffold of 4-imidazolyl quinoline. Moreover, the most potent hit XHN27 at 10 and 50 µmol/L inhibited the proliferation of T47D cells by 45.3% and 35.2%, respectively. The docking study revealed that XHN27 docked within the active site of aromatase and might form a hydrogen bond and had a π-cation interaction with amino acid residues of the protein. CONCLUSION: XHN27, an imidazolyl quinoline derivative of flavonoid, is a potent aromatase inhibitor with anti-proliferation activity against breast cancer in vitro. The established assay can be used in HTS for discovering novel aromatase inhibitor.

Bifunctional Cu(II)-containing PDA-PEI copolymer dots: Demonstration of a dual-mode platform for colorimetric-fluorescent detection of glyphosate in the environment.

The reliable and accurate detection of glyphosate is urgently demanded because it is related to food and environmental safety. In this contribution, a PDA-PEI/Cu2+ complex that possesses peroxidase-mimetic activity and stimulus-responsive fluorescence was fabricated by coordinating Cu2+ with polydopamine-polyethyleneimine copolymer dots (PDA-PEI CPDs). With the introduction of Cu2+, the fluorescence intensity of PDA-PEI CPDs dropped sharply owing to the electron transfer effect. As a peroxidase-mimicking nanozyme, the PDA-PEI/Cu2+ complex owns catalytic capacity to oxidize the colorless 3,3',5,5'-tetramethylbenzidine (TMB) into blue oxTMB, leading a further fluorescence quenching by internal filtering effect by oxTMB. Once the glyphosate participated, the fluorescence signal of PDA-PEI CPDs is recovered significantly because of the formation of more stable Glyp-Cu2+ complexes, meanwhile the peroxidase-mimicking activity of PDA-PEI/Cu2+ complex could be strongly hindered. According to this principle, a novel and extremely convenient 'turn off' colorimetric and 'turn on' fluorescence sensing platform can be established for dual-mode detection of glyphosate. The favorable sensitivity and selectivity and were verified in the analysis of glyphosate in the environment through the marriage of dual-signal sensing platform. The detection limit of the dual-mode glyphosate sensing platform was 103.82 ng/mL for colorimetric assay and 16.87 ng/mL for fluorescent assay, respectively. Satisfactory recoveries in the range of 96.40%-104.66% were obtained, indicating the potential of this method for application in complicated real sample. Thereby, this strategy broadens the applications of polydopamine nanomaterials and holds a promising application in determination of pesticide residues.

Redox-regulated synthesis of fluorescent polydopamine nanoparticles for detection of butyrylcholinesterase activity.

Butyrylcholinesterase (BChE) is an enzyme which is relevant to a variety of diseases, and often serve as a common biomarker of health. In this work, a novel fluorescence sensor based on redox-regulated synthesis of polydopamine nanoparticles (PDANPs) has been developed for simple and sensitive sensing BChE activity. A facile and rapid one-step approach for the preparation of fluorescent PDANPs uses potassium permanganate to oxidize dopamine. We demonstrated that the fluorescence intensity of PDANPs is dependent on the dose of potassium permanganate. Butyrylcholinesterase catalyzes the hydrolysis of butyrylthiocholine iodide (BTCh) to produce thiolcholine (TCh) which in a redox reaction with potassium permanganate prevents the formation of fluorescent PDANP. As a result, the activity of BChE can be determined in line with changes in the fluorescence of PDANPs. Based on this finding, a convenient and label-free fluorescence sensor for BChE activity was established via redox-control of the fluorescence intensity of PDANPs. A dynamic response range for BChE is acquired within 0.5 âˆ¼ 200 U/L along with a detection limit of 0.047 U/L. Importantly, the proposed method achieves practical application toward BChE in human sera. Moreover, its satisfying performance for screening of inhibitors was also proved. Hence, the proposed sensor holds great potential for cholinesterase-related biomedical investigation.

Polyethyleneimine-protected silver cluster for label-free and highly selective detection of 2,4,6-trinitrotoluene.

Sensitive and selective detection of 2,4,6-trinitrotoluene (TNT) is critical for environmental protection and public health. In this work, a convenient synthesis strategy for preparation of fluorescent PEI-AgNCs was described and further a facile and label-free sensing strategy for detection of TNT was developed. The hyperbranched polyethyleneimine (PEI) were used as template to one-step synthesize functional PEI-AgNCs with bright fluorescence signal and rich amino groups on their surface. PEI can specifically bind to electron-deficient TNT through donor-receptor interaction to form Meissenheimer complex. Interestingly, the absorption spectra of the Meissenheimer complex overlap with the fluorescence emission peak of PEI-AgNCs, thus quenching fluorescence of PEI-Ag NCs through fluorescence resonance energy transfer (FRET). Furthermore, this bonding process also initiate aggregation of PEI-AgNCs and quench the fluorescence of PEI-AgNCs by the aggregation-induced quenching (AIQ) effect. The novel method demonstrates sensitivity with a detection limit for TNT have been obtained as 17 nM. In addition, the proposed sensing method also has good selectivity over other potential interference and displayed a good potential application value in real water samples with satisfactory recoveries, offering a promising platform for sensing TNT in public safety and security environment protection.