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1.
Sensors (Basel) ; 21(4)2021 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-33546145

RESUMO

A hollow biconical fiber is proposed and experimentally demonstrated for vibration sensing. It is fabricated by creating an air micro-cavity in single-mode fiber, followed by tapering it. Experimental results show that the device is highly sensitive to bending with a sensitivity of 21.30 dB/m-1. When it is exposed to vibration, its transmission loss is modulated periodically, then based on the measured transmission, the vibration frequency can be demodulated accurately. The acoustic vibration testing results show that the proposed device can detect and demodulate the exciting acoustic frequency accurately and distinguish its sound intensity, and the maximum signal to noise ratio (SNR) achieves up to 59 dB. Moreover, cantilever beam testing proves its performance reliable. Additionally, the sensing head has the advantages of a lightweight, compact size (with a total length of less than 250 µm), and insensitivity of temperature. All these features indicate the proposed sensor has a promising potential in the engineering field.

2.
Org Biomol Chem ; 2021 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-33538747

RESUMO

A facile, DAST-mediated intramolecular cyclization of 3-hydroxy-3-(2-((3-methoxybenzyl)oxy)phenyl)indolin-2-one derivatives for the synthesis of spirooxindoles fused with dibenzoxepine moieties is described. The success of this reaction is highly dependent on the choice of solvent (promoted by DCM and 1,2-DCE) and the electronic nature of the pendant aromatic ring, which is favored by the presence of electron-donating substituents. The reaction is believed to proceed through an intramolecular Friedel-Crafts-type reaction. Various dibenzoxepine-fused spirooxindoles were successfully synthesized in up to 98% yield. This methodology provides libraries of structurally diverse and medicinally important small molecules that could aid in the search for new bioactive molecules.

3.
Sensors (Basel) ; 21(3)2021 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-33530437

RESUMO

This paper presents a graphene-Au coated photonic crystal fiber (PCF) sensor in the visible regime. Designing a side-polish D-shaped plane over the PCF's defect of the periodic air holes can effectively enhance the evanescent field. Graphene on gold can enhance the sensor's sensitivity because it can stably adsorb biomolecules and increase the propagation constant of the surface plasmon polariton (SPP). Using the finite element method (FEM), we demonstrated that the sensing performance is greatly improved by optimizing the PCF's geometric structural parameter. The proposed PCF sensor exhibited high performance with a maximum wavelength sensitivity of 4200 nm/RIU, maximum amplitude sensitivity of 450 RIU-1, and refractive index resolution of 2.3 × 10-5 RIU in the sensing range 1.32-1.41. This research provides a potential application for the design a new generation of highly sensitive biosensors.

4.
Med Biol Eng Comput ; 59(1): 165-173, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33387183

RESUMO

Nowadays, deep learning-based models have been widely developed for atrial fibrillation (AF) detection in electrocardiogram (ECG) signals. However, owing to the inevitable over-fitting problem, classification accuracy of the developed models severely differed when applying on the independent test datasets. This situation is more significant for AF detection from dynamic ECGs. In this study, we explored two potential training strategies to address the over-fitting problem in AF detection. The first one is to use the Fast Fourier transform (FFT) and Hanning-window-based filter to suppress the influence from individual difference. Another is to train the model on the wearable ECG data to improve the robustness of model. Wearable ECG data from 29 patients with arrhythmia were collected for at least 24 h. To verify the effectiveness of the training strategies, a Long Short-Term Memory (LSTM) and Convolution Neural Network (CNN)-based model was proposed and tested. We tested the model on the independent wearable ECG data set, as well as the MIT-BIH Atrial Fibrillation database and PhysioNet/Computing in Cardiology Challenge 2017 database. The model achieved 96.23%, 95.44%, and 95.28% accuracy rates on the three databases, respectively. Pertaining to the comparison of the accuracy rates on each training set, the accuracy of the model trained in conjunction with the proposed training strategies only reduced by 2%, while the accuracy of the model trained without the training strategies decreased by approximately 15%. Therefore, the proposed training strategies serve as effective mechanisms for devising a robust AF detector and significantly enhanced the detection accuracy rates of the resulting deep networks.

5.
J Med Chem ; 64(1): 677-694, 2021 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-33370104

RESUMO

A search for structurally diversified Tyk2 JH2 ligands from 6 (BMS-986165), a pyridazine carboxamide-derived Tyk2 JH2 ligand as a clinical Tyk2 inhibitor currently in late development for the treatment of psoriasis, began with a survey of six-membered heteroaryl groups in place of the N-methyl triazolyl moiety in 6. The X-ray co-crystal structure of an early lead (12) revealed a potential new binding pocket. Exploration of the new pocket resulted in two frontrunners for a clinical candidate. The potential hydrogen bonding interaction with Thr599 in the pocket was achieved with a tertiary amide moiety, confirmed by the X-ray co-crystal structure of 29. When the diversity search was extended to nicotinamides, a single fluorine atom addition was found to significantly enhance the permeability, which directly led to the discovery of 7 (BMS-986202) as a clinical Tyk2 inhibitor that binds to Tyk2 JH2. The preclinical studies of 7, including efficacy studies in mouse models of IL-23-driven acanthosis, anti-CD40-induced colitis, and spontaneous lupus, will also be presented.

6.
Biomed Res Int ; 2020: 3828249, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33274207

RESUMO

The occurrence of diarrhea-predominant irritable bowel syndrome (IBS-D) is the result of multiple factors, and its pathogenesis has not yet been clarified. Emerging evidence indicates abnormal changes in gut microbiota and bile acid (BA) metabolism have a close relationship with IBS-D. Gut microbiota is involved in the secondary BA production via deconjugation, 7α-dehydroxylation, oxidation, epimerization, desulfation, and esterification reactions respectively. Changes in the composition and quantity of gut microbiota have an important impact on the metabolism of BAs, which can lead to the occurrence of gastrointestinal diseases. BAs, synthesized in the hepatocytes, play an important role in maintaining the homeostasis of gut microbiota and the balance of glucose and lipid metabolism. In consideration of the complex biological functional connections among gut microbiota, BAs, and IBS-D, it is urgent to review the latest research progress in this field. In this review, we summarized the alterations of gut microbiota in IBS-D and discussed the mechanistic connections between gut microbiota and BA metabolism in IBS-D, which may be involved in activating two important bile acid receptors, G-protein coupled bile acid receptor 1 (TGR5) and farnesoid X receptor (FXR). We also highlight the strategies of prevention and treatment of IBS-D via regulating gut microbiota-bile acid axis, including probiotics, fecal microbiota transplantation (FMT), cholestyramine, and the cutting-edge technology about bacteria genetic engineering.

7.
Entropy (Basel) ; 22(4)2020 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-33286185

RESUMO

Sample entropy (SampEn) is widely used for electrocardiogram (ECG) signal analysis to quantify the inherent complexity or regularity of RR interval time series (i.e., heart rate variability (HRV)), with the hypothesis that RR interval time series in pathological conditions output lower SampEn values. However, ectopic beats can significantly influence the entropy values, resulting in difficulty in distinguishing the pathological situation from normal situations. Although a theoretical operation is to exclude the ectopic intervals during HRV analysis, it is not easy to identify all of them in practice, especially for the dynamic ECG signal. Thus, it is important to suppress the influence of ectopic beats on entropy results, i.e., to improve the robustness and stability of entropy measurement for ectopic beats-inserted RR interval time series. In this study, we introduced a physical threshold-based SampEn method, and tested its ability to suppress the influence of ectopic beats for HRV analysis. An experiment on the PhysioNet/MIT RR Interval Databases showed that the SampEn use physical meaning threshold has better performance not only for different data types (normal sinus rhythm (NSR) or congestive heart failure (CHF) recordings), but also for different types of ectopic beat (atrial beats, ventricular beats or both), indicating that using a physical meaning threshold makes SampEn become more consistent and stable.

8.
Entropy (Basel) ; 22(5)2020 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-33286292

RESUMO

Due to the wide inter- and intra-individual variability, short-term heart rate variability (HRV) analysis (usually 5 min) might lead to inaccuracy in detecting heart failure. Therefore, RR interval segmentation, which can reflect the individual heart condition, has been a key research challenge for accurate detection of heart failure. Previous studies mainly focus on analyzing the entire 24-h ECG recordings from all individuals in the database which often led to poor detection rate. In this study, we propose a set of data refinement procedures, which can automatically extract heart failure segments and yield better detection of heart failure. The procedures roughly contain three steps: (1) select fast heart rate sequences, (2) apply dynamic time warping (DTW) measure to filter out dissimilar segments, and (3) pick out individuals with large numbers of segments preserved. A physical threshold-based Sample Entropy (SampEn) was applied to distinguish congestive heart failure (CHF) subjects from normal sinus rhythm (NSR) ones, and results using the traditional threshold were also discussed. Experiment on the PhysioNet/MIT RR Interval Databases showed that in SampEn analysis (embedding dimension m = 1, tolerance threshold r = 12 ms and time series length N = 300), the accuracy value after data refinement has increased to 90.46% from 75.07%. Meanwhile, for the proposed procedures, the area under receiver operating characteristic curve (AUC) value has reached 95.73%, which outperforms the original method (i.e., without applying the proposed data refinement procedures) with AUC of 76.83%. The results have shown that our proposed data refinement procedures can significantly improve the accuracy in heart failure detection.

9.
Nanoscale ; 12(45): 23140-23149, 2020 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-33191417

RESUMO

van der Waals (vdW) transition metal oxides have attracted extensive attention due to their intriguing physical and chemical properties. However, primary drawbacks of these materials are the lack of band structure tunability and substandard optical properties, which severely hinder their implementation in nanophotonic applications. Atomic intercalation is an emerging structural engineering approach for two-dimensional vdW materials to engineer the atomic structure and modify the optical properties, thereby broadening their range of applications. Herein, we synthesized tin-intercalated ultrathin α-MoO3 (Sn-MoO3) nanoribbons via chemical intercalation method and then investigated the broadband nonlinear optics (NLO) of stable few-layer α-MoO3 by performing a Z-scan laser measurement and femtosecond-resolved transient absorption (TA) spectroscopy. Sn-MoO3 showed a stable structure of Mo-O-Sn-O-Mo and a shorter relaxation time than pristine MoO3, indicating the accelerated recombination process of electrons and holes. Furthermore, Sn-MoO3 nanoribbons were used as an optical saturable absorber for ultrafast photonics; a highly stable femtosecond laser with a pulse width of 467 fs was generated from a single-mode fiber in the telecommunication band (1550 nm). These results indicate that atomic intercalation is an effective way to modulate the band structure and nonlinear optical properties of α-MoO3, which hold a great potential in the generation of ultrafast mode-locked laser pulses for optical communication technologies.

10.
ACS Appl Mater Interfaces ; 12(41): 46509-46518, 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-32940461

RESUMO

Black arsenic phosphorus (b-AsP), as one kind of novel two-dimensional (2D) materials, bridges the band gap between black phosphorus and graphene. Thanks to its great advantages, including high carrier mobility, excellent in-plane anisotropy, and broad tunability band gap, b-AsP has aroused great interest in fields of photonics and photoelectronics. In this paper, ultrathin 2D b-AsP nanomaterials were fabricated by the liquid-phase exfoliation method, and their strong broadband linear and nonlinear absorptions were characterized by ultraviolet-visible-infrared and Z-scan technology. The experimental determination of the nonlinear absorption coefficient and low saturation intensity of b-AsP were -0.23 cm/GW and 3.336 GW/cm2, respectively. Based on density functional theory, the partial charge density and band structure at the conduction band minimum and valence band maximum were calculated, which further proves the excellent optical properties of 2D b-AsP. By first using 2D b-AsP as a novel saturable absorber in both erbium-doped and thulium-doped fiber lasers, mode-locked soliton pulses can stably operate at 1.5 and 2 µm. The laser pulses generated by 2D b-AsP possess higher stability to resist self-splitting than those generated by other 2D material-based mode-lockers. These experimental results highlight that 2D b-AsP has great application potential as a novel optical material in ultrafast photonics from near- to mid-infrared regimes.

11.
Crit Care Med ; 48(11): e1091-e1096, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32885937

RESUMO

OBJECTIVES: Early detection of sepsis is critical in clinical practice since each hour of delayed treatment has been associated with an increase in mortality due to irreversible organ damage. This study aimed to develop an explainable artificial intelligence model for early predicting sepsis by analyzing the electronic health record data from ICU provided by the PhysioNet/Computing in Cardiology Challenge 2019. DESIGN: Retrospective observational study. SETTING: We developed our model on the shared ICUs publicly data and verified on the full hidden populations for challenge scoring. PATIENTS: Public database included 40,336 patients' electronic health records sourced from Beth Israel Deaconess Medical Center (hospital system A) and Emory University Hospital (hospital system B). A total of 24,819 patients from hospital systems A, B, and C (an unidentified hospital system) were sequestered as full hidden test sets. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 168 features were extracted on hourly basis. Explainable artificial intelligence sepsis predictor model was trained to predict sepsis in real time. Impact of each feature on hourly sepsis prediction was explored in-depth to show the interpretability. The algorithm demonstrated the final clinical utility score of 0.364 in this challenge when tested on the full hidden test sets, and the scores on three separate test sets were 0.430, 0.422, and -0.048, respectively. CONCLUSIONS: Explainable artificial intelligence sepsis predictor model achieves superior performance for predicting sepsis risk in a real-time way and provides interpretable information for understanding sepsis risk in ICU.

12.
Small ; 16(35): e2002252, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32734683

RESUMO

Optical nonlinearity in 2D materials excited by spatial Gaussian laser beam is a novel and peculiar optical phenomenon, which exhibits many novel and interesting applications in optical nonlinear devices. Passive photonic devices, such as optical switches, optical logical gates, photonic diodes, and optical modulators, are the key compositions in the future all-optical signal-processing technologies. Passive photonic devices using 2D materials to achieve the device functionality have attracted widespread concern in the past decade. In this Review, an overview of the spatial self-phase modulation (SSPM) in 2D materials is summarized, including the operating mechanism, optical parameter measurement, and tuning for 2D materials, and applications in photonic devices. Moreover, some current challenges are also proposed to solve, and some possible applications of SSPM method are predicted for the future. Therefore, it is anticipated that this summary can contribute to the application of 2D material-based spatial effect in all-optical signal-processing technologies.

13.
J Org Chem ; 85(17): 11519-11530, 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32786620

RESUMO

Unnatural amino acids play an important role in peptide based drug discovery. Herein, we report a class of differentially protected azatryptophan derivatives synthesized from N-tosyl-3-haloazaindoles 1 and Fmoc-protected tert-butyl iodoalanine 2 via a Negishi coupling. Through ligand screening, Pd2(dba)3/XPhos was found to be a superior catalyst for the coupling of 1 with the zinc derivative of 2 to give tert-butyl (S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-3-(1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)propanoate derivatives 3 in 69-91% isolated yields. In addition, we have demonstrated that the protecting groups, namely, Ts, Fmoc, and tBu, can be easily removed selectively.

14.
IEEE Trans Biomed Eng ; PP2020 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-32746064

RESUMO

OBJECTIVE: This paper presents a novel heart sound segmentation algorithm based on Temporal-Framing Adaptive Network (TFAN), including state transition loss and dynamic inference. METHODS: In contrast to previous state-of-the-art approaches, TFAN does not require any prior knowledge of the state duration of heart sounds and is therefore likely to generalize to non sinus rhythm. TFAN was trained on 50 recordings randomly chosen from Training set A of the 2016 PhysioNet/Computer in Cardiology Challenge and tested on the other 12 independent databases (2,099 recordings and 52,180 beats). And further testing of performance was conducted on databases with three levels of increasing difficulty (LEVEL-I, -II and -III). RESULTS: TFAN achieved a superior F1 score for all 12 databases except for `Test-B', with an average of 96.72%, compared to 94.56% for logistic regression hidden semi-Markov model (LR-HSMM) and 94.18% for bidirectional gated recurrent neural network (BiGRNN). Moreover, TFAN achieved an overall F1 score of 99.21%, 94.17%, 91.31% on LEVEL-I, -II and -III databases respectively, compared to 98.37%, 87.56%, 78.46% for LR-HSMM and 99.01%, 92.63%, 88.45% for BiGRNN. CONCLUSION: TFAN therefore provides a substantial improvement on heart sound segmentation while using less parameters compared to BiGRNN. SIGNIFICANCE: The proposed method is highly flexible and likely to apply to other non-stationary time series. Further work is required to understand to what extent this approach will provide improved diagnostic performance, although it is logical to assume superior segmentation will lead to improved diagnostics.

15.
Nanotechnology ; 31(48): 485706, 2020 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-32717736

RESUMO

Two-dimensional materials have attracted increasing attention because of their excellent mechanical, thermodynamic, magnetic, electrical and optical properties. Here, a new two-dimensional material of tin sulfide (SnS) is experimentally prepared. It is layered like black phosphorus and owns distinct optoelectronic properties, but eliminates the disadvantage of instability. The nonlinear saturable absorption characteristics of the SnS nanosheets is investigated at 1563.3 nm by the double-balanced detection method. The obtained modulation depth and saturation intensity are 5.4% and 66.3 MW/cm2, respectively. A passively harmonic mode-locked erbium-doped fiber laser based on the SnS saturable absorber (SA) has been demonstrated. The results show that mode-locking with fundamental frequency of 5.47 MHz is realized at pump power of 28.38 mW. With the increase of pump power, the laser can operate from fundamental frequency to high-order harmonic mode-locking. The maximum repetition rate of 412.73 MHz has been obtained, which is equivalent to the 76th harmonic mode-locking. This work reveals that SnS nanosheets is a novel and efficient SA with high damage threshold, which will find potential applications in optical communication, photoelectric detection, laser medicine, etc.

16.
Biomed Res Int ; 2020: 9267475, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32626771

RESUMO

Purpose: Macrophage aging is involved with the occurrence and progression of age-related macular degeneration (AMD). The purpose of this study was to identify the specific microRNAs (miRNA), mRNAs, and their interactions underlying macrophage aging and response to cholesterol through bioinformatical analysis in order to get a better understanding of the mechanism of AMD. Methods: The microarray data were obtained from Gene Expression Omnibus (accession GSE111304 and GSE111382). The age-related differentially expressed genes in macrophages were identified using R software. Further miRNA-mRNA interactions were analyzed through miRWalk, mirTarBase, starBase, and then produced by Cytoscape. The functional annotations including Gene Ontology and KEGG pathways of the miRNA target genes were performed by the DAVID and the STRING database. In addition, protein-protein interaction network was constructed to identify the key genes in response to exogenous cholesterol. Results: When comparing aged and young macrophages, a total of 14 miRNAs and 101 mRNAs were detected as differentially expressed. Besides, 19 validated and 544 predicted miRNA-mRNA interactions were detected. Lipid metabolic process was found to be associated with macrophage aging through functional annotations of the miRNA targets. After being treated with oxidized and acetylated low-density lipoprotein, miR-714 and 16 mRNAs differentially expressed in response to both kinds of cholesterol between aged and young macrophages. Among them, 6 miRNA-mRNA predicted pairs were detected. The functional annotations were mainly related to lipid metabolism process and farnesyl diphosphate farnesyl transferase 1 (FDFT1) was identified to be the key gene in the difference of response to cholesterol between aged and young macrophages. Conclusions: Lipid metabolic process was critical in both macrophage aging and response to cholesterol thus was regarded to be associated with the occurrence and progression of AMD. Moreover, miR-714-FDFT1 may modulate cholesterol homeostasis in aged macrophages and have the potential to be a novel therapeutic target for AMD.

17.
J Org Chem ; 85(16): 10988-10993, 2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32687358

RESUMO

We describe an efficient synthetic route to differentially protected diester, 1-(tert-butyl) 4-methyl (1R,2S,4R)-2-methylcyclohexane-1,4-dicarboxylate (+)-1, via palladium-catalyzed methoxycarbonylation of an enol triflate derived from a Hagemann's ester derivative followed by a stereoselective Crabtree hydrogenation. Diester 1 is a novel chiral synthon useful in drug discovery and was instrumental in the generation of useful SAR during a RORγt inverse agonist program. In addition, we describe a second-generation synthesis of the clinical candidate BMS-986251, using diester 1 as a critical component.

18.
Nanoscale Horiz ; 5(4): 705-713, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32226968

RESUMO

Two-dimensional (2D) metal-free sheets with atomic thickness have been highly considered as promising candidates for fluorescent probes, due to their intriguing characteristics. In this work, 2D ultrathin boron nanosheets (B NSs) with a surface defect nanolayer can be effectively prepared by modified liquid phase exfoliation. The as-prepared ultrathin B NSs show blue fluorescence characteristics even with a quantum yield efficiency of up to 10.6%. Such luminescent behavior originates from the quantum confinement effect and the existence of a surface defect layer. In light of the advantages of being environmentally friendly, having high photostability and good biocompatibility, for the first time we have shown that ultrathin B NSs can be used as an emerging fluorescent probe for application in cellular bioimaging. It is believed that this work will open new avenues for ultrathin B NSs in biomedical fields, and it will also inspire the development of other elemental 2D nanomaterials.

19.
Physiol Meas ; 41(5): 054004, 2020 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-32268306

RESUMO

OBJECTIVE: Premature beats (PB), typically presenting as premature ventricular contractions (PVC) and premature atrial contractions (PAC), may foreshadow stroke or sudden cardiac death. APPROACH: A rule-based real-time PB detection system was proposed for timely diagnosis of common PAC and PVC in an ambulatory setting and to reduce the cognitive load for physicians. The proposed method consists of three procedures: (1) extraction of the RR interval, QRS complex template, width and height; (2) rough detection of PB candidates using rules corresponding to abnormality in rhythm and morphology; and (3) refined detection using three types of correction. The method was trained using randomly selected single-lead waveforms sourced from the China Physiological Signal Challenge 2018 (CPSC2018) database, and the method was tested on the 12-lead CPSC2018 database, the MIT-BIH-AR database and the wearable ECG database. MAIN RESULTS: Four quantitative parameters, namely sensitivity, positive predictive value, accuracy and F1 measure, were used to assess performance. The F1 measure for normal beats, PACs, and PVCs were 99.37, 90.6, and 90.85% in training data (93.61% across all beats). Satisfactory results on the 12-lead CPSC2018 database indicated that the method had a good generalization ability between leads. Although the results on the MIT-BIH-AR database were not comparable with other methods, it showed stability in different testing databases. In addition, the test results on wearable ECGs manifested that the method was robust and could provide a good algorithm basis for IoT applications. SIGNIFICANCE: We have developed a rule-based method for real-time PB detection in single-lead ECG, which balances the computational complexity and recognition accuracy, indicating the clinical significance of the method.

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