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Background: Nonalcoholic fatty liver disease (NAFLD) shares common pathogenic mechanisms of type 2 diabetes mellitus (T2DM) with upregulated advanced glycation end products (AGEs). Here, we aim to investigate the effect of FPS-ZM1, an inhibitor for receptor for AGEs (RAGE), on lipid deposition in the liver of mice., Methods: KK-Ay mice were used as models of T2DM with NAFLD, while C57BL/6j mice were controls. Additionally, KK-Ay mice were treated with DMSO (with a concentration of 1%), with or without FPS-ZM1 (3 mg/kg/day, i.p). Lipid deposition in hepatocytes was observed using oil red O stain. Levels of AGEs and RAGE were measured. Sterol regulatory element-binding protein-1c (SREBP-1c), as well as nuclear factor κB p65 (p65 nfκb) and mitogen-activated protein kinase p38 (p38 MAPK), were also detected., Results: Lipid deposition is increased in the hepatocytes of KK-Ay mice compared to C57BL/6j mice. In addition, not only were the levels of AGEs elevated in plasma, but also the levels of RAGE in liver tissue. Although total SREBP-1c levels did not change in the liver of diabetic mice, mature SREBP-1c increased in KK-Ay mice with diabetes mellitus. Moreover, diabetic mice showed increased levels of phosphorylated-p65 nfκb (p-p65 nfκb) and phosphorylated-p38 MAPK (p-p38 MAPK). On the contrary, FPS-ZM1 decreased lipid deposition in liver cells, as well as mature SREBP-1c, p-p65 nfκb and p-p38 MAPK levels in liver tissue., Conclusion: Generally, FPS-ZM1 may attenuate lipid deposition in hepatocytes of diabetic mice via SREBP-1c down-regulation. This may depend on the downregulation of p65 nfκb and p38 MAPK phosphorylation., (© 2024. The Author(s).)

As the number of patients with cardiovascular diseases (CVDs) increases annually, a reliable and automated system for detecting electrocardiogram (ECG) abnormalities is becoming increasingly essential. Scholars have developed numerous methods of arrhythmia classification using machine learning or deep learning. However, the issue of low classification rates of individual classes in inter-patient heartbeat classification remains a challenge. This study proposes a method for inter-patient heartbeat classification by fusing dual-channel squeeze-and-excitation residual neural networks (SE-ResNet) and expert features. In the preprocessing stage, ECG heartbeats extracted from both leads of ECG signals are filtered and normalized. Additionally, nine features representing waveform morphology and heartbeat contextual information are selected to be fused with the deep neural networks. Using different filter and kernel sizes for each block, the SE-residual block-based model can effectively learn long-term features between heartbeats. The divided ECG heartbeats and extracted features are then input to the improved SE-ResNet for training and testing according to the inter-patient scheme. The focal loss is utilized to handle the heartbeat of the imbalance category. The proposed arrhythmia classification method is evaluated on three open-source databases, and it achieved an overall F1-score of 83.39 % in the MIT-BIH database. This system can be applied in the scenario of daily monitoring of ECG and plays a significant role in diagnosing arrhythmias., Competing Interests: Declaration of competing interest The authors declared that they have no conflicts of interest to this work., (Copyright © 2024. Published by Elsevier Ltd.)

Gene therapy has shown significant potential in treating various diseases, particularly inherited blood disorders such as hemophilia, sickle cell disease, and thalassemia. Advances in understanding the regulatory network of disease-associated genes have led to the identification of additional therapeutic targets for treatment, especially for β-hemoglobinopathies. Erythroid regulatory factor BCL11A offers the most promising therapeutic target for β-hemoglobinopathies and reduction of its expression using the commercialized gene therapy product Casgevy was approved for use in the UK and USA in 2023. Notably, the emergence of innovative gene editing technologies has further broadened the gene therapy landscape, presenting new possibilities for treatment. Intensive studies indicate that base editing and prime editing, built upon CRISPR technology, enable precise single-base modification in hematopoietic stem cells for addressing inherited blood disorders ex vivo and in vivo. In this review, we present an overview of the current landscape of gene therapies, focusing on clinical research and gene therapy products for inherited blood disorders, evaluation of potential gene targets, and the gene editing tools employed in current gene therapy practices, which provides an insight for the establishment of safer and more effective gene therapy methods for a wider range of diseases in the future., Competing Interests: Conflict of interest The authors declared no competing interests., (Copyright © 2024. Published by Elsevier Ltd.)

Purpose: Intravenous narcotic agents, such as etomidate and metomidate, has been widely spread and abused in the world, including in Korea and China; thus, it is important to establish validated and sensitive analytical method for these compounds. Human hair as a biological sample has various advantages, including a wide detection window of drugs, compared to other typical samples, such as urine and blood in investigation. The purpose of this communication is to develop a reliable and useful method for the simultaneous detection and quantification of etomidate and metomidate in human hair samples by ultraperformance liquid chromatography combined with triple quadrupole mass spectrometry (UPLC-MS/MS), and to apply it for authentic samples in abuse cases., Methods: The hair samples were washed with a detergent solution, followed by with water and acetone. After drying, they were cut into approximately 2 mm sections and then ground to powder by a low-temperature grinder. The 20 mg of hair powder plus internal standard in 1 mL of methanol was vortexed and then centrifuged to obtain the supernatant layer, followed by subjecting to analysis., Results: The coefficient of determination (r 2 ) values of the calibration curves of etomidate and metomidate in the hair samples were both more than 0.99 in the range of 1-500 ng/mg and 1-500 pg/mg, respectively. The limits of detection and lower limits of quantification were 0.5 and 1 pg/mg, respectively, for the both target compounds. Other tested validation data were all satisfactory. Etomidate and metomidate could be detected in the all hair samples and cigarette oil, which were seized by the police. The concentrations of etomidate and metomidate obtained from 10 samples from suspects were 5.48-45.7 ng/mg and 3.60-377 pg/mg, respectively. The concentrations of etomidate and metomidate in the cigarette oil were 95.8 μg/mg and 2.8 μg/mg, respectively., Conclusions: In this study, a simple and reliable analytical method for etomidate and metomidate in the human hair has been established. To the best of our knowledge, this is the first report to establish a method for the simultaneous detection and quantification of etomidate and metomidate in the human hair, and to apply it to authentic samples seized in authentic cases., (© 2024. The Author(s), under exclusive licence to Japanese Association of Forensic Toxicology.)

Litchi pericarp is rich in polyphenols, and demonstrates significant biological activity. This study assessed the therapeutic effects of litchi pericarp extract (LPE) on type 2 diabetes mellitus in db/db mice. The results showed that LPE ameliorated symptoms of glucose metabolism disorder, oxidative stress, inflammatory response, and insulin resistance in db/db mice. The mechanistic studies indicated that LPE activates adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) and suppresses the protein expression of phosphoenolpyruvate carboxykinase (PEPCK), thereby reducing hepatic gluconeogenesis. Additionally, LPE facilitates the translocation of nuclear factor erythroid2-related factor 2 (Nrf2) into the cell nucleus, initiating the transcription of antioxidant factors superoxide dismutase (SOD) and NAD(P)H: quinone oxidoreductase 1 (NQO1), which alleviate oxidative stress and reduce oxidative damage. Furthermore, LPE blocks nuclear factor kappa-B (NF-κB) nuclear translocation and subsequent inflammatory response initiation, thereby reducing inflammation. These findings indicate that LPE addresses type 2 diabetes mellitus by activating the AMPK energy metabolic pathway and regulating the Nrf2 oxidative stress and NF-κB inflammatory signaling pathways.

Strong field ionization injects a transient vacancy in the atom which is entangled to the outgoing photoelectron. When the electron is finally detached, the ion is populated at different excited states with part of coherence information lost. The preserved coherence of matter after interacting with intense short pulses has important consequences on the subsequent nonequilibrium evolution and energy relaxation. Here we employ attosecond transient absorption spectroscopy to measure the time-delay of resonant transitions of krypton vacancy during their creation. We have observed that the absorptions by the two spin-orbit split states are modulated at different paces when varying the time-delay between the near-infrared pumping pulse and the attosecond probing pulse. It is shown that the coupling of the ions with the remaining field leads to a suppression of ionic coherence. Comparison between theory and experiments uncovers that coherent Raman coupling induces time-delay between the resonant absorptions, which provides insight into laser-ion interactions enriching attosecond chronoscopy., (© 2024. The Author(s).)

Background: Long-term monitoring of Electrocardiogram (ECG) recordings is crucial to diagnose arrhythmias. Clinicians can find it challenging to diagnose arrhythmias, and this is a particular issue in more remote and underdeveloped areas. The development of digital ECG and AI methods could assist clinicians who need to diagnose arrhythmias outside of the hospital setting., Methods: We constructed a large-scale Chinese ECG benchmark dataset using data from 272,753 patients collected from January 2017 to December 2021. The dataset contains ECG recordings from all common arrhythmias present in the Chinese population. Several experienced cardiologists from Shanghai First People's Hospital labeled the dataset. We then developed a deep learning-based multi-label interpretable diagnostic model from the ECG recordings. We utilized Accuracy, F1 score and AUC-ROC to compare the performance of our model with that of the cardiologists, as well as with six comparison models, using testing and hidden data sets., Results: The results show that our approach achieves an F1 score of 83.51%, an average AUC ROC score of 0.977, and 93.74% mean accuracy for 6 common arrhythmias. Results from the hidden dataset demonstrate the performance of our approach exceeds that of cardiologists. Our approach also highlights the diagnostic process., Conclusions: Our diagnosis system has superior diagnostic performance over that of clinicians. It also has the potential to help clinicians rapidly identify abnormal regions on ECG recordings, thus improving efficiency and accuracy of clinical ECG diagnosis in China. This approach could therefore potentially improve the productivity of out-of-hospital ECG diagnosis and provides a promising prospect for telemedicine., (© 2024. The Author(s).)

The present study investigated the impact of saponins of tomato extract (STE) on non-alcoholic fatty liver disease (NAFLD). The findings demonstrated that introducing STE in NAFLD mice revealed promising results in ameliorating symptoms of oxidative stress, lipid metabolism disorders, visceral fat deposition and fatty liver disease. Moreover, the mechanistic studies have demonstrated that STE delivers its effects by activating adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK), thereby suppressing downstream protein expression associated with fatty acid synthesis. In such conditions, lipid metabolism can be improved. Simultaneously, STE enhanced nuclear factor erythroid 2-related factor 2 (Nrf2) and entry into the nucleus and initiated the transcription of downstream antioxidant factors, thereby relieving oxidative stress induced by a high-fat diet and lowering oxidative damage to the liver. Such results imply that the administration of STE can be regarded as a viable treatment option for NAFLD, providing a mechanism that can regulate the AMPK and Nrf2 signaling pathways.

Hypertension is one of the most challenging public health problems worldwide. Previous studies suggested that the Uncaria rhynchophylla Scrophularia Formula (URSF), a medical institution preparation of the affiliated Hospital of Shandong University of Traditional Chinese Medicine, is effective for essential hypertension. However, the efficacy of URSF for hypertension remains unclear. We aimed to clarify the anti-hypertensive mechanism of the URSF. The material basis of URSF was identified by the LC-MS. We also evaluated the antihypertensive efficacy of URSF on SHR rats by body weight, blood pressure and biochemical indicators. The LC-MS spectrometry-based serum non-targeted metabolomics was used to seek potential biomarkers and relevant pathways for URSF in the treatment of SHR rats. 56 biomarkers were metabolically disturbed in SHR rats in the model group compared with the control group. After URSF intervention, 13 biomarkers showed a recovery in the optimal method compared with the other three groups. We identified 3 metabolic pathways in which URSF is involved: the arachidonic acid metabolism pathway, the niacin and nicotinamide metabolism pathway, and the purine metabolism pathway. These discoveries offer a basis for the study of URSF for the treatment of hypertension., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this.paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Polyketone compounds are powerful building blocks to synthesize various organic functional materials. Despite that a great many number of planar and non-planar polyketone building blocks have been developed, one issue is that generally there are only ketone functional groups on the molecular skeleton, which will constrain their transformation and further limit the development of functional materials. In this work, we report the design and synthesis of a building block 9,10-diethyl-9,10-ethenoanthracene-2,3,6,7(9 H ,10 H )-tetraone with additional vinyl functional groups. In addition, its azaacene derivatives were also synthesized, and their preliminary physicochemical properties were studied., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Verticillium wilt caused by Verticillium dahliae is a serious vascular disease in cotton (Gossypium spp.). V. dahliae induces the expression of the CAROTENOID CLEAVAGE DIOXYGENASE 7 (GauCCD7) gene involved in strigolactone (SL) biosynthesis in Gossypium australe, suggesting a role for SLs in Verticillium wilt resistance. We found that the SL analog rac-GR24 enhanced while the SL biosynthesis inhibitor TIS108 decreased cotton resistance to Verticillium wilt. Knock-down of GbCCD7 and GbCCD8b genes in island cotton (Gossypium barbadense) decreased resistance, whereas overexpression of GbCCD8b in upland cotton (Gossypium hirsutum) increased resistance to Verticillium wilt. Additionally, Arabidopsis (Arabidopsis thaliana) SL mutants defective in CCD7 and CCD8 putative orthologs were susceptible, whereas both Arabidopsis GbCCD7- and GbCCD8b-overexpressing plants were more resistant to Verticillium wilt than wild-type (WT) plants. Transcriptome analyses showed that several genes related to the jasmonic acid (JA)- and abscisic acid (ABA)-signaling pathways, such as MYELOCYTOMATOSIS 2 (GbMYC2) and ABA-INSENSITIVE 5, respectively, were upregulated in the roots of WT cotton plants in responses to rac-GR24 and V. dahliae infection but downregulated in the roots of both GbCCD7- and GbCCD8b-silenced cotton plants. Furthermore, GbMYC2 suppressed the expression of GbCCD7 and GbCCD8b by binding to their promoters, which might regulate the homeostasis of SLs in cotton through a negative feedback loop. We also found that GbCCD7- and GbCCD8b-silenced cotton plants were impaired in V. dahliae-induced reactive oxygen species (ROS) accumulation. Taken together, our results suggest that SLs positively regulate cotton resistance to Verticillium wilt through crosstalk with the JA- and ABA-signaling pathways and by inducing ROS accumulation., Competing Interests: Conflict of interest statement: The authors declared that there is no any competing interests., (© American Society of Plant Biologists 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Traditional Chinese medicine (TCM) has been practiced for thousands of years with clinical efficacy. Natural products and their effective agents such as artemisinin and paclitaxel have saved millions of lives worldwide. Artificial intelligence is being increasingly deployed in TCM. By summarizing the principles and processes of deep learning and traditional machine learning algorithms, analyzing the application of machine learning in TCM, reviewing the results of previous studies, this study proposed a promising future perspective based on the combination of machine learning, TCM theory, chemical compositions of natural products, and computational simulations based on molecules and chemical compositions. In the first place, machine learning will be utilized in the effective chemical components of natural products to target the pathological molecules of the disease which could achieve the purpose of screening the natural products on the basis of the pathological mechanisms they target. In this approach, computational simulations will be used for processing the data for effective chemical components, generating datasets for analyzing features. In the next step, machine learning will be used to analyze the datasets on the basis of TCM theories such as the superposition of syndrome elements. Finally, interdisciplinary natural product-syndrome research will be established by unifying the results of the two steps outlined above, potentially realizing an intelligent artificial intelligence diagnosis and treatment model based on the effective chemical components of natural products under the guidance of TCM theory. This perspective outlines an innovative application of machine learning in the clinical practice of TCM based on the investigation of chemical molecules under the guidance of TCM theory., (© 2023. The Author(s).)

Background: In recent years, the emergence of new diseases and resistance to known diseases have led to increasing demand for new drugs. By means of bibliometric analysis, this paper studied the relevant articles on drug repositioning in recent years and analyzed the current research foci and trends., Methodology: The Web of Science database was searched to collect all relevant literature on drug repositioning from 2001 to 2022. These data were imported into CiteSpace and bibliometric online analysis platforms for bibliometric analysis. The processed data and visualized images predict the development trends in the research field., Results: The quality and quantity of articles published after 2011 have improved significantly, with 45 of them cited more than 100 times. Articles posted by journals from different countries have high citation values. Authors from other institutions have also collaborated to analyze drug rediscovery. Keywords found in the literature include molecular docking (N=223), virtual screening (N=170), drug discovery (N=126), machine learning (N=125), and drug-target interaction (N=68); these words represent the core content of drug repositioning., Conclusion: The key focus of drug research and development is related to the discovery of new indications for drugs. Researchers are starting to retarget drugs after analyzing online databases and clinical trials. More and more drugs are being targeted at other diseases to treat more patients, based on saving money and time. It is worth noting that researchers need more financial and technical support to complete drug development., Competing Interests: The authors declare that the research was conducted without any commercial or financial relationships construed as a potential conflict of interest., (© 2023 Lang et al.)

Backgrounds: Dyslipidemia is a prominent risk factor for cardiovascular diseases and one of the primary independent modifiable factors of diabetes and stroke. Statins can significantly improve the prognosis of dyslipidemia, but its side effects cannot be ignored. Traditional Chinese Medicine (TCM) has been used in clinical practice for more than 2000 years in China and has certain traits in treating dyslipidemia with little side effect. Previous research has shown that Mutual Obstruction of Phlegm and Stasis (MOPS) is the most common dyslipidemia type classified in TCM. However, how to compose diagnostic factors in TCM into diagnostic rules relies heavily on the doctor's experience, falling short in standardization and objectiveness. This is a limit for TCM to play its advantages of treating dyslipidemia with MOPS., Methods: In this study, the syndrome diagnosis in TCM was transformed into the prediction and classification problem in artificial intelligence The deep learning method was employed to build the classification prediction models for dyslipidemia. The models were built and trained with a large amount of multi-centered clinical data on MOPS. The optimal model was screened out by evaluating the performance of prediction models through loss, accuracy, precision, recall, confusion matrix, PR and ROC curve (including AUC)., Results: A total of 20 models were constructed through the deep learning method. All of them performed well in the prediction of dyslipidemia with MOPS. The model-11 is the optimal model. The evaluation indicators of model-11 are as follows: The true positive (TP), false positive (FP), true negative (TN) and false negative (FN) are 51, 15, 129, and 9, respectively. The loss is 0.3241, accuracy is 0.8672, precision is 0.7138, recall is 0.8286, and the AUC is 0.9268. After screening through 89 diagnostic factors of TCM, we identified 36 significant diagnosis factors for dyslipidemia with MOPS. The most outstanding diagnostic factors from the importance were dark purple tongue, slippery pulse and slimy fur, etc., Conclusions: This study successfully developed a well-performing classification prediction model for dyslipidemia with MOPS, transforming the syndrome diagnosis problem in TCM into a prediction and classification problem in artificial intelligence. Patients with dyslipidemia of MOPS can be accurately recognized through limited information from patients. We also screened out significant diagnostic factors for composing diagnostic rules of dyslipidemia with MOPS. The study is an avant-garde attempt at introducing the deep-learning method into the research of TCM, which provides a useful reference for the extension of deep learning method to other diseases and the construction of disease diagnosis model in TCM, contributing to the standardization and objectiveness of TCM diagnosis., Competing Interests: Conflict of interestAll authors declare that there is no conflict of interest., (© The Author(s) 2023.)

A method for identification and quantification of 2-methoxyqualone, an newly emerging quinazolinone derivative recreational drug, in human scalp hair was established using gas chromatography (GC)-tandem mass spectrometry (MS/MS). In this report, authentic cases are presented, in which the suspects were seized by police security bureau; the police in China requested our laboratory to identify and quantify the involved drug(s) of abuse in the hair samples of the suspects. After washing and cryo-grinding the authentic hair samples, the target compound was extracted with methanol, and the solvent layer was evaporated to dryness. The residue was reconstituted in methanol and analyzed by GC-MS/MS. 2-Methoxyqualone concentrations in the hair were between 35.1 and 116 pg/mg. The calibration curve of the substance in hair samples showed a good linearity in the concentration range of 10-1000 pg/mg (r > 0.998); the extraction recovery rate, 88.8-105.6 %; the interday and intraday precisions and accuracies (biases), not greater than 8.9 %. 2-Methoxyqualone in human hair had good stability under three different storage conditions at room (20 °C), refrigerated (4 °C) and frozen (- 20 °C) temperatures for at least 7 days. In the present report, simple and rapid quantification method for 2-methoxyqualone in human scalp hair have been established using GC-MS/MS and it could successfully be applied to authentic forensic toxicological cases. To our knowledge, this is the first report for quantification of 2-methoxyqualone in human hair samples., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: National Natural Science Foundation of China (Grant no. 81860331)., (Copyright © 2023. Published by Elsevier B.V.)

Purpose: The information on analytical methods for 4-quinazolinone recreational drugs, such as methaqualone, etaqualone and 2-methoxyqualone, is almost scant. In this study, product ion spectra of gas chromatography-tandem mass spectrometry (GC-MS/MS) with different collision energies were presented for these drugs. Because 2-methoxyqualone is a new recreational drug discovered in dubious tablets very recently, much more detailed data obtained by different types of mass spectrometry instruments, and quantification data of 2-methoxyqualone in the tablet together with its validation were demonstrated., Methods: The methods for analyses were GC-MS/MS, high-resolution ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry and liquid chromatography-tandem mass spectrometry., Results: The GC-MS/MS product ion spectra of the three compounds with different collision energies have not been reported before. They were very useful to tentatively identify unknown compounds. If a reference standard is available, the final identification and quantification can be achieved by measurements of product ion spectra and in selected reaction monitoring mode very easily by GC-MS/MS. The final identification and quantification for the new 2-methoxyqualone were performed in this way. The content of the compound was 69.8 ± 0.5% (w/w) in the tablet. Acetaminophen and caffeine coexisted in the tablet with approximate concentrations at 10 and 5%, respectively., Conclusions: In this article, we have presented product ion spectra of methaqualone, etaqualone and 2-methoxyqualone at different collision energies by GC-MS/MS for the first time. In addition, this is the first paper to describe the details of quantification of 2-methoxyqualone in the authentic seized product., (© 2022. The Author(s), under exclusive licence to Japanese Association of Forensic Toxicology.)

The objective of this study is to construct a multi-department symptom-based automatic diagnosis model. However, it is difficult to establish a model to classify plenty of diseases and collect thousands of disease-symptom datasets simultaneously. Inspired by the thought of "knowledge graph is model", this study proposes to build an experience-infused knowledge model by continuously learning the experiential knowledge from data, and incrementally injecting it into the knowledge graph. Therefore, incremental learning and injection are used to solve the data collection problem, and the knowledge graph is modeled and containerized to solve the large-scale multi-classification problems. First, an entity linking method is designed and a heterogeneous knowledge graph is constructed by graph fusion. Then, an adaptive neural network model is constructed for each dataset, and the data is used for statistical initialization and model training. Finally, the weights and biases of the learned neural network model are updated to the knowledge graph. It is worth noting that for the incremental process, we consider both the data and class increments. We evaluate the diagnostic effectiveness of the model on the current dataset and the anti-forgetting ability on the historical dataset after class increment on three public datasets. Compared with the classical model, the proposed model improves the diagnostic accuracy of the three datasets by 5%, 2%, and 15% on average, respectively. Meanwhile, the model under incremental learning has a better ability to resist forgetting., (© Shanghai Jiao Tong University 2022.)

As the number of people suffering from cardiovascular diseases increases every year, it becomes essential to have an accurate automatic electrocardiogram (ECG) diagnosis system. Researchers have adopted different methods, such as deep learning, to investigate arrhythmias classification. However, the importance of ECG waveform features is generally ignored when deep learning approaches are applied to classification tasks. P-wave, QRS-wave, and T-wave, containing plenty of physiological information, are three critical waves in the ECG heartbeat. The accurate localization of these critical ECG wave components is a prerequisite for ECG classification and diagnosis. In this study, a novel P-QRS-T wave localization method based on hybrid neural networks is proposed. The raw ECG signal is preprocessed sequentially by filtering, heartbeat extraction, and data standardization. The hybrid neural network is constructed by combining the residual neural network (ResNet) and the Long Short-Term Memory (LSTM). It predicts the relative positions of the P-peak, QRS-peak, and T-peak for each heartbeat. The proposed algorithm was validated on four ECG databases with input noise of different signal-to-noise ratio (SNR) levels. The results show that the proposed method can accurately predict the positions of the three key waves. The proposed P-QRS-T localization approach can improve the efficiency of ECG delineation. Integrated with cardiac disease classification methods, it can contribute to the development of advanced automatic ECG diagnosis systems., Competing Interests: Declaration of competing interest The authors declared that they have no conflicts of interest to this work., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Analytical procedure for detection and quantification of etaqualone in human blood and urine using GC-MS/MS was established and applied to authentic human samples obtained from volunteers. A liquid-liquid extraction method was employed. Each 1.0 mL of blood or urine was alkalized and extracted with diethyl ether. The solvent layer was evaporated to dryness and reconstituted with methanol then analyzed by GC-MS/MS. linear relationships within the concentration range of 1-100 ng/mL were obtained in calibrators for both blood and urine, demonstrating correlation coefficients values being>0.999. For blood and urine samples, the intra-day assay precision and accuracy values are each less than 3.65%, 7.13%, and 6.02%, 9.12%; those values of the inter-day assay are each less than 1.82%, 6.74%, and 3.99%, 7.41%. The extraction recovery rates for etaqualone ranged from 98.7% to 106%. The lower limit of quantifications was 1.0 ng/mL in both blood and urine. Stabilities of etaqualone in blood and urine were satisfactory under various temperatures within 15 days. 8.51 and 2.06 ng/mL of etaqualone in blood and urine were detected at 4 h later oral ingestion; 6.91 and 3.94 ng/mL of etaqualone were also detected 30 min and 2 h later smoking from blood and urine., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Currently, due to lack of large-scale datasets containing multiple arrhythmias and acute coronary syndrome-related diseases, AI-aided diagnosis for cardiac diseases is limited in clinical scenarios. Whether AI-based ECG diagnosis can assist cardiologists to improve performance has not been reported. We constructed a large-scale dataset containing multiple high-regional-incidence arrhythmias and ACS-related diseases, including 162,622 12-lead ECGs collected between January 2018 and March 2021. We presented a deep learning model for clinical ECG diagnosis of multiple cardiac diseases. Results show that our model for diagnosing 15 cardiac abnormalities achieved 88.216% accuracy, and its average AUC ROC score reached 0.961. On the board-certified re-annotated dataset, its performance surpasses that of cardiologists in non-reference group. Moreover, with aid of labels given by our model, accuracy and efficiency for cardiologist increased by 13.5% and 69.9% than non-reference group. Our approach provides solutions for AI-aided diagnosis systems of cardiac diseases in applications., Competing Interests: The authors declare no competing interests., (© 2022 The Author(s).)

We propose a novel approach based on the subcycle injection of carriers to extend the high-energy cutoff in solid-state high harmonics. The mechanism is first examined by employing the standard single-cell semiconductor Bloch equation (SC SBE) method for one-dimensional (1D) Mathieu potential model for ZnO subjected to the intense linearly polarized midinfrared laser field and extreme-ultraviolet pulse. Then, we use coupled solution of Maxwell propagation equation and SC SBE to propagate the fundamental laser field through the sample, and find that the high-harmonics pulse train from the entrance section of the sample can inject carriers to the conduction bands with attosecond timing, subsequently leading to a dramatic extension of high-energy cutoff in harmonics from the backside. We predict that for a peak intensity at 2×10^{11}  W/cm^{2}, as a result of the self-seeding, the high-energy cutoff shifts from 20th (7.75 eV) order to around 50th (19.38 eV) order harmonics.

Purpose: An analytical method for quantitation of sibutramine in human hair using gas chromatography (GC)-isotope dilution tandem mass spectrometry (MS/MS) was newly established. In this article, a case is presented, in which a 3.5-year-old male child accidentally ingested chocolate-like product containing sibutramine, showing various symptoms; he could survived the crisis. About 1 month after the incident, his scalp hair sample was subjected to analysis for the causative sibutramine., Method: After cryo-grinding for the hair sample, target compound was extracted with methanol, and the solvent layer was evaporated to dryness. The residue was reconstituted in methanol and analyzed by GC-MS/MS, using the selected reaction monitoring (SRM) mode with a deuterated isotope internal standard., Results: The substance was identified as sibutramine; its concentration in the hair sample of the child was 58.6 pg/mg. The calibration curve of sibutramine in hair samples had a good linear relationship in the concentration range of 20-200 pg/mg (r > 0.99); the extraction recovery rate 85.2-91.8%; the interday and intraday precision and accuracy (bias) examined not greater than 9.6%. Sibutramine in human hair had good stability under 3 different storage conditions at room (20 °C), refrigerated (4 °C) and frozen ( - 20 °C) temperatures for at least 7 days., Conclusions: It should be expected that the method established in this study would contribute to rapid determinations of sibutramine. To our knowledge, this is the first report describing quantitation of sibutramine in an authentic human hair sample by GC-MS/MS., (© 2021. Japanese Association of Forensic Toxicology.)

Purpose: To test synthetic cannabinoid (SCs) in parent forms from living human, the hairs seems to be one of the best samples, because of the non-invasiveness upon their collection. The purpose of this study is to establish a method for quantification of MDMB-4en-PINACA and ADB-BUTINACA, the most recently abused SCs in hair samples, using gas chromatography-tandem mass spectrometry (GC-MS/MS)., Methods: The collected hair samples were washed with a detergent solution, following by water and acetone. After drying cutting them into about 2 mm sections, they were ground by a cryogenic grinder into powder. The 50-mg powder with internal standard(s) plus 1 mL methanol were vortexed, and centrifuged to obtain the supernatant layer. After its evaporation and reconstitution with 50 µL methanol, 1-µL aliquot of it was subjected to analysis., Results: The standard calibration curves were created for both MDMB-4en-PINACA and ADB-BUTINACA in blank hair samples; good linear curves were obtained in the range of 20-20,000 pg/mg with correlation coefficients greater than 0.99. The limits of detection and limits of quantification were 10 and 20 pg/mg, respectively. Other validation parameters were all satisfactory. The concentrations of MDMB-4en-PINACA obtained from 3 authentic subjects and ADB-BUTINACA obtained from 3 authentic subjects were 26.2-806 pg/mg and 63.1-430 pg/mg, respectively., Conclusions: In the present article, the details of simple and rapid quantification of MDMB-4en-PINACA and ADB-BUTINACA in human scalp hair have been established. To our knowledge, this is the first report for quantification of SCs in hair samples by GC-MS/MS., (© 2022. The Author(s), under exclusive licence to Japanese Association of Forensic Toxicology.)

Introduction: With the widespread availability of portable electrocardiogram (ECG) devices, there will be a surge in ECG diagnoses. Traditional computer-aided diagnosis of arrhythmia mainly relies on the rules of medical knowledge, which are insufficient due to the limitations of data quality and human expert knowledge. The research of arrhythmia detection methods based on artificial intelligence (AI) techniques can assist physicians in high-precision arrhythmia diagnosis. AI algorithms can also be embedded in smart ECG devices to help more people perform early screening for arrhythmia., Areas Covered: The primary objective of this paper is to describe the application of AI methods in the process of arrhythmia detection. Meanwhile, the advantages and limitations of various approaches in different applications are summarized to provide guidance and reference for future research work., Expert Opinion: Machine learning (ML) and deep learning (DL) algorithms can be more effectively employed to handle ECG signal denoising and quality assessment, wave detection and delineation, and arrhythmia classification problems. The DL approach can automatically learn deep representation features and temporal features of the ECG signal for heartbeat or rhythm classification. The application of AI methods for arrhythmia detection systems will significantly relieve the pressure on physicians to analyze ECGs.

In plants, long noncoding RNAs (lncRNAs) regulate disease resistance against fungi and other pathogens. However, the specific mechanism behind this regulation remains unclear. In this study, we identified disease resistance-related lncRNAs as well as their regulating genes and assessed their functions by infection of cotton (Gossypium) chromosome segment substitution lines with Verticillium dahliae. Our results demonstrated that lncRNA7 and its regulating gene Pectin methylesterase inhibitor 13 (GbPMEI13) positively regulated disease resistance via the silencing approach, while ectopic overexpression of GbPMEI13 in Arabidopsis (Arabidopsis thaliana) promoted growth and enhanced resistance to V. dahliae. In contrast, lncRNA2 and its regulating gene Polygalacturonase 12 (GbPG12) negatively regulated resistance to V. dahliae. We further found that fungal disease-related agents, including the pectin-derived oligogalacturonide (OG), could downregulate the expression of lncRNA2 and GbPG12, leading to pectin accumulation. Conversely, OG upregulated the expression of lncRNA7, which encodes a plant peptide phytosulfokine (PSK-α), which was confirmed by lncRNA7 overexpression and Ultra Performance Liquid Chromatography Tandem Mass Spectrometry (UPLC-MS) experiments. We showed that PSK-α promoted 3-Indoleacetic acid (IAA) accumulation and activated GbPMEI13 expression through Auxin Response Factor 5. Since it is an inhibitor of pectin methylesterase (PME), GbPMEI13 promotes pectin methylation and therefore increases the resistance to V. dahliae. Consistently, we also demonstrated that GbPMEI13 inhibits the mycelial growth and spore germination of V. dahliae in vitro. In this study, we demonstrated that lncRNA7, lncRNA2, and their regulating genes modulate cell wall defense against V. dahliae via auxin-mediated signaling, providing a strategy for cotton breeding., (© American Society of Plant Biologists 2022. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Pompano ( Trachinotus ovatus ) is one of the important economic marine fishes in the south coast of China. At present, the research on the basic biology of pompano is relatively weak, which has seriously affected the development of this economic important fish. The liver is an important digestive and metabolic organ of fish which plays an important regulatory role in its growth and development. It is necessary to clarify the effects of sea bream gonadotropin releasing hormone (sbGnRH) on liver physiology and metabolic enzyme activity. The effects of sbGnRH peptides (10 ng/gbw) on the physiological and biochemical indices and metabolic enzyme activities of pompano liver were studied. It was found that after injection of 10 ng/gbw sbGnRH peptides, the contents of albumin, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, glucose, creatine kinase, iron, magnesium, aspartate aminotransferase, alanine aminotransferase and creatinine increased, while of cholesterol and calcium contents decreased. The activities of amylase, lipase, pyruvate kinase, acyl CoA oxidase, superoxide dismutase, phospholipid hydroperoxide glutathione peroxidase, catalase, glucose-6-phosphate dehydrogenase, fatty acid synthase and lipoprotein lipase increased, while the activities of malic enzyme, carnitine acyl, carnitine translocation, acetyl CoA carboxylase and malondialdehyde decreased. Three hours after the injection of different concentrations of sbGnRH peptides (0 and 10 ng/gbw), the transcriptome sequences of the two groups of livers were sequenced. After quality control and removal of some low-quality data, clean reads of 21,283,647、19,427,359、21,873,990、21,732,174、23,660,062 and 21,592,338 were obtained respectively. In this study, 99 genes were screened and identified as differentially expressed genes, including 77 up-regulated genes and 22 down-regulated genes. According to the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) pathway analyses, these pathways and the typical genes involved can be divided into cellular processes, environmental information processing, genetic information processing, diseases, metabolism and organismal systems. The results from this study provide a the oretical basis for studying the effects of sbGnRH on the physiology, biochemistry and metabolic enzyme activities of liver in pompano., Competing Interests: Author JL is employed by Guangdong Havwii agricultural Group Co., LTD. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ren, Liu, Ndandala, Li, Guo, Li and Chen.)

Objective: To explore the mechanism and principles of traditional Chinese medicine (TCM) in the management of radiation pneumonia., Methods: The targets of radiation pneumonia were obtained by screening the GeneCards, OMIM, TTD, DrugBank, and HERB databases, analyzing ADME parameters. In addition, compounds and Chinese herbs that can act on the targets were screened from the TCMSP database. The core target compounds for TCM were used to construct the target-compound, compound-traditional Chinese medicine, and target-compound-traditional Chinese medicine networks. These networks were further used to select the core targets, compounds, and TCM. The binding strength between the core targets and compounds was determined using AutoDock Vina. The trajectory for the molecular dynamics simulation was completed by Desmond version 2020., Results: A total of 55 active targets in radiation pneumonia were identified. Subsequently, 137 candidate compounds and 469 Chinese herbs were matched. Frequency statistics showed that the Chinese herbs that could interfere with radiation pneumonia were mainly bitter, spicy, and sweet, with both cold and warm properties. Moreover, they mainly belonged to liver and lung channels. The core targets included TNF, IL-6, TGF- β 1, and TP53. The most important components were quercetin, resveratrol, and (-)-epigallocatechin-3-gallate. Moreover, the most significant traditional Chinese herbs were Perilla pueraria , ephedra, Lonicerae japonicae , and sea buckthorn. Furthermore, analysis of 222 sets of receptor-ligand docking results suggested that the compounds had good docking activity to their core targets. By combining the docking binding energy, we determined that the chemical compounds had strong binding energy to the targets., Conclusion: Using network pharmacology, we explored the potential mechanism of TCM in the treatment of radiation pneumonia. The general rules for application of TCM in the treatment of radiation pneumonia were summarized. This study provides baseline information for future research on the development of TCM for the management of radiation pneumonia., Competing Interests: All authors declare that there are no conflicts of interest., (Copyright © 2022 Wenchao Dan et al.)

Eucalyptol (1,8-cineole) is a biologically active cyclic monoterpenoid. In a preliminary study, we used gas chromatography-mass spectrometry to detect eucalyptol in the serum and brain tissue of rats after oral administration. However, the absorption characteristics in vivo and pharmacokinetic parameters of eucalyptol have not been published to date. The present study aims to develop and validate a simple, sensitive GC-MS/MS method with quadrupole mass analyzer type for the quantitative analysis of eucalyptol in rat serum and apply it to a pharmacokinetic study. The assay showed linearity of concentration range from 50 to 5,000 pg/ml with a limit of quantitation of 50 pg/ml. Intra- and inter-day precision for eucalyptol were 4.4-13.0 and <15.0%, respectively, and accuracy was within 10% for quality control samples. The recovery and stability results showed that the method was accurate and stable for quantitative analysis. The developed analytical method was successfully applied to a pharmacokinetic study after a single oral administration of eucalyptol in rat subjects. The serum concentration-time profiles indicate that the absorption characteristics of eucalyptol after oral administration are similar to those for intravenous administration., (© 2021 John Wiley & Sons, Ltd.)

Objective: Secretion of glucagon-like peptide 1 (GLP-1) and its effect on target organs were impaired in individuals with obesity. However, its mechanism needs to be further studied. We aim to explore the roles of the receptor of GLP-1 (GLP-1R) involved in high-fat-diet- (HFD-) induced kidney damage improved by emodin., Methods: Male C57bl/6 mice were fed with HFD diet and therapied by emodin. NRK-52E cells were cultured and treated with palmitic acid or low-density lipoprotein cholesterol (LDL-C). Emodin was used to remedy the NRK-52E cell damage. GW9662 was administrated to block the function of peroxisome proliferator-activated receptor γ (PPAR- γ ). GLP-1 in the plasma was measured by ELISA. PPAR- γ and GLP-1R in the kidney and NRK-52E cells were detected by western blotting. The interaction between PPAR- γ protein and GLP-1R promoter regions was observed by chromatin immunoprecipitation (ChIP)., Results: Postprandial GLP-1 levels in plasma, as well as PPAR- γ and GLP-1R, decreased in kidney tissue of HFD mice, while they were reserved by emodin treatment. Although PPAR- γ and GLP-1R were not downregulated by LDL-C, they were suppressed by palmitic acid. Interestingly, GLP-1R mRNA was detected by PCR in the mixture pulled down with PPAR- γ antibody. Additionally, downregulation of PPAR- γ and GLP-1R by palmitic acid was remanded by emodin. Moreover, GW9662, an inhibitor of PPAR- γ , abolished the protective effect of emodin., Conclusion: The kidney damage of HFD mice seems to be alleviated by emodin via the upregulation of GLP-1R in kidney tissue., Competing Interests: All authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Jinlei Liu et al.)

We describe a new type of ultra-small magneto-gold nanoparticle (MGN) with folic acid (FA)-based tumour targeting and multimodal imaging-guided photothermal therapy (PTT) properties that can be used as a theranostic nanoagent. The nanoagent integrates these MGNs-FA with surface modifications, and as expected, is monodisperse, and exhibits small size, strong NIR absorption, photothermal stability, good relaxivity and X-ray absorption coefficient, tumour targeting and excellent biocompatibility. Based on these properties, the nanoagent was successfully tested, both as a photothermal agent for high PTT efficacy and as a multimodality contrast agent for T 1 - & T 2 -MRI/CT/PA imaging in vitro and in vivo . Notably, the results of in vivo theranostic experiments with these MGNs-FA showed that they are highly effective and safe, indicating that they are efficient and promising theranostic agents that permit comprehensive imaging for diagnosis and therapy., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Although traditional Chinese medicine is effective and safe for the treatment of angiogenesis, the in vivo intervention mechanism is diverse, complex, and largely unknown. Therefore, we aimed to explore the active ingredients of traditional Chinese medicine and their mechanisms of action against angiogenesis. Data on angiogenesis-related targets were collected from GeneCards, Therapeutic Target Database, Online Mendelian Inheritance in Man, DrugBank, and DisGeNET. These were matched to related molecular compounds and ingredients in the traditional Chinese medicine system pharmacology platform. The data were integrated and based on the condition of degree > 1, and relevant literature, target-compound, compound-medicine, and target-compound-medicine networks were constructed using Cytoscape. Molecular docking was used to predict the predominant binding combination of core targets and components. We obtained 79 targets for angiogenesis; 41 targets were matched to 3839 compounds, of which 110 compounds were selected owing to their high correlation with angiogenesis. Fifty-five combinations in the network were obtained by molecular docking, among which PTGS2-astragalin (-9.18 kcal/mol), KDR-astragalin (-7.94 kcal/mol), PTGS2-quercetin (-7.41 kcal/mol), and PTGS2-myricetin (-7.21 kcal/mol) were top. These results indicated that the selected potential core compounds have good binding activity with the core targets. Eighty new combinations were obtained from the network, and the top combinations based on affinity were KDR-beta-carotene (-10.13 kcal/mol), MMP9-beta-sitosterol (-8.04 kcal/mol), MMP9-astragalin (-7.82 kcal/mol), and MMP9-diosgenin (-7.51 kcal/mol). The core targets included PTGS2, KDR, VEGFA, and MMP9. The essential components identified were astragalin, kaempferol, myricetin, quercetin, and β -sitosterol. The crucial Chinese medicines identified included Polygoni Cuspidati Rhizoma et Radix, Morus alba Root Bark, and Forsythiae Fructus. By systematically analysing the ingredients of traditional Chinese medicine and their targets, it is possible to determine their potential mechanisms of action against pathological angiogenesis. Our study provides a basis for further research and the development of new therapeutics for angiogenesis., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Wingyan Yun et al.)

In this study, the role of traditional Chinese medicine (TCM) in relieving epidermal growth factor receptor-tyrosine kinase inhibitor- (EGFR-TKI-) associated diarrhea was discussed by network pharmacology and data mining. Prediction of drug targets by introducing the EGFR-TKI molecular structures into the SwissTargetPrediction platform and diarrhea-related targets in the DrugBank, GeneCards, DisGeNET, and OMIM databases were obtained. Compounds in the drug-disease target intersection were screened by absorption, distribution, metabolism, and excretion parameters and Lipinski's rule in Traditional Chinese Medicine Systems Pharmacology. TCM-containing compounds were selected, and information on the property, taste, and meridian tropism of these TCMs was summarized and analyzed. A target-compound-TCM network diagram was constructed, and core targets, compounds, and TCMs were selected. The core targets and components were docked by AutoDock Vina (Version 1.1.2) to explore the target combinations of related compounds and evaluate the docking activity of related targets and compounds. Twenty-three potential therapeutic TCM targets for the treatment of EGFR-TKI-related diarrhea were obtained. There were 339 compounds acting on potential therapeutic targets, involving a total of 402 TCMs. The results of molecular docking showed good binding between the core targets and compounds, and the binding between the core targets and compounds was similar to that of the core target and the recommended drug loperamide. TCMs have multitarget characteristics and are present in a variety of compounds used for relieving EGFR-TKI-associated diarrhea. Antitumor activity and the efficacy of alleviating diarrhea are the pharmacological basis of combining TCMs with EGFR-TKI in the treatment of non-small-cell lung cancer. The core targets, compounds, and TCMs can provide data to support experimental and clinical studies on the relief of EGFR-TKI-associated diarrhea in the future., Competing Interests: All authors declare no conflicts of interest., (Copyright © 2021 Shuaihang Hu et al.)

Background: Long non-coding RNA (lncRNA) GAS5 is associated with hypoxia-induced diseases whereas hypoxia-inducible factor-1α (HIF-1α) plays an important role in hypoxic injury of cells. The current study explores the regulatory functions of GAS5/HIF-1α which co-play in anoxic injury among rat cardiomyocytes H9C2 cells., Methods: Hypoxia in vitro model was established through anoxic incubation while normal culture of H9C2 cells was considered as control. The expression levels of GAS5 and HIF-1α were quantified through RT-qPCR. CCK-8 was applied to determine cell viability. Cell apoptosis rate was calculated using flow cytometry whereas inflammatory cytokines were detected using ELISA method. The impact of downregulating GAS5 or HIF-1α or both upon hypoxic cells was assessed on the basis of changes in cell viability, apoptosis, and inflammatory response. The activity of JAK1/STAT3 signaling was evaluated through RT-qPCR for mRNA expression. AG490 was introduced to inactivate JAK1/STAT3 pathway and to unveil the impact of JAK1/STAT3 signaling on GAS5/HIF-1α and cell viability, apoptosis and inflammation in hypoxic cells., Results: The results infer that hypoxia suppressed cell viability, promoted inflammation and apoptosis among H9C2 cells. GAS5 or HIF-1α recorded higher expression in hypoxia-induced cells whereas the cell viability got restored with reduction in inflammation and apoptosis. The downregulation of HIF-1α enhanced the protective effect of knocking down GAS5 in hypoxia H9C2 cells. JAK1/STAT3 signaling pathway got activated in hypoxic cells and was regulated by GAS5 and HIF-1α. The inhibition of signaling pathway increased the cell viability but it decreased both inflammation and apoptosis., Conclusions: GAS5 and HIF-1α could regulate hypoxic injury in H9C2 cells through JAK1/STAT3 signaling pathway. This scenario suggests that the inhibitors of GAS5 and HIF-1α may synergize with AG-490 to protect myocardial cells from hypoxic injury., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/cdt-20-773). The authors have no conflicts of interest to declare., (2021 Cardiovascular Diagnosis and Therapy. All rights reserved.)

The novel strong field autoionization (SFAI) dynamics is identified and investigated by channel-resolved angular streaking measurements of two electrons and two ions for the double-ionized CO. Comparing with the laser-assisted autoionization calculations, we demonstrate the electrons from SFAI are generated from the field-induced decay of the autoionizing state with a following acceleration in the laser fields. The energy-dependent photoelectron angular distributions further reveal that the subcycle ac-Stark effect modulates the lifetime of the autoionizing state and controls the emission of SFAI electrons in molecular frame. Our results pave the way to control the emission of resonant high-harmonic generation and trace the electron-electron correlation and electron-nuclear coupling by strong laser fields. The lifetime modulation of quantum systems in the strong laser field has great potential for quantum manipulation of chemical reactions and beyond.

Methods: The targets of antineoplastic drugs with cardiotoxicity were obtained from the National Center for Biotechnology Information (NCBI) database, China national knowledge infrastructure (CNKI) database, and Swiss Target Prediction platform. Then, the cardiotoxicity-related targets were derived from the Gene Cards, Disgenet, OMIM, and DrugBank databases, as well as the drug of current clinical guidelines. The targets both in these two sets were regarded as potential targets to alleviate ADIC. Then, candidate compounds and herbs were matched via Traditional Chinese Medicine Systems Pharmacology (TCMSP) platform. Cytoscape3.7.1 was used to set up the target-compound-herb network. Molecular docking between core targets and compounds was performed with AutodockVina1.1.2. The rules of herbs were summarized by analyzing their property, flavor, and channel tropism., Results: Twenty-one potential targets, 332 candidate compounds, and 400 kinds of herbs were obtained. Five core targets including potassium voltage-gated channel subfamily H member 2 (KCNH2), cyclin-dependent kinase 1 (CDK1), matrix metalloproteinase 2 (MMP2), mitogen-activated protein kinase1 (MAPK1), and tumor protein p53 (TP53) and 29 core compounds (beta-sitosterol, quercetin, kaempferol, etc.) were collected. Five core herbs (Yanhusuo, Gouteng, Huangbai, Lianqiao, and Gancao) were identified. Also, the TCM against ADIC were mainly bitter and acrid in taste, warm in property, and distributed to the liver and lung meridians., Conclusion: TCM against ADIC has great potential. Our study provides a new method and ideas for clinical applications of integrated Chinese and western medicine in treating ADIC., Competing Interests: All authors declare that there are no conflicts of interest., (Copyright © 2020 Wenchao Dan et al.)

Respiratory burst oxidase homologs (Rbohs) play a predominant role in reactive oxygen species (ROS) production, which is crucial in plant growth, differentiation, as well as their responses to biotic and abiotic stresses. To date, however, there is little knowledge about the function of cotton Rboh genes. Here, we identified a total of 87 Rbohs from five sequenced Gossypium species (the diploids Gossypium arboreum , Gossypium raimondii , and Gossypium australe , and the allotetraploids Gossypium hirsutum and Gossypium barbadense ) via BLAST searching their genomes. Phylogenetic analysis of the putative 87 cotton Rbohs revealed that they were divided into seven clades. All members within the same clade are generally similar to each other in terms of gene structure and conserved domain arrangement. In G. barbadense , the expression levels of GbRbohs in the CladeD were induced in response to a fungal pathogen and to hormones (i.e., jasmonic acid and abscisic acid), based upon which the main functional member in CladeD was discerned to be GbRboh5/18. Further functional and physiological analyses showed that the knock-down of GbRboh5/18 expression attenuates plant resistance to Verticillium dahliae infection. Combined with the molecular and biochemical analyses, we found less ROS accumulation in GbRboh5/18-VIGS plants than in control plants after V. dahliae infection. Overexpression of GbRboh5/18 in G. barbadense resulted in more ROS accumulation than in control plants. These results suggest that GbRboh5/18 enhances the cotton plants' resistance against V. dahliae by elevating the levels of ROS accumulation. By integrating phylogenetic, molecular, and biochemical approaches, this comprehensive study provides a detailed overview of the number, phylogeny, and evolution of the Rboh gene family from five sequenced Gossypium species, as well as elucidating the function of GbRboh5/18 for plant resistance against V. dahliae . This study sheds fresh light on the molecular evolutionary properties and function of Rboh genes in cotton, and provides a reference for improving cotton's responses to the pathogen V. dahliae ., (Copyright © 2020 Chang, Li, Shi, Geng, Geng, Liu, Zhang and Cai.)

In this work, one kind of biocompatible and all-in-one dual-modal nanoprobe, based on Au nanoparticles and NIR emissive semiconducting fluorescence polymers, was developed by the one-step solvent-mediated self-assembly method for in vivo X-ray computed tomography (CT) and fluorescence bioimaging for the first time. After preparation, a series of comprehensive evaluations were performed, and the nanoprobe exhibited smart size and modification, good compatibility, inducement of autophagy, long blood circulation, unconspicuous in vivo toxicity, and excellent fluorescence/CT imaging effects. Overall, the studies in this work assuredly indicate that the synthesized Au@FP nanoparticles as a noninvasive contrast agent is suitable for in vivo fluorescence/X-ray CT bimodality biomedical imaging and diagnosis.

A novel sandwich-assay electrochemical immunosensor for simultaneous determination of autophagic biomarkers was introduced for the first time, the gold-reduced grapheme oxide nanocomposite (Au/r-GO) set as a good conductive platform with super high specific area, and provided more binding sites for the both antibodies of Beclin-1 and LC3B-II. While Au nanocages (AuNCs) served as good conductive platform to encapsulate a large amount of redox probe and secondary antibodies for signal amplification, due to the abundant reactive oxygen functional groups on its surface. Through differential pulse voltammetry (DPV) measurements, two separate signals can be detected directly in a single run, which represent the existence of Belin-1 and LC3B-II. Under optimized conditions, the electrochemical immunosensor exhibited good sensitivity and selectivity for the simultaneous determination of Beclin-1 and LC3B-II with linear ranges of 0.1-100 ng/mL. The detection limit for Beclin-1 and LC3B-II is 0.02 and 0.03 ng/mL respectively. This method was also applied for the analysis of Beclin-1 and LC3B-II levels in experimental cellular protein lysates, and the results were in good agreement with those of enzyme linked immunosorbent assay. This approach gives a promising simple, sensitive and quantitative strategy for the detection of autophagy.

Background: Traditional activity recognition solutions are not widely applicable due to a high cost and inconvenience to use with numerous sensors. This paper aims to automatically recognize physical activity with the help of the built-in sensors of the widespread smartphone without any limitation of firm attachment to the human body., Methods: By introducing a method to judge whether the phone is in a pocket, we investigated the data collected from six positions of seven subjects, chose five signals that are insensitive to orientation for activity classification. Decision trees (J48), Naive Bayes and Sequential minimal optimization (SMO) were employed to recognize five activities: static, walking, running, walking upstairs and walking downstairs., Results: The experimental results based on 8,097 activity data demonstrated that the J48 classifier produced the best performance with an average recognition accuracy of 89.6% during the three classifiers, and thus would serve as the optimal online classifier., Conclusions: The utilization of the built-in sensors of the smartphone to recognize typical physical activities without any limitation of firm attachment is feasible.

The tranSMART knowledge management and high-content analysis platform is a flexible software framework featuring novel research capabilities. It enables analysis of integrated data for the purposes of hypothesis generation, hypothesis validation, and cohort discovery in translational research. tranSMART bridges the prolific world of basic science and clinical practice data at the point of care by merging multiple types of data from disparate sources into a common environment. The application supports data harmonization and integration with analytical pipelines. The application code was released into the open source community in January 2012, with 32 instances in operation. tranSMART's extensible data model and corresponding data integration processes, rapid data analysis features, and open source nature make it an indispensable tool in translational or clinical research.

A novel, efficient, and accurate fingerprinting method using high performance liquid chromatography-photodiode array detection has been developed and optimized for the investigation and demonstration of the variance in chemical properties among Siraitia grosvenorii fruits from different origins. The effects of growth stages, cultivated varieties, collection locations, and fruit portions of the herb on chromatographic fingerprints were examined. Eleven compounds were identified on chromatograms by comparing the retention time and UV spectrum of each peak separately with those of external references. The results revealed that chromatographic fingerprints, combining similarity or hierarchical clustering analysis along with reference compounds, could efficiently identify and distinguish S. grosvenorii fruits from different sources, which provided helpful clues for studying the plants' secondary metabolites and benefitted quality control.

A method for the determination of esculeoside A in Lycopersicon esculentum MILL by high performance liquid chromatography (HPLC) with evaporative light scattering detection (ELSD) was established. The results showed that esculeoside A had good linearity in the range of 0.61-3.05 mg with the correlation coefficient of 0. 999 5. The average recoveries were 97.9%-104.8% with the relative standard deviations (RSD) < or = 4.14% (n=5). The method is simple, sensitive and suitable for the analysis of esculeoside A and quality control for the raw material and extract of Lycopersicon esculentum MILL.

Siraitia grosvenorii, a traditional Chinese fruit, belongs to the family Cucurbitaceae and has been used as a pulmonary demulcent and emollient for the treatment of dry cough, sore throat, dire thirst, and constipation in folk medicine. A high performance liquid chromatographic method was developed for simultaneous determining the contents of mogroside V, mogroside IV A, mogroside III, 11-oxomogroside III, mogroside II E and 11-oxomogroside II E in Siraitia grosvenorii fruits. The chromatographic analysis was carried out on a ZORBAX SB-C18 column (150 mm x 4.6 mm, 5 microm). The mobile phase was water (A) and acetonitrile (B) with gradient elution (0-3 min, 20% B - 30% B; 3-8 min, 30% B - 35% B; 8-9 min, 35% B). The flow rate was maintained at 0. 8 mL/min. The detection wavelength was set at 203 nm and the column temperature was controlled at 30 degrees C. The sample injection volume was 10 microL. The calibration curves were linear over the ranges of 0.04 - 1.0 mg/mL, 0.011 - 0.68 mg/mL, 0.010 - 0.80 mg/mL, 0.0097 - 0.58 mg/mL, 0.025 - 1.0 mg/mL and 0.013 - 0.76 mg/mL (r > 0.999 1) for the above cucurbitane triterpene glycosides, respectively. The average recoveries were 99. 65% for mogroside V , 101.6% for mogroside IV A, 97. 05% for mogroside m, 103. 1% for 11-oxomogroside I, 99. 25% for mogroside II E, and 103.0% for 11-oxomogroside II E, with the relative standard deviations of 0.83%, 3.1%, 1.9%, 3.3%, 0.59% and 2.0%, respectively. This simple, rapid and accurate method is suitable for quality control and determination of raw materials and products of Siraitia grosvenorii fruits.

Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.

Studies on the constituents of the unripe fruits of Siraitia grosvenori led to the isolation of three new cucurbitane triterpene glycosides, 11-oxomogroside III (10), 11-dehydroxymogroside III (11), and 11-oxomogroside IV A (12). Their structures were determined on the basis of detailed analyses of 1D, 2D-NMR spectroscopic methods. All of the compounds isolated from the unripe fruits of S. grosvenori were tested for cytotoxic activities against tumor cells, HCT-116 and SMMC-7721.

Here we report a high-quality draft genome sequence of the domestic dog (Canis familiaris), together with a dense map of single nucleotide polymorphisms (SNPs) across breeds. The dog is of particular interest because it provides important evolutionary information and because existing breeds show great phenotypic diversity for morphological, physiological and behavioural traits. We use sequence comparison with the primate and rodent lineages to shed light on the structure and evolution of genomes and genes. Notably, the majority of the most highly conserved non-coding sequences in mammalian genomes are clustered near a small subset of genes with important roles in development. Analysis of SNPs reveals long-range haplotypes across the entire dog genome, and defines the nature of genetic diversity within and across breeds. The current SNP map now makes it possible for genome-wide association studies to identify genes responsible for diseases and traits, with important consequences for human and companion animal health.