关键词： hepatocellular carcinoma   liver cancer   phytochemicals   natural compounds   metastasis  

摘要： Simple Summary: Hepatocellular carcinoma (HCC) is globally ranked as the sixth most diagnosed cancer, and the second most deadly cancer. To worsen matters, there are only limited therapeutic options currently available;therefore, it is necessary to find a reservoir from which new HCC treatments may be acquired. The field of phytomedicine may be the solution to this problem, as it offers an abundance of plant-derived molecules, which show capabilities of being effective against HCC proliferation, invasion, migration, and metastasis. In our review, we collect and analyze current evidence regarding these promising phytochemical effects on HCC, and delve into their potential as future chemotherapies. Additionally, information on the signaling behind these numerous phytochemicals is provided, in an attempt to understand their mechanisms. This review makes accessible the current body of knowledge pertaining to phytochemicals as HCC treatments, in order to serve as a reference and inspiration for further research into this subject. Hepatocellular carcinoma (HCC) is the most abundant form of liver cancer. It accounts for 75-85% of liver cancer cases and, though it ranks globally as the sixth most common cancer, it ranks second in cancer-related mortality. Deaths from HCC are usually due to metastatic spread of the cancer. Unfortunately, there are many challenges and limitations with the latest HCC therapies and medications, making it difficult for patients to receive life-prolonging care. As there is clearly a high demand for alternative therapy options for HCC, it is prudent to turn to plants for the solution, as their phytochemicals have long been used and revered for their many medicinal purposes. This review explores the promising phytochemical compounds identified from pre-clinical and clinical trials being used either independently or in conjunction with already existing cancer therapy treatments. The phytochemicals discussed in this review were classified into severa

关键词： cholesterol   dispatched1   hedgehog   morphogen   patched1   scube2   shedding  

摘要： Two posttranslational lipid modifications present on all Hedgehog (Hh) morphogens-an N-terminal palmitate and a C-terminal cholesterol-are established and essential regulators of Hh biofunction. Yet, for several decades, the question of exactly how both lipids contribute to Hh signaling remained obscure. Recently, cryogenic electron microscopy revealed different modes by which one or both lipids may contribute directly to Hh binding and signaling to its receptor Patched1 (Ptc). Some of these modes demand that the established release factor Dispatched1 (Disp) extracts dual-lipidated Hh from the cell surface, and that another known upstream signaling modulator called Scube2 chaperones the dual-lipidated morphogen to Ptc. By mechanistically and biochemically aligning this concept with established in vivo and recent in vitro findings, this reflection identifies remaining questions in lipidated Hh transport and evaluates additional mechanisms of Disp- and Scube2-regulated release of a second bioactive Hh fraction that has one or both lipids removed.

关键词： matrix factorization   association prediction   epithelial-mesenchymal transition  

摘要： Motivation: The epithelial-mesenchymal transition (EMT) is a cellular-developmental process activated during tumor metastasis. Transcriptional regulatory networks controlling EMT are well studied;however, alternative RNA splicing also plays a critical regulatory role during this process. Unfortunately, a comprehensive understanding of alternative splicing (AS) and the RNA-binding proteins (RBPs) that regulate it during EMT remains largely unknown. Therefore, a great need exists to develop effective computational methods for predicting associations of RBPs and AS events. Dramatically increasing data sources that have direct and indirect information associated with RBPs and AS events have provided an ideal platform for inferring these associations. Results: In this study, we propose a novel method for RBP-AS target prediction based on weighted data fusion with sparse matrix tri-factorization (WDFSMF in short) that simultaneously decomposes heterogeneous data source matrices into low-rank matrices to reveal hidden associations. WDFSMF can select and integrate data sources by assigning different weights to those sources, and these weights can be assigned automatically. In addition, WDFSMF can identify significant RBP complexes regulating AS events and eliminate noise and outliers from the data. Our proposed method achieves an area under the receiver operating characteristic curve (AUC) of , which shows that WDFSMF can effectively predict RBP-AS event associations with higher accuracy compared with previous methods. Furthermore, this study identifies significant RBPs as complexes for AS events during EMT and provides solid ground for further investigation into RNA regulation during EMT and metastasis. WDFSMF is a general data fusion framework, and as such it can also be adapted to predict associations between other biological entities.

关键词： Guinea worm   Reproductive number   Intervention   Paratenic hosts   Domestic dogs  

摘要： Guinea worm (Dracunculus medinensis) has exerted a high human health burden in parts of Africa. Complete eradication of Guinea worm disease (dracunculiasis) may be delayed by the circulation of the parasite in domestic dogs. As with humans, dogs acquire the parasite by directly ingesting infected copepods, and recent evidence suggests that consuming frogs that ingested infected copepods as tadpoles may be a viable transmission route (paratenic route). To understand the relative contributions of direct and paratenic transmission routes, we developed a mathematical model that describes transmission of Guinea worm between dogs, copepods and frogs. We explored how the parasite basic reproductive number (R-0) depends on parameters amenable to actionable interventions under three scenarios: frogs/tadpoles do not consume copepods;tadpoles consume copepods but frogs do not contribute to transmission;and frogs are paratenic hosts. We found a non-monotonic relationship between the number of dogs and R-0. Generally, frogs can contribute to disease control by removing infected copepods from the waterbody even when paratenic transmission can occur. However, paratenic transmission could play an important role in maintaining the parasite when direct transmission is reduced by interventions focused on reducing copepod ingestion by dogs. Together, these suggest that the most effective intervention strategies may be those which focus on the reduction of copepods, as this reduces outbreak potential irrespective of the importance of the paratenic route. (C) 2021 Australian Society for Parasitology. Published by Elsevier Ltd. All rights reserved.

关键词： Deep eutectic solvents   Nanofluid   CNT   Freezing point   Thermal degradation   Vapour pressure   Weight loss   Activation energy  

摘要： We investigated Deep eutectic solvents (DES) in this study as a potential substitute for conventional heat transfer fluids. Methyl-triphenylphosphonium-bromide (MTPB) and choline chloride (ChCl) as the hydrogen bond acceptors (HBAs), and ethylene glycol (EG) and triethylene glycol (TEG) as the hydrogen bond donors (HBDs), were used to form DESs. The molar ratio of HBA to HBD was varied between 1:3 and 1:5 to produce a total of 11 DESs. In each of these DESs, carbon nanotube (CNT) was added and dispersed at a constant concentration of 0.04 wt% to form DES-CNT-nanofluids. There was no surfactant added for stabilisation. The nano fluids were homogenised using an ultrasonic bath at 37 kHz for 4 h at room temperature. The freezing points of DES-CNT-nanofluids were analysed using differential scanning calorimetry while their thermal degradations, vapour pressures and weight losses were analysed using a thermogravimetric analyser. DES-CNTnanofluids were found to have lower freezing points (down to-117.90 degrees C) as compared to EG and TEG, valued at-13.40 and-4.0 degrees C, respectively. The addition of HBA, such as MTPB and ChCl to form DESs, was found to increase the thermal stability of EG and TEG from 105 to 128 degrees C to 130 and 220 degrees C, respectively. Furthermore, the vapour pressures of DESs derived from EG and TEG, independently, were lower than that of pure EG and TEG by about 73% and 45%, correspondingly. The dispersion of CNT in DESs enhanced their thermal stabilities, activation energies and their kinetic parameters. The degradation reaction order was also determined through Friedman and Avrami models, respectively. Thus, DES has been proven to be a potential substitute for conventional heat transfer fluids due to its improved properties. (c) 2021 Taiwan Institute of Chemical Engineers. Published by Elsevier B.V. All rights reserved.

关键词： scalarane sesterterpenoids   synthesis   natural terpenoids   X-ray analysis  

摘要： Scalarane sesterterpenoids emerged as interesting bioactive natural products which were isolated extensively from marine sponges and shell-less mollusks. Some representatives were also reported recently from superior plants. Many scalarane sesterterpenoids displayed a wide spectrum of valuable properties, such as antifeedant, antimicrobial, antifungal, antitubercular, antitumor, anti-HIV properties, cytotoxicity and stimulation of nerve growth factor synthesis, as well as anti-inflammatory activity. Due to their important biological properties, many efforts have been undertaken towards the chemical synthesis of natural scalaranes. The main synthetic challenges are connected to their complex polycyclic framework, chiral centers and different functional groups, in particular the oxygenated functional groups at the C-12 position, which are prerequisites of the biological activity of many investigated scalaranes. The current work addresses this problem and the synthesis of 17-oxo-20-norscalaran-12 alpha,19-O-lactone is described. It was performed via the 12 alpha-hydroxy-ent-isocopal-13(14)-en-15-al obtained from (-)-sclareol as an accessible starting material. The tetracyclic lactone framework was built following an addition strategy, which includes the intramolecular Michael addition of a diterpenic acetoacetic ester and an intramolecular aldol condensation reaction as key synthetic steps. The structure and stereochemistry of the target compound have been proven by X-Ray diffraction method.

关键词： COVID-19   Multisystem inflammatory syndrome in children (MIS-C)   Cardiac   Myocarditis   Coronary artery aneurysms   Arrhythmia  

摘要： Purpose of Review To review the spectrum of cardiac manifestations and treatments of multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus disease 2019 (COVID-19). Recent Findings Studies demonstrate that up to 80% of children with MIS-C may have cardiac involvement on a spectrum of severity. Cardiac manifestations include myocarditis, coronary artery aneurysms, conduction abnormalities, and arrhythmias. Current treatments, including inotropic support, immunomodulatory therapy, and anti-coagulation, have been effective at resolving these cardiac findings in the majority of patients. COVID-19 can also cause myocarditis in the acute stage of illness and recent descriptions of COVID-19 vaccine myocarditis have occurred. Cardiac manifestations are common in MIS-C and should be assessed for at presentation and during the clinical course as indicated.

关键词： Cannabis sativa L.   alternative splicing   non-coding RNAs   gene expression and regulation  

摘要： It is of significance to mine the structural genes related to the biosynthetic pathway of fatty acid (FA) and cellulose as well as explore the regulatory mechanism of alternative splicing (AS), microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) in the biosynthesis of cannabinoids, FA and cellulose, which would enhance the knowledge of gene expression and regulation at post-transcriptional level in Cannabis sativa L. In this study, transcriptome, small RNA and degradome libraries of hemp 'Yunma No.1' were established, and comprehensive analysis was performed. As a result, a total of 154, 32 and 331 transcripts encoding key enzymes involved in the biosynthesis of cannabinoids, FA and cellulose were predicted, respectively, among which AS occurred in 368 transcripts. Moreover, 183 conserved miRNAs, 380 C. sativa-specific miRNAs and 7783 lncRNAs were predicted. Among them, 70 miRNAs and 17 lncRNAs potentially targeted 13 and 17 transcripts, respectively, encoding key enzymes or transporters involved in the biosynthesis of cannabinoids, cellulose or FA. Finally, the crosstalk between AS and miRNAs or lncRNAs involved in cannabinoids and cellulose was also predicted. In summary, all these results provided insights into the complicated network of gene expression and regulation in C. sativa.

关键词： Medicine/Public Health   general   Pediatrics   Pediatric Surgery