In this task, you're given a paragraph from the research paper and your task is to generate a suitable title for the research paper based on the given paper. Under 100 words is a good title length.
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Question: Main point: Hydroxychloroquine was found to be more potent than chloroquine at inhibiting SARS-CoV-2 in vitro. Hydroxychloroquine sulfate 400 mg given twice daily for 1 day, followed by 200 mg twice daily for 4 more days is recommended to treat SARS-CoV-2 infection. Abstract Background. The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) first broke out in Wuhan (China) and subsequently spread worldwide. Chloroquine has been sporadically used in treating SARS-CoV-2 infection. Hydroxychloroquine shares the same mechanism of action as chloroquine, but its more tolerable safety profile makes it the preferred drug to treat malaria and autoimmune conditions. We propose that the immunomodulatory effect of hydroxychloroquine also may be useful in controlling the cytokine storm that occurs late-phase in critically ill SARS-CoV-2 infected patients. Currently, there is no evidence to support the use of hydroxychloroquine in SARS-CoV-2 infection. Methods. The pharmacological activity of chloroquine and hydroxychloroquine was tested using SARS-CoV-2 infected Vero cells. Physiologically-based pharmacokinetic models (PBPK) were implemented for both drugs separately by integrating their in vitro data. Using the PBPK models, hydroxychloroquine concentrations in lung fluid were simulated under 5 different dosing regimens to explore the most effective regimen whilst considering the drug's safety profile. Results. Hydroxychloroquine (EC50=0.72 μM) was found to be more potent than chloroquine (EC50=5.47 μM) in vitro. Based on PBPK models results, a loading dose of 400 mg twice daily of hydroxychloroquine sulfate given orally, followed by a maintenance dose of 200 mg given twice daily for 4 days is recommended for SARS-CoV-2 infection, as it reached three times the potency of chloroquine phosphate when given 500 mg twice daily 5 days in advance. Hydroxychloroquine was found to be more potent than chloroquine to 4 / 25 inhibit SARS-CoV-2 in vitro.

Answer: In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)


Question: Bio-fluids contain various circulating cell-free RNA transcripts (ccfRNAs). The composition of 20 these ccfRNAs varies between bio-fluids and constitute tantalizing biomarker candidates for 21 several pathologies. ccfRNAs have also been demonstrated as mediators of cellular 22 communication, yet little is known about their function in physiological and developmental 23 settings and most works are limited to in-vitro studies. Here, we have developed iTAG-RNA, a 24 novel method for the unbiased tagging of RNA transcripts in mice in-vivo. We used this method 25 to isolate hepatocytes and kidney proximal epithelial cells-specific transcriptional response to a 26 dietary challenge without interfering with the tissue architecture, and to identify multiple 27 hepatocyte-secreted ccfRNAs in plasma. We also identified transfer of these hepatic derived 28 ccfRNAs to adipose tissue, where they likely serve as a buffering mechanism to maintain 29 cholesterol and lipid homeostasis. Our findings directly demonstrate in-vivo transfer of RNAs 30 between tissues and highlight its implications for endocrine signaling and homeostasis. Little is known about the biological function of circulating cell-free RNAs (ccfRNA). Found to be 34 associated with exosomes, lipoproteins, ribonucleoproteins and more, these transcripts can be 35 isolated and sequenced from multiple bio-fluids such as plasma, lymph, cerebral fluids, breast milk 36 and more [1, 2]. ccfRNAs are directly implicated in the development of several pathologies 37 including cancer and obesity [3][4][5] and are intensively studied as disease biomarkers [6, 7]. Despite 38 this, the role they play in physiological and developmental settings and in mediating cell-to-cell 39 communication remains largely unknown. In-vitro, a growing number of works demonstrate the 40 relevance of RNA based cellular communication [8][9][10][11], however in-vivo evidence is still limited. This discrepancy is partly due to the difficulties posed to tracking ccfRNAs from transcriptional 42 source to potential sites of action in-vivo. Indeed the tools available to study ccfRNAs in 43 physiological settings are limited and very few studies attempt to tackle this problem directly. One work found evidence to suggest that the majority of circulating miRNAs originate in adipose 45 tissue and that some of the adipose derived miRNAs may play a role in the regulation of liver 46 Fgf21 levels [12]. However, this work focuses on miRNA and does not directly demonstrate 47 transfer of RNAs between tissues nor directly identify adipose secreted RNAs. Transfer of miRNAs was also demonstrated between epithelial cells of the caput epididymis to 49 maturing spermatozoa, leading to a shift in sperm RNA content during its maturation [13]. This 50 study made use of 4-thiouracil-tagging (TU-tagging) [14] combined with SLAM-Seq [15] to 51 demonstrate loading of miRNAs transcribed in caput epididymis into maturing spermatozoa. TU-52 tagging entails cell-type specific expression of uracil phosphoribosyltransferase (UPRT) and 53 administration of 4-thiouracil, with the assumption that only cells expressing UPRT would 54 incorporate 4-thiouracil into transcribing RNA. Thio-RNA can then be purified and used for 55 downstream gene expression analyses, or alternatively combined with SLAM-Seq to identify 56 labeled transcripts. TU-tagging has proven useful in several additional systems [14, 16, 17], 57 however, given endogenous [18] and alternative [19] pathways for uracil incorporation, the 58 labeling specificity in this method remains unclear. In addition, as is demonstrated in Herzog et. 59 al [15] and by Sharma et. al [13], labeling with TU-tagging of PolI and PolIII transcripts is 60 inefficient, rendering tRNAs and ribosomal transcripts unlabeled. Indeed there are only a limited number of techniques enabling in-vivo targeted labeling of RNAs. 62 In addition to TU-tagging, 5-ethynylcytosine-tagging (EC-tagging) [20] is a new method, which 63 utilizes cell-type specific co-expression of cytosine deaminase (CD) with UPRT to achieve RNA 64 labeling with 5-ethynyluridine (5EU) following administration of 5-ethynylcytosine. Both TU and 65 EC tagging use cre-recombination to express the relevant enzymes in a tissue specific manner and 66 stochastic expression from the cre-promoter may lead to unwanted expression of the enzymes in 67 different tissues [21]. Finally, one recently developed method called Mime-seq allows for cell type 68 specific labeling of microRNA [22]. In this method, tissue specific expression of a plant derived 69 methyltransferase mediates a 3′-terminal 2′-O-methylation of microRNAs that, when combined 70 with a methylation dependent library construction, allows for sequencing of tissue specific 71 microRNAs. Mime-seq allows labeling of miRNAs alone leaving other RNA biotypes unlabeled. 72 Given the need for a technique that allows for a Cre-independent and unbiased labeling of total 73 RNA transcription in-vivo, we developed iTAG-RNA [For In-vivo Targeted Tagging of RNA]. 74 This method incorporates mouse genetics with a novel uridine analog and an established RNA 75 labeling chemistry to allow tagging of total RNA in target cells in-vivo. Using iTAG-RNA we are 76 able to identify transcriptional re-programming of hepatocytes in-vivo following an acute high fat 77 diet stress and to enrich for and identify hepatocyte derived plasma ccfRNAs. Moreover, we are 78 able to identify RNA-based liver-to-adipose RNA transfer. These liver derived ccfRNAs include 79 variable coding and non-coding RNAs such as miRNAs and tRNAs. Among the miRNAs 80 transferred from liver to adipose tissue we find mir-33, mir-10b and mir130a, which target major 81 regulators of cholesterol and lipid efflux and bio-synthesis such as Srebf1 [23], Abca1 [23, 24], 82 Ppara [25] and Pparg [26] respectively. 83 Our study demonstrates for the first time an unbiased technique that allows labelling, tracking and 84 quantification of variable types of ccfRNAs from their transcriptional source to downstream 85 tissues, in which they can potentially act to regulate expression of target genes. We demonstrate 86 RNA-based liver-to-adipose transfer of a myriad of RNA transcripts and their response to an 87 environmental challenge. The continued identification and characterization of RNA based 88 signaling in-vivo is imperative for the understanding of developmental, physiological and 89 pathological processes, and can aid in the future development of relevant disease biomarkers. 90 91 Results . CC-BY-NC-ND 4.0 International license is made available under a

Answer: In-vivo targeted tagging of RNA isolates cell specific transcriptional responses to environmental stimuli and identifies liver-to-adipose RNA transfer 2 3


Question: Context: Coptidis rhizome (CR), also known as Huanglian in Chinese, is the rhizome of Coptis chinensis Franch., C. deltoidea C.Y. Cheng et Hsiao, or C. teeta Wall (Ranunculaceae). It has been widely used to treat bacillary dysentery, diabetes, pertussis, sore throat, aphtha, and eczema in China. Objectives: The present paper reviews the latest advances of CR, focusing on the botany, phytochemistry, traditional usages, pharmacokinetics, pharmacology and toxicology of CR and its future perspectives. Methods: Studies from 1985 to 2018 were reviewed from books; PhD. and MSc. dissertations; the state and local drug standards; PubMed; CNKI; Scopus; the Web of Science; and Google Scholar using the keywords Coptis, Coptidis Rhizoma, Huanglian, and goldthread. Results: Currently, 128 chemical constituents have been isolated and identified from CR. Alkaloids are the characteristic components, together with organic acids, coumarins, phenylpropanoids and quinones. The extracts/compounds isolated from CR cover a wide pharmacological spectrum, including antibacterial, antivirus, antifungal, antidiabetic, anticancer and cardioprotective effects. Berberine is the most important active constituent and the primary toxic component of CR. Conclusions: As an important herbal medicine in Chinese medicine, CR has the potential to treat various diseases. However, further research should be undertaken to investigate the clinical effects, toxic constituents, target organs and pharmacokinetics, and to establish criteria for quality control, for CR and its related medications. In addition, the active constituents, other than alkaloids, in both raw and processed products of CR should be investigated. ARTICLE HISTORY

Answer:
Coptidis Rhizoma: a comprehensive review of its traditional uses, botany, phytochemistry, pharmacology and toxicology