Specific binding of G-quadruplex in SARS-CoV-2 RNA by RHAU peptide.

G-quadruplexes (G4s) are reported to present on the SARS-CoV-2 RNA genome and control various viral activities. Specific ligands targeting those viral nucleic acid structures could be investigated as promising detection methods or antiviral reagents to suppress this menacing virus. Herein, we demonstrate the binding between a G4 structure in the RNA of SARS-CoV-2 and a fluorescent probe created by fusing a parallel-G4 specific RHAU53 and a cyan fluorescent protein. The specific binding of G4 in SARS-CoV-2 by RHAU peptide was easily detected under the fluorescence spectrometer. The drawbacks of this approach and potential solutions are also discussed.

RHAU Peptides Specific for Parallel G-Quadruplexes: Potential Applications in Chemical Biology.

G-quadruplexes (G4s) are non-canonical nucleic acid structures formed by guanine (G)-rich sequences, which are ubiquitously found in the human genome and transcriptome. Targeting G4s by specific ligands provides a powerful tool to monitor and regulate G4s-associated biological processes. RHAU peptides, derived from the G4-binding motif of "RNA Helicase associated with AU-rich element" (RHAU), have emerged as extraordinary ligands for specific recognition of parallel G4s. This review highlights the significances of recent studies investigating potential applications of the engineered RHAU peptides incorporated to different functional moieties.

Construction of a G-quadruplex-specific DNA endonuclease.

We generated a novel G-quadruplex (G4)-specific endonuclease by fusing a G4 recognition domain of the RHAU helicase with a cleavage domain of the Fok1 nuclease. The fusion protein can specifically bind a parallel G4 and cleave a double-stranded DNA (dsDNA) next to it. The new endonuclease could be used to detect a G4 in a long dsDNA, providing a useful tool for mapping the formation of G4s in the genome.

Nutritional Status and Feeding Regimen of Patients with Esophagus Cancer-A Study from Vietnam.

BACKGROUND: Esophagus cancer patients are at high risk of malnutrition. This study was performed to assess the nutritional status and dietary intake of newly diagnosed esophageal cancer patients in Vietnam National Cancer Hospital (NCH). METHODS: A cross-sectional study was conducted on 206 early esophageal cancer inpatients after gastrostomy from September 2017 to June 2018. The chi-squared test, Fisher exact test, and Mann-Whitney test were performed. The software of the Vietnam National Institute of Nutrition was used to evaluate the dietary intake of patients. RESULTS: All the participants were male with a mean age of 57.1 ± 8.5 years. Overall, 87.4% of patients had dysphagia. Furthermore, 82.5% and 90.8% of patients reported weight loss one and six months pre-diagnosis, respectively. Moreover, 52.9% of patients suffered from mild/moderate malnutrition and 29.6% of patients had severe malnutrition according to the Patient-Generated Subjective Global Assessment (PG-SGA). The body mass index (BMI) and mid upper arm circumference (MUAC) measurement revealed 47.6% and 50% of undernourished patients, respectively. The proportions of patients having malnutrition were 10.7%, 55.8%, and 27.2% according to albumin, prealbumin, and total lymphocyte counts, respectively. The means of energy, protein, lipid, and carbohydrate in the patients' 24 h preoperative diets were 973.6 ± 443.0 kcal/day, 42.4 ± 21.6 g/day, 31.0 ± 15.5 g/day, and 130.0 ± 64.5 g/day. The total energy, total protein, animal protein, total lipid, and plant lipid in the dietary intake of patients were strongly correlated with age, economic classification, and PG-SGA (each p < 0.05). The total energy intake increased day by day, with the average energy intake of 1343.9 ± 521.3 kcal on the seventh day. Energy and protein response rates increased day by day and were highest at 7 days post-operation at 18.0% and 19.4%. CONCLUSION: Malnutrition and insufficient intake are noteworthy in esophageal cancer patients. The PG-SGA is strongly correlated with the dietary intake of patients. The results from this study will help medical staff to prevent malnutrition and improve the nutritional status of esophageal cancer inpatients. Furthermore, public awareness should be raised on recognizing weight loss as an early symptom of esophageal cancer and the utilization of preoperative assessment tools for nutritional assessment and malnutrition management.

Potent and Selective Knockdown of Tyrosine Kinase 2 by Antisense Oligonucleotides.

Tyrosine kinase 2 (TYK2) is a member of the JAK family of nonreceptor tyrosine kinase, together with JAK1, JAK2, and JAK3. JAKs are important signaling mediators of many proinflammatory cytokines and represent compelling pharmacological targets for autoimmune and inflammatory diseases. Pan-acting small-molecule JAK inhibitors were approved for the treatment of rheumatoid arthritis and ulcerative colitis. However, their limited selectivity among JAK members have led to undesirable side effects, driving a search toward specific JAK inhibitors. Recently, TYK2 has emerged as a target of choice for the treatment of autoimmune diseases and severe COVID-19 with an optimum balance between efficacy and safety, based on observations from human genetics studies and clinical outcomes of several agents targeting cytokine pathways for which TYK2 plays an essential role. In this article, we address selective targeting of TYK2 from the genetic sequence space through development of antisense oligonucleotides (ASOs) against TYK2 mRNA. Potent ASO candidates were identified from the screening of over 200 ASOs using locked nucleic acid gapmer design. The lead ASOs exhibited potent and selective knockdown of TYK2 mRNA and protein across a panel of model human cell lines in a dose-dependent manner, showing no reduction in the mRNA and protein expression levels of other JAK paralogs. In agreement with the depletion of TYK2 proteins, several TYK2-mediated cytokine signaling pathways, including IFN-α and IL-12, were inhibited upon ASO treatment. Our results established the TYK2 ASOs as investigational tool compound and potential therapeutic agent for the treatment of autoimmune diseases and severe COVID-19.