Chemical-guided SHAPE sequencing (cgSHAPE-seq) informs the binding site of RNA-degrading chimeras targeting SARS-CoV-2 5' untranslated region.

One of the hallmarks of RNA viruses is highly structured untranslated regions (UTRs) which are often essential for viral replication, transcription, or translation. In this report, we discovered a series of coumarin derivatives that bind to a four-way RNA helix called SL5 in the 5' UTR of the SARS-CoV-2 RNA genome. To locate the binding site, we developed a sequencing-based method namely cgSHAPE-seq, in which an acylating probe was directed to crosslink with the 2'-OH group of ribose at the binding site to create read-through mutations during reverse transcription.

In vitro evaluation of frozen thawed kangayam bull semen enriched with antioxidants.

The aim of this study was to assess the in vitro penetration rate of antioxidant enriched frozen thawed Kangayam bull semen. For the current investigation, 5-7-year-old Kangayam bulls were used. The semen was collected twice per week and two ejaculates were collected each time.

Unraveling Facial Nerve Palsy: A Case Series Highlighting Diagnostic and Therapeutic Challenges.

Facial nerve palsy (FNP) may arise from multiple etiological reasons, including anatomical anomalies, circulatory complications, and infectious agents. This case series underscores the importance of a comprehensive diagnostic approach to identify the precise etiology, including structural abnormalities, vascular anomalies, or infectious illnesses. Here, we present three distinct occurrences of FNP, emphasizing the varied diagnostic difficulties and therapeutic strategies.

ZEB1-mediated fibroblast polarization controls inflammation and sensitivity to immunotherapy in colorectal cancer.

The EMT-transcription factor ZEB1 is heterogeneously expressed in tumor cells and in cancer-associated fibroblasts (CAFs) in colorectal cancer (CRC). While ZEB1 in tumor cells regulates metastasis and therapy resistance, its role in CAFs is largely unknown. Combining fibroblast-specific Zeb1 deletion with immunocompetent mouse models of CRC, we observe that inflammation-driven tumorigenesis is accelerated, whereas invasion and metastasis in sporadic cancers are reduced.

Structural Evaluations of a Selective Human STING Agonist and Its Use in Macrophage Immunotherapies.

Previously we identified a non-nucleotide agonist BDW568 that selectively activates the human STING allele. Here, we further characterized the mechanism of BDW568 and highlighted its potential use for selectively controlling the activation of engineered macrophages that constitutively express STING as a genetic adjuvant. We obtained the crystal structure of the C-terminal domain of STING complexed with BDW-OH (active metabolite) at 1.

Palladium-Catalyzed Dearomatization of Benzothiophenes: Isolation and Functionalization of a Discrete Dearomatized Intermediate.

A Pd-catalyzed decarboxylative dearomatization reaction of a heterocyclic substrate enables access to an uncommon reaction intermediate that rearomatizes in the presence of amine bases in a net C-H functionalization sequence. The dearomatized benzo[]thiophene intermediate bears an exocyclic alkene that can be functionalized through cycloaddition and halogenation reactions to deliver complex heterocyclic products.

In Vitro Characterization of of Aseel and Kadaknath Chicken Breeds against Newcastle Disease Virus Infection.

Newcastle disease (ND) is highly contagious and usually causes severe illness that affects all over the world, including domestic poultry. Depending on the virus's virulence, it can impact the nervous, respiratory, and digestive systems and cause up to 100% mortality. The genes are activated in response to viral infection.

Structural and Biological Evaluations of a Non-Nucleoside STING Agonist Specific for Human STING Variants.

Previously we identified a non-nucleotide tricyclic agonist BDW568 that activates human STING (stimulator of interferon genes) gene variant containing A230 in a human monocyte cell line (THP-1). STING alleles, including HAQ and AQ, are less common STING variants in human population. To further characterize the mechanism of BDW568, we obtained the crystal structure of the C-terminal domain of STING complexed with BDW-OH (active metabolite of BDW568) at 1.

Chemical-guided SHAPE sequencing (cgSHAPE-seq) informs the binding site of RNA-degrading chimeras targeting SARS-CoV-2 5' untranslated region.

One of the hallmarks of RNA viruses is highly structured untranslated regions (UTRs) in their genomes. These conserved RNA structures are often essential for viral replication, transcription, or translation. In this report, we discovered and optimized a new type of coumarin derivatives, such as and , which bind to a four-way RNA helix called SL5 in the 5' UTR of the SARS-CoV-2 RNA genome.

Molecular Iodine-Promoted [3 + 2] Oxidative Cyclization for the Synthesis of Heteroarene-Fused [1,2,4] Thiadiazoles/Selenadiazoles.

Two new classes of heteroarene-fused [1,2,4]thiadiazole and [1,2,4]selenadiazole are synthesized through the iodine-mediated [3 + 2] oxidative cyclization of 2-aminoheteroarenes and isothiocyanates/isoselenocyanates. This oxidative [3 + 2] annulation strategy is highly regiospecific to proceed a selective C-N bond formation at the endo-nitrogen of 2-aminoheteroarenes followed by an intramolecular oxidative N-S/N-Se bond formation. It is the first example of an I-mediated oxidative nitrogen-selenium (N-Se) bond formation.

Connecting remote C-H bond functionalization and decarboxylative coupling using simple amines.

Transition metal-catalysed C-H functionalization and decarboxylative coupling are two of the most notable synthetic strategies developed in the past 30 years. Here, we connect these two reaction pathways using bases and a simple Pd-based catalyst system to promote a para-selective C-H functionalization reaction from benzylic electrophiles. Experimental and computational mechanistic studies suggest a pathway that involves an uncommon Pd-catalysed dearomatization of the benzyl moiety followed by a base-enabled rearomatization through a formal 1,5-hydrogen migration.

One-Pot Synthesis of Unsymmetrical Bis-Heterocycles: Benzimidazole-, Benzoxazole-, and Benzothiazole-Linked Thiazolidines.

A one-pot, three-component synthesis of benzimidazole-linked thiazolidines from 2-cyanomethyl benzimidazole, iso-, isothio-, or isoselenocyanates and 1,2-dichloroethane is reported. Isolation of the key intermediate formed during the course of the reaction validates its mechanistic pathway. Under the same reaction conditions, benzimidazole-linked/fused thiazinanes were obtained when 1,3-dichloropropane or diiodomethane was used.

Whole-genome sequencing of human Pegivirus variant from an Egyptian patient co-infected with hepatitis C virus: a case report.

Background: Human pegivirus (HPgV) is structurally similar to hepatitis C virus (HCV) and was discovered 20 years ago. Its distribution, natural history and exact rule of this viral group in human hosts remain unclear. Our aim was to determine, by deep next-generation sequencing (NGS), the entire genome sequence of HPgV that was discovered in an Egyptian patient while analyzing HCV sequence from the same patient.

Synthesis of Leu-Enkephalin Peptidomimetics Containing Trifluoromethylalkenes as Amide Isopolar Mimics.

Fluorinated peptidomimetics are valuable substrates for exploring peptide backbone conformations and for perturbing physicochemical properties of probe compounds. However, in some cases synthetic limitations restrict installation of the fluorinated peptidomimetics into the desired probe compounds. For instance, trifluoromethylalkenes have served as amide isopolar mimics, but are rarely utilized, because many standard peptide-coupling conditions promote the isomerization of the alkene to thermodynamically favored positions.

Phycoremediation resultant lipid production and antioxidant changes in green microalgae Chlorella Sp.

In this investigation, we report on the treatment of tannery wastewater using microalgae Chlorella species to produce lipid and fatty acid as well as changes in antioxidant metabolism during the treatment. The variation in growth, production of pigments, antioxidant metabolism, lipid and fatty acids, and nutrient removal from wastewater during the remediation were observed. Surprisingly, a profuse growth was found in 50% diluted tannery wastewater (TW), which supported to accumulate high yield of lipid (18.

Regioselective Synthesis of Pyranone-Fused Indazoles via Reductive Cyclization and Alkyne Insertion.

A novel and efficient method for the one-pot synthesis of 2 H-indazole from readily available building blocks is reported. The reaction of 2-nitrobenzylamines with zinc and ammonium formate underwent partial reduction to nitroso-benzylamine followed by an intramolecular cyclization to afford 2 H-indazole via N-N bond formation. The carboxylic acid moiety of indazole was proceeded to regioselective alkyne insertion under ruthenium catalysis to form pyranone-fused indazoles.

A multi-disciplinary perspective on emergent and future innovations in peer review.

Peer review of research articles is a core part of our scholarly communication system. In spite of its importance, the status and purpose of peer review is often contested. What is its role in our modern digital research and communications infrastructure? Does it perform to the high standards with which it is generally regarded? Studies of peer review have shown that it is prone to bias and abuse in numerous dimensions, frequently unreliable, and can fail to detect even fraudulent research.

Genome sequencing and analysis of the first spontaneous Nanosilver resistant bacterium strain SCDR1.

Background: is a common uropathogenic bacterium that can cause major complications in patients with long-standing indwelling catheters or patients with urinary tract anomalies. In addition, is a common cause of chronic osteomyelitis in Diabetic foot ulcer (DFU) patients. We isolated from a Diabetic ulcer patient.

Cascade Synthesis of Benzimidazole-Linked Pyrroles via Copper Catalyzed Oxidative Cyclization and Ketonization.

A three-component cascade reaction of 2-aminobenzimidazole, aldehyde, and terminal alkyne has been explored for an efficient synthesis of benzimidazole-linked tetrasubstituted pyrroles. The reaction sequence involves the formation of propargylamine, insertion of a terminal alkyne, and a ring opening reaction followed by an intramolecular carbonylative cyclization under aerobic conditions. It represents a novel strategy to the construction of C═N, C═C, C═O bonds and a new five-membered 2-ketopyrrole ring.

The Use of Next-Generation Sequencing in the Identification of a Fastidious Pathogen: A Lesson From a Clinical Setup.

is the causal agent of bacillary hemoglobinuria in cattle, goat, sheep, and ruminants. In this study, we report the first recorded human-infecting strain collected from an 18-year-old woman diagnosed with acute lymphoblastic leukemia. After failure of traditional techniques, only next-generation sequencing (NGS) technology in combination with bioinformatics, phylogenetic, and pathogenomics analyses revealed that our King Faisal Specialist Hospital and Research Center (KFSHRC) bacterial isolate belongs to species.

Three Component Divergent Reactions: Base-Controlled Amphiphilic Synthesis of Benzimidazole-Linked Thiazetidines and Fused Thiadiazines.

A divergent reaction of 2-aminobenzimidazole with isothiocyanates and dihalomethanes has been developed for the selective synthesis of benzoimidazothiazetidine and benzoimidazothiadiazine. A single-pot reaction of 2-aminobenzimidazole in the presence of sodium hydride delivers benzoimidazothiazetidine, whereas triethylamine promotes the formation of benzoimidazothiadiazine via a sequential stepwise fashion. The reaction sequence involves the initial formation of thiourea followed by regioselective nucleophilic addition and intramolecular ring-closing with dihalo electrophiles.

Copper catalyzed aerobic oxidative cyclization and ketonization: one pot synthesis of benzoimidazo[1,2-a]imidazolones.

A highly efficient synthesis of benzoimidazo[1,2-a]imidazolone through a novel oxidative 5-exo-dig cyclization-ketonization cascade of 2-aminobenzimidazole, aldehyde and terminal alkyne has been explored under aerobic conditions. The reaction proceeds through copper-catalyzed addition of terminal alkynes to imines derived from 2-aminobenzimidazole with aldehyde followed by intramolecular cyclization. The atmospheric molecular oxygen acts as an oxygen source for the newly formed carbonyl group in the final product.

Skeletally Diverse Synthesis of Indole-Fused Diazocine and Diazepine Frameworks by One-Pot, Two-Component Cascade Reaction.

An expeditious and novel strategy has been explored for the synthesis of structurally diverse indole-fused diazocine and diazepine derivatives. A substrate-based diversification approach of methyl-3-aminoindole/indoline benzoates coupled with the Pictet-Spengler reaction and three different reaction cascades furnished indolodiazepine and indoloquinoxalines. The formation of indolodiazocines proceeds through an initial condensation followed by intramolecular alkylation.