O-glycosylation of SARS-CoV-2 spike protein by host O-glycosyltransferase strengthens its trimeric structure.

Protein O-glycosylation, also known as mucin-type O-glycosylation, is one of the most abundant glycosylation in mammalian cells. It is initially catalyzed by a family of polypeptide GalNAc transferases (ppGalNAc-Ts). The trimeric spike protein (S) of SARS-CoV-2 is highly glycosylated and facilitates the virus's entry into host cells and membrane fusion of the virus.

Integrative multi-omics analyses reveal vesicle transport as a potential target for thoracic aortic aneurysm.

Background: Thoracic aortic aneurysm (TAA) refers to dilation and enlargement of the thoracic aorta caused by various reasons. Most patients have no apparent symptoms in the early stage and are subject to a poor prognosis once the aneurysm ruptures. It is crucial to identify individuals who are predisposed to TAA and to discover effective therapeutic targets for early intervention.

Glycosidase-activated HS donorsto enhance chemotherapy efficacy.

Hydrogen sulfide (HS) plays a critical role in cancer biology. Herein, we developed a series of glycosidase-triggered hydrogen sulfide (HS) donors by connecting sugar moieties (including glucose, galactose and mannose) to COS donors via a self-immolative spacer. In the presence of corresponding glycosidases, HS was gradually released from these donors in PBS buffer with releasing efficiencies from 36 to 67 %.

Exoproteome analysis of Pseudomonas aeruginosa response to high alkane stress.

Microbial biodegradation serves as an effective approach to treat oil pollution. However, the application of such methods for the degrading long-chain alkanes still encounters significant challenges. Comparative proteomics has extensively studied the intracellular proteins of bacteria that degrade short- and medium-chain alkanes, but the role and mechanism of extracellular proteins in many microorganism remain unclear.

Specific pupylation as IDEntity reporter (SPIDER) for the identification of protein-biomolecule interactions.

Protein-biomolecule interactions play pivotal roles in almost all biological processes. For a biomolecule of interest, the identification of the interacting protein(s) is essential. For this need, although many assays are available, highly robust and reliable methods are always desired.

/identification of zein degraded peptides using HPLC-MS/MS and their safety evaluation.

The identification of degraded products of implanted scaffolds is desirable to avoid regulatory concerns.identification of products produced by the degradation of natural protein-based scaffolds is complex and demands the establishment of a routine analytical method. In this study, we developed a method for the identification of peptides produced by the degradation of zein bothandusing high performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS).

Targeted delivery of Nitric Oxide triggered by α-Glucosidase to Ameliorate NSAIDs-induced Enteropathy.

Nonsteroidal anti-inflammatory drugs (NSAIDs) increase risks of severe small intestinal injuries. Development of effective therapeutic strategies to overcome this issue remains challenging. Nitric oxide (NO) as a gaseous mediator plays a protective role in small intestinal injuries.

Nitric oxide improves regeneration and prevents calcification in bio-hybrid vascular grafts via regulation of vascular stem/progenitor cells.

Vascular bypass surgery continues to use autologous grafts and often suffers from a shortage of donor grafts. Decellularized xenografts derived from porcine veins provide a promising candidate because of their abundant availability and low immunogenicity. Unfortunately, transplantation outcomes are far from satisfactory because of insufficient regeneration and adverse pathologic remodeling.

An Injectable Dual-Function Hydrogel Protects Against Myocardial Ischemia/Reperfusion Injury by Modulating ROS/NO Disequilibrium.

Acute myocardial infarction (MI) is the leading cause of death worldwide. Exogenous delivery of nitric oxide (NO) to the infarcted myocardium has proven to be an effective strategy for treating MI due to the multiple physiological functions of NO. However, reperfusion of blood flow to the ischemic tissues is accompanied by the overproduction of toxic reactive oxygen species (ROS), which can further exacerbate tissue damage and compromise the therapeutic efficacy.

Potential Clinical Value of Biomarker-Guided Emergency Triage for Thoracic Aortic Dissection.

Thoracic aortic dissection (TAD) is a high-risk vascular disease. The mortality rate of untreated TADs in 24 h was as high as 50%. Thus, rapid diagnosis of TAD in the emergency department would get patients to the right treatments to save their lives.

Piperazine-Coumarin based fluorescence probe with enhanced brightness and solubility for bio-thiol detection and esophageal carcinoma diagnosis.

The development of novel fluorescent dyes for bio-thiol is of great importance in biological, clinical and pharmaceutical sciences. Given the importance of bio-thiol anticipating in numerous physiological processes, there is a great need to construct fluorescent biosensors with high quality to detect them. Fluorophores, especially those used in bio-system, usually require high-quality properties such as high brightness, good water solubility, bio-compatible and photostability.

Nitrate-functionalized patch confers cardioprotection and improves heart repair after myocardial infarction via local nitric oxide delivery.

Nitric oxide (NO) is a short-lived signaling molecule that plays a pivotal role in cardiovascular system. Organic nitrates represent a class of NO-donating drugs for treating coronary artery diseases, acting through the vasodilation of systemic vasculature that often leads to adverse effects. Herein, we design a nitrate-functionalized patch, wherein the nitrate pharmacological functional groups are covalently bound to biodegradable polymers, thus transforming small-molecule drugs into therapeutic biomaterials.

Gut Microbiota in NSAID Enteropathy: New Insights From Inside.

As a class of the commonly used drugs in clinical practice, non-steroidal anti-inflammatory drugs (NSAIDs) can cause a series of adverse events including gastrointestinal injuries. Besides upper gastrointestinal injuries, NSAID enteropathy also attracts attention with the introduction of capsule endoscopy and double balloon enteroscopy. However, the pathogenesis of NSAID enteropathy remains to be entirely clarified.

Comprehensive analysis of O-glycosylation of amyloid precursor protein (APP) using targeted and multi-fragmentation MS strategy.

Background: The aberrant proteolytic processing of amyloid precursor protein (APP) into amyloid β peptide (Aβ) in brain is a critical step in the pathogenesis of Alzheimer's disease (AD). As an O-glycosylated protein, O-glycosylation of APP is considered to be related to Aβ generation. Therefore, comprehensive analysis of APP O-glycosylation is important for understanding its functions.

Rational design of near-infrared fluorescent probes for superoxide anion radical: Enhancement of self-stability and sensitivity by self-immolative linker.

Fluorescent imaging of cellular superoxide anion radical (O) is of great significance to investigate reactive oxygen species-related pathophysiological processes and drug metabolism. However, the application of this technique is far away from maximum partially due to the lack of suitable probes. In this work, we propose a new strategy for design of near-infrared (NIR) O fluorescent probes in which p-cresol is used as a self-immolative linker to conjugate the NIR fluorophore DDAO (9H-1,3-Dichloro-7-hydroxy-9,9-dimethylacridine-2-one) with the O-sensing group (i.

Synthesis of difluoroalkylated 2-azaspiro[4.5]decane derivatives via copper-catalyzed difluoroalkylation/dearomatization of N-benzylacrylamides.

An efficient method for the synthesis of difluoroalkylated 2-azaspiro[4.5]decanes via copper-catalyzed difluoroalkylation of N-benzylacrylamides with ethyl bromodifluoroacetate has been established. The reaction experienced a tandem radical addition and dearomatizing cyclization process.

Photoactive NO hybrids with pseudo-zero-order release kinetics for antimicrobial applications.

Bacterial infection is a major threat to the health and life of humans due to the development of drug resistance, which is related to biofilm formation. Nitric oxide (NO) has emerged as an important factor in regulating biofilm formation. In order to harness the potential benefits of NO and develop effective antibacterial agents, we designed and synthesized a new class of NO hybrids in which the active scaffold benzothienoazepine was tagged with a nitroso group and further conjugated with quaternary ammoniums or phosphoniums.

Copper-Catalyzed Trifluoromethylation of Ynones Coupled with Dearomatizing Spirocyclization of Indoles: Access to CF-Containing Spiro[cyclopentane-1,3'-indole].

A one-pot protocol for the Cu(I)-catalyzed difunctionalization of indolyl ynones has been achieved via trifluoromethylation of alkyne followed by dearomatizing spirocyclization of indoles. This cascade process enables constructing diverse CF-containing spiro[cyclopentane-1,3'-indole] scaffolds in moderate to excellent yields which have challenging quaternary spirocyclic carbon and tetrasubstituted alkenes.

Synthesis of Central Chirality-Containing Triarylmethanols and Triarylmethyl Radicals with Extraordinarily Stable Configurations.

Triarylmethanol adopts a propeller-shaped conformation with either right-handed () or left-handed () configuration. Herein, new triarylmethanols with two chiral centers were obtained via introduction of two -hydroxyl groups on the side chains, affording four stereoisomers. These four stereoisomers were easily separated by silica gel column chromatography into two pairs of propeller-shaped enantiomers, as shown by NMR and X-ray crystallographic studies.

Interplay between the bacterial protein deacetylase CobB and the second messenger c-di-GMP.

As a ubiquitous bacterial secondary messenger, c-di-GMP plays key regulatory roles in processes such as bacterial motility and transcription regulation. CobB is the Sir2 family protein deacetylase that controls energy metabolism, chemotaxis, and DNA supercoiling in many bacteria. Using an Escherichia coli proteome microarray, we found that c-di-GMP strongly binds to CobB.

Synthesis and Characterization of Hydrophilic Trityl Radical TFO for Biomedical and Biophysical Applications.

Tetrathiatriarylmethyl (TAM, trityl) radicals have found wide applications as spin probes/labels for EPR spectroscopy and imaging, and as polarizing agents for dynamic nuclear polarization. The high hydrophilicity of TAM radicals is essential for their biomedical applications. However, the synthesis of hydrophilic TAM radicals (e.

Targeted delivery of nitric oxide via a 'bump-and-hole'-based enzyme-prodrug pair.

The spatiotemporal generation of nitric oxide (NO), a versatile endogenous messenger, is precisely controlled. Despite its therapeutic potential for a wide range of diseases, NO-based therapies are limited clinically due to a lack of effective strategies for precisely delivering NO to a specific site. In the present study, we developed a novel NO delivery system via modification of an enzyme-prodrug pair of galactosidase-galactosyl-NONOate using a 'bump-and-hole' strategy.

A mitochondria-targeted nitric oxide donor triggered by superoxide radical to alleviate myocardial ischemia/reperfusion injury.

A novel mitochondria-targeted superoxide-responsive nitric oxide donor was developed by incorporation of diphenylphosphinyl and triphenylphosphonium groups into diazeniumdiolate, enabling remarkable protection against ischemia/reperfusion injury in H9c2 cells and isolated rat hearts.