Design, synthesis, and structure-activity relationships of xanthine derivatives as broad-spectrum inhibitors of coronavirus replication.

Illuminated by insights into the hijacking of host cellular metabolism by coronaviruses, we identified an initial hit compound 7030B-C5, characterized by a xanthine scaffold, via a cellular-level phenotypic screening from a domestic repertoire of lipid-modulating agents. A series of derivatives were synthesized and optimized through comprehensive structure-activity relationship (SAR) studies focusing on the N-1, C-8, and N-7 positions of xanthine and preliminary exploration on the N-3 position and parent nucleus. Compounds 10e, 10f and 10o, featuring modifications at the N-7 position, showed inhibitory activity with half maximal effective concentration (EC) values in the three-digit nanomolar range against human coronavirus-229E (HCoV-229E).

Research Progress on the Quality, Extraction Technology, Food Application, and Physiological Function of Rice Bran Oil.

Rice bran oil is recommended by the World Health Organization as one of the three major healthy edible oils (along with corn and sesame oils), owing to its unique fatty acid composition and functional components. This study screened, organized, and analyzed a large number of studies retrieved through keyword searches, and investigated the nutritional value and safety of rice bran oil. It reviews the stability of raw rice bran materials and the extraction and refining process of rice bran oil and discusses food applications and sub-health regulations.

Preparation and Characterization of Hydroxylated Recombinant Collagen by Incorporating Proline and Hydroxyproline in Proline-Deficient .

Collagen possesses distinctive chemical properties and biological functions due to its unique triple helix structure. However, recombinant collagen expressed in without post-translational modifications such as hydroxylation lacks full function since hydroxylation is considered to be critical to the stability of the collagen triple-helix at body temperature. Here, a proline-deficient strain was constructed and employed to prepare hydroxylated recombinant collagens by incorporating proline (Pro) and hydroxyproline (Hyp) from the culture medium.

Sodium-glucose cotransporter-2 inhibitors versus dipeptidyl peptidase IV inhibitors and risk of dementia among patients with type 2 diabetes and comorbid mental disorders: A population-based cohort study.

Aim: To evaluate whether the use of sodium-glucose cotransporter-2 (SGLT2) inhibitors which have shown potential neuroprotective effects, is associated with lower risk of dementia in patients with type 2 diabetes (T2D) and comorbid mental disorders, who are considerably more susceptible to dementia.

Methods: Using the nationwide healthcare data of South Korea between 2010 and 2022, we conducted a retrospective cohort study among patients with T2D and comorbid mental disorders initiating SGLT2 inhibitors versus active comparator (Dipeptidyl Peptidase IV (DPP4) inhibitors). Hazard ratios (HRs) and rate differences (RDs) per 1000 person-years of incident dementia were estimated after weighting by propensity score fine stratification method.

Effects of on Sensorineural Hearing Loss via Neuronal Gene Regulation.

Sensorineural hearing loss (SNHL), characterized by damage to the inner ear or auditory nerve, is a prevalent auditory disorder. This study explores the potential of (CAE) as a therapeutic agent for SNHL. In vivo experiments were conducted using zebrafish and mouse models.

Sodium-Glucose Cotransporter-2 Inhibitors, Dulaglutide, and Risk for Dementia : A Population-Based Cohort Study.

Background: Both sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may have neuroprotective effects in patients with type 2 diabetes (T2D). However, their comparative effectiveness in preventing dementia remains uncertain.

Objective: To compare the risk for dementia between SGLT2 inhibitors and dulaglutide (a GLP-1 RA).

Simulation of the dynamic processes of microplastic suspension and deposition in a lake sediment-water system.

The occurrence of microplastics in aquatic environments has attracted increasing interest from both the public and scientists, especially their migration behaviors. Although several environmental behaviors of microplastics have been studied, the issue of microplastic suspension and deposition in lake sediment-water systems remains to be elucidated. In this study, we built an indoor sediment-water system with input and output rivers that simulated the actual situations in lakes, and aimed to explore the suspension and deposition behavior of microplastics using eight group experiments.

Carrimycin inhibits coronavirus replication by decreasing the efficiency of programmed -1 ribosomal frameshifting through directly binding to the RNA pseudoknot of viral frameshift-stimulatory element.

The pandemic of SARS-CoV-2 worldwide with successive emerging variants urgently calls for small-molecule oral drugs with broad-spectrum antiviral activity. Here, we show that carrimycin, a new macrolide antibiotic in the clinic and an antiviral candidate for SARS-CoV-2 in phase III trials, decreases the efficiency of programmed -1 ribosomal frameshifting of coronaviruses and thus impedes viral replication in a broad-spectrum fashion. Carrimycin binds directly to the coronaviral frameshift-stimulatory element (FSE) RNA pseudoknot, interrupting the viral protein translation switch from ORF1a to ORF1b and thereby reducing the level of the core components of the viral replication and transcription complexes.

Autoclaving-treated germinated brown rice relieves hyperlipidemia by modulating gut microbiota in humans.

Introduction: Germinated brown rice is a functional food with a promising potential for alleviating metabolic diseases. This study aimed to explore the hypolipidemic effects of autoclaving-treated germinated brown rice (AGBR) and the underlying mechanisms involving gut microbiota.

Methods: Dietary intervention with AGBR or polished rice (PR) was implemented in patients with hyperlipidemia for 3 months, and blood lipids were analyzed.

Construction and Mechanism Exploration of Highly Efficient System for Bacterial Ghosts Preparation Based on Engineered Phage ID52 Lysis Protein E.

Bacterial ghosts (BGs) are hollow bacterial cell envelopes with intact cellular structures, presenting as promising candidates for various biotechnological and biomedical applications. However, the yield and productivity of BGs have encountered limitations, hindering their large-scale preparation and multi-faceted applications of BGs. Further optimization of BGs is needed for the commercial application of BG technology.

Phage tailspike protein coated gold nanoparticles combined with smartphone for rapid bacterial detection and photothermal sterilization.

The integration of recognition and therapeutic functions in multifunctional biosensors is of great importance in guaranteeing food security and reducing the occurrence of foodborne illness caused by foodborne pathogens. In this study, a biosensor utilizing a "sense-and-treat" approach was developed by integrating phage tailspike protein (TSP) with gold nanoparticles (AuNPs@TSP). The synthesized AuNPs@TSP showed strong binding affinity towards Salmonella typhimurium causing color changes and exhibited effective bactericidal activity when exposed to near-infrared (NIR) irradiation.

A Simple Tube Escape Assay to Test Learning and Memory in Zebrafish with Minimized Habituation.

Various methods have been used in rodents to evaluate learning and memory. Although much less frequently used, the zebrafish emerges as an alternative model organism in this context. For example, it allows assessing potential behavioral deficits because of neurodevelopmental disorders or environmental neurotoxins.

Comparative Effectiveness and Safety of Ticagrelor and Clopidogrel in Patients With or Without Chronic Liver Disease: A Nationwide Cohort Study.

Background: Although the effectiveness and safety of ticagrelor versus clopidogrel may differ in patients with chronic liver disease, there is a scarcity of evidence comparing ticagrelor and clopidogrel in patients with chronic liver disease. We aimed to evaluate the risk of major adverse cardiovascular events (MACE) and major bleeding associated with ticagrelor versus clopidogrel in patients undergoing percutaneous coronary intervention (PCI) due to acute coronary syndrome by chronic liver disease status.

Methods: Using the Korean healthcare claim database, we included adult patients who underwent PCI and initiated ticagrelor or clopidogrel treatment within 7 days of an acute coronary syndrome diagnosis.

Characterization of a cell wall hydrolase with high activity against vegetative cells, spores and biofilm of Bacillus cereus.

Bacillus cereus is a prevalent foodborne pathogen that induces food poisoning symptoms such as vomiting and diarrhea. Its capacity to form spores and biofilm enables it to withstand disinfectants and antimicrobials, leading to persistent contamination during food processing. Consequently, it is necessary to develop novel and efficient antimicrobial agents to control B.

A pan-PPAR agonist E17241 ameliorates hyperglycemia and diabetic dyslipidemia in KKAy mice via up-regulating ABCA1 in islet, liver, and white adipose tissue.

Objective: Type 2 diabetes mellitus (T2DM) is a common chronic metabolic disease. Peroxisome proliferator-activated receptors (PPARs) play crucial roles in regulating glucolipid metabolism. Previous studies showed that E17241 could ameliorate atherosclerosis and lower fasting blood glucose levels in ApoE mice.

Glial senescence enhances α-synuclein pathology owing to its insufficient clearance caused by autophagy dysfunction.

Parkinson's disease (PD) is characterized by the pathological accumulation of α-synuclein (α-syn) and loss of dopaminergic neurons in the substantia nigra. Aging is a significant risk factor for PD. The accumulation of senescent glial cells in the aged brain contributes to PD progression by inducing chronic neuroinflammatory processes.

Specific separation and sensitive detection of foodborne pathogens by phage-derived bacterial-binding protein-nano magnetic beads coupled with smartphone-assisted paper sensor.

Foodborne pathogen infection poses a significant threat to public health and is considered as one of the most serious hazards in global food safety. Herein, a sensitive and efficient method for on-site monitoring of foodborne pathogens was developed by using a smartphone-assisted paper-sensor combined with phage-derived bacterial-binding proteins-nano magnetic beads (PBPs-MBs). PBPs including tail fiber protein (TFP:gp13), cell-wall binding domain (CBD) of endolysin and tailspike protein (TSP) coated on the surface of MBs were applied for rapid separation and enrichment of targeted bacteria (Escherichia coli O157:H7, Staphylococcus aureus and Salmonella typhimurium, respectively) from food samples in 20 min before detection on paper-based sensors.

Expanding structural diversity of 5'-aminouridine moiety of sansanmycin via mutational biosynthesis.

Sansanmycins represent a family of uridyl peptide antibiotics with antimicrobial activity specifically against (including drug-resistant ) and . They target translocase I (MraY) to inhibit bacterial cell wall assembly. Given the unique mechanism of action, sansanmycin has emerged as a potential lead compound for developing new anti-tuberculosis drugs, while the 5'-aminouridine moiety plays a crucial role in the pharmacophore of sansanmycin.

Feasibility Analysis of Polyurethane-Prepolymer-Modified Bitumen Used for Fully Reclaimed Asphalt Pavement (FRAP).

Asphalt pavement recycling technology with high reclaimed asphalt pavement (RAP) content has always been limited by unsatisfactory pavement performance and the rising cost of pavement materials. To address these challenges, polyurethane-prepolymer-modified bitumen (PPB) was proposed to be utilized as the asphalt binder of fully reclaimed asphalt pavement (FRAP) in this study. The proper formula of the PPB binder was determined based on a range of tests.

(±) Pestalactone D and pestapyrone F, two new isocoumarins from an endolichenic Pestalotiopsis rhododendri.

Three isocoumarins, including two new compounds, (±) pestalactone D (1) and pestapyrone F (2), as well as one known compound, pestapyrone D (3), were isolated from the culture of the endolichenic Pestalotiopsis rhododendri LF-19-12. The planar structures of all compounds were elucidated by NMR and MS spectra. And the absolute configurations of 1 were confirmed by single crystal X-ray diffraction analysis, indicative of it as a racemate of 4S/12S and 4R/12R enantiomers.

Generation of a Focused THz Vortex Beam from a Spintronic THz Emitter with a Helical Fresnel Zone Plate.

Similar to optical vortex beams, terahertz (THz) vortex beams (TVBs) also carry orbital angular momentum (OAM). However, little research has been reported on the generation of TVBs. In this paper, based on the detour phase technique, we design a series of spintronic terahertz emitters with a helical Fresnel zone plate (STE-HFZP) to directly generate focused TVBs with topological charges (TCs) of = ±1, ±2 and ±3, respectively.

Isolation of and with Anti- Activity and Identification of the Anti- Substance.

The adoption of intensive farming has exacerbated disease outbreaks in aquaculture, particularly vibriosis caused by . The use of probiotics to control is recognized as a good alternative to antibiotics for avoiding the development of antibiotic-resistant bacteria. In this study, two strains of B.

Antibacterial MccM as the Major Microcin in Nissle 1917 against Pathogenic Enterobacteria.

Probiotic Nissle 1917 (EcN) possesses excellent antibacterial effects on pathogenic enterobacteria. The microcins MccM and MccH47 produced in EcN played critical roles, but they are understudied and poorly characterized, and the individual antibacterial mechanisms are still unclear. In this study, three EcN mutants (Δ, Δ and ΔΔ) were constructed and compared with wild-type EcN (EcN wt) to test for inhibitory effects on the growth of O157: H7, (SE), and (ST).