Impact of Regulatory Post-Market Safety Advisories on Prescribing Practices: An Interrupted Time Series Analysis.

Less frequent adverse drug reactions are usually discovered after a drug's release to the market, making effective and timely communication of regulatory post-market advisories essential for preventing emerging adverse effects. Time series analysis is a key study design for assessing the impact of post-market safety advisories. However, most previous studies have focused on narrow evaluations, limiting systematic assessment of how different safety advisories affect prescribing practices.

Discovery of Diphenyl Ether Derivatives as Novel BK Channel Activators: Structure-Activity Relationship, Cryo-EM Complex Structures, and Animal Studies.

The BK channel, a large-conductance calcium-activated potassium channel, plays a crucial role in maintaining the homeostasis of the micturition cycle and airway-related functions. In this study, we optimized a novel BK channel activator, , with a diphenyl ether structure identified from library screening. This led to the discovery of potent activators, (EC = 0.

Atherosclerotic Cardiovascular Disease in Cancer Survivors: Current Evidence, Risk Prediction, Prevention, and Management.

While advances in cancer treatment have led to improved survival rates, cancer survivors are at a significant risk of developing atherosclerotic cardiovascular disease (ASCVD). This review examines the risk, diagnosis, and prevention of ASCVD in this population. Cancer survivors, especially those diagnosed with certain types, face a significantly higher risk of developing ASCVD than the general population.

Cryo-EM structures reveal the H/citrate symport mechanism of INDY.

I'm Not Dead Yet (INDY) functions as a transporter for citrate, a key metabolite in the citric acid cycle, across the plasma membrane. Partial deficiency of INDY extends lifespan, akin to the effects of caloric restriction. In this work, we use cryo-electron microscopy to determine structures of INDY in the presence and absence of citrate and in complex with the well-known inhibitor 4,4'-diisothiocyano-2,2'-disulfonic acid stilbene (DIDS) at resolutions ranging from 2.

Anticancer therapeutic effect of magnetic guided cobalt ferrite/doxorubicin-loaded ROS-responsive bilirubin nanoparticles in a colon cancer model.

Purpose: The aim of this study is to synthesize the cobalt iron oxide (CoFe) and doxorubicin (Dox)-loaded chitosan bilirubin (ChiBil) nanoparticles and to investigate the anticancer therapeutic effect of the synthesized nanoparticles under magnetic guidance in a colon cancer.

Materials And Methods: ChiBil-CoFe-Dox nanoparticles were synthesized by conjugating CoFe and Dox and then loaded onto ChiBil nanoparticles. Synthesis were characterized using thermogravimetric (TGA) analysis, inductive coupled plasma (ICP) analysis, dynamic light scattering (DLS), zeta potential and field emission-transmission electron microscopy (FE-TEM).

Galvanic hydrogenation reaction in metal oxide.

Rational reforming of metal oxide has a potential importance to modulate their inherent properties toward appealing characteristics for various applications. Here, we present a detailed fundamental study of the proton migration phenomena between mediums and propose the methodology for controllable metal oxide hydrogenation through galvanic reactions with metallic cation under ambient atmosphere. As a proof of concept for hydrogenation, we study the role of proton adoption on the structural properties of molybdenum trioxide, as a representative, and its impact on redox characteristics in Li-ion battery (LiB) systems using electrochemical experiments and first-principles calculation.

Leuconostoc aquikimchii sp. nov., a Lactic Acid Bacterium Isolated from Cabbage Watery Kimchi.

Two Gram-stain-positive, facultatively anaerobic, non-hemolytic, coccoid-shaped bacterial strains, designated MS01 and MS02, were isolated from cabbage watery kimchi in the Republic of Korea. Cellular growth occurred at 5-25 ℃ (optimum, 20 ℃), pH 5-8 (optimum, pH 7) and in the presence of 0-5% (w/v) NaCl (optimum, 1%). Results of 16S rRNA gene-based phylogenetic analyses showed that strains MS01 and MS02 shared identical sequences, clustered within the Leuconostoc clade in phylogenetic trees, and were most closely related to Leuconostoc inhae IH003 and Leuconostoc gasicomitatum LMG 18811 with sequence similarities of 98.

Targeting sphingosine 1-phosphate and sphingosine kinases in pancreatic cancer: mechanisms and therapeutic potential.

Pancreatic cancer is known to be the most lethal cancer. Fewer new treatments are being developed for pancreatic cancer as compared to other cancers. The bioactive lipid S1P, which is mainly regulated by sphingosine kinase 1 (SK1) and sphingosine kinase 2 (SK2) enzymes, plays significant roles in pancreatic cancer initiation and exacerbation.

In Vivo Differentiation of Endogenous Bone Marrow-Derived Cells into Insulin-Producing Cells Using Four Soluble Factors.

Four soluble factors-putrescine, glucosamine, nicotinamide, and signal transducer and activator of transcription 3 (STAT3) inhibitor BP-1-102-were shown to differentiate bone marrow mononucleated cells (BMNCs) into functional insulin-producing cells (IPCs) in vitro. Transplantation of these IPCs improved hyperglycemia in diabetic mice. However, the role of endogenous BMNC regeneration in this effect was unclear.

Dexamethasone nanocrystals-embedded hydroxypropyl methylcellulose hydrogel increases cochlear delivery and attenuates hearing loss following intratympanic injection.

Herein, dexamethasone (DEX) nanocrystalline suspension (NS)-embedded hydrogel (NS-G) was constructed using a hydroxypropyl methylcellulose (HPMC) polymer to enhance cochlear delivery and attenuate hearing loss following intratympanic (IT) injection. Hydrophobic steroidal nanocrystals were prepared using a bead milling technique and incorporated into a polysaccharide hydrogel. The NS-G system with HPMC (average molecular weight, 86,000 g/mol; 15 mg/mL) was characterized as follows: rod-shaped drug crystalline; particle size <300 nm; and constant complex viscosity ≤1.

Mapping spatial organization and genetic cell-state regulators to target immune evasion in ovarian cancer.

The drivers of immune evasion are not entirely clear, limiting the success of cancer immunotherapies. Here we applied single-cell spatial and perturbational transcriptomics to delineate immune evasion in high-grade serous tubo-ovarian cancer. To this end, we first mapped the spatial organization of high-grade serous tubo-ovarian cancer by profiling more than 2.

Cryo-EM structure of the human glucose transporter GLUT7.

GLUT7 is a Class II glucose transporter predominantly expressed at the apical membrane of enterocytes in the small intestine. Here, we report the cryo-EM structure of nanodisc-reconstituted human GLUT7 in the apo state at 3.3 Å resolution.

Cavernous Hemangioma of the Mastoid Antrum.

Hemangioma is a common vascular neoplasm that arises in the head and neck regions but is rare in the petrous bone. We report the first case of a solitary cavernous hemangioma in the mastoid antrum. A 68-year-old woman visited our hospital with a complaint of tinnitus without any other symptoms.

Carbon materials and their metal composites for biomedical applications: A short review.

Carbon materials and their hybrid metal composites have garnered significant attention in biomedical applications due to their exceptional biocompatibility. This biocompatibility arises from their inherent chemical stability and low toxicity within biological systems. This review offers a comprehensive overview of carbon nanomaterials and their metal composites, emphasizing their biocompatibility-focused applications, including drug delivery, bioimaging, biosensing, and tissue engineering.

Discovery of Triazolopyrimidine Derivatives as Selective P2X3 Receptor Antagonists Binding to an Unprecedented Allosteric Site as Evidenced by Cryo-Electron Microscopy.

The P2X3 receptor (P2X3R), an ATP-gated cation channel predominantly expressed in C- and Aδ-primary afferent neurons, has been proposed as a drug target for neurological inflammatory diseases, e.g., neuropathic pain, and chronic cough.

Activation mechanism and novel binding sites of the BK channel activator CTIBD.

The large-conductance calcium-activated potassium (BK) channel, which is crucial for urinary bladder smooth muscle relaxation, is a potential target for overactive bladder treatment. Our prior work unveiled CTIBD as a promising BK channel activator, altering and This study investigates CTIBD's activation mechanism, revealing its independence from the Ca and membrane voltage sensing of the BK channel. Cryo-electron microscopy disclosed that two CTIBD molecules bind to hydrophobic regions on the extracellular side of the lipid bilayer.

Catabolism of 2-keto-3-deoxy-galactonate and the production of its enantiomers.

2-Keto-3-deoxy-galactonate (KDGal) serves as a pivotal metabolic intermediate within both the fungal D-galacturonate pathway, which is integral to pectin catabolism, and the bacterial DeLey-Doudoroff pathway for D-galactose catabolism. The presence of KDGal enantiomers, L-KDGal and D-KDGal, varies across these pathways. Fungal pathways generate L-KDGal through the reduction and dehydration of D-galacturonate, whereas bacterial pathways produce D-KDGal through the oxidation and dehydration of D-galactose.

Structure, dimeric conformation, and coenzyme versatility of p-hydroxybenzoate hydroxylase from Arthrobacter sp. PAMC25564.

p-Hydroxybenzoate hydroxylase (PHBH) catalyzes the ortho-hydroxylation of 4-hydroxybenzoate (4-HB) to protocatechuate (PCA). PHBHs are commonly known as homodimers, and the prediction of pyridine nucleotide binding and specificity remains an ongoing focus in this field. Therefore, our study aimed to determine the dimerization interface in AspPHBH from Arthrobacter sp.

Magnet-Guided Temozolomide and Ferucarbotran Loaded Nanoparticles to Enhance Therapeutic Efficacy in Glioma Model.

The aim of the study was to synthesize liposomal nanoparticles loaded with temozolomide and ferucarbotran (LTF) and to evaluate the theranostic effect of LTF in the glioma model. We synthesized an LTF that could pass through the Blood Brain Barrier (BBB) and localize in brain tumor tissue with the help of magnet guidance. We examined the chemical characteristics.

Oxygen Vacancy-Controlled CuO/N,Se Co-Doped Porous Carbon via Plasma-Treatment for Enhanced Electro-Reduction of Nitrate to Green Ammonia.

The electrochemical nitrate reduction reaction (NORR) is of significance in regards of environmentally friendly issues and green ammonia production. However, relatively low performance with a competitive hydrogen evolution reaction (HER) is a challenge to overcome for the NORR. In this study, oxygen vacancy-controlled copper oxide (CuO) catalysts through a plasma treatment are successfully prepared and supported on high surface area porous carbon that are co-doped with N, Se species for its enhanced electrochemical properties.

Cryo-EM structure of cadmium-bound human ABCB6.

ATP-binding cassette transporter B6 (ABCB6), a protein essential for heme biosynthesis in mitochondria, also functions as a heavy metal efflux pump. Here, we present cryo-electron microscopy structures of human ABCB6 bound to a cadmium Cd(II) ion in the presence of antioxidant thiol peptides glutathione (GSH) and phytochelatin 2 (PC2) at resolutions of 3.2 and 3.