Mechanistic insights into how mixing factors govern polyelectrolyte-surfactant complexation in RNA lipid nanoparticle formulation.

Hypothesis: Lipid nanoparticle self-assembly is a complex process that relies on ion pairing between nucleic acids and hydrophobic cationic lipid counterions for encapsulation. The chemical factors influencing this process, such as formulation composition, have been the focus of recent research. However, the physical factors, particularly the mixing protocol, which directly modulates these chemical factors, have yet to be mechanistically examined using a reproducible mixing platform comparable to the industry standard.

Advancing drug discovery: Thiadiazole derivatives as multifaceted agents in medicinal chemistry and pharmacology.

In this dispensation of rapid scientific and technological advancements, significant efforts are being made to curb health-related diseases. Research discoveries have highlighted the value of heterocyclic compounds, particularly thiadiazole derivatives, due to their diverse pharmacological activities. These compounds play a crucial role in therapeutic medicine and the development of effective drugs.

Investigating under-reported human papillomavirus genotypes in Grenadian women through self-sampling for cervical cancer screening.

Objective: To compare the adequacy, agreement, and acceptability of Papanicolaou testing (cytology) for cervical cancer screening using self-collected samples compared to physician-collected samples in Grenada in the Caribbean. Furthermore, the study identifies the human papillomavirus (HPV) genotypes present among asymptomatic women testing positive for HPV, the etiologic cause of cervical cancer.

Methods: Participants were divided into two groups and two cervical samples were collected from the women in each group: a self-collected sample and a physician-collected sample.

Frequency-Domain Low-Wavenumber Hyperspectral Stimulated Raman Scattering Microscopy.

In recent years, stimulated Raman scattering (SRS) microscopy has experienced rapid technological advancements and has found widespread applications in chemical analysis. Hyperspectral SRS (hSRS) microscopy further enhances the chemical selectivity in imaging by providing a Raman spectrum for each pixel. Time-domain hSRS techniques often require interferometry and ultrashort femtosecond laser pulses.

Non-kinase off-target inhibitory activities of clinically-relevant kinase inhibitors.

Protein kinases are responsible for a myriad of cellular functions, such as cell cycle, apoptosis, and proliferation. Because of this, kinases make excellent targets for therapeutics. During the process to identify clinical kinase inhibitor candidates, kinase selectivity profiles of lead inhibitors are typically obtained.

Giant polyketide synthase enzymes biosynthesize a giant marine polyether biotoxin.

are harmful haptophyte algae that cause massive environmental fish-kills. Their polyketide polyether toxins, the , are amongst the largest nonpolymeric compounds in nature, alongside structurally-related health-impacting "red-tide" polyether toxins whose biosynthetic origins have been an enigma for over 40 years. Here we report the 'PKZILLAs', massive polyketide synthase (PKS) genes, whose existence and challenging genomic structure evaded prior detection.

Discovery of imidazo[1,2-]pyridazine-containing TAK1 kinase inhibitors with excellent activities against multiple myeloma.

Current treatment options for patients with multiple myeloma (MM) include proteasome inhibitors, anti-CD38 antibodies, and immunomodulatory agents. However, if patients have continued disease progression after administration of these treatments, there are limited options. There is a need for effective targeted therapies of MM.

Spatiotemporally Precise Optical Manipulation of Intracellular Molecular Activities.

Controlling chemical processes in live cells is a challenging task. The spatial heterogeneity of biochemical reactions in cells is often overlooked by conventional means of incubating cells with desired chemicals. A comprehensive understanding of spatially diverse biochemical processes requires precise control over molecular activities at the subcellular level.

α-Gal Nanoparticles in CNS Trauma: I. In Vitro Activation of Microglia Towards a Pro-Healing State.

Background: Macrophages and microglia play critical roles after spinal cord injury (SCI), with the pro-healing, anti-inflammatory (M2) subtype being implicated in tissue repair. We hypothesize that promoting this phenotype within the post-injured cord microenvironment may provide beneficial effects for mitigating tissue damage. As a proof of concept, we propose the use of nanoparticles incorporating the carbohydrate antigen, galactose-α-1,3-galactose (α-gal epitope) as an immunomodulator to transition human microglia (HMC3) cells toward a pro-healing state.

Best method to determine DNA G-quadruplex folding: The H-C HSQC NMR experiment.

NMR spectroscopy is the major method for G-quadruplex structure determination under physiologically relevant solution conditions. Unlike duplex B-DNA, in which all nucleotides adopt an anti glycosidic conformation, the core tetrad-guanines in a G-quadruplex can adopt anti or syn glycosidic conformation depending on the folding structure. An experimental method that can clearly and unambiguously determine syn and anti tetrad-Gs in a G-quadruplex is highly desirable and necessary.

Association between cigarette smoke exposure and urinary bladder cancer in Scottish terriers in a cohort study.

Canine urothelial carcinoma (UC) initially responds favorably to treatment, but is ultimately lethal in most cases. Research to identify modifiable risk factors to prevent the cancer is essential. The high breed-associated risk for UC, e.

Evaluation of RapidChek® SELECT™ for the detection of Salmonella spp. in environmental samples from a veterinary hospital.

Nosocomial salmonellosis in hospitalized animals is a recognized hazard, especially in large animal clinics. A standardized culture protocol (SCP) for detecting Salmonella spp. in environmental samples using a 48-h enrichment step results in a 5-day turnaround time for negative results.

Dual FLT3/haspin kinase inhibitor based on 3-pyrazolo[4,3-]quinoline scaffold with activities against acute myeloid leukemia.

The 3-pyrazolo[4,3-]quinoline core, a privileged fusion moiety from quinoline and indazole, facilely synthesized in a one flask multi-component Doebner-Povarov reaction, is a newly described kinase hinge binder. Previous works have demonstrated that the 3-pyrazolo[4,3-]quinoline moiety can be tuned, judicious substitution patterns, to selectively inhibit cancer-associated kinases, such as FLT3 and haspin. A first generation 3-pyrazolo[4,3-]quinoline-based haspin inhibitor, HSD972, and FLT3 inhibitor, HSD1169, were previously disclosed as inhibitors of various cancer cell lines.

Rational Design and Development of Selective BRD7 Bromodomain Inhibitors and Their Activity in Prostate Cancer.

Bromodomain-containing proteins are readers of acetylated lysine and play important roles in cancer. Bromodomain-containing protein 7 (BRD7) is implicated in multiple malignancies; however, there are no selective chemical probes to study its function in disease. Using crystal structures of BRD7 and BRD9 bromodomains (BDs) bound to BRD9-selective ligands, we identified a binding pocket exclusive to BRD7.

Early Identification of Root Damages Caused by Western Corn Rootworms Using a Minimally Invasive Root Phenotyping Robot-MISIRoot.

Western corn rootworm (WCR) is one of the most devastating corn rootworm species in North America because of its ability to cause severe production loss and grain quality damage. To control the loss, it is important to identify the infection of WCR at an early stage. Because the root system is the earliest feeding source of the WCR at the larvae stage, assessing the direct damage in the root system is crucial to achieving early detection.

Extreme genome diversity and cryptic speciation in a harmful algal-bloom-forming eukaryote.

Harmful algal blooms of the toxic haptophyte Prymnesium parvum are a recurrent problem in many inland and estuarine waters around the world. Strains of P. parvum vary in the toxins they produce and in other physiological traits associated with harmful algal blooms, but the genetic basis for this variation is unknown.

Facilitators of and barriers to COVID-19 vaccination in Grenada: a qualitative study.

Objectives: To identify the factors contributing to coronavirus disease 2019 (COVID-19) vaccine hesitancy in Grenada.

Methods: A phenomenological study was conducted using semi-structured interviews at vaccination and pop-up testing clinics during a spike in COVID-19 cases on the island. Interview questions were developed using the health belief model related to perceived threat of COVID-19, perceived benefits of and barriers to COVID-19 vaccination, and cues to action.

Using focus groups to plan culturally acceptable primary cervical cancer screening in Grenada, West Indies.

Objective: To document Grenadian women's knowledge about cervical cancer and human papillomavirus (HPV) infection, as well as their attitudes towards primary cervical cancer screening methods.

Methods: In this qualitative study, we used focus groups in Grenada to gather information concerning women's knowledge about, attitudes towards and perceptions of screening for cervical cancer and general knowledge about HPV. Ten focus groups comprising 73 participants representing 5 of the 6 parishes in Grenada were conducted with women aged 19-59.

Finite Element Analysis of Extrinsic Parameters on the Onset of Tensile Strength in Powders.

Most food, pharmaceutical, and chemical industries rely heavily on the supply of free-flowing powders that finds their application in raw materials, additives, and manufactured products. Improper storage conditions combined with environmental factors affect the free-flowing ability of powders. An undesirable transformation of these free-flowing powders into a coherent mass that resists flow is called caking.

Energy-Dependent Particle Size Distribution Models for Multi-Disc Mill.

Comminution is important in the processing of biological materials, such as cereal grains, wood biomass, and food waste. The most popular biomaterial grinders are hammer and roller mills. However, the grinders with great potential in the processing of biomass are mills that use cutting, e.

Mindful Lawyering: a Pilot Study on Mindfulness Training for Law Students.

Objectives: Many US law schools are now offering elective courses in mindfulness training to alleviate disproportionately high levels of anxiety, depression, stress, and disordered alcohol use among law students. To date, empirical evidence on the effectiveness of these courses has been lacking. The aim of this pilot study was to explore the feasibility and impact of a 13-week mindfulness course, "Mindful Lawyering," specifically tailored to law students.