CYP5122A1 encodes an essential sterol C4-methyl oxidase in Leishmania donovani and determines the antileishmanial activity of antifungal azoles.

Visceral leishmaniasis is a life-threatening parasitic disease, but current antileishmanial drugs have severe drawbacks. Antifungal azoles inhibit the activity of cytochrome P450 (CYP) 51 enzymes which are responsible for removing the C14α-methyl group of lanosterol, a key step in ergosterol biosynthesis in Leishmania. However, they exhibit varying degrees of antileishmanial activities in culture, suggesting the existence of unrecognized molecular targets.

Discovery of pyrazole-based analogs as CDK2 inhibitors with apoptotic-inducing activity: design, synthesis and molecular dynamics study.

The discovery of novel CDK2 inhibitors is crucial for developing targeted anticancer therapies. Thus, in this study, we aimed to design, synthesize, and evaluate a series of novel pyrazole derivatives (2a-g, 7a-d, 8a and b, 9, and 10) for their potential as CDK2/cyclin A2 enzyme inhibitors. The newly synthesized compounds were screened at 50 μM for CDK2 inhibition, followed by IC profiling of the most promising candidates.

A Pilot Study: Treatment of High Alcohol Consumption in a Novel Minipig Model of Alcohol Use Disorder.

Three medications are FDA approved in the US for treatment of Alcohol Use Disorder (AUD), and a few others are used off-label. Patient compliance and efficacy in the broader population are major hurdles for current AUD medications. As a consequence, there is an urgent need for improved pharmacotherapeutics to complement behavioral approaches.

Hormetic and transcriptomic responses of the toxic alga Prymnesium parvum to glyphosate.

Growth of the toxic alga Prymnesium parvum is hormetically stimulated with environmentally relevant concentrations of glyphosate. The mechanisms of glyphosate hormesis in this species, however, are unknown. We evaluated the transcriptomic response of P.

Disordered eating and cardiometabolic risk factors in Chinese women: evidence from the China Health and Nutrition Survey.

Disordered eating (DE) is associated with elevated cardiometabolic risk (CMR) factors, yet little is known about this association in non-Western countries. We examined the association between DE characteristics and CMR and tested the potential mediating role of BMI. This cross-sectional study included 2005 Chinese women (aged 18-50 years) from the 2015 China Health and Nutrition Survey.

Phenotypic profiling based on body fluid traces discovered at the scene of crime: Raman spectroscopy of urine stains for race differentiation.

Modern criminal investigations heavily rely on trace bodily fluid evidence as a rich source of DNA. DNA profiling of such evidence can result in the identification of an individual if a matching DNA profile is available. Alternatively, phenotypic profiling based on the analysis of body fluid traces can significantly narrow down the pool of suspects in a criminal investigation.

Comparison of Day-Specific Serum LH, Estradiol, and Progesterone with Mira Monitor Urinary LH, Estrone-3-glucuronide, and Pregnanediol-3-glucuronide Levels in Ovulatory Cycles.

: Fertility tracking apps and devices are now currently available, but urinary hormone levels lack accuracy and sensitivity in timing the start of the 6-day fertile window and the precise 24 h interval of transition from ovulation to the luteal phase. We hypothesized the serum hormones estradiol (E2) and progesterone (P) might be better biomarkers for these major ovulatory cycle events, using appropriate mathematical tools. : Four women provided daily blood samples for serum E2, P, and LH (luteinizing hormone) levels throughout their entire ovulatory cycles, which were indexed to the first day of dominant follicle (DF) collapse (defined as Day 0) determined by transvaginal sonography; therefore, ovulation occurred in the 24 h interval of Day -1 (last day of maximum diameter DF) to Day 0.

Signaling through the nicotinic acetylcholine receptor in the liver protects against the development of metabolic dysfunction-associated steatohepatitis.

Metabolic dysfunction-associated steatohepatitis (MASH) is the progressive form of liver steatosis, the most common liver disease, and substantially increases the mortality rate. However, limited therapies are currently available to prevent MASH development. Identifying potential pharmacological treatments for the condition has been hampered by its heterogeneous and complex nature.

Chlorogenic Acid and Cinnamaldehyde in Combination Inhibit Metastatic Traits and Induce Apoptosis via Akt Downregulation in Breast Cancer Cells.

Most reported breast cancer-associated deaths are directly correlated with metastatic disease. Additionally, the primary goal of treating metastatic breast cancer is to prolong life. Thus, there remains the need for more effective and safer strategies to treat metastatic breast cancer.

Effects of Drought Stress on Abscisic Acid Content and Its Related Transcripts in - Monosomic Addition Lines.

Climate change has resulted in an increased demand for Japanese bunching onions L., genomes FF) with drought resistance. A complete set of alien monosomic addition lines of with extra chromosomes from shallot ( L.

Rethinking the Esterquats: Synthesis, Stability, Ecotoxicity and Applications of Esterquats Incorporating Analogs of Betaine or Choline as the Cation in Their Structure.

Esterquats constitute a unique group of quaternary ammonium salts (QASs) that contain an ester bond in the structure of the cation. Despite the numerous advantages of this class of compounds, only two mini-reviews discuss the subject of esterquats: the first one (2007) briefly summarizes their types, synthesis, and structural elements required for a beneficial environmental profile and only briefly covers their applications whereas the second one only reviews the stability of selected betaine-type esterquats in aqueous solutions. The rationale for writing this review is to critically reevaluate the relevant literature and provide others with a "state-of-the-art" snapshot of choline-type esterquats and betaine-type esterquats.

Low Vitamin D Levels in Patients with Symptoms of Gastroparesis: Relationships with Nausea and Vomiting, Gastric Emptying and Gastric Myoelectrical Activity.

Unlabelled: Patients with gastroparesis (Gp) often have diets deficient in calories, electrolytes, and vitamins. Vitamin D levels have been reported to be low in some patients with Gp but has not been systematically studied.

Aims: To determine vitamin D levels and relationships among symptoms, gastric emptying and gastric myoelectrical activity (GMA) in patients with symptoms of Gp.

Genetic variations associated with telomere length predict the risk of recurrence of non-oropharyngeal head and neck squamous cell carcinoma.

Genetic factors underlying lymphocyte telomere length (LTL) may provide insights into genomic stability and integrity, with direct links to susceptibility to cancer recurrence. Polymorphisms in telomere-associated genes are strongly associated with LTL and cancer risk, while few large studies have explored the associations between LTL-related polymorphisms and recurrence risk of non-oropharyngeal head and neck squamous cell carcinoma (non-OPHNSCC). Totally 1403 non-OPHNSCC patients were recruited and genotyped for 16 LTL-related polymorphisms identified by genome-wide association studies.

The role of recurrent trauma on post-traumatic stress disorder symptoms and substance use among trauma exposed youth.

Comorbidity between post-traumatic stress disorder (PTSD) and substance use disorder may be explained by a prospective trauma risk conferred by both conditions. The current study modeled concurrent and prospective associations of trauma, PTSD symptoms, and substance use (SU) behavior among trauma exposed youth (ages 8-20). Clinical interviews assessed trauma exposure, PTSD symptom severity, and SU behavior at baseline and at six- and 12-month follow up study visits (N = 2,069).

Chemogenetic Manipulation of Amygdala Kappa Opioid Receptor Neurons Modulates Amygdala Neuronal Activity and Neuropathic Pain Behaviors.

Neuroplasticity in the central nucleus of the amygdala (CeA) plays a key role in the modulation of pain and its aversive component. The dynorphin/kappa opioid receptor (KOR) system in the amygdala is critical for averse-affective behaviors in pain conditions, but its mechanisms are not well understood. Here, we used chemogenetic manipulations of amygdala KOR-expressing neurons to analyze the behavioral consequences in a chronic neuropathic pain model.

Renal manifestations in adult-onset Still's disease: a systematic review.

Objective: We aimed to review the literature on the clinical presentation, renal pathology, treatment, and outcome of renal manifestations in adult-onset Still's disease (AOSD).

Methods: We used PRISMA guidelines for our systematic review and included all English-language original articles from inception till September 15, 2023, on AOSD and kidney involvement in any form. Data on patient demographics, diagnostic criteria, clinical presentation, renal pathology, treatment employed including dialysis, outcome, cause of death were collected and analyzed.