An evolutionarily conserved metabolite inhibits biofilm formation in Escherichia coli K-12.

Methylerythritol cyclodiphosphate (MEcPP) is an intermediate in the biosynthesis of isoprenoids in plant plastids and in bacteria, and acts as a stress signal in plants. Here, we show that MEcPP regulates biofilm formation in Escherichia coli K-12 MG1655. Increased MEcPP levels, triggered by genetic manipulation or oxidative stress, inhibit biofilm development and production of fimbriae.

Deep-m5U: a deep learning-based approach for RNA 5-methyluridine modification prediction using optimized feature integration.

Background: RNA 5-methyluridine (m5U) modifications play a crucial role in biological processes, making their accurate identification a key focus in computational biology. This paper introduces Deep-m5U, a robust predictor designed to enhance the prediction of m5U modifications. The proposed method, named Deep-m5U, utilizes a hybrid pseudo-K-tuple nucleotide composition (PseKNC) for sequence formulation, a Shapley Additive exPlanations (SHAP) algorithm for discriminant feature selection, and a deep neural network (DNN) as the classifier.

Rapid Exploration of Chemical Space by High-Throughput Desorption Electrospray Ionization Mass Spectrometry.

This study leverages accelerated reactions at the solution/air interface of microdroplets generated by desorption electrospray ionization (DESI) to explore the chemical space. DESI is utilized to synthesize drug analogs at an overall rate of 1 reaction mixture per second, working on the low-nanogram scale. Transformations of multiple drug molecules at specific functionalities (phenol, hydroxyl, amino, carbonyl, phenyl, thiophenyl, and alkenyl) are achieved using electrophilic/nucleophilic, redox, C-H functionalization, and coupling reactions.

Combining vitamin E metabolite 13'-carboxychromanol and a lactic acid bacterium synergistically mitigates colitis and colitis-associated dysbiosis in mice.

Synbiotics may be useful to mitigate intestinal diseases such as ulcerative colitis. Here we show that combining 13'-carboxychromanol (δT3-13'), a metabolite of vitamin E δ-tocotrienol (δT3) via omega-oxidation, and Lactococcus lactis subsp. cremori (L.

Negative Emotion (dys)regulation Predicts Distorted Time Perception: Preliminary Experimental Evidence and Implications for Psychopathology.

Objective: Accurate time perception is crucial to daily life but vulnerable to interference, particularly through negative affect, which dilates individuals' sense of time passing. Regulation strategies like rumination, and disorders like borderline personality disorder (BPD), are linked to time distortion, yet their interrelationships remain untested. We investigated whether rumination and BPD symptoms increase time dilation in negative affective states to understand the clinical implications of time distortion.

Stability indicating RP-HPLC method development and validation for quantification of impurities in gonadotropin-releasing hormone (Elagolix): Robustness study by quality by design.

The purpose of this research was to establish and validate a reverse phase HPLC method for the determination of Elagolix impurities in pharmaceutical dosage form. Mobile phase A, consisting of 10 mM sodium dihydrogen phosphate (pH 6.0) and acetonitrile in a 95:5 v/v ratio, and mobile phase B, containing 85:10:5 v/v/v of acetonitrile, Milli-Q water, and methanol, were used to achieve the method's specificity in the analytical column Kromasil 100-C18 (250 mm × 4.

ω-Carboxyl terminated cellulose esters are effective crystallization inhibitors for challenging drugs.

Polymeric additives are widely used to delay drug crystallization from supersaturated solutions, which is critical for enhancing oral bioavailability by amorphous solid dispersion (ASD). The efficacy of these polymers relies on their capacity to inhibit nucleation and subsequent crystal growth. Drug nucleation is pivotal to crystallization; therefore, effective polymers are essential for suppressing nucleation from supersaturated solutions.

Evaluation of Alpha-Synuclein and Tau Antiaggregation Activity of Urea and Thiourea-Based Small Molecules for Neurodegenerative Disease Therapeutics.

Alzheimer's disease (AD) and Parkinson's disease (PD) are multifactorial, chronic diseases involving neurodegeneration. According to recent studies, it is hypothesized that the intraneuronal and postsynaptic accumulation of misfolded proteins such as α-synuclein (α-syn) and tau, responsible for Lewy bodies (LB) and tangles, respectively, disrupts neuron functions. Considering the co-occurrence of α-syn and tau inclusions in the brains of patients afflicted with subtypes of dementia and LB disorders, the discovery and development of small molecules for the inhibition of α-syn and tau aggregation can be a potentially effective strategy to delay neurodegeneration.

Sibling socialization of alcohol use during adolescence: An integrated model of sibling influence processes.

Background And Aims: Research demonstrates that siblings, especially older siblings, make unique contributions to adolescents' substance use above and beyond shared genetics and shared parenting. Older siblings' influences on younger adolescent siblings' alcohol use operate through both direct and indirect pathways. Using three waves of longitudinal data, the present study tested an integrated model of sibling influence processes focused on the linkages between older adolescent siblings' earlier alcohol use and younger adolescent siblings' later alcohol use.

Dissolution, phase behavior and mass transport of amorphous solid dispersions in aspirated human intestinal fluids.

Amorphous solid dispersions (ASDs) typically show improved dissolution and generate supersaturated solutions, enhancing the oral bioavailability of poorly soluble drugs. To gain insights into intraluminal ASD behavior, we utilized two poorly soluble drugs with different crystallization tendencies, atazanavir and posaconazole, prepared as ASDs at a 10% drug loading with hydroxypropyl methylcellulose acetyl succinate (HPMCAS). We evaluated their release in aspirated fasted-state human intestinal fluid (FaHIF), and multi-component fasted-state simulated intestinal fluid (composite-FaSSIF), characterizing the supersaturation profiles and drug-rich nanodroplets that formed.

Triticum monococcum subsp. monococcum and aegilopoides: new sources of resistance to the dipteran pest, Hessian fly (Diptera: Cecidomyiidae).

The Hessian fly, Mayetiola destructor (Say) belonging to the order Diptera (family: Cecidomyiidae), is a destructive pest of host wheat (Triticum aestivum L.) causing significant economic losses. Although planting resistant wheat cultivars harboring an effective Hessian fly resistance gene (H) is the most economical and environmentally friendly pest management strategy, it imposes selection pressure on the insect populations and can lead to the evolution of Hessian fly virulence.

1α,25-Dihydroxyvitamin D Downregulates Adipocyte Impact on Breast Cancer Cell Migration and Adipokine Release.

Background/objectives: Excess adiposity is associated with a higher risk of breast cancer metastasis and mortality. Evidence suggests that dietary vitamin D inhibits breast cancer metastasis. However, the mechanistic link between vitamin D's regulation of adipocyte metabolism and metastasis has not been previously investigated.

Demand-driven capacity building for public health nutrition research in Lao PDR.

In Laos, rates of undernutrition, especially among children under 5 years of age, remain high. In response, a large multidisciplinary team embarked on a multi-year project in Laos beginning in 2019 with the purpose of institutional strengthening around public health nutrition research. This paper summarizes the Applied Nutrition Research Capacity Building project's activities, immediate project results, and prospects for sustaining impacts into the future.

Amorphous Solid Dispersion Formation for Enhanced Release Performance of Racemic and Enantiopure Praziquantel.

Praziquantel (PZQ) is the treatment of choice for schistosomiasis, which affects more than 250 million people globally. Commercial tablets contain the crystalline racemic compound (-PZQ) which limits drug dissolution and oral bioavailability and can lead to unwanted side effects and poor patient compliance due to the presence of the -enantiomer. While many approaches have been explored for improving PZQ's dissolution and oral bioavailability, studies focusing on investigating its release from amorphous solid dispersions (ASDs) have been limited.

Comprehensive model for predicting toxic equivalents (TEQ) reduction due to dechlorination of polychlorinated dibenzo-p-dioxin and dibenzofurans (PCDD/F congeners).

Remediation-focused predictive tools for polychlorinated dibenzo-p-dioxins (PCDD) and polychlorinated dibenzofurans (PCDF) rely on transformation models to evaluate the reduction in total contaminant load and toxic equivalency (TEQ). In this study, a comprehensive model predicting the profiles of PCDD/F congeners and the associated TEQs was developed. The model employs first-order kinetics to describe the transformation of 256 reactions for 75 PCDD congeners and 421 reactions for 135 PCDF congeners.

Fipronil-infused sodium polyacrylate gels provide effective management of Argentine ants in conservation areas.

Background: Various types of hydrogel compounds have recently been developed for controlling invasive and pest ants in a range of environmental settings including agricultural, urban and natural areas. The current study evaluated the potential of sodium polyacrylate (ACR) hydrogels to effectively deliver liquid baits to Argentine ants.

Results: Relative to standard polyacrylamide (PAM) hydrogels, individual ACR hydrogel particles were approximately five-fold heavier; this may affect how ants interact with the bait particles, and further influence bait uptake and efficacy.