Structure-guided drug repurposing identifies aristospan as a potential inhibitor of β-lactamase: insights from virtual screening and molecular dynamics simulations.

The rise of β-Lactamase mediated antibiotic resistance is a major concern for public health; hence, there is an urgent need to find new treatment approaches. Structure-guided drug repurposing offers a promising approach to swiftly deliver essential therapeutics in the fight against escalating antibiotic resistance. Here, a structure-guided virtual screening approach was used involving drug profiling, molecular docking, and molecular dynamics (MD) simulation to identify existing drugs against β-Lactamase-associated drug resistance.

Comparative efficiency of Geotrichum candidum microcapsules prepared with alginate and in combination with other polymers: In vitro evaluation.

Microencapsulation is utilized to protect probiotics, such as Geotrichum candidum, ensuring their survival, stability, and targeted release. The encapsulation efficiency depends on factors such as the type and concentration of the polymers and the encapsulation method. In this study, G.

Impaired axon initial segment structure and function in a model of developmental and epileptic encephalopathy.

Developmental and epileptic encephalopathies (DEE) are rare but devastating and largely intractable childhood epilepsies. Genetic variants in , encoding a scaffolding protein important for the organization of the postsynaptic density of inhibitory synapses, are associated with DEE accompanied by complex neurological phenotypes. In a mouse model carrying a patient-derived variant associated with severe disease, we observed aggregation of postsynaptic proteins and loss of functional inhibitory synapses at the axon initial segment (AIS), altered axo-axonic synaptic inhibition, disrupted action potential generation, and complex seizure phenotypes consistent with clinical observations.

Ameliorative Role of Vitamin C against Cypermethrin Induced Oxidative Stress and DNA Damage in (Hamilton, 1822) Using Single Cell Gel Electrophoresis.

The present study was undertaken to evaluate cypermethrin (CYP)-induced oxidative stress [reactive oxygen species (ROS) and lipid peroxidation (LPO) in gills, muscles, brain, and liver tissues] and DNA damage/genotoxicity (peripheral blood erythrocytes) in a freshwater teleost rohu () and the protective role of vitamin C. The LC of CYP against rohu was found to be 4.5 µg/L in a semi-static culture system through probit analysis.

Valine and Inflammation Drive Epilepsy in a Mouse Model of ECHS1 Deficiency.

ECHS1 Deficiency (ECHS1D) is a rare and devastating pediatric disease that currently has no defined treatments. This disorder results from missense loss-of-function mutations in the gene that result in severe developmental delays, encephalopathy, hypotonia, and early death. ECHS1 enzymatic activity is necessary for the beta-oxidation of fatty acids and the oxidation of branched-chain amino acids within the inner mitochondrial matrix.

Ecological patterns of phytoplankton across lake cross-section: insights into co-evolution of physicochemical conditions in Chashma Lake on Indus River.

Physicochemical properties of water influence planktonic diversity and distribution, which is essential in obtaining basic knowledge of aquatic biodiversity. Thus current study aims to investigate the spatiotemporal diversity, abundance ratio, and distribution of phytoplankton species and their association with water quality parameters of Chashma Lake, Pakistan. During the study period from 2018 to 2019, we measured 13 physicochemical parameters across three selected sampling sites (S1, S2, and S3) in Chashma Lake, revealing both spatial and temporal variability.

Gain-of-function mutations of TRPV4 acting in endothelial cells drive blood-CNS barrier breakdown and motor neuron degeneration in mice.

Blood-CNS barrier disruption is a hallmark of numerous neurological disorders, yet whether barrier breakdown is sufficient to trigger neurodegenerative disease remains unresolved. Therapeutic strategies to mitigate barrier hyperpermeability are also limited. Dominant missense mutations of the cation channel transient receptor potential vanilloid 4 (TRPV4) cause forms of hereditary motor neuron disease.

An approach to optimizing dietary protein to growth and body composition in walking catfish, Clarias batrachus (Linneaeus, 1758).

Clarias batrachus is a commercially important food fish. In the present study, effect of varying dietary protein levels was evaluated on the survival, growth parameters and proximate composition of C. batrachus.

Optimization of inclusion level of lipid in larval diet of Labeo rohita (Hamilton, 1822).

Formulation and preparation of larval feed according to the requirement of Indian major carp is a prerequisite for improving the survival (%) and growth during early developmental stages. A feeding trial of 50 days in a replicate of five was conducted to determine the optimal inclusion levels of fish oil (lipid) in the larval diet of Labeo rohita. Four isonitrogenous (50% CP) nanoparticulate diets with four lipid inclusion levels, L5 (5%), L7 (7%), L9 (9%), and L11 (11%) were prepared and fed to four groups of rohu (Labeo rohita) larvae.

Plural molecular and cellular mechanisms of pore domain encephalopathy.

variants in children with neurodevelopmental impairment are difficult to assess due to their heterogeneity and unclear pathogenic mechanisms. We describe a child with neonatal-onset epilepsy, developmental impairment of intermediate severity, and G256W heterozygosity. Analyzing prior KCNQ2 channel cryoelectron microscopy models revealed G256 as a node of an arch-shaped non-covalent bond network linking S5, the pore turret, and the ion path.

Loss of Endothelial TDP-43 Leads to Blood Brain Barrier Defects in Mouse Models of Amyotrophic Lateral Sclerosis and Frontotemporal Dementia.

Loss of nuclear TDP-43 occurs in a wide range of neurodegenerative diseases, and specific mutations in the gene that encodes the protein are linked to familial Frontal Temporal Lobar Dementia (FTD), and Amyotrophic Lateral Sclerosis (ALS). Although the focus has been on neuronal cell dysfunction caused by TDP-43 variants, mRNA transcripts are expressed at similar levels in brain endothelial cells (ECs). Since increased permeability across the blood brain barrier (BBB) precedes cognitive decline, we postulated that altered functions of TDP-43 in ECs contributes to BBB dysfunction in neurodegenerative disease.

Physiological and histopathological effects of polystyrene nanoparticles on the filter-feeding fish Hypophthalmichthys molitrix.

Excessive use of plastics in daily life is causing plastic pollution in aquatic environment and threatening the aquatic life. Therefore, research on the plastic pollution in aquatic environment is crucial to understand its impact and develop effective solution for safeguarding aquatic life and ecosystem. The current study investigated the effects of water borne polystyrene nanoparticles (PS-NPs) on hemato-immunological indices, serum metabolic enzymes, gills, and liver antioxidant parameters, plasma cortisol level and histopathological changes in liver and gill tissues of the widely distributed fish Hypophthalmichthys molitrix.

Reduced toxic effects of nano‑copper sulfate in comparison of bulk CuSO on biochemical parameters in the Rohu (Labeo rohita).

Considering the wide application of nanoparticles in various fields of life and growing concern regarding their toxic effects, the present study was designed with the aim to evaluate the potential risks of using copper sulfate nanoparticles (CuSO-NPs) in comparison to bulk form. Nanoparticles of CuSO, having mean size of 73 nm were prepared by ball milling method, and fingerlings of Labeo rohita were exposed to two levels, 20 and 100 μg L of CuSO in both bulk and nano forms for 28 days and their comparative effects on the metallothioneins (MTs), heat shock proteins 70 (HSP 70), lipid profile, cholesterol (CHOL) and triglyceraldehyde (TG) levels, activities of some metabolic enzymes Alanine transaminase (ALT), Aspartate transaminase (AST) Akaline phosphatase (ALP), and genes expressions of HSP-70, TNF-α and IL1-ß were investigated. CuSO showed the concentration and particle type dependent effects.

Optimization of Selenium Inclusion Level in the Larval Diet of Labeo rohita.

The nutritional requirement of fish larvae remains a limiting factor in advanced aquaculture. Micronutrients are crucial for early development, but their dietary inclusion level in the larval feed of carps has not been standardized. The present study was executed to determine the optimum dietary inclusion level of organic and inorganic selenium in the larval feed of Rohu, Labeo rohita.

Predictors and Outcomes of Infections in ICU Patients With Cirrhosis: A Single-Center Observational Study.

Background: Patients with cirrhosis are susceptible to infections, especially by multidrug-resistant organisms (MDROs). There are limited data on the incidence of culture-positive infections and the validity of Sepsis 3-criteria in patients with cirrhosis admitted to the intensive care unit (ICU) in India, which we aimed to assess.

Methods: In this prospective study, we included consecutive patients with cirrhosis admitted to the ICU between November 1, 2021, and April 30, 2022.

Stathmin-2 loss leads to neurofilament-dependent axonal collapse driving motor and sensory denervation.

The mRNA transcript of the human STMN2 gene, encoding for stathmin-2 protein (also called SCG10), is profoundly impacted by TAR DNA-binding protein 43 (TDP-43) loss of function. The latter is a hallmark of several neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). Using a combination of approaches, including transient antisense oligonucleotide-mediated suppression, sustained shRNA-induced depletion in aging mice, and germline deletion, we show that stathmin-2 has an important role in the establishment and maintenance of neurofilament-dependent axoplasmic organization that is critical for preserving the caliber and conduction velocity of myelinated large-diameter axons.

Antibiotics With or Without Rifaximin for Acute Hepatic Encephalopathy in Critically Ill Patients With Cirrhosis: A Double-Blind, Randomized Controlled (ARiE) Trial.

Introduction: Critically ill patients with cirrhosis admitted to the intensive care unit (ICU) are usually on broad-spectrum antibiotics because of suspected infection or as a hospital protocol. It is unclear if additional rifaximin has any synergistic effect with broad-spectrum antibiotics in ICU patients with acute overt hepatic encephalopathy (HE).

Methods: In this double-blind trial, patients with overt HE admitted to ICU were randomized to receive antibiotics (ab) alone or antibiotics with rifaximin (ab + r).

Advances and Opportunities in Nanoparticle Drug Delivery for Central Nervous System Disorders: A Review of Current Advances.

This narrative review provides an overview of the current advances, challenges, and opportunities in nanoparticle drug delivery for central nervous system (CNS) disorders. The treatment of central nervous system disorders is challenging due to the blood-brain barrier (BBB), which limits the delivery of therapeutic agents to the brain. Promising approaches to address these issues and improve the efficacy of CNS disease therapies are provided by nanoparticle-based drug delivery systems.

MED12 mutation activates the tryptophan/kynurenine/AHR pathway to promote growth of uterine leiomyomas.

Uterine leiomyomas cause heavy menstrual bleeding, anemia, and pregnancy loss in millions of women worldwide. Driver mutations in the transcriptional mediator complex subunit 12 (MED12) gene in uterine myometrial cells initiate 70% of leiomyomas that grow in a progesterone-dependent manner. We showed a distinct chromatin occupancy landscape of MED12 in mutant MED12 (mut-MED12) versus WT-MED12 leiomyomas.

Therapeutic Role of Hemp (Cannabis sativa) Against Copper-Induced Toxicity in Labeo rohita and Cirrhinus mrigala.

For decades hemp has been used as a therapeutic agent for enhancing immunity in animals. Current study was conceptualized to find out the protective role of dietary hemp seed products (hemp seed oil (HO) and hemp seed (HS)) against copper-induced toxicity in fish. Fingerlings of Labeo rohita (Rohu) and Cirrhinus mrigala (Mrigal) were exposed to copper at 20% of the 96 h LC (1.

Mechanism of cryptic splice-polyadenylation and its correction for TDP-43 proteinopathies.

Loss of nuclear TDP-43 is a hallmark of neurodegeneration in TDP-43 proteinopathies, including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). TDP-43 mislocalization results in cryptic splicing and polyadenylation of pre-messenger RNAs (pre-mRNAs) encoding stathmin-2 (also known as SCG10), a protein that is required for axonal regeneration. We found that TDP-43 binding to a GU-rich region sterically blocked recognition of the cryptic 3' splice site in pre-mRNA.