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Plasticity among cell lineages is a fundamental, but poorly understood, property of regenerative tissues. In the gut tube, the small intestine absorbs nutrients, whereas the colon absorbs electrolytes. In a striking display of inherent plasticity, adult colonic mucosa lacking the chromatin factor SATB2 is converted to small intestine. Using proteomics and CRISPR-Cas9 screening, we identify MTA2 as a crucial component of the molecular machinery that, together with SATB2, restrains colonic plasticity. MTA2 loss in the adult mouse colon activated lipid absorptive genes and functional lipid uptake. Mechanistically, MTA2 co-occupies DNA with HNF4A, an activating pan-intestinal transcription factor (TF), on colonic chromatin. MTA2 loss leads to HNF4A release from colonic chromatin, and accumulation on small intestinal chromatin. SATB2 similarly restrains colonic plasticity through an HNF4A-dependent mechanism. Our study provides a generalizable model of lineage plasticity in which broadly-expressed TFs are retained on tissue-specific enhancers to maintain cell identity and prevent activation of alternative lineages, and their release unleashes plasticity.

The shelf life of whole wheat bread (WWB) significantly impacts its freshness and overall quality. This research investigated the impact of chitosan lactate (CL) on various characteristics influencing the shelf life of WWB, including its physical, chemical, textural, antimicrobial, and sensory attributes. These characteristics were evaluated by conducting various experiments such as physical inspection, moisture, impedance, swelling, color, texture, FTIR, microbiological, and sensory analysis. CL with different concentrations was incorporated into WWB formulations: P0.0 (0.0% w/w CL, control), P0.5 (0.5% w/w CL), P1.0 (1.0% w/w CL), P2.0 (2.0% w/w CL), and P3.0 (3.0% w/w CL). The inclusion of CL promoted the Maillard reaction (MR) compared to P0.0. The promotion of MR resulted in the formation of a shinier crust, which increased as the CL content was increased. P0.5 comprised large-sized pores and exhibited increased loaf height. CL-containing WWB formulations showed an increased moisture content and decreased impedance values compared to the control. FTIR analysis of P0.5 demonstrated the enhanced interaction and bonding of water molecules. P0.5 demonstrated optimal textural, colorimetric, and antimicrobial properties compared to other formulations. The sensory attributes of WWBs remain unchanged despite CL addition. In conclusion, P0.5 exhibited optimal characteristics associated with better quality and prolonged shelf life. [ABSTRACT FROM AUTHOR]

Tetramethrin (TMT) is a commonly used insecticide and has a carcinogenic and neurodegenerative effect on humans. The binding mechanism and toxicological implications of TMT to human serum albumin (HSA) were examined in this study employing a combination of biophysical and computational methods indicating moderate binding affinity and potential hepato and renal toxicity. Fluorescence quenching experiments showed that TMT binds to HSA with a moderate affinity, and the binding process was spontaneous and predominantly enthalpy‐driven. Circular dichroism spectroscopy revealed that TMT binding did not induce any significant conformational changes in HSA, resulting in no changes in its alpha‐helix content. The binding site and modalities of TMT interactions with HSA as computed by molecular docking and molecular dynamics simulations revealed that it binds to Sudlow site II of HSA via hydrophobic interactions through its dimethylcyclopropane carboxylate methyl propanyl group. The structural dynamics of TMT induce proper fit into the binding site creating increased and stabilizing interactions. Additionally, molecular mechanics–Poisson Boltzmann surface area calculations also indicated that non‐polar and van der Waals were found to be the major contributors to the high binding free energy of the complex. Quantum mechanics (QM) revealed the conformational energies of the binding confirmation and the degree of deviation from the global minimum energy conformation of TMT. The results of this study provide a comprehensive understanding of the binding mechanism of TMT with HSA, which is important for evaluating the toxicity of this insecticide in humans. [ABSTRACT FROM AUTHOR]

Endotracheal intubation and central venous catheter (CVC) insertion are generally performed on the patient in the supine position. In traumatic cases, manual in-line stabilization and Sellick’s maneuver make airway management difficult. CVC insertion in the lateral position is not reported in the literature. A 30- year-old male with a history of falls from height presented with iron rods pierced into the right hand and right leg. The patient was intubated with manual in-line stabilization and Sellick’s maneuver in a lateral position. Due to the technical difficulty on the right side, CVC was inserted on the left side in a lateral position. Needle orientation was modified as per the position of the patient, and the left arm was pulled during the CVC insertion. The most experienced anesthesiologists should attempt for the best outcome. Wherever available, CVC should be inserted under ultrasonic guidance. With the landmark technique, the three-dimensional orientation of the anatomy should be kept in mind while attempting CVC insertion in an abnormal position. [ABSTRACT FROM AUTHOR]

The identification of genetic biomarkers that play a crucial role in cancer survival is challenging, but requires attention. The present study aimed to identify common biomarkers that affect the survival of patients with cancer. For this purpose, The Cancer Genome Atlas datasets of liver, lung, cervical and pancreatic cancers were used to identify differentially expressed genes (DEGs) that have an impact on cancer survival. The STRING database and ComplexHeatmap package were used to develop a protein-protein interaction network and heatmaps of the DEGs, respectively. The inhibitors of DEGs were identified using CMap software. Molecular docking and molecular dynamics simulations were performed using PyRx and NAMD software. Of note, two common genes [human NDC80 kinetochore complex component (NDC80) and human disks large-associated protein 5] in liver and lung cancers and five common genes [human minichromosome maintenance complex component (MCM)2, origin recognition complex subunit 1, cell division cycle 45, MCM3 and human DNA topoisomerase II alpha] in cervical and liver cancers were found to significantly affect overall survival. Several inhibitors of these seven common genes were identified and it was found that cytochalasin (NDC80 inhibitor) demonstrated the highest binding affinity. The results of molecular dynamics suggested that cytochalasin B can be used as a therapeutic drug in cancers with a high expression of NDC80. In addition, the present study identified unique biomarkers present in specific types of cancer and these data were validated using the c-BioPortal database. The c-BioPortal data analysis demonstrated that the expression of the cytochrome P450 family 2 subfamily C member 9 and acyl-CoA dehydrogenase short chain genes, together with the American Joint Committee on Cancer Pathological Staging, can be used as prognostic markers of liver cancer recurrence (AUC value=0.71). No such data were obtained for other cancers. On the whole the present study highlights that the selection of DEGs as potential treatment targets should be based on their effects on cancer survival along with tumor stages. [ABSTRACT FROM AUTHOR]

Dextromethorphan or DXM is an effective and harmless cough and cold suppressant available in many cold and cough preparations. At maximum dosage, it mimics hallucinogenic and psychoactive effects in human body and hence it is appealing for abuse. In this work, a detailed study of an antitussive agent i.e. Dextromethorphan which is a semi-synthetic opioid and a replacement of codeine and pholcodine in various cough linctuses has been described extensively. This review also revolves around the structured detailing of Dextromethorphan, its physical and chemical properties as well its pharmacokinetics in human body and also its effect on human brain and its relationship with NMDA receptors. This study also focuses on the emergence of Dextromethorphan as new drug of abuse due to its easy availability and as it possesses similar effects with LSD and other hallucinogens when taken in overdose in addition with the Toxicological analysis of Dextromethorphan from biological matrices using respective analytical methods. [ABSTRACT FROM AUTHOR]

The plasma clearance and tissue distribution in mice of the versatile capsid of bacteriophage Q[beta] are determined by decorating the particles with gadolinium complexes using the [Cu.sup.I]-mediated azide-alkyne cycloaddition reaction. The results have shown that nanoparticle trafficking is designed in predictable ways by chemical and genetic modifications that modulate surface charge.