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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.

This study investigates the impact of incorporating carboxymethyl tamarind gum (CMT) at varying concentrations (0 %–3 % w/w) into whole wheat bread (WWB) by analyzing several physicochemical properties. The results indicate that the loaf height of CMT2 (1 % CMT) increased by 8 % compared to the control (CMT0, without CMT) (p < 0.05), with more evenly distributed pores observed in CMT2. CMT formulations showed higher moisture content and lower impedance values than CMT0. Color analysis revealed that CMT2 had a 16 % higher L* value and a 19 % lower browning index. Microscopic analysis indicated glossier structures in CMT-containing samples, with CMT2 displaying the lowest hardness (7.46 N ± 0.11) (p < 0.05), 21 % lower than CMT0. Microbial analysis showed that CMT2 had the lowest total viable count (TVC) at 81 ± 6.55 CFU/g (p < 0.05) after 2 days, 68 % lower than CMT0. Overall, CMT2 demonstrated superior characteristics and extended shelf life. [ABSTRACT FROM AUTHOR]

Background: Chemoresistance is a major challenge in the effective treatment of cancer patients. This study aimed to identify common chemoresistance-associated genes that impact cancer survival. Methods: RNA-sequencing datasets for colorectal cancer (CRC) and ovarian cancer (OC) were analyzed using the gene expression omnibus (GEO) database and R Studio. Survival analysis was conducted using patient data from the cBioPortal database, where patients were stratified into high- and low-risk groups based on gene expression levels. Molecular dynamics simulations were performed to compare the binding energies of inhibitors targeting the identified genes. Results: Six common chemoresistance-associated genes were identified in both CRC and OC: cyclin-dependent kinase 2 (CDK2) , inhibitor of differentiation (ID1) , DUSP6, c-JUN, PLA2G2A , and SKP2. The expression of these genes was also evaluated in chemosensitive and chemoresistant oral cancer samples. Survival analysis revealed that high expression of CDK2 and ID1 significantly reduced the disease-free survival (DFS) of CRC and oral cancer patients with Grade II, III, or IV tumors. Conversely, low expression of ID1 was associated with reduced DFS in OC patients. Molecular simulations showed that the inhibitors dinaciclib (for CDK2) and vinblastine (for ID1) had higher binding energies compared to other inhibitors. Conclusion: The present study highlights the significance of CDK2 and ID1 as important mediators of chemoresistance and their potential as therapeutic targets to improve the survival of cancer patients exhibiting drug resistance. [ABSTRACT FROM AUTHOR]

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]