Human microRNA miR-197-3p positively regulates HIV-1 virion infectivity through its target DDX52 by stabilizing Vif protein expression.

MicroRNAs are a part of the integral regulatory mechanisms found in eukaryotic cells that help in maintaining cellular homeostasis by modulating the expression of target genes. However, during stress conditions like viral infection, the expression profile of the microRNAs change, thereby directly modulating the expression of viral genes and/or indirectly targeting the virus by regulating the host genes. The present study intends to identify previously uncharacterized cellular microRNAs, which are significantly modulated upon HIV-1 infection.

Effects of quenched disorder on the kinetics and pathways of phase transition in a soft colloidal system.

Although impurities are unavoidable in real-world and experimental systems, most numerical studies on nucleation focus on pure (impurity-free) systems. As a result, the role of impurities in phase transitions remains poorly understood, especially for systems with complex free energy landscapes featuring one or more intermediate metastable phases. In this study, we employed Monte Carlo simulations to investigate the effects of static impurities (quenched disorder) of varying length scales and surface morphologies on the crystal nucleation mechanism and kinetics in the Gaussian core model system-a representative model for soft colloidal systems.

Apoptosis-Inducing Activity of a 2-Hydroxyphenyl Benzamide-Based Self-Assembled Anion Channel.

Despite the significant interest in designing artificial ion channels, there is limited availability of channel-forming molecules to tackle complex issues, especially in biological systems. Moreover, a major challenge is the scarcity of chloride transporters that can selectively induce toxicity in cancer cells while minimizing harm to normal healthy cells. This work reports a series of 2-hydroxyphenyl benzamide-based small molecules 1 a-1 c, which self-assemble to form barrel rosette-type artificial ion channels that adequately transport chloride ions across membranes.

A Full Good Manufacturing Practice-Compliant Protocol for Corneal Stromal Stem Cell Cultivation.

Corneal scarring, a significant cause of global blindness, results from various insults, including trauma, infections, and genetic disorders. The conventional treatment to replace scarred corneal tissues includes partial or full-thickness corneal transplantation using healthy donor corneas. However, only 1 in 70 individuals with treatable corneal scarring can undergo surgery, due to the limited supply of transplantable donor tissue.

Inhibition of STAT3 by 2-Methoxyestradiol suppresses M2 polarization and protumoral functions of macrophages in breast cancer.

Background: Breast cancer metastasis remains the leading cause of cancer-related deaths in women worldwide. Infiltration of tumor-associated macrophages (TAMs) in the tumor stroma is known to be correlated with reduced overall survival. The inhibitors of TAMs are sought after for reprogramming the tumor microenvironment.

Isolation, Culture, and Quality Assessment of Clinical-Grade Corneal Stromal Stem Cells.

The challenge of treating corneal scarring through keratoplasties lies in the limited availability of donor tissue. Various studies have shown the therapeutic use of cultivated corneal stromal stem cells (CSSCs) to mitigate tissue inflammation and suppress fibrosis and scar tissue formation in preclinical corneal wound models. To develop CSSC therapy for clinical trials on patients with corneal scarring, it is necessary to generate clinical-grade CSSCs in compliant to Good Manufacturing Practice (GMP) regulations.

β-Carboline-based light and pH dual stimuli-responsive ion transporters induce cancer cell death.

Light and pH dual-responsive ion transporters offer better applicability for cancer due to higher tunability and low cytotoxicity. Herein, we demonstrate the development of pH-responsive β-carboline-based ionophores and photocleavable-linker appended β-carboline-based proionophores to facilitate the controlled transport of Cl across membranes, leading to apoptotic and autophagic cancer cell death.

Food waste generation and its industrial utilization: An overview.

Food waste is produced for intended human consumption and is normally lost, discharged, contaminated, or finally degraded. The rising problem of food waste is increasing rapidly, so every sector is involved in minimizing food waste generation as well as waste management from collection to disposal, and scientists are developing the best eco-friendly and sustainable solutions for all sectors in the food supply chain, from the agricultural sector to the industrial sector and even up to the retailer to human consumption. Sustainable management is needed for the food wastes in the agricultural and industrial sectors, which are a major burning headache for environmentalists, health departments, and the government all over the earth.

Rutaecarpine-inspired scaffold-hopping strategy and Ullmann cross-coupling based synthetic approach: Identification of pyridopyrimidinone-indole based novel anticancer chemotypes.

Natural products as starting templates have shown historically major contribution to development of drugs. Inspired by the structure-function of an anticancer natural alkaloid Rutaecarpine, the Scaffold-hopped Acyclic Analogues of Rutaecarpine (SAAR) with 'N'-atom switch (1°-hop) and ring-opening (2°-hop) were investigated. A new synthetic route was developed for an effective access to the analogues, i.

The miR-183/96/182 cluster regulates sensory innervation, resident myeloid cells and functions of the cornea through cell type-specific target genes.

The conserved miR-183/96/182 cluster (miR-183C) is expressed in both corneal resident myeloid cells (CRMCs) and sensory nerves (CSN) and modulates corneal immune/inflammatory responses. To uncover cell type-specific roles of miR-183C in CRMC and CSN and their contributions to corneal physiology, myeloid-specific miR-183C conditional knockout (MS-CKO), and sensory nerve-specific CKO (SNS-CKO) mice were produced and characterized in comparison to the conventional miR-183C KO. Immunofluorescence and confocal microscopy of flatmount corneas, corneal sensitivity, and tear volume assays were performed in young adult naïve mice; 3' RNA sequencing (Seq) and proteomics in the trigeminal ganglion (TG), cornea and CRMCs.

Regenerative Therapy for Corneal Scarring Disorders.

The cornea is a transparent and vitally multifaceted component of the eye, playing a pivotal role in vision and ocular health. It has primary refractive and protective functions. Typical corneal dysfunctions include opacities and deformities that result from injuries, infections, or other medical conditions.

Good manufacturing practice production of human corneal limbus-derived stromal stem cells and in vitro quality screening for therapeutic inhibition of corneal scarring.

Background: Mesenchymal stem cells in the adult corneal stroma (named corneal stromal stem cells, CSSCs) inhibit corneal inflammation and scarring and restore corneal clarity in pre-clinical corneal injury models. This cell therapy could alleviate the heavy reliance on donor materials for corneal transplantation to treat corneal opacities. Herein, we established Good Manufacturing Practice (GMP) protocols for CSSC isolation, propagation, and cryostorage, and developed in vitro quality control (QC) metric for in vivo anti-scarring potency of CSSCs in treating corneal opacities.

A niche-mimicking polymer hydrogel-based approach to identify molecular targets for tackling human pancreatic cancer stem cells.

Background: Pancreatic adenocarcinoma (PAAD) is one of the most fatal human cancers, but effective therapies remain to be established. Cancer stem cells (CSCs) are highly resistant to anti-cancer drugs and a deeper understanding of their microenvironmental niche has been considered important to provide understanding and solutions to cancer eradication. However, as the CSC niche is composed of a wide variety of biological and physicochemical factors, the development of multidisciplinary tools that recapitulate their complex features is indispensable.

FBXW2 suppresses breast tumorigenesis by targeting AKT-Moesin-SKP2 axis.

Oncogene Moesin plays critical role in initiation, progression, and metastasis of multiple cancers. It exerts oncogenic activity due to its high-level expression as well as posttranslational modification in cancer. However, factors responsible for its high-level expression remain elusive.

Quinoline Thiourea-Based Zinc Ionophores with Antibacterial Activity.

The increasing resistance of bacteria to commercially available antibiotics threatens patient safety in healthcare settings. Perturbation of ion homeostasis has emerged as a potential therapeutic strategy to fight against antibacterial resistance and other channelopathies. This study reports the development of 8-aminoquinoline (QN) derivatives and their transmembrane Zn transport activities.

Novel class of photochromic molecules exhibiting photo-switching in the solid state.

Photo-switching compounds are widely used as super-resolution imaging agents, anti-counterfeiting dyes, and molecules that are able to control drug-receptor interactions. However, advancement of this field has been limited by the number of classes of molecules that exhibit this phenomenon, and thus there are growing activities to discover new photo-switching compounds that diversify and improve current applications and include the so-called donor-acceptor Stenhouse adducts. Herein, a new class of compounds, phenylindole alkene dimers, are presented as a novel class of photochromic molecules that exhibit photo-switching in the solid state.

Feeding enhances fibronectin adherence of quiescent lymphocytes through non-canonical insulin signalling.

Nutritional availability during fasting and refeeding affects the temporal redistribution of lymphoid and myeloid immune cells among the circulating and tissue-resident pools. Conversely, nutritional imbalance and impaired glucose metabolism are associated with chronic inflammation, aberrant immunity and anomalous leukocyte trafficking. Despite being exposed to periodic alterations in blood insulin levels upon fasting and feeding, studies exploring the physiological effects of these hormonal changes on quiescent immune cell function and trafficking are scanty.

Asymmetrically Coordinated Heterodimetallic Ir-Ru System: Synthesis, Computational, and Anticancer Aspects.

Herein, we present an unprecedented formation of a heterodinuclear complex [{(ppy)Ir}(μ-phpy){Ru(tpy)}](ClO) {[](ClO)} using terpyridyl/phenylpyridine as ancillary ligands and asymmetric phpy as a bridging ligand. The asymmetric binding mode (NN-∩-NNC) of the phpy ligand in {[](ClO)} is confirmed by H, C, H-H correlated spectroscopy (COSY), high-resolution mass spectrum (HRMS), single-crystal X-ray crystallography techniques, and solution conductivity measurements. Theoretical investigation suggests that the highest occupied molecular orbital (HOMO) and the least unoccupied molecular orbital (LUMO) of [] are located on iridium/ppy and phpy, respectively.

Anomalous Vapor and Ice Nucleation in Water at Negative Pressures: A Classical Density Functional Theory Study.

In contrast to the abundance of work on the anomalous behavior of water, the relationship between the water's thermodynamic anomalies and kinetics of phase transition from metastable water is relatively unexplored. In this work, we have employed classical density functional theory to provide a unified and coherent picture of nucleation (both vapor and ice) from metastable water at negative pressure conditions. Our results suggest a peculiar nonmonotonic temperature dependence of vapor-liquid surface tension at temperatures where vapor-liquid coexistence is metastable with respect to the ice phase.

An innate pathogen sensing strategy involving ubiquitination of bacterial surface proteins.

Sensing of pathogens by ubiquitination is a critical arm of cellular immunity. However, universal ubiquitination targets on microbes remain unidentified. Here, using in vitro, ex vivo, and in vivo studies, we identify the first protein-based ubiquitination substrates on phylogenetically diverse bacteria by unveiling a strategy that uses recognition of degron-like motifs.

An accelerated Rauhut-Currier dimerization enabled the synthesis of (±)-incarvilleatone and anticancer studies.

The total synthesis of racemic incarvilleatone has been achieved by utilizing unexplored accelerated Rauhut-Currier (RC) dimerization. The other key steps of the synthesis are oxa-Michael and aldol reactions in a tandem sequence. Racemic incarvilleatone was separated by chiral HPLC and the configuration of each enantiomer was determined by single-crystal X-ray analysis.

A novel molecular reporter for probing protein DNA recognition: An optical spectroscopic and molecular modeling study.

A novel benzo[a]phenoxazine-based fluorescent dye LV2 has been employed as a molecular reporter to probe recognition of a linker histone protein H1 by calf-thymus DNA (DNA). Fluorescence lifetime of LV2 buried in the globular domain of H1 (∼2.1 ns) or in the minor groove of DNA (∼0.

Ccn2a-FGFR1-SHH signaling is necessary for intervertebral disc homeostasis and regeneration in adult zebrafish.

Intervertebral disc (IVD) degeneration is the primary cause of back pain in humans. However, the cellular and molecular pathogenesis of IVD degeneration is poorly understood. This study shows that zebrafish IVDs possess distinct and non-overlapping zones of cell proliferation and cell death.