Can conformational flexibility influence the self-assembly behavior and sensing efficacy of fluorogenic amphiphiles? A case study with bisbenzimidazole-based probes.

In this work, we have explored the metal ion sensing properties of two bisbenzimidazole-based fluorescent probes, that differ in their conformational flexibility, in an aqueous medium. The compound with a flexible methyl spacer (1) experienced blue shifts in its absorption and emission maxima (along with a turn-off response) upon the addition of Hg ions. On the contrary, the compound with a relatively rigid structure (2) showed red shifts in both its absorption and emission maxima (along with a turn-off response) when treated with Hg under similar conditions.

Optimizing Linezolid: Transforming It into a Selective MAO-B Inhibitor via a Toxicity-to-Activity Optimization Approach.

Linezolid, a widely used oxazolidinone antibiotic, exhibits potent activity against resistant bacterial infections but is associated with serotonergic toxicity, primarily due to its inhibition of monoamine oxidase (MAO). MAOs, consisting of MAO-A and MAO-B isoforms, play crucial roles in neurotransmitter metabolism, with implications for neurodegenerative disorders like Parkinson's and Alzheimer's diseases. This study aims to optimize Linezolid's structure to transform it into a selective MAO-B inhibitor.

Unfolding the Potential of Pyrrole- and Indole-Based Allylidene Hydrazine Carboximidamides as Antimicrobial Agents.

Antimicrobial drug resistance is a significant global health challenge, causing hundreds of thousands of deaths annually and severely impacting healthcare systems worldwide. Several reported antimicrobial compounds have a guanidine motif, as the positive charge on guanidine promotes cell lysis. Therefore, pyrrole- and indole-based allylidene hydrazine carboximidamide derivatives with guanidine motifs are proposed as antimicrobial agents that mimic cationic antimicrobial peptides (CAMPs).

Modulation in the charge transfer characteristics of flexible bis-benzimidazole probes: independent sensing mechanisms for Hg and F.

Flexible bis-benzimidazole-based V-shaped amphiphilic probes (1 and 2) that form a fluorescent nanoscopic assembly in aqueous media have been designed. The ion-binding properties of compound 1 are investigated in both polar protic (water) and aprotic (acetonitrile) solvents. In acetonitrile, the compound shows a distinct chromogenic response towards Hg (LOD: 8.

Targeting the epigenome with advanced delivery strategies for epigenetic modulators.

Epigenetics mechanisms play a significant role in human diseases by altering DNA methylation status, chromatin structure, and/or modifying histone proteins. By modulating the epigenetic status, the expression of genes can be regulated without any change in the DNA sequence itself. Epigenetic drugs exhibit promising therapeutic efficacy against several epigenetically originated diseases including several cancers, neurodegenerative diseases, metabolic disorders, cardiovascular disorders, and so forth.

Engaging a highly fluorescent conjugated polymer network for probing endogenous hypochlorite in macrophage cells: improved sensitivity signal amplification.

We have employed a triazine-based conjugated polymer network (CPN) for the selective detection of hypochlorite in a semi-aqueous environment. CPNs have been widely employed in gas capture, separation, and adsorption, but the fluorescent properties of CPNs possessing extensive π-conjugated systems tend to be unexplored. Herein, we report the photophysical properties of the CPN and investigate its sensing capability towards hypochlorite.

Unveiling structural components of dibenzofuran-based MMP-12 inhibitors: a comparative classification-dependent analysis with molecular docking-based virtual screening and molecular dynamics simulation.

Unlabelled: The implication of matrix metalloproteinase-12 (MMP-12) in various major disorders including cancer, COPD, cardiovascular disorders, and neurological diseases makes it a potential target for drug discovery. Contemplating the significance of MMP-12, a number of MMP-12 inhibitors were designed, synthesized and tested throughout the world but the non-selective nature of most of those molecules can lead to adverse drug interactions. In contradiction, the dibenzofuran (DBF) and dibenzothiophene (DBT) derivatives showed highly potent and selective MMP-12 inhibition.

Design, Synthesis and in vitro Evaluation of Primaquine and Diaminoquinazoline Hybrid Molecules Against the Malaria Parasite.

In this study, we built on the known inhibitory potential of diaminoquinazolines (DAQs) against different stages of Plasmodium development and designed a convenient two-step synthesis to combine DAQ with primaquine (PQ) pharmacophore. The PQ-DAQ hybrids displayed potent in vitro activities in the low nanomolar range (IC 135.20-398.

Structure and dynamics of piperidinium based amino acid ionic liquids: a computational investigation.

Context: There has been growing interest in amino acid ionic liquids because of their low-cost synthesis and superior biodegradability and biocompatibility compared to traditional ionic liquids. In this study, we have investigated the structure and dynamics of three ionic liquids consisting of N-butyl N-methyl piperidinium [Pip] cation with amino acid (lysine [Lys], histidine [His], and arginine [Arg]) anions. The radial distribution functions, the spatial distribution functions, and the coordination numbers have been used to analyze the structure in the bulk phase.

Deep learning-based encryption scheme for medical images using DCGAN and virtual planet domain.

The motivation for this article stems from the fact that medical image security is crucial for maintaining patient confidentiality and protecting against unauthorized access or manipulation. This paper presents a novel encryption technique that integrates the Deep Convolutional Generative Adversarial Networks (DCGAN) and Virtual Planet Domain (VPD) approach to enhance the protection of medical images. The method uses a Deep Learning (DL) framework to generate a decoy image, which forms the basis for generating encryption keys using a timestamp, nonce, and 1-D Exponential Chebyshev map (1-DEC).

Novel therapeutic targets for cardiorenal syndrome.

Cardiorenal syndrome (CRS) is an interdependent dysfunction of the heart and kidneys, where failure in one organ precipitates failure in the other. The pathophysiology involves sustained renin-angiotensin-aldosterone-system (RAAS) activation, mitochondrial dysfunction, inflammation, fibrosis, oxidative stress and tissue remodeling, culminating in organ dysfunction. Existing therapies targeting the RAAS, diuretics and other agents have limitations, including diuretic resistance and compensatory sodium reabsorption.

An integrated DEA-fuzzy AHP method for prioritization of renewable energy sources in India.

As India's population grows and urbanization accelerates, energy demand is increasing sharply while conventional sources fall behind. To tackle energy shortages and climate change, India must prioritize renewable energy sources (RES), which offer sustainable solutions. The country is rich in RES, which can enhance fuel mix for electricity generation.

TEMPO-Mediated Direct C(sp)-H Alkoxylation/Aryloxylation of 1,4-Quinones.

A convenient and efficient transition-metal-free method has been developed for the C(sp)-H alkoxylation/aryloxylation of 1,4-quinones by direct cross-dehydrogenative coupling with readily available alcohols and phenols in the presence of TEMPO under simple and mild conditions. The method allowed the installation of a wide range of alkoxy/aryloxy groups, exhibited high functional group tolerance, showed a broad substrate scope, afforded good to excellent yields of products in a simple one-pot operation, and could be performed on a gram scale. Mechanistic investigation indicated the involvement of the radical pathway.

The Effects of Electronic Cigarettes on Oral Microbiome and Metabolome in 3D Tissue-Engineered Models.

Background And Aim: Recent studies have shown that electronic cigarettes (ECs) use disrupts the oral microbiome composition and diversity, impairing the metabolic pathways of the mucosal cells. However, to date, no reports have evaluated the role of EC exposure in the context of oral metabolome. Hence, the aim of this study was to investigate the role of EC aerosol exposure in the dysregulation of the oral microbiome and metabolome profile using in vitro 3D organotypic models of human oral mucosa.

Solid lipid nanoparticles for increased oral bioavailability of acalabrutinib in chronic lymphocytic leukaemia.

Acalabrutinib (ACP) is a first-line treatment for chronic lymphocytic leukemia but suffers from poor and variable oral bioavailability due to its pH-dependent solubility, CYP3A4 metabolism, and P-gp efflux. Thus, the objective of this study was to improve the solubility and dissolution behaviour, in turn enhancing bioavailability, by formulating solid lipid nanoparticles (SLNs). ACP loaded SLNs (ACP-SLNs) were prepared via solvent-free hot emulsification followed by a double sonication process.

Beyond metabolic messengers: Bile acids and TGR5 as pharmacotherapeutic intervention for psychiatric disorders.

Psychiatric disorders pose a significant global health challenge, exacerbated by the COVID-19 pandemic and insufficiently addressed by the current treatments. This review explores the emerging role of bile acids and the TGR5 receptor in the pathophysiology of psychiatric conditions, emphasizing their signaling within the gut-brain axis. We detail the synthesis and systemic functions of bile acids, their transformation by gut microbiota, and their impact across various neuropsychiatric disorders, including major depressive disorder, general anxiety disorder, schizophrenia, autism spectrum disorder, and bipolar disorder.

LncRNA MALAT1 as a potential diagnostic and therapeutic target in kidney diseases.

Long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript1 (MALAT1) has emerged as a crucial biomarker and therapeutic target for kidney diseases, including acute kidney injury (AKI), chronic kidney disease (CKD), diabetic kidney disease (DKD), lupus nephritis (LN), and renal cell carcinoma (RCC). LncRNAs are non-coding RNAs that have more than 200 nucleotides that play a crucial role in gene regulation at the post-translational stage, transcriptional, and epigenetic levels. LncRNA MALAT1 regulates gene expression and modulates cellular functions such as proliferation, inflammation, apoptosis, and fibrosis, which are key pathophysiology of kidney diseases.

Preeminent designing of complementary TRANSFER and COMPLEMENT alongside excitation modulated molecular logic systems.

This article describes an optically adjustable, dual complementary molecular TRANSFER and COMPLEMENT logic gate as well as an extremely rare design of excitation-modulated logic systems using a pyrene coupled bis(indolyl)methane derivative (1) in Brij-58 micelles, triggered by different chemical stimuli. We have looked into the optical response of the probe molecule towards variety of analytes, including OH, CN, Hg, EDTA ., at various excitation channels, in order to achieve this goal.

An overview of matrix metalloproteinase-12 in multiple disease conditions, potential selective inhibitors, and drug designing strategies.

Matrix metalloproteases (MMPs) are the proteolytic enzymes accountable for extracellular matrix (ECM) modification through their Zn-dependent catalytic activity. Among these, MMP-12 is one of the crucial MMPs that contributes to various disease states including different types of cancers and other major pathophysiological conditions including COPD, asthma, emphysema, skin diseases, arthritis, vascular diseases, and neurological disorders. The majority of the MMP-12 inhibitors should have three constitutional pharmacophoric features (i.

Derivatives of D(-)-glutamine-based MMP-2 inhibitors as an effective remedy for the management of chronic myeloid leukemia-Part-III: Synthesis, biological screening and in silico binding interaction analysis.

Tyrosine kinase inhibitors (TKIs) have markedly improved the overall survival rate of patients with chronic myeloid leukemia (CML), enabling them to achieve a normal life expectancy. However, toxicity, relapse, and drug resistance continue to pose major challenges in the clinical treatment of CML. The progression of leukemia is directly connected to higher expression levels and enzymatic actions of matrix metalloproteinase-2 (MMP-2).

Insights of Zinc Ion Storage in Chilli-Stem Derived Porous Carbon Enabling Ultrastability and High Energy Density of Zinc-Ion Hybrid Supercapacitors.

Aqueous zinc ion hybrid supercapacitors (ZIHSCs) are promising as low-cost and safe energy storage devices for next-generation applications. Still, their energy-power performance and durability are far from satisfactory. Here, we present an energy-dense, and ultrastable ZIHSC realized using activated porous carbons derived from chilli-stems.

Membrane-Bound Bisindolyl-Based Chromogenic Probes: Analysis of Cyanogenic Glycosides in Agricultural Crops for Possible Remediation.

Cyanogenic glycosides are plant-derived, nitrogen-containing secondary metabolites that release toxic cyanide ions upon hydrolysis by glycosidic enzymes. Therefore, consuming food items enriched with such compounds without proper remediation can cause acute cyanide intoxication. Thus, in this work, we utilize cyanide-responsive oxidized bisindole-based chromogenic probes to detect cyanogenic glycosides, such as amygdalin and linamarin (LOD: 0.

TBK1 Reprograms Metabolism in Breast Cancer: An Integrated Omics Approach.

Metabolic rewiring is required for cancer cells to survive in harsh microenvironments and is considered to be a hallmark of cancer. Specific metabolic adaptations are required for a tumor to become invasive and metastatic. Cell division and metabolism are inherently interconnected, and several cell cycle modulators directly regulate metabolism.

Discovery of novel hybrid tryptamine-rivastigmine molecules as potent AChE and BChE inhibitors exhibiting multifunctional properties for the management of Alzheimer's disease.

Contemporary research evidence has corroborated a gradual loss of central cholinergic neurons in Alzheimer's Disease (AD). This progressive deterioration leads to cognitive dysfunction and impaired motor activity, culminating in the brain cell's death in the disease. The approved drugs for AD treatment can only offer relief from symptoms without addressing the underlying pathological hallmarks of the disease.