Innovative Electrodeposition of Bimetallic Cu–Sn in a Stable Nonelectroactive Pyrophosphate-Based Bath: Reduction and Nucleation Growth Analysis

The timeless allure of Cu–Sn-based intermetallics, commonly known as bronze, stems from their remarkable versatility across a wide range of applications. When used as coatings on stainless steel, Cu–Sn brings forth a host of advantages including enhanced aesthetics, corrosion resistance, low surface tension, weldability, and ductility. However, the electroplating of Cu–Sn onto stainless steel by using acidic baths proves to be a costly affair due to the inherent instability of the acidic solution. Moreover, the short lifespan of the bath necessitates the use of expensive additives. In this study, we present an innovative approacha stable and cost-effective basic pyrophosphate-based electrolyte bath, to deposit Cu, Sn, and Cu–Sn coatings. Through X-ray diffraction analysis, the Cu–Sn coatings on stainless steel are found to predominantly consist of Cu13.7Sn and Cu3Sn phases, with a minor presence of elemental Sn. Impressively, the Cu–Sn bath exhibits a high current efficiency of 92% and demonstrates exceptional long-term stability, maintaining its integrity for over a year even when exposed to ambient air. To gain deeper insights into the nucleation and growth mechanisms, we conduct a comprehensive investigation employing cyclic voltammetric and chronoamperometric studies. By employing the Scharifker–Hills model, we meticulously analyze the nucleation and growth steps, while further analysis of the cyclic voltammetric results allows us to unravel the intricacies of diffusion kinetics during deposition

First Evidence of the Liposome-Mediated Deintercalation of Anticancer Drug Doxorubicin from the Drug–DNA Complex: A Spectroscopic Approach

Biocompatible liposomes were used for the first time to study the deintercalation process of a prominent anticancer drug, doxorubicin (DOX), from doxorubicin-intercalated DNA (DOX–DNA complex) under controlled experimental conditions. The study revealed that anionic liposomes (DMPG liposomes) appeared to be the most effective to bring in the highest percentage of drug release while cationic liposomes (DOTAP liposomes) scored the lowest percentage of release. The drug release was primarily attributed to the electrostatic interaction between liposomes and drug molecules. Apart from this interaction, changes in the hydrophobicity of the medium upon addition of liposomes to the DNA–drug solution accompanied by lipoplex formation between DNA and liposomes were also attributed to the observed deintercalation. The CD and the time-resolved rotational relaxation studies confirmed that lipoplex formation took place between liposomes and DNA owing to electrostatic interaction. The confocal study revealed that in the postrelease period, DOX binds with liposomes. The reason behind the binding is electrostatic interaction as well as the unique bilayer structure of liposomes which helps it to act as a “hydrophobic sink” for DOX. The study overall highlighted a novel strategy for deintercalation of drug using biocompatible liposomes, as the release of the drug can be controlled over a period of time by varying the concentration and composition of the liposomes

Biofilm Impeding AgNPs Target Skin Carcinoma by Inducing Mitochondrial Membrane Depolarization Mediated through ROS Production

Reactive oxygen species (ROS) are a double-edged sword that possesses both beneficial and harmful effects. Although basic research on skin cancer prevention has undergone a huge transformation, cases of recurrence with higher rates of drug resistance are some of its drawbacks. Therefore, targeting mitochondria by ROS overproduction provides an alternate approach for anticancer therapy. In the present study, green-synthesized silver nanoparticles (AgNPs) were explored for triggering the ROS production in A431 skin carcinoma cells. The synthesized AgNPs were characterized for size, charge, morphology, and phase through high-throughput DLS, Fe-SEM, XRD, and ATR-FTIR techniques. Their physiochemical properties with hemoglobin and blood plasma were screened through hemolysis, hemagglutination assay, and circular dichroism spectroscopy confirmed their nontoxic nature. The AgNPs also exhibited additional efficacy in inhibiting biofilm produced by V. cholerae and B. subtilis, thereby facilitating better applicability in wound-healing biomaterials. The depolarization of mitochondrial membrane potential ΔΨm through excess ROS production was deduced to be the triggering force behind the apoptotic cell death mechanism of the skin carcinoma. Subsequent experimentation through DNA fragmentation, comet tail formation, cell membrane blebbing, and reduced invasiveness potentials through scratch assay confirmed the physiological hallmarks of apoptosis. Thus, depolarizing mitochondrial membrane potential through green-synthesized AgNPs provides an economic, nontoxic, specific approach for targeting skin carcinoma with additional benefits of antibacterial activities

Type I Interferon Programs Innate Myeloid Dynamics and Gene Expression in the Virally Infected Nervous System

<div><p>Viral infections of central nervous system (CNS) often trigger inflammatory responses that give rise to a wide range of pathological outcomes. The CNS is equipped with an elaborate network of innate immune sentinels (e.g. microglia, macrophages, dendritic cells) that routinely serve as first responders to these infections. The mechanisms that underlie the dynamic programming of these cells following CNS viral infection remain undefined. To gain insights into this programming, we utilized a combination of genomic and two-photon imaging approaches to study a pure innate immune response to a noncytopathic virus (lymphocytic choriomeningitis virus) as it established persistence in the brain. This enabled us to evaluate how global gene expression patterns were translated into myeloid cell dynamics following infection. Two-photon imaging studies revealed that innate myeloid cells mounted a vigorous early response to viral infection characterized by enhanced vascular patrolling and a complete morphological transformation. Interestingly, innate immune activity subsided over time and returned to a quasi-normal state as the virus established widespread persistence in the brain. At the genomic level, early myeloid cell dynamics were associated with massive changes in CNS gene expression, most of which declined over time and were linked to type I interferon signaling (IFN-I). Surprisingly, in the absence of IFN-I signaling, almost no differential gene expression was observed in the nervous system despite increased viral loads. In addition, two-photon imaging studies revealed that IFN-I receptor deficient myeloid cells were unresponsive to viral infection and remained in a naïve state. These data demonstrate that IFN-I engages non-redundant programming responsible for nearly all innate immune activity in the brain following a noncytopathic viral infection. This Achilles' heel could explain why so many neurotropic viruses have acquired strategies to suppress IFN-I.</p></div

Carbon Dots as Nanodispersants for Multiwalled Carbon Nanotubes: Reduced Cytotoxicity and Metal Nanoparticle Functionalization

The colloidal stabilization of multiwalled carbon nanotubes (MWCNTs) in an aqueous medium through noncovalent interactions has potential benefits toward the practical use of this one-dimensional carbonaceous material for biomedical applications. Here, we report that fluorescent carbon nanodots can efficiently function as dispersing agents in the preparation of stable aqueous suspensions of CNTs at significant concentrations (0.5 mg/mL). The amphiphilic nature of carbon dots with a hydrophobic graphitic core could effectively interact with the CNT surface, whereas hydrophilic oxygenated functionalization on the C-dot surface provided excellent water dispersibility. The resultant CNT-C-dot composite showed significantly reduced cytotoxicity compared to that of unmodified or protein-coated CNTs, as demonstrated by cell viability and proliferation assays. Furthermore, the reducing capability of C-dots could be envisaged toward the formation of a catalytically active metal nanoparticle-CNT-C-dot composite without the addition of any external reducing or stabilizing agents that showed excellent catalytic activity toward the reduction of <i>p</i>-nitrophenol in the presence of NaBH₄. Overall, the present work establishes C-dots as an efficient stabilizer for aqueous dispersions of CNTs, leading to an all-carbon nanocomposite that can be useful for different practical applications

PAWR-mediated suppression of BCL2 promotes switching of 3-azido withaferin A (3-AWA)-induced autophagy to apoptosis in prostate cancer cells

<div><p>An active medicinal component of plant origin with an ability to overcome autophagy by inducing apoptosis should be considered a therapeutically active lead pharmacophore to control malignancies. In this report, we studied the effect of concentration-dependent 3-AWA (3-azido withaferin A) sensitization to androgen-independent prostate cancer (CaP) cells which resulted in a distinct switching of 2 interrelated conserved biological processes, i.e. autophagy and apoptosis. We have observed 3 distinct parameters which are hallmarks of autophagy in our studies. First, a subtoxic concentration of 3-AWA resulted in an autophagic phenotype with an elevation of autophagy markers in prostate cancer cells. This led to a massive accumulation of MAP1LC3B and EGFP-LC3B puncta coupled with gradual degradation of SQSTM1. Second, higher toxic concentrations of 3-AWA stimulated ER stress in CaP cells to turn on apoptosis within 12 h by elevating the expression of the proapoptotic protein PAWR, which in turn suppressed the autophagy-related proteins BCL2 and BECN1. This inhibition of BECN1 in CaP cells, leading to the disruption of the BCL2-BECN1 interaction by overexpressed PAWR has not been reported so far. Third, we provide evidence that <i>pawr-</i>KO MEFs exhibited abundant autophagy signs even at toxic concentrations of 3-AWA underscoring the relevance of PAWR in switching of autophagy to apoptosis. Last but not least, overexpression of EGFP-LC3B and DS-Red-BECN1 revealed a delayed apoptosis turnover at a higher concentration of 3-AWA in CaP cells. In summary, this study provides evidence that 3-AWA is a strong anticancer candidate to abrogate protective autophagy. It also enhanced chemosensitivity by sensitizing prostate cancer cells to apoptosis through induction of PAWR endorsing its therapeutic potential.</p></div

Multifunctional Inosine Monophosphate Coordinated Metal–Organic Hydrogel: Multistimuli Responsiveness, Self-Healing Properties, and Separation of Water from Organic Solvents

Outfitted with numerous coordination and hydrogen bonding sites, nucleotides represent a class of naturally occurring ligands for coordination with metals leading to both hard and soft materials for a wide range of applications. Reported herein, a new multistimuli-responsive metal–organic hydrogel through the spontaneous self-associative complexation of inosine 5′-monophosphate (IMP) with Ag­(I) ions in aqueous medium. The strong and optically transparent hydrogels were formed without the aid of any external influences such as heating/cooling cycles or ultrasonication and comprise of an interconnected matrix of nanofilaments constructed from helically stacked, chiral arrays of Ag-IMP dimers. The metallogel exhibits diverse properties including self-healing, stimuli-responsiveness, transparency, and injectibility. The direct gelation specificity to Ag (I) ions is highly phase selective only to water, and the ability of the freeze-dried xerogel to gel water is exploited for the separation of water from various organic solvents. Further, the Ag-IMP hydrogel exhibits efficient antibacterial activity against both Gram-negative <i>Escherichia coli</i> (<i>E. coli</i>) and Gram-positive <i>Staphylococcus aureus</i> (<i>S. aureus</i>) bacteria. Ag nanoparticles could be generated <i>in situ</i> without disrupting the hydrogel network through photoreduction by light. The robustness and multidimensional applicability combined with ease of synthesis make this coordination driven hydrogel a prospective material for environmental and biomedical applications

Multifunctional Inosine Monophosphate Coordinated Metal–Organic Hydrogel: Multistimuli Responsiveness, Self-Healing Properties, and Separation of Water from Organic Solvents

Outfitted with numerous coordination and hydrogen bonding sites, nucleotides represent a class of naturally occurring ligands for coordination with metals leading to both hard and soft materials for a wide range of applications. Reported herein, a new multistimuli-responsive metal–organic hydrogel through the spontaneous self-associative complexation of inosine 5′-monophosphate (IMP) with Ag­(I) ions in aqueous medium. The strong and optically transparent hydrogels were formed without the aid of any external influences such as heating/cooling cycles or ultrasonication and comprise of an interconnected matrix of nanofilaments constructed from helically stacked, chiral arrays of Ag-IMP dimers. The metallogel exhibits diverse properties including self-healing, stimuli-responsiveness, transparency, and injectibility. The direct gelation specificity to Ag (I) ions is highly phase selective only to water, and the ability of the freeze-dried xerogel to gel water is exploited for the separation of water from various organic solvents. Further, the Ag-IMP hydrogel exhibits efficient antibacterial activity against both Gram-negative <i>Escherichia coli</i> (<i>E. coli</i>) and Gram-positive <i>Staphylococcus aureus</i> (<i>S. aureus</i>) bacteria. Ag nanoparticles could be generated <i>in situ</i> without disrupting the hydrogel network through photoreduction by light. The robustness and multidimensional applicability combined with ease of synthesis make this coordination driven hydrogel a prospective material for environmental and biomedical applications

Multifunctional Inosine Monophosphate Coordinated Metal–Organic Hydrogel: Multistimuli Responsiveness, Self-Healing Properties, and Separation of Water from Organic Solvents

Outfitted with numerous coordination and hydrogen bonding sites, nucleotides represent a class of naturally occurring ligands for coordination with metals leading to both hard and soft materials for a wide range of applications. Reported herein, a new multistimuli-responsive metal–organic hydrogel through the spontaneous self-associative complexation of inosine 5′-monophosphate (IMP) with Ag­(I) ions in aqueous medium. The strong and optically transparent hydrogels were formed without the aid of any external influences such as heating/cooling cycles or ultrasonication and comprise of an interconnected matrix of nanofilaments constructed from helically stacked, chiral arrays of Ag-IMP dimers. The metallogel exhibits diverse properties including self-healing, stimuli-responsiveness, transparency, and injectibility. The direct gelation specificity to Ag (I) ions is highly phase selective only to water, and the ability of the freeze-dried xerogel to gel water is exploited for the separation of water from various organic solvents. Further, the Ag-IMP hydrogel exhibits efficient antibacterial activity against both Gram-negative <i>Escherichia coli</i> (<i>E. coli</i>) and Gram-positive <i>Staphylococcus aureus</i> (<i>S. aureus</i>) bacteria. Ag nanoparticles could be generated <i>in situ</i> without disrupting the hydrogel network through photoreduction by light. The robustness and multidimensional applicability combined with ease of synthesis make this coordination driven hydrogel a prospective material for environmental and biomedical applications

Th subset expansion in spleens of <i>cd47</i>^<i>-/-</i> and WT mice infected with <i>C</i>. <i>albicans</i>.

<p>Intracellular flow cytometry was performed on splenocytes at day 7 PI. Splenocytes were stimulated with PMA/ionomycin, and cytokine profiles were measured by five color multi-parameter flow cytometry. (A) Representative flow plots of CD4+ T cells from spleens of <i>C</i>. <i>albicans</i> infected WT vs <i>cd47</i>^<i>-/-</i> mice analyzed for intracellular IFNγ, IL-4, Il-17 and Foxp3 expression. Uninfected WT and <i>cd47</i>^<i>-/-</i> mice showed no difference in expression (data not shown). (B) Cumulative bar graph presenting the percentages of Th1 (IFNγ+), Th2 (IL-4+), Th17 (IL-17+), and Treg (Foxp3+) CD4+ T cells in infected WT and <i>cd47</i>^<i>-/-</i> mice. Results from 5 mice per group were analyzed using two-way ANOVA with post Bonferroni comparison test.</p