Antisense Oligonucleotide Embedded Context Responsive Nanoparticles Derived from Synthetic Ionizable Lipids for lncRNA Targeted Therapy of Breast Cancer.

The long noncoding RNAs (lncRNA) are primarily associated with several essential gene regulations but are also connected to cancer metabolism and progression. HOTAIR and MALAT1 are two such lncRNAs that are detected in malignancies of various origins and are responsible for the poor prognosis of cancer patients. Due to these factors, the lncRNAs have emerged as prime targets for the development of anticancer therapeutics. However, nonviral delivery of lncRNA-targeted antisense oligonucleotides (ASOs) still remains a critical challenge while maintaining their structural and functional integrity. Herein, we have designed and synthesized a new series of ionizable lipids with variations in their head groups to prepare lipid nanoparticle (LNP) formulation along with cholesterol-based twin cationic lipid and amphiphilic zwitterionic lipid. The context responsiveness of these formulations in delivering the ASOs has been thoroughly investigated by various bioanalytical techniques, and an optimum formulation has been identified. The LNPs are utilized to deliver the ASOs targeting HOTAIR lncRNA in human cancer cell lines and MALAT1 lncRNA in mouse models. This study thus standardizes an advanced nanomaterial system for nonviral gene delivery that has been validated by a considerable reduction in the target lncRNA level under in vitro and a significant reduction in tumor volume under in vivo settings.

A Nano-Aggregatable Acedan Derivative for Clathrin-Mediated Cellular Uptake and Two-Photon Imaging of Diabetes-Associated Lipid Droplets.

Lipid droplets (LDs), the essential cytosolic fat storage organelles, have emerged as pivotal regulators of cellular metabolism and are implicated in various diseases. The noninvasive monitoring of LDs necessitates fluorescent probes with precise organelle selectivity and biocompatibility. Addressing this need, we have engineered a probe by strategically modifying the structure of a conventional two-photon-absorbing dipolar dye, acedan. This innovative approach induces nanoaggregate formation in aqueous environments, leading to aggregation-induced fluorescence quenching. Upon cellular uptake via clathrin-mediated endocytosis, the probe selectively illuminates within LDs through a disassembly process, effectively distinguishing LDs from the cytosol with exceptional specificity. This breakthrough enables the high-fidelity imaging of LDs in both cellular and tissue environments. In a pioneering investigation, we probed LDs in a diabetes model induced by streptozotocin, unveiling significantly heightened LD accumulation in cardiac tissues compared to other organs, as evidenced by TP imaging. Furthermore, our exploration of a lipopolysaccharide-mediated cardiomyopathy model revealed an LD accumulation during heart injury. Thus, our developed probe holds immense potential for elucidating LD-associated diseases and advancing related research endeavors.

Anticancer Prodrug Capable of Mitochondria-Targeting, Light-Triggered Release, and Fluorescence Monitoring.

Mitigating the adverse effects of anticancer agents requires innovative prodrug engineering. In this study, we showcase the potential of our o-quinone methide-based trigger-release-conjugation platform as a versatile tool for constructing advanced prodrug systems. Using this platform, we achieved the light-triggered release of an anticancer drug mechlorethamine, targeting mitochondrial DNA. The entire process was adeptly tracked through the emission of fluorescence signals, revealing notable effects across various cancer cell lines compared to a normal cell line. Exploring alternative cancer-associated triggers, including enzymes, and incorporating cancer/tumor-specific targeting elements could lead to effective prodrugs with reduced cytotoxicity.

Nitroreductase-Triggered Fluorophore Labeling of Cells and Tissues under Hypoxia.

Several reductases, including nitroreductase, are upregulated under hypoxic conditions characterized by an oxygen-deficient microenvironment. Given that hypoxia is a prominent feature of solid tumors, our investigation focused on developing a bioconjugative probe designed for staining tissue under hypoxic conditions, particularly activated by nitroreductase. This probe, developed using our trigger-release-bioconjugation system rooted in the ortho-quinone methide chemistry, exhibited selective activation by nitroreductase and fluorophore labeling within mitochondria and endoplasmic reticulum. As a result, it displayed sustained fluorescence that persisted even after washing steps in cells and tissues. We applied this innovative probe to stain mouse kidney tissue in an acute kidney injury model induced by inadequate oxygen supply. Among various organ tissues examined, only kidney tissue showed significantly higher fluorescence in the injury model compared with the control tissue, as revealed by two-photon microscopic imaging. This research presents a promising avenue for the development of practical staining agents for image-guided tumor surgery.

Hyperinsulinemic State and Hypokalemic Quadriparesis in Tropical Fever: Is There a Link?

It is rare for quadriparesis to manifest as a symptom of tropical illnesses. With a history of only one fever episode one week prior, our patient, a 48-year-old male with obesity and prediabetes, who was also known to have ankylosing spondylitis, presented with acute onset flaccid quadriparesis. He did not exhibit any additional symptoms of dengue, such as bleeding tendencies, petechial rashes, thrombocytopenia, or febrile episodes. Upon examination, it was discovered that he had extremely low serum potassium levels and was dengue non-specific antigen 1 (NS1) positive. His hyperinsulinemia, as seen by elevated C peptide levels, most likely caused a transcellular shift that was then triggered by the dengue infection, leading to hypokalemic paralysis.

Chromone-Based Cd(II) Fluorescent Coordination Polymer Fabricated to Study Optoelectronic and Explosive Sensing Properties.

Here, electrical conductivity and explosive sensing properties of multifunctional chromone-Cd(II)-based coordination polymers (CPs) (1-4) have been explored. The presence of different pseudohalide linkers, thiocyanate ions, and dicyanamide ions resulted in 1D and 3D architecture in the CPs. Thin film devices developed from CPs 1-4 (complex-based Schottky devices, CSD1, CSD2, CSD3, and CSD4, respectively) showed semiconductor behavior. Their conductivity values increased under photo illumination (1.37 × 10-5, 1.85 × 10-5, 1.61 × 10-5, and 2.01 × 10-5 S m-1 under dark conditions and 5.06 × 10-5, 8.78 × 10-5, 7.26 × 10-5, and 10.21 × 10-5 S m-1 under light). The nature of the I-V plots of these thin film devices under light irradiation and dark are nonlinear rectifying, which has been observed in Schottky barrier diodes (SBDs). All four CPs (1-4) exhibited highly selective fluorescence quenching-based sensing properties toward well-known explosives, 2,4-dinitrophenol (DNP) and 2,4,6-trinitrophenol (TNP). The limit of detection (LOD) values are 55, 28, 27, and 31 µM for TNP and 78, 44, 32, and 41 µM for DNP for complexes 1-4, respectively. A structure property correlation has been established to explain optoelectronic and explosive sensing properties.

A novel recurrence-based approach for investigating multiphase flow dynamics in bubble column reactors.

In chemical industries, multiphase flows in a bubble column reactor are frequently observed. The nonlinearity associated with bubble hydrodynamics, such as bubble-bubble and bubble-liquid interactions, gives rise to complex spatiotemporal patterns with increased gas or liquid velocities, which are extremely difficult to model and predict. In the current study, we propose a new, computationally efficient recurrence-based approach involving the angular separation between suitably defined state vectors and implement it on the experimental multiphase flow variables. The experimental dataset that consists of image frames obtained using a high-speed imaging system is generated by varying air and water flow rates in a bubble column reactor setup. The recurrence plots using the new approach are compared with those derived from conventional recurrence, considering standard benchmark problems. Further, using the recurrence plots and recurrence quantification from the new recurrence methodology, we discover a transition from a high recurrence state to a complex regime with very low recurrence for an increase in airflow rate. Determinism exhibits a rise for the decrease in airflow rate. A sharp decline in determinism and laminarity, signifying the quick shift to complex dynamics, is more prominent for spatial recurrence than temporal recurrence, indicating that the rise in airflow rate significantly impacts the spatial location of bubbles. We identify three regimes that appeared as distinct clusters in the determinism-laminarity plane. The bubbly regime, characterized by high values of determinism and laminarity, is separated by an intermediate regime from the slug flow regime, which has low determinism and laminarity.

TiO2 nanorods decorated Si nanowire hierarchical structures for UV light activated photocatalytic application.

Water remediation techniques like photolysis have recently piqued the interest of many researchers due to water contamination resulting from heavy industrialization and urbanization. In the current work, as-synthesized TiO2 nanorod decorated vertically aligned silicon nanowire (SiNW) leads to a hierarchical morphological structure formation. The photocatalytic nature of the fabricated SiNW/TiO2 nanoheterojunction is examined by the dye degradation of textile pollutants like methylene blue (MB), rhodamine B (RhB), and eosin B (EB). The catalytic dye degradation investigations revealed that 4 h hydrothermal synthesis of TiO2 on the surface of SiNW (ST4) exhibited excellent catalytic behaviour. In the presence of H2O2 and UV irradiation, the ST4 nanoheterostructure can degrade 98.89% of the model pollutant methylene blue (MB) in 15 min, demonstrating remarkable photocatalytic performance. The direct Z-scheme heterojunction exhibited by the SiNW/TiO2 structure facilitates a more efficient charge transfer mechanism with higher reducing and oxidizing ability leading to enhanced photocatalytic behaviour. The degradation pathway examined by LC-MS studies demonstrated the complete breakdown of the organic MB dye molecules ultimately mineralizing into CO2, H2O, and other inorganic substances. The photocatalyst ST4 exhibited excellent reusability and stability after multiple cycles of dye degradation enabling its use in practical water purification purposes.

Leveraging Wettability Engineering to Develop Three-Layer DIY Face Masks From Low-Cost Materials.

With the rapid spread of COVID-19 worldwide, the demand for appropriate face masks in the market has also skyrocketed. To ease strain on the supply of masks to the essential healthcare sector, it has become imperative that ordinary people rely more on home-made masks that can be easily put together using commonly available materials, while at the same time performing reasonably at arresting the ingress or egress of airborne droplets. Here, we propose a simple do-it-yourself (DIY) method for preparing a three-layered face mask that deploys two hydrophobic polypropylene nonwoven layers interspaced with a hydrophilic cellulosic cloth. The first hydrophobic layer, facing the user, allows high-momentum droplets (e.g., expelled by a sneeze or cough) to pass through and get absorbed in the next hydrophilic layer, thereby keeping the skin in contact with the mask dry and comfortable. The third (outermost) hydrophobic layer prevents penetration of the liquids from the middle layer to the outside, and also arrests any airborne droplets on its exterior. Simple tests show that our masks perform better in arresting the droplet transmission as compared to surgical masks available in the market.