Chenodeoxycholic Acid-Modified Polyethyleneimine Nano-Composites Deliver Low-Density Lipoprotein Receptor Genes for Lipid-Lowering Therapy by Targeting the Liver.

Lipid-lowering drugs, especially statins, are extensively utilized in clinical settings for the prevention of hyperlipidemia. Nevertheless, prolonged usage of current lipid-lowering medications is associated with significant adverse reactions. Therefore, it is imperative to develop novel therapeutic agents for lipid-lowering therapy. In this study, a chenodeoxycholic acid and lactobionic acid double-modified polyethyleneimine (PDL) nanocomposite as a gene delivery vehicle for lipid-lowering therapy by targeting the liver, are synthesized. Results from the in vitro experiments demonstrate that PDL exhibits superior transfection efficiency compared to polyethyleneimine in alpha mouse liver 12 (AML12) cells and effectively carries plasmids. Moreover, PDL can be internalized by AML12 cells and rapidly escape lysosomal entrapment. Intravenous administration of cyanine5.5 (Cy5.5)-conjugated PDL nanocomposites reveals their preferential accumulation in the liver compared to polyethyleneimine counterparts. Systemic delivery of low-density lipoprotein receptor plasmid-loaded PDL nanocomposites into mice leads to reduced levels of low-density lipoprotein cholesterol (LDL-C) and triglycerides (TC) in the bloodstream without any observed adverse effects on mouse health or well-being. Collectively, these findings suggest that low-density lipoprotein receptor plasmid-loaded PDL nanocomposites hold promise as potential therapeutics for lipid-lowering therapy.

Community structure characteristics of ichthyoplankton during the water-sediment regulation scheme in the Yellow River in 2020 and 2021.

The Water-Sediment Regulation Scheme (WSRS) will deliver large amounts of water and sand to the Yellow River basin within a short period of time. This will significantly change the physicochemical environment of the Yellow River estuary and the surrounding marine ecosystem. Its effects on the spatial and temporal distribution patterns of ichthyoplankton are still unknown. In this study, six surface horizontal trawl surveys of ichthyoplankton were conducted during the WSRS in 2020 and 2021 using plankton nets. The results were as follows: (1) the estuarine sedentary fish Cynoglossus joyeri was the main species controlling the succession pattern of summer ichthyoplankton communities in the Yellow River estuary. (2) The WSRS influenced the ichthyoplankton community structure by changing the runoff, salinity, and suspension environment in the estuary. (3) The northern and southeastern parts of the estuary near Laizhou Bay were the main aggregation areas of the ichthyoplankton community.

Discriminant Analysis of the Nutritional Components between Organic Eggs and Conventional Eggs: A 1H NMR-Based Metabolomics Study.

The difference of nutrient composition between organic eggs and conventional eggs has always been a concern of people. In this study, 1H nuclear magnetic resonance (NMR) technique combined with multivariate statistical analyses was conducted to identify the metabolite different in egg yolk and egg white in order to reveal the nutritional components information between organic and conventional eggs. The results showed that the nutrient content and composition characteristics were different between organic and conventional eggs, among which the content of glucose, putrescine, amino acids and their derivatives were found higher in the organic eggs yolk, while phospholipids were demonstrated higher in conventional eggs yolk. Organic acid, alcohol, amine, choline and amino acids were higher in conventional eggs white, but glucose and lactate in organic egg were higher. Our study demonstrated that there are more nutritive components and higher nutritional value in organic eggs than conventional eggs, especially for the growth and development of infants and young children, and conventional eggs have more advantages in promoting lipid metabolism, preventing fatty liver, and reducing serum cholesterol. Eggs have important nutritional value to human body, and these two kinds of eggs can be selected according to the actual nutrient needs.

Preparation and Immune Effect of HEV ORF2 P206@PLGA Nanoparticles.

The hepatitis E virus (HEV) is an important pathogen that threatens global public health. One-third of the world's population lives in the epidemic area of HEV, causing 20 million infections and 70,000 deaths annually. In China, HEV transmission has changed from human-to-human transmission of HEV1 to zoonotic transmission of HEV4, causing hepatitis outbreaks throughout the country. Protecting vulnerable groups, such as practitioners related to animal husbandry and downstream consumers who are immune deficient or pregnant, from HEV infections is an urgent task. At present, the commercial human vaccine, Hecolin® (HEV 239 vaccine), is licensed for use only in China. HEV 239 vaccine is a human vaccine developed for HEV1. Although it has a cross-protective effect on HEV4, the level of immune protection is still different. To address the transformation of domestic HEV transmission modes, there is an urgent need to develop a new vaccine against zoonotic HEV4. P206@PLGA is a vaccine candidate in which nanomaterials are used to encapsulate viral capsid proteins for the immunization of livestock animals. Our experiments show that P206@PLGA has excellent biocompatibility and safety. In addition, P206@PLGA can effectively induce animals to produce a high titer of antibodies against HEV4, and thus has the potential to become a veterinary vaccine for the prevention of HEV. This approach provides a new concept for HE prevention to reduce the transmission of HEV in farms and protect susceptible populations.

Switchable smart porous surface for controllable liquid transportation.

Controllable liquid transportation through a smart porous membrane is realized by manipulating the surface wetting properties and external stimuli, and has been intensively studied. However, the liquid transportation, e.g., permeation and moving process, at the interface is generally uninterrupted, i.e., the opening and closing of the interface is irreversible. Herein, we present a new strategy to achieve magnetic adaptive switchable surfaces, i.e., liquid-infused micro-nanostructured porous composite film surfaces, for controllable liquid transportation, via modulation of the magnetic field. The liquid transportation process can be interrupted and restarted on the porous composite film because its pore structure can be quickly closed and opened owing to the adaptive morphological transformation of the magnetic liquid with a varying magnetic field. That is, the liquid permeation process occurs due to the open pore structure of the composite film when the external magnetic field is added, while the permeation process can be interrupted owing to the self-repairing closure of the pore when the magnetic field is removed, and the moving process can be achieved. Thus a magnetic field induced switchable porous composite film can serve as a valve to control liquid permeation based transportation, which opens new avenues for artificial liquid gating devices for flow, smart separation, and droplet microfluidics.

Stretch-Enhanced Anisotropic Wetting on Transparent Elastomer Film for Controlled Liquid Transport.

Direction-controlled wetting surfaces, special for lubricating oil infused anisotropic surfaces, have attracted great research interest in directional liquid collection, expelling, transfer, and separation. Nonetheless, there are still existing difficulties in achieving directional and continuous liquid transport. Herein, we present a strategy to achieve directional liquid transport on transparent lubricating oil infused elastomer film with V-shaped prisms microarray (VPM). The results reveal that the water wetting direction in the parallel and staggered arrangement of the VPM structure surface with lubricating oil infusion is the opposite, which is completely different from the wetting direction on the usual VPM surface in air. Moreover, asymmetric stretching can enhance or weaken the directional water wetting tendency on the lubricating oil infused VPM elastomer film and even can reverse the droplet wetting direction. In a closed moist environment, tiny droplets gradually coalesce and then slip away from the lubricating oil infused VPM surface to keep the surface transparent, due to the cooperation of imbalanced Laplace pressure, resulting from the anisotropic geometric structures, varying VPMs spacing, and gravity. Thus, this work provides a paradigm to design and fabricate a type of surface engineering material in the application fields of directional expelling, liquid collection, anti-biofouling, anti-icing, drag reduction, anticorrosion, etc.

Toxicity, biodistribution and oxidative damage caused by zirconia nanoparticles after intravenous injection.

Background: As a promising nanomaterial for biomedical applications, zirconia nanoparticles (ZrO2) have aroused concern recently, but the toxicity of ZrO2 in vivo has received little attention. Purpose: The aim of this study is to demonstrate the systematic single dose toxicity, biodistribution and oxidative damage of ZrO2 in vivo after intravenous injection in mice. Materials and methods: Ten ICR mice were used at the high dose of ZrO2 including 600, 500, 400 and 300mg/kg. Maximum tolerated dose (MTD) of 150 nm ZrO2 was determined as 500mg/kg. Hematology analysis and blood biochemical assay were determined for the evaluation of oxidative damage caused by ZrO2. Biodistribution of ZrO2 was investigated by ICP-OES and TEM. Results: Mice treated with higher dose (500mg/kg) showed significant spread in white blood cell counts (p<0.05). Especially, the serum ALT levels of 500mg/kg groups increased significantly (p<0.05) compared with the control group. ZrO2 particles would not induce any changes in appearance and micromorphology of liver at 100 and 350mg/kg. Spleen samples showed no significant changes in micromorphology of the lymphoid follicles and in the size of the red pulp after injection of ZrO2 at all doses. The serum of ZrO2-treated animals (350 and 500mg/kg) has reduced levels of SOD compared to the control group (p<0.05). ZrO2 persists in membrane-enclosed vesicles called lysosomes in the liver and spleen macrophages without abnormal changes of ultrastructure. Conclusion: These findings would contribute to the future development of ZrO2-based drug delivery system and other biomedical applications.

Molecular imaging of peroxynitrite with HKGreen-4 in live cells and tissues.

Peroxynitrite (ONOO(-)), the product of a radical combination reaction of nitric oxide and superoxide, is a potent biological oxidant involved in a broad spectrum of physiological and pathological processes. Herein we report the development, characterization, and biological applications of a new fluorescent probe, HKGreen-4, for peroxynitrite detection and imaging. HKGreen-4 utilizes a peroxynitrite-triggered oxidative N-dearylation reaction to achieve an exceptionally sensitive and selective fluorescence turn-on response toward peroxynitrite in chemical systems and biological samples. We have thoroughly evaluated the utility of HKGreen-4 for intracellular peroxynitrite imaging and, more importantly, demonstrated that HKGreen-4 can be efficiently employed to visualize endogenous peroxynitrite generated in Escherichia coli-challenged macrophages and in live tissues from a mouse model of atherosclerosis. This probe should serve as a powerful molecular imaging tool to explore peroxynitrite biology under a variety of physiological and pathological contexts.

Synthetic fluorescent probes for imaging of peroxynitrite and hypochlorous acid in living cells.

Peroxynitrite (ONOO(-)) and hypochlorous acid (HOCl) are two highly reactive oxygen species generated in biological systems. The overproduction of peroxynitrite or hypochlorous acid is implicated in a broad array of human pathologies including vascular, immunological, and neurodegenerative diseases. However, unambiguous detection of these reactive oxygen species has been relatively difficult due to their short biological half-lives and multiple reaction pathways. Based on their specific chemical reactions, we have developed fluorescent probes HKGreen-1 and HKOCl-1 for highly sensitive detection of peroxynitrite and hypochlorous acid, respectively. Both probes have been demonstrated to be able to discriminate corresponding reactive species from other reactive oxygen and nitrogen species (ROS and RNS) in not only chemical systems but also biological systems. The endogenous production of peroxynitrite in neuronal cells under oxygen-glucose deprivation (OGD) conditions has been visualized for the first time by utilizing HKGreen-1 probe, whilst the endogenous production of hypochlorous acid in macrophage cells upon stimulation with LPS, IFN-gamma, and PMA has been imaged by utilizing HKOCl-1 probe.

BODIPY-based fluorescent probe for peroxynitrite detection and imaging in living cells.

A fluorescent probe, HKGreen-2, has been developed based on a specific reaction between ketone and peroxynitrite (ONOO(-)). This probe is highly sensitive and selective for the detection of peroxynitrite not only in abiotic but also in biological systems. With this probe, we successfully detected peroxynitrite generated in murine macrophage cells activated by phorbol 12-myristate 13-acetate (PMA), interferon-gamma (IFN-gamma), and lipopolysaccharide (LPS). This new probe will be a useful tool for studying the roles of peroxynitrite in biological processes.

A highly specific BODIPY-based fluorescent probe for the detection of hypochlorous acid.

A fluorescent probe, HKOCl-1, has been successfully developed for the detection of hypochlorous acid on the basis of a specific reaction with p-methoxyphenol. The formation of HOCl has been successfully detected not only in an abiotic system but also in an enzymatic system (myeloperoxidase/H2O2/Cl(-) system) and in living macrophage cells upon stimulation. This new probe might be used as an efficient tool for probing the roles HOCl plays in biological systems.

A highly selective fluorescent probe for the detection and imaging of peroxynitrite in living cells.

We have found a specific reaction between ketone 1 and peroxynitrite (ONOO-), rather than other reactive oxygen species and reactive nitrogen species generated in the biological system. On the basis of this reaction, we have successfully developed a new fluorescent probe HKGreen-1, which is highly selective for the detection of peroxynitrite in living cells. Before the oxidation with peroxynitrite, the dichlorofluorescein part is masked and the probe is nonfluorescent. However, upon reaction with peroxynitrite, the fluorophore is released, resulting in strong enhancement in fluorescence intensity.