Light-Responsive Smart Nanoliposomes: Harnessing the Azobenzene Moiety for Controlled Drug Release under Near-Infrared Irradiation.

The azobenzene moiety is an intriguing structure that deforms under UV and visible light, indicating a high potential for biomedical applications. However, its reaction to UV radiation is problematic because of its high energy and low tissue penetration. Unlike previous research on azobenzene structures in photoresponsive materials, this study presents a novel method for imparting photostimulation-responsive properties to liposomes by incorporating the azobenzene moiety and extending the light wavelength with up-conversion nanoparticles. First, the azobenzene structure was incorporated into a phospholipid molecule to create Azo-PSG, which could spontaneously form vesicle assemblies in aqueous solutions and isomerizes within 1 h of light exposure. Furthermore, orthogonal up-conversion nanoparticles with a core-shell structure were created by sequentially growing lanthanide rare earths in the shell layer, which efficiently converts near-infrared light into ultraviolet (400 nm) and blue-green (540 nm) light. Combining these core-shell structured up-conversion nanomaterials with Azo-PSG molecules resulted in the creation of a near-infrared light-responsive smart nanoliposome system. Under near-infrared light irradiation, UCNPs emit UV and blue-green light, causing conformational changes in Azo-PSG molecules that allow drug release within 6 h. The reversible structural shift of Azo-PSG in response to light stimulation holds enormous promise for improving drug release techniques. This novel technique also expands the usage of UV-responsive compounds beyond their constraints of low penetration and high biotoxicity, allowing for rapid medication release under NIR light.

Clinical Applicable Carboxymethyl Chitosan with Gel-Forming and Stabilizing Properties Based on Terminal Sterilization Methods of Electron Beam Irradiation.

Carboxymethyl chitosan (CMC)-based hydrogels have great potential for clinical applications, but a critical sterilization process must be addressed to bring them to market. Compared to ethylene oxide sterilization or heat sterilization, irradiation sterilization avoids alkylation and heat damage, while available studies on γ-irradiated other polysaccharides show that solution polysaccharides are susceptible to degradation or cross-linking. Aiming at the challenges brought by the γ-irradiation process of polysaccharide aqueous solution, this paper innovatively proposes the lyophilized CMC using electron beam (EB) irradiation, which not only avoids the generation of free radicals in the irradiated water leading to the degradation and cross-linking of polysaccharides but also retains the properties of CMC in terms of gel formation, stabilization, and clinical application. We used FTIR, TG, GPC, and microbial load tests to demonstrate that lyophilized CMC did not have significant changes in structure and molecular weight after EB irradiation, complied with the requirements for sterilization, and still had gel stability, thus proving that lyophilized CMC could be used for EB irradiation and met the requirements for clinical application. Therefore, this work is expected to further advance CMC injectable hydrogels toward clinical applications and provide a new direction for the sterilization processes of other polysaccharide hydrogels.

Simply and Cheaply Prepared Liposomal Membrane for Nanocarriers: High Encapsulation Efficiency Based on Broad Regulation of Surface Charges and pH-Switchable Performance.

The zeta potential of nanoparticles impacts their distribution and metabolism in the body as well as their interaction with medications of varying charges, hence altering therapeutic efficacy and safety. In this paper, the external charges of liposomes were regulated by utilizing a simple and economical method based on competition for protons of cationic chitosan (CS) and anion hyaluronic acid (HA). The charge regulation of a liposomal membrane is generally accomplished by adjusting the ratio of charged lipids within a liposome (e.g., cationic DOTAP or anionic DOPS), the stability of which was maintained by the coating materials of cationic chitosan (CS) or anion hyaluronic acid (HA). A series of nanoparticles could respond to pH-stimulation with adjustable surface charge. Moreover, the sizes of liposomes coated with CS and HA remain within a narrow range. In vitro cytotoxicity tests revealed that the nanocarriers were safe, and the nanoparticles containing antitumor medicines were efficient in tumor therapy. Considering liposomes with different external surface charges could be aimed at diverse therapy purposes. The strategies for regulating liposomal surface charges with high encapsulation rates and certain release cycles reported here could provide a versatile platform as carriers for the delivery of drugs and other macromolecules into human bodies.

Steroids Therapy in Patients With Severe COVID-19: Association With Decreasing of Pneumonia Fibrotic Tissue Volume.

Background: We use longitudinal chest CT images to explore the effect of steroids therapy in COVID-19 pneumonia which caused pulmonary lesion progression. Materials and Methods: We retrospectively enrolled 78 patients with severe to critical COVID-19 pneumonia, among which 25 patients (32.1%) who received steroid therapy. Patients were further divided into two groups with severe and significant-severe illness based on clinical symptoms. Serial longitudinal chest CT scans were performed for each patient. Lung tissue was segmented into the five lung lobes and mapped into the five pulmonary tissue type categories based on Hounsfield unit value. The volume changes of normal tissue and pneumonia fibrotic tissue in the entire lung and each five lung lobes were the primary outcomes. In addition, this study calculated the changing percentage of tissue volume relative to baseline value to directly demonstrate the disease progress. Results: Steroid therapy was associated with the decrease of pneumonia fibrotic tissue (PFT) volume proportion. For example, after four CT cycles of treatment, the volume reduction percentage of PFT in the entire lung was -59.79[±12.4]% for the steroid-treated patients with severe illness, and its p-value was 0.000 compared to that (-27.54[±85.81]%) in non-steroid-treated ones. However, for the patient with a significant-severe illness, PFT reduction in steroid-treated patients was -41.92[±52.26]%, showing a 0.275 p-value compared to -37.18[±76.49]% in non-steroid-treated ones. The PFT evolution analysis in different lung lobes indicated consistent findings as well. Conclusion: Steroid therapy showed a positive effect on the COVID-19 recovery, and its effect was related to the disease severity.

An on-demand and on-site shape-designable mineralized hydrogel with calcium supply and inflammatory warning properties for cranial repair applications.

Although more than 2.2 million cranial repair surgical operations are performed every year, orthopedic doctors still dream of excellent artificial repair materials with suitable strength, on-site and on-demand fast-shaping properties, and bone induction properties. However, fast-shaping and high-strength properties seem to contradict each other, and even mineralized hydrogels, which already have excellent strength and bone induction properties, are not ideal candidates, since they lack the plasticity needed for complex craniofacial surface use during the essential mechanism of the process of the cleavage of inorganic ions, nucleation, and growth. Here, we report a novel mineralized hydrogel based on dispersing mineral ions prior to use and then inducing inorganic formation by decreasing the temperature, which endows the hydrogels with the characteristics of precise customization at an appropriate degree of mineralization and simultaneously achieves suitable mechanical properties and sufficient calcium supply for bone regeneration. Additionally, the calcium ion content in the water of the matrix will change with the temperature, and, thus, the conductivity of the mineralized hydrogels will change accordingly. This implements the ability to warn of inflammation in a timely fashion in the form of a temperature sensor. Therefore, this temperature-responsive hydrogel effectively achieves the aim of versatile material design.

Longitudinal Chinese Population Structural Fetal Brain Atlases Construction: toward precise fetal brain segmentation.

In magnetic resonance imaging (MRI) studies of fetal brain development, structural brain atlases usually serve as essential references for the fetal population. Individual images are spatially normalized into a common or standard atlas space to extract regional information on volumetric or morphological brain variations. However, the existing fetal brain atlases are mostly based on MR images obtained from Caucasian populations and thus are not ideal for the characterization of the brains of the Chinese population due to neuroanatomical differences related to genetic factors. In this paper, we use an unbiased template construction algorithm to create a set of age-specific Chinese fetal atlases between 21-35 weeks of gestation from 115 normally developing fetal brains. Based on the 4D spatiotemporal atlas, the morphologically developmental patterns, e.g., cortical thickness, sulcal and gyral patterns, were quantified from in utero MRI. Additionally, after applying the Chinese fetal atlases and Caucasian fetal atlases to an independent Chinese pediatric dataset, we find that the Chinese fetal atlases result in significantly higher accuracy than the Caucasian fetal atlases in guiding brain tissue segmentation. These results suggest that the Chinese fetal brain atlases are necessary for quantitative analysis of the typical and atypical development of the Chinese fetal population in the future.

Age-specific structural fetal brain atlases construction and cortical development quantification for chinese population.

In magnetic resonance imaging (MRI) studies of fetal brain development, structural brain atlases usually serve as essential references for the fetal population. Individual images are usually normalized into a common or standard space for analysis. However, the existing fetal brain atlases are mostly based on MR images obtained from Caucasian populations and thus are not ideal for the characterization of the fetal Chinese population due to neuroanatomical differences related to genetic factors. In this paper, we use an unbiased template construction algorithm to create a set of age-specific Chinese fetal atlases between 21-35 weeks of gestation from 115 normal fetal brains. Based on the 4D spatiotemporal atlas, the morphological development patterns, e.g., cortical thickness, cortical surface area, sulcal and gyral patterns, were quantified. The fetal brain abnormalities were detected when referencing the age-specific template. Additionally, a direct comparison of the Chinese fetal atlases and Caucasian fetal atlases reveals dramatic anatomical differences, mainly in the medial frontal and temporal regions. After applying the Chinese and Caucasian fetal atlases separately to an independent Chinese fetal brain dataset, we find that the Chinese fetal atlases result in significantly higher accuracy than the Caucasian fetal atlases in guiding brain tissue segmentation. These results suggest that the Chinese fetal brain atlases are necessary for quantitative analysis of the typical and atypical development of the Chinese fetal population in the future. The atlases with their parcellations are now publicly available at https://github.com/DeepBMI/FBA-Chinese.

Aldose Reductase Inhibitor Engeletin Suppresses Pelvic Inflammatory Disease by Blocking the Phospholipase C/Protein Kinase C-Dependent/NF-κB and MAPK Cascades.

Pelvic inflammatory disease (PID) is a common inflammation in the upper reproductive tract in women and may cause serious and costly consequences without effective treatment. Engeletin is a flavanonol glycoside and a naturally derived aldose reductase (AR) inhibitor that is widely distributed in vegetables, fruits, and plant-based foods. The present study investigated the anti-PID activity of engeletin in a mucilage-induced rat model of PID and LPS-stimulated RAW 264.7 macrophages. Engeletin significantly reduced inflammation and ameliorated the typical uterine pathological changes in PID rats. Engeletin also inhibited AR-dependent PLC/PKC/NF-κB and MAPK inflammatory pathways, as indicated by the suppression of the phosphorylation levels of PLC, PKC, p38, ERK, and JNK and the nuclear translocation of NF-κB p65. In vitro studies demonstrated that engeletin significantly inhibited inflammatory mediator expression and enhanced the phagocytic ability of LPS-induced RAW 264.7 macrophages. RNA interference of AR prevented the engeletin-induced inhibition of inflammatory mediators. Engeletin also inhibited AR-dependent PLC/PKC/NF-κB and MAPK inflammatory pathways, which was consistent with the in vivo results. These findings support engeletin as a potential agent for prevention or treatment of PID.