Isolation, genome analysis and comparison of a novel parainfluenza virus 5 from a Siberian tiger (Panthera tigris).

Paramyxoviruses are important pathogens affecting various animals, including mammals and humans. Parainfluenza virus 5 (PIV5)-a member of the family Paramyxoviridae-is a major threat to the health of mammals and humans. However, studies on terrestrial wild animals infected with PIV5 are scanty. In this study, we utilized reverse transcription PCR to detect PIV5 infection in the visceral organ tissues of a Siberian tiger (Panthera tigris ssp. altaica) with vomiting, diarrhea, and dyspnea before its death. A novel PIV5 (named SR strain) with a slowly progressive cytopathic effect was isolated in Vero cells and validated using a transmission electron microscope. Full-length sequencing and analysis revealed that the whole genome of the PIV5 SR strain contained 15,246 nucleotides (nt) and seven non-overlapping genes (3'-N-V/P-M-F-SH-HN-L-5') encoding eight proteins. Phylogenetic analysis of three PIV5 strains identified in the same zoo confirmed that PIV5 strains SR and ZJQ-221 shared the closest genetic relationship as they were clustered in the same branch, while the recently found Siberian tiger strain SZ2 kept a certain distance and formed a relatively unique branch. Furthermore, mutations of nt and amino acids (aa) between strains ZJQ-221, SR, and SZ2 were identified. In summary, we report the identification and genomic characterization of a novel PIV5 strain SR isolated in a Siberian tiger, which may help future research on interspecific transmission mechanisms.

Exploration of Q-Marker of Rhubarb Based on Intelligent Data Processing Techniques and the AUC Pooled Method.

Rhubarb, as a traditional Chinese medicine, has several positive therapeutic effects, such as purging and attacking accumulation, clearing heat and purging fire, cooling blood, and detoxification. Recently, Rhubarb has been used in prescriptions for the prevention and treatment of COVID-19, with good efficacy. However, the exploration of effective quantitative approach to ensure the consistency of rhubarb's therapeutic efficacy remains a challenge. In this case, this study aims to use non-targeted and targeted data mining technologies for its exploration and has comprehensively identified 72 rhubarb-related components in human plasma for the first time. In details, the area under the time-concentration curve (AUC)-pooled method was used to quickly screen the components with high exposure, and the main components were analyzed using Pearson correlation and other statistical analyses. Interestingly, the prototype component (rhein) with high exposure could be selected out as a Q-marker, which could also reflect the metabolic status changes of rhubarb anthraquinone in human. Furthermore, after comparing the metabolism of different species, mice were selected as model animals to verify the pharmacodynamics of rhein. The in vivo experimental results showed that rhein has a positive therapeutic effect on pneumonia, significantly reducing the concentration of pro-inflammatory factors [interleukin (IL)-6 and IL-1ß] and improving lung disease. In short, based on the perspective of human exposure, this study comprehensively used intelligent data post-processing technologies and the AUC-pooled method to establish that rhein can be chosen as a Q-marker for rhubarb, whose content needs to be monitored individually.

Antioxidant Thermogelling Formulation for Burn Wound Healing.

Burns are the most common and devastating form of wounds and are usually accompanied by abnormal inflammation, inadequate extracellular matrix production, reduced angiogenesis, and lack of growth factor stimulation, which can significantly delay wound healing and lead to complications. Pearl powder, a traditional Chinese medicine, has been used to treat wound healing. In the present study, we found that supercritical CO2 extracted pearl peptides in the size range of ">10kd" have great potential to promote wound healing at the cellular level. Antioxidant hydrogels were designed using selenium-containing block-functionalized PEG/PPG polymers. Pearl peptide components were combined into polymeric materials to develop new promising wound dressings. It was shown that pearl peptide hydrogels increased skin fibroblast viability, enhanced cellular resistance to oxidative stress, enhanced tissue remodeling, promoted angiogenesis, and exhibited enhanced promotion in wound healing.

Dual Tumor Microenvironment Remodeling by Glucose-Contained Radical Copolymer for MRI-Guided Photoimmunotherapy.

Aberrant glucose metabolism and immune evasion are recognized as two hallmarks of cancer, which contribute to poor treatment efficiency and tumor progression. Herein, a novel material system consisting of a glucose and TEMPO (2,2,6,6-tetramethylpiperidin-1-yl)oxyl) at the distal ends of PEO-b-PLLA block copolymer (glucose-PEO-b-PLLA-TEMPO), is designed to encapsulate clinical therapeutics CUDC101 and photosensitizer IR780. The specific core-shell rod structure formed by the designed copolymer renders TEMPO radicals excellent stability against reduction-induced magnetic resonance imaging (MRI) silence. Tumor-targeting moiety endowed by glucose provides the radical copolymer outstanding multimodal imaging capabilities, including MRI, photoacoustic imaging, and fluorescence imaging. Efficient delivery of CUDC101 and IR780 is achieved to synergize the antitumor immune activation through IR780-mediated photodynamic therapy (PDT) and CUDC101-triggered CD47 inhibition, showing M1 phenotype polarization of tumor-associated macrophages (TAMs). More intriguingly, this study demonstrates PDT-stimulated p53 can also re-educate TAMs, providing a combined strategy of using dual tumor microenvironment remodeling to achieve the synergistic effect in the transition from cold immunosuppressive to hot immunoresponsive tumor microenvironment.

Effectiveness of an ocular adhesive polyhedral oligomeric silsesquioxane hybrid thermo-responsive FK506 hydrogel in a murine model of dry eye.

Dry eye is a common ocular disease that results in discomfort and impaired vision, impacting an individual's quality of life. A great number of drugs administered in eye drops to treat dry eye are poorly soluble in water and are rapidly eliminated from the ocular surface, which limits their therapeutic effects. Therefore, it is imperative to design a novel drug delivery system that not only improves the water solubility of the drug but also prolongs its retention time on the ocular surface. Herein, we develop a copolymer from mono-functional POSS, PEG, and PPG (MPOSS-PEG-PPG, MPEP) that exhibits temperature-sensitive sol-gel transition behavior. This thermo-responsive hydrogel improves the water solubility of FK506 and simultaneously provides a mucoadhesive, long-acting ocular delivery system. In addition, the FK506-loaded POSS hydrogel possesses good biocompatibility and significantly improves adhesion to the ocular surface. In comparison with other FK506 formulations and the PEG-PPG-FK506 (F127-FK506) hydrogel, this novel MPOSS-PEG-PPG-FK506 (MPEP-FK506) hydrogel is a more effective treatment of dry eye in the murine dry eye model. Therefore, delivery of FK506 in this POSS hydrogel has the potential to prolong drug retention time on the ocular surface, which will improve its therapeutic efficacy in the management of dry eye.

Emerging Biomaterials-Based Strategies for Inhibiting Vasculature Function in Cancer Therapy.

The constant feeding of oxygen and nutrients through the blood vasculature has a vital role in maintaining tumor growth. Interestingly, recent endeavors have shown that nanotherapeutics with the strategy to block tumor blood vessels feeding nutrients and oxygen for starvation therapy can be helpful in cancer treatment. However, this field has not been detailed. Hence, this review will present an exhaustive summary of the existing biomaterial based strategies to disrupt tumor vascular function for effective cancer treatment, including hydrogel or nanogel-mediated local arterial embolism, thrombosis activator loaded nano-material-mediated vascular occlusion and anti-vascular drugs that block tumor vascular function, which may be beneficial to the design of anti-cancer nanomedicine by targeting the tumor vascular system.

The role of gut microbiota in tumorigenesis and treatment.

A large number of microbial communities exist in normal human intestinal tracts, which maintain a relatively stable dynamic balance under certain conditions. Gut microbiota are closely connected with human health and the occurrence of tumors. The colonization of certain intestinal bacteria on specific sites, gut microbiota disturbance and intestinal immune disorders can induce the occurrence of tumors. Meanwhile, gut microbiota can also play a role in tumor therapy by participating in immune regulation, influencing the efficacy of anti-tumor drugs, targeted therapy of engineered probiotics and fecal microbiota transplantation. This article reviews the role of gut microbiota in the occurrence, development, diagnosis and treatment of tumors. A better understanding of how gut microbiota affect tumors will help us find more therapies to treat the disease.

Flexible polymeric nanosized micelles for ophthalmic drug delivery: research progress in the last three years.

The eye is a complex structure with a variety of anatomical barriers and clearance mechanisms, so the provision of safe and effective ophthalmic drug delivery technology is a major challenge. In the past few decades, a number of reports have shown that nano-delivery platforms based on polymeric micelles are of great interest, because of their hydrophobic core that encapsulates lipid-soluble drugs and small size with high penetration, allowing long-term drug retention and posterior penetration in the eye. Furthermore, as an ocular delivery platform, polymeric micelles not only cover the single micellar drug delivery system formed by poloxamer, chitosan or other polymers, but also include composite drug delivery systems like micelle-encapsulated hydrogels and micelle-embedded contact lenses. In this review, a number of ophthalmic micelles that have emerged in the last three years will be systematically reviewed, with a summary of and discussion on their unique advantages or unique drug delivery performance. Last but not least, the current challenges of polymeric micelle formulations in potential clinical ophthalmic therapeutic applications will also be proposed, which might be helpful for future design of ocular drug delivery formulations.

AuNPs Decorated PLA Stereocomplex Micelles for Synergetic Photothermal and Chemotherapy.

A unique platform for combined photothermal and chemotherapy using PLA stereocomplex (PLA SC) micelles-induced hybrid gold nanocarriers is designed. The PLA SC micelles, made from the self-assembly of poly(ethylene glycol)-block-poly(l-lactide) (PEG-PLLA) and poly(2-(dimethylamino) ethyl methacrylate)-block-poly(d-lactide) (PDMAEMA-PDLA), for the first time are used as a template to fabricate the hybrid PLA SC@Au core-shell nanocarriers, in which the anticancer drugs are encapsulated within the core, while the Au nanoparticles are tethered in the shell via the in situ reduction of AuCl4- by PDMAEMA. The obtained PLA SC@Au hybrid nanocarriers exhibit low toxicity and remarkable photothermal effect. Upon near-infrared laser irradiation, the on-site photothermal therapy can further induce an accelerated drug release from the hybrid nanocarrier reservoir via hyperthermia heating of the nanocarriers, thus leading to a synergistic photothermal and chemotherapy toward a significantly improved efficacy in tumor shrinkage. The as-designed PLA SC@Au hybrid nanocarriers, with their biocompatible compositions, dual-drug delivery characteristics, and combined photothermal/chemotherapy, show high potential as a novel platform for cancer treatment.

Efficacy of Water-Soluble Pearl Powder Components Extracted by a CO2 Supercritical Extraction System in Promoting Wound Healing.

Pearl powder is a biologically active substance that is widely used in traditional medicine, skin repair and maintenance. The traditional industrial extraction processes of pearl powder are mainly based on water, acid or enzyme extraction methods, all of which have their own drawbacks. In this study, we propose a new extraction process for these active ingredients, specifically, water-soluble components of pearl powder extracted by a CO2 supercritical extraction system (SFE), followed by the extraction efficiency evaluation. A wound-healing activity was evaluated in vitro and in vivo. This demonstrated that the supercritical extraction technique showed high efficiency as measured by the total protein percentage. The extracts exhibited cell proliferation and migration-promoting activity, in addition to improving collagen formation and healing efficiency in vivo. In brief, this study proposes a novel extraction process for pearl powder, and the extracts were also explored for wound-healing bioactivity, demonstrating the potential in wound healing.