Chemical Stability of Ascorbic Acid Integrated into Commercial Products: A Review on Bioactivity and Delivery Technology

The L-enantiomer of ascorbic acid is commonly known as vitamin C. It is an indispensable nutrient and plays a key role in retaining the physiological process of humans and animals. L-gulonolactone oxidase, the key enzyme for the de novo synthesis of ascorbic acid, is lacking in some mammals including humans. The functionality of ascorbic acid has prompted the development of foods fortified with this vitamin. As a natural antioxidant, it is expected to protect the sensory and nutritional characteristics of the food. It is thus important to know the degradation of ascorbic acid in the food matrix and its interaction with coexisting components. The biggest challenge in the utilization of ascorbic acid is maintaining its stability and improving its delivery to the active site. The review also includes the current strategies for stabilizing ascorbic acid and the commercial applications of ascorbic acid.

Adaptation of Fire-Fighting Systems to Localization of Fires in the Premises: Review

Fire protection is a basic safety issue for all categories of buildings. The criteria for effective fire suppression and the characteristics of extinguishing systems in insulated areas depend on a combination of factors. The main influences include the type of combustible material, ambient temperature, type of spray extinguisher, air inflow and outflow conditions, and space geometry. This article analyzes the most widely used fire-extinguishing technologies in different locations. The main aspects of using the pulsed delivery technology of extinguishing liquid are considered. Based on the analysis of publications from the last decade, it is possible to develop intelligent systems for recording fires and extinguishing fires in the premises.

Advances in Injectable In Situ-Forming Hydrogels for Intratumoral Treatment

Chemotherapy has been linked to a variety of severe side effects, and the bioavailability of current chemotherapeutic agents is generally low, which decreases their effectiveness. Therefore, there is an ongoing effort to develop drug delivery systems to increase the bioavailability of these agents and minimize their side effects. Among these, intratumoral injections using in situ-forming hydrogels can improve drugs’ bioavailability and minimize drugs’ accumulation in non-target organs or tissues. This review describes different types of injectable in situ-forming hydrogels and their intratumoral injection for cancer treatment, after which we discuss the antitumor effects of intratumoral injection of drug-loaded hydrogels. This review concludes with perspectives on the future applicability of, and challenges for, the adoption of this drug delivery technology.

Lipid nanoparticles incorporating a GalNAc ligand enable in vivo liver ANGPTL3 editing in wild-type and somatic LDLR knockout non-human primates

Standard lipid nanoparticles (LNPs) deliver gene editing cargoes to hepatocytes through receptor-mediated uptake via the low-density lipoprotein receptor (LDLR). Homozygous familial hypercholesterolemia (HoFH) is a morbid genetic disease characterized by complete or near-complete LDLR deficiency, markedly elevated blood low-density lipoprotein cholesterol (LDL-C) levels, and premature atherosclerotic cardiovascular disease. In order to enable in vivo liver gene editing in HoFH patients, we developed a novel LNP delivery technology that incorporates a targeting ligand - N-acetylgalactosamine (GalNAc) - which binds to the asialoglycoprotein receptor (ASGPR). In a cynomolgus monkey (Macaca fascicularis) non-human primate (NHP) model of HoFH created by somatic knockout of the LDLR gene via CRISPR-Cas9, treatment with GalNAc-LNPs formulated with an adenine base editor mRNA and a guide RNA (gRNA) targeting the ANGPTL3 gene yielded ~60% whole-liver editing and ~94% reduction of blood ANGPTL3 protein levels, whereas standard LNPs yielded minimal editing. Moreover, in wild-type NHPs, the editing achieved by GalNAc-LNPs compared favorably to that achieved by standard LNPs, suggesting that GalNAc-LNP delivery technology may prove useful across a range of in vivo therapeutic applications targeting the liver.

Reimagining connected care in the era of digital medicine (Preprint)

UNSTRUCTURED The Covid-19 pandemic accelerated the adoption of digital health tools such as telehealth and remote patient monitoring (RPM), which offer exciting opportunities for expanded connected care at a distance. But while the mode of clinicians’ interactions with patients and their health data has transformed, the larger framework of how we deliver care is still driven by a model of episodic care that does not facilitate this new frontier. Fully realizing a transformation to a system of continuous connected care augmented by digital technology will require a shift in clinicians’ and health systems’ approach to care delivery technology and its associated data volume and complexity. In this article, we present a solution that organizes and optimizes the interaction of automated technologies with human oversight, allowing for the maximal use of data-rich technologies while preserving the pieces of medical care considered “uniquely human.” We review implications of this “augmented continuous connected care” model for clinical practice, and offer human-centered design-informed next steps to encourage innovation around these important issues.

CRISPR/Cas9 Delivery System Engineering for Genome Editing in Therapeutic Applications

The clustered regularly interspaced short palindromic repeats (CRISPR)/associated protein 9 (CRISPR/Cas9) systems have emerged as a robust and versatile genome editing platform for gene correction, transcriptional regulation, disease modeling, and nucleic acids imaging. However, the insufficient transfection and off-target risks have seriously hampered the potential biomedical applications of CRISPR/Cas9 technology. Herein, we review the recent progress towards CRISPR/Cas9 system delivery based on viral and non-viral vectors. We summarize the CRISPR/Cas9-inspired clinical trials and analyze the CRISPR/Cas9 delivery technology applied in the trials. The rational-designed non-viral vectors for delivering three typical forms of CRISPR/Cas9 system, including plasmid DNA (pDNA), mRNA, and ribonucleoprotein (RNP, Cas9 protein complexed with gRNA) were highlighted in this review. The vector-derived strategies to tackle the off-target concerns were further discussed. Moreover, we consider the challenges and prospects to realize the clinical potential of CRISPR/Cas9-based genome editing.

491 Supporting Virtual Student Inclusivity

Since 2005, Michigan State University has offered an online graduate-level course in animal welfare assessment. The course was designed to overcome geographic barriers in terms of limited instructor expertise in welfare at individual universities and to reach an international student audience. Over 280 students have taken the course—including undergraduate, veterinary, and graduate students; practicing veterinarians; and professionals. Students have attended from 22 states and 13 different countries, including Thailand, Canada, Nepal, Kenya, China, and Australia. The course was designed and continues to be modified to accommodate students attending from different time zones, with different types of technology, and with different speeds and reliabilities of Internet access. An asynchronous format is used, with content delivered via short, recorded lectures and videos as well as electronically available textbook chapters and journal articles. In response to student and instructor needs, the course has evolved from a tech heavy but bandwidth intensive format to one using simpler technology and less bandwidth to reduce student barriers to participate and ensure equitable content access and engagement. Content is offered through the Desire 2 Learn course management system at MSU, which also performs accessibility checks of content. Lectures and videos are captioned to help accommodate visually impaired students or those in noisy environments and PDF handout versions of lecture slides are also made available. Rubrics and examples are used to guide completion of assignments. In 2020, the course was co-taught by MSU, Texas A&M and Virginia Tech. Several class meetings were held via Zoom to allow students to meet and interact with each other, though issues with scheduling prohibited all students from attending. Feedback surveys indicate students are generally satisfied with course content, delivery technology and interactions with instructors and peers. Creating an inclusive virtual environment requires attention to student constraints, with simpler typically being more accommodating.

Injectable non-immunogenic PEG-like conjugate that forms a subcutaneous depot and enables sustained delivery of a peptide drug

Many biologics have a short plasma half-life, and their conjugation to polyethylene glycol (PEG) is commonly used to solve this problem. Unfortunately, PEG is immunogenic and forms vacuoles, and improvement in PEGylated drugs' half-life is at an asymptote. Here, we developed a PEG-like, non-immunogenic, and injectable conjugate technology for sustained delivery of biologics. An optimal poly[oligo(ethylene glycol) methyl ether methacrylate] (POEGMA) depot of exendin, a peptide drug used in the clinic in treating type 2 diabetes, outperformed PEG, non-depot-forming POEGMA, and a clinical sustained-release exendin-4 formulation in efficacy and pharmacokinetics. Notably, POEGMA was non-immunoreactive, while PEG induced a persistent anti-PEG immune response, leading to its subsequent doses' early clearance and loss of efficacy. POEGMA did not induce vacuolization. Solving these problems of PEG and improving upon its half-life benefits by creating injectable POEGMA conjugates that form a drug depot under the skin and provide sustained efficacy breathe new life into an established and valuable drug delivery technology that is facing an impasse.