tet2 and tet3 regulate cell fate specification and differentiation events during retinal development.

Tet enzymes are epigenetic modifiers that impact gene expression via 5mC to 5hmC oxidation. Previous work demonstrated the requirement for Tet and 5hmC during zebrafish retinogenesis. mutants possessed defects in the formation of differentiated retinal neurons, but the mechanisms underlying these defects are unknown.

Altering the interfacial rheology of and with N-acetyl cysteine and cysteamine.

Introduction: Chronic lung infection due to bacterial biofilms is one of the leading causes of mortality in cystic fibrosis (CF) patients. Among many species colonizing the lung airways, and are two virulent pathogens involved in mechanically robust biofilms that are difficult to eradicate using airway clearance techniques like lung lavage. To remove such biological materials, glycoside hydrolase-based compounds are commonly employed for targeting and breaking down the biofilm matrix, and subsequently increasing cell susceptibility to antibiotics.

Mechanism and Effect of HNF4α Decrease in a Rat Model of Cirrhosis and Liver Failure.

Background & Aims: HNF4α, a master regulator of liver development and the mature hepatocyte phenotype, is down-regulated in chronic and inflammatory liver disease. We used contemporary transcriptomics and epigenomics to study the cause and effects of this down-regulation and characterized a multicellular etiology.

Methods: Progressive changes in the rat carbon tetrachloride model were studied by deep RNA sequencing and genome-wide chromatin immunoprecipitation sequencing analysis of transcription factor (TF) binding and chromatin modification.

Intramuscular Nanofat Injection Promotes Inflammation-Induced Gastrocnemius Regeneration in a Syngeneic Rat Sciatic Nerve Injury Model.

Background: Mechanical emulsification of adipose tissue to concentrate protein and stromal cell components (ie, nanofat) has gained considerable interest in clinical practice. Although the regenerative potential of nanofat has largely been used in aesthetic applications, these effects have considerable potential in reconstruction as well. Here, the authors investigated the therapeutic properties of nanofat injected directly into the denervated gastrocnemius after a sciatic nerve injury in Lewis rats.

Design and In Vitro Evaluation of an Artificial Placenta Made From Hollow Fiber Membranes.

For infants born at the border of viability, care practices and morbimortality rates vary widely between centers. Trends show significant improvement, however, with increasing gestational age and weight. For periviable infants, the goal of critical care is to bridge patients to improved outcomes.

A microarray patch SARS-CoV-2 vaccine induces sustained antibody responses and polyfunctional cellular immunity.

Sustainable global immunization campaigns against COVID-19 and other emerging infectious diseases require effective, broadly deployable vaccines. Here, we report a dissolvable microarray patch (MAP) SARS-CoV-2 vaccine that targets the immunoresponsive skin microenvironment, enabling efficacious needle-free immunization. Multicomponent MAPs delivering both SARS-CoV-2 S1 subunit antigen and the TLR3 agonist Poly(I:C) induce robust antibody and cellular immune responses systemically and in the respiratory mucosa.

Microfluidic Systems For Manufacturing of Microparticle-Based Drug-Delivery Systems: Design, Construction, and Operation.

Particles synthesized from biodegradable polymers hold great potential as controlled drug delivery systems. Continuous flow platforms based on microfluidics offer attractive advantages over conventional batch-emulsification techniques for the scalable fabrication of drug-loaded particles with controlled physicochemical properties. However, widespread utilization of microfluidic technologies for the manufacturing of drug-loaded particles has been hindered largely by the lack of practical guidelines toward cost-effective development and reliable operation of microfluidic systems.

Micro-Technologies for Assessing Microbial Dynamics in Controlled Environments.

With recent advances in microfabrication technologies, the miniaturization of traditional culturing techniques has provided ideal methods for interrogating microbial communities in a confined and finely controlled environment. Micro-technologies offer high-throughput screening and analysis, reduced experimental time and resources, and have low footprint. More importantly, they provide access to culturing microbes in their natural environments and similarly, offer optical access to real-time dynamics under a microscope.

Mechanistic studies of PEG-asparaginase-induced liver injury and hepatic steatosis in mice.

PEGylated-l-asparaginase (PEG-ASNase) is a chemotherapeutic agent used to treat pediatric acute lymphoblastic leukemia (ALL). Its use is avoided in adults due to its high risk of liver injury including hepatic steatosis, with obesity and older age considered risk factors of the injury. Our study aims to elucidate the mechanism of PEG-ASNase-induced liver injury.

Droplet-based microsystems as novel assessment tools for oral microbial dynamics.

The human microbiome comprises thousands of microbial species that live in and on the body and play critical roles in human health and disease. Recent findings on the interplay among members of the oral microbiome, defined by a personalized set of microorganisms, have elucidated the role of bacteria and yeasts in oral health and diseases including dental caries, halitosis, and periodontal infections. However, the majority of these studies rely on traditional culturing methods which are limited in their ability of replicating the oral microenvironment, and therefore fail to evaluate key microbial interactions in microbiome dynamics.

Serotonin transporter-mediated molecular axis regulates regional retinal ganglion cell vulnerability and axon regeneration after nerve injury.

Molecular insights into the selective vulnerability of retinal ganglion cells (RGCs) in optic neuropathies and after ocular trauma can lead to the development of novel therapeutic strategies aimed at preserving RGCs. However, little is known about what molecular contexts determine RGC susceptibility. In this study, we show the molecular mechanisms underlying the regional differential vulnerability of RGCs after optic nerve injury.

Research Techniques Made Simple: Skin-Targeted Drug and Vaccine Delivery Using Dissolvable Microneedle Arrays.

Skin-targeted drug delivery is broadly employed for both local and systemic therapeutics and is an important tool for discovery efforts in cutaneous biology. Recently, emerging technologies support efforts toward skin-targeted biocargo delivery for local and systemic therapeutic benefit. Effective targeting of bioactive molecules, including large (molecular weight > 500 Da) or complex (hydrophilic and charged) molecules, to defined cutaneous microenvironments is intrinsically challenging owing to the protective barrier function of the skin.

Cell trafficking and regulation of osteoblastogenesis by extracellular vesicle associated bone morphogenetic protein 2.

Extracellular vesicles (EVs) are characterized by complex cargo composition and carry a wide array of signalling cargo, including growth factors (GFs). Beyond surface-associated GFs, it is unclear if EV intralumenal growth factors are biologically active. Here, bone morphogenetic protein-2 (BMP2), loaded directly into the lumen of EVs designated engineered BMP2-EVs (eBMP2-EVs), was comprehensively characterized including its regulation of osteoblastogenesis.

Advances in Multiplexed Paper-Based Analytical Devices for Cancer Diagnosis: A Review of Technological Developments.

Cancer is one of the leading causes of death worldwide producing estimated cost of $161.2 billion in the US in 2017 only. Early detection of cancer would not only reduce cancer mortality rates but also dramatically reduce healthcare costs given that the 17 million new cancer cases in 2018 are estimated to grow 27.

Cell salvage in trauma.

Purpose Of Review: The collection of shed blood and its reinfusion has been termed 'cell salvage' or 'autotransfusion'. This review will summarize the historical foundation of cell salvage and summarize recent literature associated with cell salvage use in trauma.

Recent Findings: There have been no publications on cell salvage in trauma during the last 2 years.

A single subcutaneous or intranasal immunization with adenovirus-based SARS-CoV-2 vaccine induces robust humoral and cellular immune responses in mice.

Optimal vaccines are needed for sustained suppression of SARS-CoV-2 and other novel coronaviruses. Here, we developed a recombinant type 5 adenovirus vector encoding the gene for the SARS-CoV-2 S1 subunit antigen (Ad5.SARS-CoV-2-S1) for COVID-19 immunization and evaluated its immunogenicity in mice.

Multicellular Systems to Translate Somatic Cell Genome Editors to Humans.

As genome editors move into clinical trials, there is a need to establish multicellular systems to rapidly assess and predict toxic effects of genome editors in physiologically relevant human models. Advancements in organoid and organs-on-chip technologies offer the possibility to create multicellular systems that replicate the cellular composition and metabolic function of native tissues. Some multicellular systems have been validated in multiple applications for drug discovery and could be easily adapted to test genome editors; other models, especially those of the adaptive immune system, will require validation before being used as benchmarks for testing genome editors.

Microarray patches enable the development of skin-targeted vaccines against COVID-19.

The COVID-19 pandemic is a serious threat to global health and the global economy. The ongoing race to develop a safe and efficacious vaccine to prevent infection by SARS-CoV-2, the causative agent for COVID-19, highlights the importance of vaccination to combat infectious pathogens. The highly accessible cutaneous microenvironment is an ideal target for vaccination since the skin harbors a high density of antigen-presenting cells and immune accessory cells with broad innate immune functions.

A mechanoresponsive PINCH-1-Notch2 interaction regulates smooth muscle differentiation of human placental mesenchymal stem cells.

Extracellular matrix (ECM) stiffness plays an important role in the decision making process of smooth muscle differentiation of mesenchymal stem cells (MSCs) but the underlying mechanisms are incompletely understood. Here we show that a signaling axis consisting of PINCH-1 and Notch2 is critically involved in mediating the effect of ECM stiffness on smooth muscle differentiation of MSCs. Notch2 level is markedly increased in ECM stiffness-induced smooth muscle differentiation of human placental MSCs.

Chemically-Induced Cross-Linking of Peptidic Fibrils for Scaffolding Polymeric Particles and Macrophages.

EAK16-II (EAK) is a self-assembling peptide (SAP) that forms β-sheets and β-fibrils through ionic-complementary interactions at physiological ionic strengths. The soft materials can be injected in vivo, creating depots of drugs and cells for rendering pharmacological and biological actions. The scope of the applications of EAK is sought to extend to tissues through which the flow of extracellular fluid tends to be limited.

A Fbxo48 inhibitor prevents pAMPKα degradation and ameliorates insulin resistance.

The adenosine monophosphate (AMP)-activated protein kinase (Ampk) is a central regulator of metabolic pathways, and increasing Ampk activity has been considered to be an attractive therapeutic target. Here, we have identified an orphan ubiquitin E3 ligase subunit protein, Fbxo48, that targets the active, phosphorylated Ampkα (pAmpkα) for polyubiquitylation and proteasomal degradation. We have generated a novel Fbxo48 inhibitory compound, BC1618, whose potency in stimulating Ampk-dependent signaling greatly exceeds 5-aminoimidazole-4-carboxamide-1-β-ribofuranoside (AICAR) or metformin.

Biorelevant and screening dissolution methods for minocycline hydrochloride microspheres intended for periodontal administration.

Currently, there is no compendial-level method to assess dissolution of particulate systems administered in the periodontal pocket. This work seeks to develop dissolution methods for extended release poly(lactic-co-glycolic acid) (PLGA) microspheres applied in the periodontal pocket. Arestin®, PLGA microspheres containing minocycline hydrochloride (MIN), is indicated for reduction of pocket depth in adult periodontitis.

Ethanol consumption synergistically increases ultraviolet radiation induced skin damage and immune dysfunction.

Background: Excessive UV radiation disrupts skin homeostasis by multiple mechanisms that extend beyond the simple erythema associated with sunburns including reduction of antioxidants, increased DNA damage, and impairment of skin immune responses. Recreational UV exposure frequently occurs concurrently with excessive ethanol (EtOH). Epidemiological studies suggest a harmful, dose-dependent impact of EtOH in the setting of high UV exposure, leading to increased severity of sunburns relative to those generated in the absence of EtOH.