Development of a biocompatible 3D hydrogel scaffold using continuous liquid interface production for the delivery of cell therapies to treat recurrent glioblastoma.

Glioblastoma (GBM) is the most common primary malignant brain tumor diagnosed in adults, carrying with it an extremely poor prognosis and limited options for effective treatment. Various cell therapies have emerged as promising candidates for GBM treatment but fail in the clinic due to poor tumor trafficking, poor transplantation efficiency, and high systemic toxicity. In this study, we design, characterize, and test a 3D-printed cell delivery platform that can enhance the survival of therapeutic cells implanted in the GBM resection cavity.

Integrating computational and experimental chemical biology revealed variable anticancer activities of phosphodiesterase isoenzyme 5 inhibitors (PDE5i) in lung cancer.

Phosphodiesterase 5 (PDE5), an enzyme responsible for catalyzing the degradation of cyclic guanosine monophosphate (cGMP), has been linked to the development of cancer. PDE5 inhibitors (PDE5i), such as sildenafil (Viagra) and tadalafil (Cialis), work by blocking the action of PDE5 and are used primarily as treatments for erectile dysfunction and arterial hypertension. Some studies suggested a potential link between PDE5i and increased cancer risk, while other studies showed preferable antitumor effects.

Shifting institutional culture to develop climate solutions with Open Science.

To address our climate emergency, "we must rapidly, radically reshape society"-Johnson & Wilkinson, All We Can Save. In science, reshaping requires formidable technical (cloud, coding, reproducibility) and cultural shifts (mindsets, hybrid collaboration, inclusion). We are a group of cross-government and academic scientists that are exploring better ways of working and not being too entrenched in our bureaucracies to do better science, support colleagues, and change the culture at our organizations.

Air Quality and Health Impacts of Onshore Oil and Gas Flaring and Venting Activities Estimated Using Refined Satellite-Based Emissions.

Emissions from flaring and venting (FV) in oil and gas (O&G) production are difficult to quantify due to their intermittent activities and lack of adequate monitoring and reporting. Given their potentially significant contribution to total emissions from the O&G sector in the United States, we estimate emissions from FV using Visible Infrared Imaging Radiometer Suite satellite observations and state/local reported data on flared gas volume. These refined estimates are higher than those reported in the National Emission Inventory: by up to 15 times for fine particulate matter (PM), two times for sulfur dioxides, and 22% higher for nitrogen oxides (NO).

APC/C prevents non-canonical order of cyclin/CDK activity to maintain CDK4/6 inhibitor-induced arrest.

Regulated cell cycle progression ensures homeostasis and prevents cancer. In proliferating cells, premature S phase entry is avoided by the E3 ubiquitin ligase APC/C (anaphase promoting complex/cyclosome), although the APC/C substrates whose degradation restrains G1-S progression are not fully known. The APC/C is also active in arrested cells that exited the cell cycle, but it is not clear if APC/C maintains all types of arrest.

Proteomic Analysis Reveals a PLK1-Dependent G2/M Degradation Program and Links PKA-AKAP2 to Cell Cycle Control.

Targeted protein degradation by the ubiquitin-proteasome system is an essential mechanism regulating cellular division. The kinase PLK1 coordinates protein degradation at the G2/M phase of the cell cycle by promoting the binding of substrates to the E3 ubiquitin ligase SCF. However, the magnitude to which PLK1 shapes the mitotic proteome has not been characterized.

Association Between Hypertension and Diabetes Control and COVID-19 Severity: National Patient-Centered Clinical Research Network, United States, March 2020 to February 2022.

Background Hypertension and diabetes are associated with increased COVID-19 severity. The association between level of control of these conditions and COVID-19 severity is less well understood. Methods and Results This retrospective cohort study identified adults with COVID-19, March 2020 to February 2022, in 43 US health systems in the National Patient-Centered Clinical Research Network.

Planar carbon electrodes for real-time quantification of hydrogen sulfide release from cells.

A planar electrode system was developed to permit the real-time, selective detection of hydrogen sulfide (HS) from stimulated cells. Planar carbon electrodes were produced stencil printing carbon ink through a laser cut vinyl mask. Electrodes were preconditioned using a constant potential amperometry methodology to prevent sensor drift resulting from elemental sulfur adsorption.

Effects of low work-function lanthanum oxides on stable electron field emissions from nanoscale emitters.

Nanoscale electron field emitters are known to produce more stable electron emissions than conventional emitters. This has been attributed to size effects; nanoscale emitters can operate with a small emission current and a low extraction voltage, which reduces the bombardment of residual gas ions on the emitter tip. However, our experiments discovered that nanoscale LaB emitters had extremely stable emissions, suggesting that chemical effects are present in addition to size effects.

Heteroarylation of unactivated C-H bonds suitable for late-stage functionalization.

The late-stage introduction of diverse heterocycles onto complex small molecules enables efficient access to new medicinally relevant compounds. An attractive approach to such a transformation would utilize the ubiquitous aliphatic C-H bonds of a complex substrate. Herein, we report a system that enables direct C-H heteroarylation using a stable, commercially available -alkenylhydroxamate with heterocyclic sulfone partners.

How Have Global River Widths Changed Over Time?

Changes in a river's width reflect natural and anthropogenic impacts on local and upstream/downstream hydraulic and hydrologic processes. Temporal variation of river width also impacts biogeochemical exchange and reflects geomorphologic evolution. However, while global maps of mean river width and dynamic water surface extent exist, there is currently no standardized global assessment of river widths that documents changes over time.

A Four Carbon Organonitrate as a Significant Product of Secondary Isoprene Chemistry.

Oxidation of isoprene by nitrate radicals (NO) or by hydroxyl radicals (OH) under high NO conditions forms a substantial amount of organonitrates (ONs). ONs impact NO concentrations and consequently ozone formation while also contributing to secondary organic aerosol. Here we show that the ONs with the chemical formula CHNO are a significant fraction of isoprene-derived ONs, based on chamber experiments and ambient measurements from different sites around the globe.

ToxCast chemical library Wnt screen identifies diethanolamine as an activator of neural progenitor proliferation.

Numerous autism spectrum disorder (ASD) risk genes are associated with Wnt signaling, suggesting that brain development may be especially sensitive to genetic perturbation of this pathway. Additionally, valproic acid, which modulates Wnt signaling, increases risk for ASD when taken during pregnancy. We previously found that an autism-linked gain-of-function mutant construct hyperactivated canonical Wnt signaling, providing a genetic means to elevate Wnt signaling above baseline levels.

Use of FLOSEAL® as a scaffold and its impact on induced neural stem cell phenotype, persistence, and efficacy.

Induced neural stem cells (iNSCs) have emerged as a promising therapeutic platform for glioblastoma (GBM). iNSCs have the innate ability to home to tumor foci, making them ideal carriers for antitumor payloads. However, the in vivo persistence of iNSCs limits their therapeutic potential.

Non-asymptotic Properties of Individualized Treatment Rules from Sequentially Rule-Adaptive Trials.

Learning optimal individualized treatment rules (ITRs) has become increasingly important in the modern era of precision medicine. Many statistical and machine learning methods for learning optimal ITRs have been developed in the literature. However, most existing methods are based on data collected from traditional randomized controlled trials and thus cannot take advantage of the accumulative evidence when patients enter the trials sequentially.

Non-Hispanic Black and Hispanic Patients Have Worse Outcomes Than White Patients Within Similar Stages of Peripheral Artery Disease.

Background Racial and ethnic disparities in outcomes following lower limb revascularization for peripheral artery disease have been ascribed to disease severity at presentation for surgery. Methods and Results We calculated 1-year risk of major adverse limb events (MALEs), major amputation, and death for patients undergoing elective revascularization for claudication or chronic limb-threatening ischemia in the Vascular Quality Initiative data (2011-2018). We report hazard ratios according to race and ethnicity using Cox (death) or Fine and Gray subdistribution hazards models (MALE and major amputation, treating death as a competing event), adjusted for patient, treatment, and anatomic factors associated with disease severity.

Correlation of alterations in the pathway with radiation failure in larynx squamous cell carcinoma.

Objectives: Patients with laryngeal squamous cell carcinoma (LSCC) often fail radiation therapy (RT), when received as monotherapy or in combination with other treatment modalities. Mechanisms for RT failure are poorly understood. We hypothesized that tumors failing RT would have increased rates of somatic mutations in genes associated with radiation resistance, particularly in genes associated with the oxidative stress pathway.

Cobalt-catalyzed aminocarbonylation of (hetero)aryl halides promoted by visible light.

The catalytic aminocarbonylation of (hetero)aryl halides is widely applied in the synthesis of amides but relies heavily on the use of precious metal catalysis. Herein, we report an aminocarbonylation of (hetero)aryl halides using a simple cobalt catalyst under visible light irradiation. The reaction extends to the use of (hetero)aryl chlorides and is successful with a broad range of amine nucleophiles.

Personalized-induced neural stem cell therapy: Generation, transplant, and safety in a large animal model.

In this study, we take an important step toward clinical translation by generating the first canine-induced neural stem cells (iNSCs). We explore key aspects of scale-up, persistence, and safety of personalized iNSC therapy in autologous canine surgery models. iNSCs are a promising new approach to treat aggressive cancers of the brain, including the deadly glioblastoma.

NF-κB sub-pathways and HIV cure: A revisit.

HIV cure is thwarted by the presence of quiescent yet replication competent HIV-1 (HIV). Antiretroviral therapy (ART) is unable to eradicate reservoirs, and upon cessation of ART, HIV will rebound. This review encompasses the curative strategies of HIV in the context of NF-κB sub-pathways that are currently exploited and demonstrate promise in the disruption of latent HIV.