Rapid-Turnaround Co-Administration of mRNA-Based MHC-I and MHC-II-Restricted Neoantigens Enhances Immune Responses of Antigen-Specific CD8 T Cells and Anti-Cancer Efficacy in Colorectal Cancer.

Personalized cancer vaccines (PCVs) represent a promising frontier in cancer immunotherapy; however, challenges in neoantigen prediction and treatment optimization persist. This study aims to introduce an innovative mRNA-based PCV platform that addresses these limitations. Co-administration of our major histocompatibility complex (MHC)-I and MHC-II-restricted neoantigens increases antigen-specific T cell responses and exhibits strong anti-cancer efficacy, significantly inducing antigen-specific CD8 T cell-immune responses.

Comparative immunologic profiling of mRNA and protein-conjugated vaccines: acute inflammatory responses and anti-PEG antibody production.

Messenger ribonucleic acid (mRNA) vaccines have become a prevalent immunization method, even as the coronavirus disease 2019 (COVID-19) pandemic recedes. However, the potential adverse effects using mRNA vaccines need to be explored in this evolving landscape. In this study, 60 participants were randomly assigned to receive either an mRNA vaccine, specifically for COVID-19, or a conventional vaccine for meningococcal disease.

Immunogenicity and protection of a triple repeat domain III mRNA vaccine against Zika virus.

Zika virus (ZIKV) infection is primarily transmitted by mosquitoes and often asymptomatic in most individuals. Infection during pregnancy can lead to severe birth defects such as congenital microcephaly, and currently, there is no approved vaccine for ZIKV. Several studies are investigating the development of ZIKV vaccine using DNA and RNA as well as recombinant protein technologies; however, the outcomes thus far have not been consistently noteworthy.

Cu-Catalyzed Hydrodechlorination of Unactivated Alkyl Chlorides Using Diisobutylaluminum Hydride.

A copper-catalyzed hydrodechlorination of primary, secondary, and tertiary alkyl chlorides using diisobutylaluminum hydride is reported. This catalytic system offers a broad substrate scope, high yields, and good functional group tolerance. Mechanistic investigations indicated that the reaction predominantly proceeds via a radical pathway, as supported by radical clock experiments.

Microfluidic Bioreactor with Fibrous Micromixers for In Vitro mRNA Transcription.

A new type of microfluidic bioreactor with fibrous micromixers for the ingredient mixing and a long macrochannel for the in vitro transcription reaction was fabricated for the continuous production of mRNA. The diameter of the fibrous microchannels in the micromixers was tuned by using an electrospun microfibrous disc with different microfiber diameters. The micromixer with a larger diameter of fibrous microchannels exhibited a better mixing performance than the others.

Marine Submicron Aerosols from the Gulf of Mexico: Polluted and Acidic with Rapid Production of Sulfate and Organosulfates.

We measured submicron aerosols (PM) at a beachfront site in Texas in Spring 2021 to characterize the "background" aerosol chemical composition advecting into Texas and the factors controlling this composition. Observations show that marine "background" aerosols from the Gulf of Mexico were highly processed and acidic; sulfate was the most abundant component (on average 57% of total PM mass), followed by organic material (26%). These chemical characteristics are similar to those observed at other marine locations globally.

Synthesis of -substituted quaternary carbon centers through KO-Bu-catalyzed aza-Michael addition of pyrazoles to cyclic enones.

This study reports an efficient and mild method for the synthesis of cyclic -amino ketones containing -substituted quaternary carbon centers the KO-Bu-catalyzed aza-Michael addition reaction of pyrazoles to -substituted cyclic ,-enones. The amination was promoted by KO-Bu (3 mol%) at ambient temperature and a wide range of new and versatile -pyrazolyl ketones were obtained in good yields. Furthermore, the KO-Bu-catalyzed one-pot diamination of a cyclic dienone with pyrazoles an aza-1,6-conjugate addition followed by an aza-1,4-conjugate addition was also explored.

Traffic, transport, and vegetation drive VOC concentrations in a major urban area in Texas.

The population of Texas has increased rapidly in the past decade. The San Antonio Field Study (SAFS) was designed to investigate ozone (O) production and precursors in this rapidly changing, sprawling metropolitan area. There are still many questions regarding the sources and chemistry of volatile organic compounds (VOCs) in urban areas like San Antonio which are affected by a complex mixture of industry, traffic, biogenic sources and transported pollutants.

Applying Protein-Protein Interactions and Complex Networks to Identify Novel Genes in Retinitis Pigmentosa Pathogenesis.

Retinitis Pigmentosa (RP) is a hereditary retinal disorder that causes the atrophy of photoreceptor rod cells. Since individual defective genes converge on the same disease, we hypothesized that all causal genes of RP belong in a complex network. To explore this hypothesis, we conducted a gene connection analysis using 161 genes attributed to RP, compiled from the Retinal Information Network, RetNet.

Assessing the atmospheric fate of pesticides used to control mosquito populations in Houston, TX.

During the summer months, urban areas are literal hot spots of mosquito-borne disease transmission and air pollution. Public health authorities release aerosolized pesticides directly into the atmosphere to help control adult mosquito populations and thereby reduce the threat of diseases, such as Zika Virus. The primary adulticides (i.

Apportioned primary and secondary organic aerosol during pollution events of DISCOVER-AQ Houston.

Understanding the drivers for high ozone (O) and atmospheric particulate matter (PM) concentrations is a pressing issue in urban air quality, as this understanding informs decisions for control and mitigation of these key pollutants. The Houston, TX metropolitan area is an ideal location for studying the intersection between O and atmospheric secondary organic carbon (SOC) production due to the diversity of source types (urban, industrial, and biogenic) and the on- and off-shore cycling of air masses over Galveston Bay, TX. Detailed characterization of filter-based samples collected during Deriving Information on Surface Conditions from Column and VERtically Resolved Observations Relevant to Air Quality (DISCOVER-AQ) Houston field experiment in September 2013 were used to investigate sources and composition of organic carbon (OC) and potential relationships between daily maximum 8 h average O and PM.

RNA interference-mediated suppression of TNF-α converting enzyme as an alternative anti-TNF-α therapy for rheumatoid arthritis.

Excessive tumor necrosis factor-α (TNF-α) is associated with the pathogenesis of rheumatoid arthritis (RA). Approximately 90% of patients with RA, who have inadequate response to methotrexate, follow anti-TNF-α therapy as the first-line immuno-treatment. However, ineffective long-term anti-TNF-α antibody cycling for 40% of non-responders to anti-TNF-α antibodies is costly and associated with various side effects, which needs alternative mechanism of action therapies.

The characterization of fine particulate matter downwind of Houston: Using integrated factor analysis to identify anthropogenic and natural sources.

The interpretation of large air pollution datasets involves a great deal of complexity. To gain a better understanding of the complicated relationships and patterns within datasets, we perform factor analysis. Between December 2015 and December 2017, fine particulate matter (PM) samples were collected at a suburban site northeast of the Houston metropolitan area, TX.

DKK1 Induced by 1,25D3 Is Required for the Mineralization of Osteoblasts.

1α,25-dihydroxyvitamin D3 (1,25D3), the most popular drug for osteoporosis treatment, drives osteoblast differentiation and bone mineralization. Wnt/β-catenin signaling is involved in commitment and differentiation of osteoblasts, but the role of the Dickkopf-related protein 1 (DKK1), a Wnt antagonist, in osteoblasts remains unknown. Here, we demonstrate the molecular mechanism of DKK1 induction by 1,25D3 and its physiological role during osteoblast differentiation.

Regulation of osteoblasts by alkaline phosphatase in ankylosing spondylitis.

Aim: Ankylosing spondylitis (AS) is characterized by excessive spinal ankylosis and bone formation. Alkaline phosphatase (ALP) activity is reported to be high in AS, but little is known about the molecular relationship between ALP and AS. The aims of this study were to investigate the relevance of ALP to AS and the role of ALP in the regulation of osteoblast differentiation in AS.

CCAAT/enhancer-binding protein beta (C/EBPβ) is an important mediator of 1,25 dihydroxyvitamin D3 (1,25D3)-induced receptor activator of nuclear factor kappa-B ligand (RANKL) expression in osteoblasts.

Receptor activator of nuclear factor kappa B ligand (RANKL) expression in osteoblasts is regulated by 1,25-dihydroxyvitamin D3 (1,25D3). CCAAT/enhancer-binding protein beta (C/EBPβ) has been proposed to function as a transcription factor and upregulate RANKL expression, but it is still uncertain how C/EBPβ is involved in 1,25D3-induced RANKL expression of osteoblasts. 1,25D3 stimulation increased the expression of RANKL and C/EPBβ genes in osteoblasts and enhanced phosphorylation and stability of these proteins.

Source apportionment of fine particulate matter organic carbon in Shenzhen, China by chemical mass balance and radiocarbon methods.

Chemical mass balance (CMB) modeling and radiocarbon measurements were combined to evaluate the sources of carbonaceous fine particulate matter (PM) in Shenzhen, China during and after the 2011 summer Universiade games when air pollution control measurements were implemented to achieve air quality targets. Ambient PM filter samples were collected daily at two sampling sites (Peking University Shenzhen campus and Longgang) over 24 consecutive days, covering the controlled and uncontrolled periods. During the controlled period, the average PM concentration was less than half of what it was after the controls were lifted.

Spatial and Temporal Distributions of Organophosphate Ester Concentrations from Atmospheric Particulate Matter Samples Collected across Houston, TX.

Atmospheric particulate matter (PM) samples were collected from four ground-based sites located in the Houston, TX (September 21-28, 2013) and were analyzed for 12 organophosphate esters (OPEs; current-use plasticizers and flame retardants). Samples analyzed included daytime, nighttime, and 24 h PM of <2.5 μm aerodynamic diameter (PM) and total suspended particulate (TSP) samples.

Spatial and Temporal Distribution of Current-Use Pesticides in Atmospheric Particulate Matter in Houston, Texas.

The atmospheric concentrations of seven current-use pesticides in particulate matter were determined at four locations throughout the Houston metropolitan area in TSP and PM samples from September 2013. Atmospheric concentrations in both TSP and PM ranged from below method detection limits (MDLs) to nearly 1100 pg m. The three compounds most frequently detected above MDLs were chlorothalonil, bifenthrin, and λ-cyhalothrin.

Pressurized liquid extraction technique for the analysis of pesticides, PCBs, PBDEs, OPEs, PAHs, alkanes, hopanes, and steranes in atmospheric particulate matter.

An analytical method has been developed for the pressurized liquid extraction (PLE) of a wide range of semi-volatile organic compounds (SVOCs) from atmospheric particulate matter. Approximately 130 SVOCs from eight compound classes were selected as molecular markers of (1) agricultural activity (30 current and historic-use pesticides), (2) industrial activity (18 PCBs), (3) consumer products and building materials (16 PBDEs, 11 OPEs), and (4) motor vehicle exhaust (22 PAHs, 16 alkanes, 9 hopanes, 8 steranes). Currently, there is no analytical method validated for the extraction of all eight compound classes in a single automated technique.