California Coast University

Stem cell markers, including NANOG, have been implicated in various cancers; however, the functional contribution of NANOG to cancer pathogenesis has remained unclear. Here, we show that NANOG is induced by Toll-like receptor 4 (TLR4) signaling via phosphorylation of E2F1 and that downregulation of Nanog slows down hepatocellular carcinoma (HCC) progression induced by alcohol western diet and hepatitis C virus protein in mice. NANOG ChIP-seq analyses reveal that NANOG regulates the expression of genes involved in mitochondrial metabolic pathways required to maintain tumor-initiating stem-like cells (TICs). NANOG represses mitochondrial oxidative phosphorylation (OXPHOS) genes, as well as ROS generation, and activates fatty acid oxidation (FAO) to support TIC self-renewal and drug resistance. Restoration of OXPHOS activity and inhibition of FAO renders TICs susceptible to a standard care chemotherapy drug for HCC, sorafenib. This study provides insights into the mechanisms of NANOG-mediated generation of TICs, tumorigenesis, and chemoresistance through reprogramming of mitochondrial metabolism.

We synthesized a series of multivariate metal-organic frameworks (MTV-MOFs) containing 36 different organic linkers with 27 unique functionalities. The functionalities present on the linkers include amine, nitro, halide, naphthalene, alkyne, alkene, alkane, ether, phenyl, pyridine, thiophene, and amide groups. These MTV-MOFs were characterized by powder X-ray diffraction to ensure the MOF-5 connectivity forms, solution-state nuclear magnetic resonance to calculate the final linker incorporations, thermogravimetric analysis to confirm the organic component of the framework, and nitrogen sorption isotherms to measure the porosity and calculate the BET surface areas of each MTV-MOF. Each linker was found to make up between 0.07 and 6.64% of the linkers in the structure, with the total framework mass consisting of 74.8-75.1% linker molecules, compared to 63.9% for the linkers in MOF-5. BET surface areas up to 1,755 m2/g were observed with 36 linkers present compared to 3,380 m2/g in MOF-5. Thirty-four of the 36 linkers had linear correlations between the starting ratio and final incorporation, indicating interactions between linkers do not heavily influence the incorporation of other linkers into the final structure.

OBJECTIVES:Bimekizumab, a monoclonal IgG1 antibody that selectively inhibits IL-17F in addition to IL-17A, previously demonstrated efficacy and was well tolerated to 1 year in patients with non-radiographic (nr-) and radiographic (r-) axial spondyloarthritis (axSpA). Here, we report bimekizumab safety and efficacy to 2 years. METHODS:Patients completing week 52 in the phase 3 studies BE MOBILE 1 (nr-axSpA; NCT03928704) and 2 (r-axSpA; NCT03928743) were eligible for an ongoing open-label extension (OLE; NCT04436640). All OLE patients received subcutaneous bimekizumab 160 mg every 4 weeks. Safety outcomes for patients who received ≥1 bimekizumab dose, and efficacy outcomes for all randomized patients, are reported to week 104. RESULTS:In the OLE (weeks 52 - 104), 70.8% (367/518) of patients reported ≥1 treatment-emergent adverse event (TEAE). Most frequent TEAEs [exposure-adjusted incidence rate per 100 patient-years (EAIR/100PY)] were SARS-CoV-2 (COVID-19) infection (25.2), nasopharyngitis (11.0) and oral candidiasis (5.4). Fungal infection EAIR/100PY was 11.8 (majority Candida infections: 6.8; most mild/moderate, none serious/systemic). Inflammatory bowel disease and uveitis rates were low; no major adverse cardiovascular events or deaths occurred. TEAE incidence rate was generally similar across weeks 0 - 52 and 52 - 104.At week 104, >50% of randomized patients (N = 586) achieved Assessment of SpondyloArthritis international Society 40% response (ASAS40); ∼60% achieved Axial Spondyloarthritis Disease Activity Score (ASDAS) low disease activity (<2.1) and >30% achieved ASDAS inactive disease (<1.3). Bimekizumab demonstrated sustained suppression of MRI inflammation at week 104, with >57% of patients achieving MRI remission. CONCLUSIONS:The safety profile of bimekizumab remained consistent with prior reports, with no new safety signals identified. 1-year efficacy was sustained to 2 years across patients with nr-axSpA and r-axSpA.

Precise robot localization at the tree level is essential for smart agriculture applications such as precision disease management and targeted nutrient distribution. Existing methods fail to achieve the required accuracy. We propose OrchLoc, a fingerprinting-based localization solution that achieves treelevel precision using a single Long Range (LoRa) gateway. Our approach utilizes channel state information (CSI) across eight channels as a localization fingerprint. To minimize labor-intensive site surveys for fingerprint database construction and maintenance, we develop a CSI generative model (CGM) that learns the relationship between CSI vectors and their corresponding locations. The CGM is fine-tuned using CSI data from static agricultural LoRa sensor nodes, enabling continuous fingerprint database updates. Extensive experiments in two orchards demonstrate that OrchLoc effectively achieves accurate tree-level localization with minimal overhead, improving robot navigation

In this paper, I will be looking at the effects generative AI has on the ways businesses operate. The inception of AI technology is widely regarded as the fourth industrial revolution and businesses can use this technology to improve their business models and to differentiate their products to stay competitive. Generative AI can be used by businesses to significantly cut back their material, labor, and other overhead costs through the use of automating daily tasks. Generative AI is also used by businesses to improve their product prototyping, by brainstorming hundreds of thousands of products daily. This technology also helps companies improve their products, since generative AI can be used to find gaps in the market to make their products more appealing to their target audience. Generative AI is an invaluable tool easily available for businesses which can help them reduce costs, prototype and manufacture products faster, innovate products by finding gaps in the market to keep their products competitive, and create a personalized shopping experience tailored toward the customer through analyzing past search and purchase history. JEL Codes: O33, L21, M15 Keywords: Generative AI, AI, Technology, Daily Tasks.