Three-Level Nanoparticle Rocket Strategy for Colorectal Cancer Therapeutics in Photothermal Therapy, Inflammation Modulation, and Cuproptosis Induction.

Disturbances in intracellular copper (Cu) homeostasis can trigger cuproptosis, a new form of cell death, which, when combined with photothermal therapy (PTT), offers a promising solution to the persistent challenges in colorectal cancer (CRC) treatment. In this study, a "three-level nanoparticle rocket" strategy is developed by engineering CuO, a multifunctional Cu-based nanoenzyme that is photothermal and has electron transfer properties and antioxidant efficiency. CuO effectively remodels the inflammatory environment by scavenging reactive oxygen species, thereby overcoming the traditional limitations of PTT.

HIV-1 with gag processing defects activates cGAS sensing.

Background: Detection of viruses by host pattern recognition receptors induces the expression of type I interferon (IFN) and IFN-stimulated genes (ISGs), which suppress viral replication. Numerous studies have described HIV-1 as a poor activator of innate immunity in vitro. The exact role that the viral capsid plays in this immune evasion is not fully understood.

Lytic efficiency of immunosuppressive drug-resistant armoured T cells against circulating HBV-related HCC in whole blood.

Recurrence of hepatitis B virus-related hepatocellular carcinoma (HBV-HCC) after liver transplant (LT) is mediated by circulating tumour cells (CTCs) and exacerbated by the immunosuppressants required to prevent graft rejection. To circumvent the effects of immunosuppressants, we developed immunosuppressive drug-resistant armoured HBV-specific T-cell receptor-redirected T cells (IDRA HBV-TCR). However, their ability to eliminate HBV-HCC circulating in the whole blood has never been tested, and whether their lytic efficacy is compatible with the number of adoptively transferred T cells has never been measured.

Neuromagnetic evidence of abnormal automatic inhibitory function in subjective memory complaint.

Subjective memory complaint (SMC), a self-perceived worsening in memory capacity concurrent with normal performance on standardized cognitive assessments, is considered a risk factor for the development of Alzheimer's disease (AD). Deficient sensory gating (SG), referring to the lack of automatic inhibition of neural responses to the second identical stimulus, has been documented in prodromal and incident AD patients. However, it remains unknown whether the cognitively normal elderly with SMC demonstrate alterations of SG function compared with those without SMC.

Immunosuppressive Drug-Resistant Armored T-Cell Receptor T Cells for Immune Therapy of HCC in Liver Transplant Patients.

Background And Aims: HBV-specific T-cell receptor (HBV-TCR) engineered T cells have the potential for treating HCC relapses after liver transplantation, but their efficacy can be hampered by the concomitant immunosuppressive treatment required to prevent graft rejection. Our aim is to molecularly engineer TCR-T cells that could retain their polyfunctionality in such patients while minimizing the associated risk of organ rejection.

Approach And Results: We first analyzed how immunosuppressive drugs can interfere with the in vivo function of TCR-T cells in liver transplanted patients with HBV-HCC recurrence receiving HBV-TCR T cells and in vitro in the presence of clinically relevant concentrations of immunosuppressive tacrolimus (TAC) and mycophenolate mofetil (MMF).

Effect of Age in Auditory Go/No-Go Tasks: A Magnetoencephalographic Study.

Response inhibition is frequently examined using visual go/no-go tasks. Recently, the auditory go/no-go paradigm has been also applied to several clinical and aging populations. However, age-related changes in the neural underpinnings of auditory go/no-go tasks are yet to be elucidated.

Discovering Putative Protein Targets of Small Molecules: A Study of the p53 Activator Nutlin.

Small molecule drugs bind to a pocket in disease causing target proteins based on complementarity in shape and physicochemical properties. There is a likelihood that other proteins could have binding sites that are structurally similar to the target protein. Binding to these other proteins could alter their activities leading to off target effects of the drug.

Age Effects on Spatiotemporal Dynamics of Response Inhibition: An MEG Study.

Inhibition, the ability to suppress irrelevant information, thoughts or movements, is crucial for humans to perform context-appropriate behaviors. It was suggested that declined cognitive performance in older adults might be attributed to inhibitory deficiencies. Although previous studies have shown an age-associated reduction in inhibitory ability, the understanding regarding its cortical spatiotemporal maps remained limited.

Age Effect on Automatic Inhibitory Function of the Somatosensory and Motor Cortex: An MEG Study.

Age-related deficiency in the top-down modulation of cognitive inhibition has been extensively documented, whereas the effects of age on a bottom-up or automatic operation of inhibitory function were less investigated. It is unknown that whether the older adults (OA)' reduced behavioral performance and neural responses are due to the insufficient bottom-up processes. Compared to behavioral assessments which have been widely used to examine the top-down control of response inhibition, electrophysiological recordings are more suitable to probe the early-stage processes of automatic inhibitory function.

Prevention and Reversal of Diabetes by All-Trans Retinoid Acid and Exendin-4 in NOD Mice.

It has been shown that all-trans retinoid acid (ATRA) hinders the development of autoimmune diabetes by inducing immune tolerance status. Meanwhile, exendin-4 increases beta-cell function and mass. Thus, we hypothesized that ATRA and exendin-4 combination therapy would prevent and reverse autoimmune diabetes.

Quantitative NanoProteomics approach for protein complex (QNanoPX) using gold nanoparticle-based DNA probe.

Affinity purification by pulldown methods using target-bound gel beads provides a powerful approach for purifying endogenous protein complexes. Such methods can be improved by using nanoparticle-based probe, coupled with immunoblot analysis or quantitative proteomics method using stable isotope labeling via liquid chromatography-mass spectrometry (LC-MS). Here, we describe sample preparation and a pulldown method using gold nanoparticle-based DNA probe for characterizing the transcriptional complex of estrogen response element (ERE).