The metabolic landscape of cancer greatly influences antitumor immunity, yet it remains unclear how organ-specific metabolites in the tumor microenvironment influence immunosurveillance. We found that accumulation of primary conjugated and secondary bile acids (BAs) are metabolic features of human hepatocellular carcinoma and experimental liver cancer models. Inhibiting conjugated BA synthesis in hepatocytes through deletion of the BA-conjugating enzyme bile acid-CoA:amino acid -acyltransferase (BAAT) enhanced tumor-specific T cell responses, reduced tumor growth, and sensitized tumors to anti-programmed cell death protein 1 (anti-PD-1) immunotherapy.
View Article and Find Full Text PDFExhausted T cells (TEX) in cancer and chronic viral infections undergo metabolic and epigenetic remodeling, impairing their protective capabilities. However, the impact of nutrient metabolism on epigenetic modifications that control TEX differentiation remains unclear. We showed that TEX cells shifted from acetate to citrate metabolism by downregulating acetyl-CoA synthetase 2 (ACSS2) while maintaining ATP-citrate lyase (ACLY) activity.
View Article and Find Full Text PDFCell Mol Gastroenterol Hepatol
December 2024
Many pathological conditions lead to defects in intestinal epithelial integrity and loss of barrier function; Sphingosine-1-phosphate (S1P) has been shown to augment intestinal barrier integrity, though the exact mechanisms are not completely understood. We have previously shown that overexpression of Sphingosine Kinase 1 (SphK1), the rate limiting enzyme for S1P synthesis, significantly increased S1P production and cell proliferation. Here we show that microRNA 495 (miR-495) upregulation led to decreased levels of SphK1 resultant from a direct effect at the SphK1 mRNA.
View Article and Find Full Text PDFBackground: Cerclage wiring is commonly used for treating fractures; however, it has several limitations, including mechanical weakness, decreased blood circulation, and technical complexity. In this study, we developed an implant using a shape memory alloy (SMA) and tested its efficacy in treating Vancouver type B1 (VB1) periprosthetic femoral fractures (PFFs) in a canine model.
Methods: The mid-diaphyseal fracture models underwent reduction via the SMA plate (SMA group) or the cerclage cable plate (cable group) method in randomly selected pelvic limbs.
Paneth cells at the bottom of small intestinal crypts secrete antimicrobial peptides, enzymes, and growth factors and contribute to pathogen clearance and maintenance of the stem cell niche. Loss of Paneth cells and their dysfunction occur commonly in various pathologies, but the mechanism underlying the control of Paneth cell function remains largely unknown. Here, we identified microRNA-195 (miR-195) as a repressor of Paneth cell development and activity by altering SOX9 translation via interaction with RNA-binding protein HuR.
View Article and Find Full Text PDFArea-selective deposition (ASD) based on self-aligned technology has emerged as a promising solution for resolving misalignment issues during ultrafine patterning processes. Despite its potential, the problems of area-selectivity losing beyond a certain thickness remain critical in ASD applications. This study reports a novel approach to sustain the area-selectivity of Ir films as the thickness increases.
View Article and Find Full Text PDFIn general, the electronic and optical properties of oxide films can significantly benefit from highly textured crystallinity. However, oxide films grown by atomic layer deposition (ALD), a powerful technique for the synthesis of high-quality, nanoscale thin films, usually exhibit amorphous or randomly oriented polycrystalline phases. Here, we demonstrate the growth of highly textured rutile phase ALD TiO films through rational substrate design.
View Article and Find Full Text PDFBackground: Oligomeric amyloid beta (oAβ) is a toxic factor that acts in the early stage of Alzheimer's disease (AD) and may initiate the pathologic cascade. Therefore, detecting oAβ has a crucial role in the early diagnosis, monitoring, and treatment of AD.
Purpose: The purpose of this study was to evaluate MRI signal changes in different mouse models and the time-dependent signal changes using our novel gadolinium (Gd)-dodecane tetraacetic acid (DOTA)- ob5 aptamer contrast agent.
The interplay of kinetic electron physics and atomic processes in ultrashort laser-plasma interactions provides a comprehensive understanding of the impact of the electron energy distribution on plasma properties. Notably, nonequilibrium electrons play a vital role in collisional ionization, influencing ionization degrees and spectra. This paper introduces a computational model that integrates the physics of kinetic electrons and atomic processes, utilizing a Boltzmann equation for nonequilibrium electrons and a collisional-radiative model for atomic state populations.
View Article and Find Full Text PDFWe report on experiments where solid-density Mg plasmas are created by heating with the focused output of the Linac Coherent Light Source x-ray free-electron laser. We study the K-shell emission from the helium- and lithium-like ions using Bragg crystal spectroscopy. Observation of the dielectronic satellites in lithium-like ions confirms that the M-shell electrons appear bound for these high charge states.
View Article and Find Full Text PDFAmong clinically used radiopharmaceuticals, iodine-123 labeled metaiodobenzylguanidine ([I]mIBG) serves for diagnosing neuroendocrine tumors and obtaining images of myocardial sympathetic innervation. mIBG, a structural analogue of norepinephrine (NE), a neurotransmitter acting in peripheral and central nerves, follows a pathway similar to NE, transmitting signals through the NE transporter (NET) located at synaptic terminals. It moves through the body without decomposing, enabling noninvasive image evaluation.
View Article and Find Full Text PDFCircular RNAs (circRNAs) are highly expressed in the mammalian intestinal epithelium, but their functions remain largely unknown. Here, we identified the circRNA Cdr1as as a repressor of intestinal epithelial regeneration and defense. Cdr1as levels increased in mouse intestinal mucosa after colitis and septic stress, as well as in human intestinal mucosa from patients with inflammatory bowel disease and sepsis.
View Article and Find Full Text PDFAm J Physiol Gastrointest Liver Physiol
December 2023
Gut barrier dysfunction occurs commonly in patients with critical disorders, leading to the translocation of luminal toxic substances and bacteria to the bloodstream. Connexin 43 (Cx43) acts as a gap junction protein and is crucial for intercellular communication and the diffusion of nutrients. The levels of cellular Cx43 are tightly regulated by multiple factors, including polyamines, but the exact mechanism underlying the control of Cx43 expression remains largely unknown.
View Article and Find Full Text PDFRapid self-renewal of the intestinal epithelium requires the activity of intestinal stem cells (ISCs) that are intermingled with Paneth cells (PCs) at the crypt base. PCs provide multiple secreted and surface-bound niche signals and play an important role in the regulation of ISC proliferation. Here, we show that control of PC function by RNA-binding protein HuR via mitochondria affects intestinal mucosal growth by altering ISC activity.
View Article and Find Full Text PDFInsomnia-related safety behaviors are behaviors that aim to mitigate the negative consequences of insomnia but inadvertently perpetuate insomnia. This study aimed to develop and evaluate a Chinese short-form of the sleep-related behavior questionnaire (SRBQ-SF), a self-report measure of insomnia-related safety behaviors, using item response theory. The Chinese version of the original SRBQ was completed by 536 Chinese-speaking adults with clinically significant insomnia.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
September 2023
Foraging theory prescribes when optimal foragers should leave the current option for more rewarding alternatives. Actual foragers often exploit options longer than prescribed by the theory, but it is unclear how this foraging suboptimality arises. We investigated whether the upregulation of cholinergic, noradrenergic, and dopaminergic systems increases foraging optimality.
View Article and Find Full Text PDFSubclinical hypothyroidism (SCH) is characterized by elevated thyroid-stimulating hormone (TSH) and normal free thyroxine levels. The Korean Thyroid Association recently issued a guideline for managing SCH, which emphasizes Korean-specific TSH diagnostic criteria and highlights the health benefits of levothyroxine (LT4) treatment. A serum TSH level of 6.
View Article and Find Full Text PDFUnderstanding the initial growth process during atomic layer deposition (ALD) is essential for various applications employing ultrathin films. This study investigated the initial growth of ALD Ir films using tricarbonyl-(1,2,3-η)-1,2,3-tri(-butyl)-cyclopropenyl-iridium and O. Isolated Ir nanoparticles were formed on the oxide surfaces during the initial growth stage, and their density and size were significantly influenced by the growth temperature and substrate surface, which strongly affected the precursor adsorption and surface diffusion of the adatoms.
View Article and Find Full Text PDFHumans are continuously exposed to benzisothiazolinone (BIT), which is used as a preservative, through multiple routes. BIT is known to be a sensitizer; in particular, dermal contact or aerosol inhalation could affect the local toxicity. In this study, we evaluated the pharmacokinetic properties of BIT in rats following various routes of administration.
View Article and Find Full Text PDFIn value-based decision making, options are selected according to subjective values assigned by the individual to available goods and actions. Despite the importance of this faculty of the mind, the neural mechanisms of value assignments, and how choices are directed by them, remain obscure. To investigate this problem, we used a classic measure of utility maximization, the Generalized Axiom of Revealed Preference, to quantify internal consistency of food preferences in , a nematode worm with a nervous system of only 302 neurons.
View Article and Find Full Text PDFAm J Physiol Cell Physiol
February 2023
Intestinal epithelial barrier defects occur commonly during a variety of pathological conditions, though their underlying mechanisms are not completely understood. Sphingosine-1-phosphate (S1P) has been shown to be a critical regulator of proliferation and of maintenance of an intact intestinal epithelial barrier, as is also sphingosine kinase 1 (SphK1), the rate-limiting enzyme for S1P synthesis. SphK1 has been shown to modulate its effect on intestinal epithelial proliferation through increased levels of c-myc.
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