Targeting the EP2 receptor ameliorates inflammatory bowel disease in mice by enhancing the immunosuppressive activity of T cells.

Inflammatory bowel diseases (IBDs) are characterized by unrestrained innate and adaptive immune responses and compromised intestinal epithelial barrier integrity. Regulatory T (T) cells are crucial for maintaining self-tolerance and immune homeostasis in intestinal tissues. Prostaglandin E (PGE), a bioactive lipid compound derived from arachidonic acid, can modulate T cell functions in a receptor subtype-specific manner.

IFN-γ-producing T1 cells and dysfunctional regulatory T cells contribute to the pathogenesis of Sjögren's disease.

Sjögren's disease (SjD) is an autoimmune disorder characterized by progressive salivary and lacrimal gland dysfunction, inflammation, and destruction, as well as extraglandular manifestations. SjD is associated with autoreactive B and T cells, but its pathophysiology remains incompletely understood. Abnormalities in regulatory T (T) cells occur in several autoimmune diseases, but their role in SjD is ambiguous.

Concurrent intratumoural T cell depletion and CD8 T cell expansion via a cleavable anti-4-1BB-interleukin-15 fusion protein.

Potent agonists of the inducible co-stimulatory receptor 4-1BB are too toxic for patients with advanced cancer. Here, on the basis of observations of a weak agonist of 4-1BB depleting regulatory T (T) cells within the tumour microenvironment without leading to substantial restoration of dysfunctional cytotoxic T cells (CTLs), we show that effective tumour control can be achieved via concurrent T cell depletion and CTL expansion through an anti-4-1BB antibody fused to interleukin-15 (IL-15) via a peptide sensitive to tumour proteases. In mouse models of advanced cancers, intraperitoneal injection of the bifunctional protein attenuated the activity of the interleukin mostly in the periphery of the primary tumour while allowing for the expansion of CTLs within the tumour microenvironment, led to more effective tumour inhibition and to lower systemic toxicity than treating the cancers with combinatorial treatment with unlinked anti-4-1BB antibody and IL-15, and reduced the resistance of tumours to checkpoint blockade.

Effect of Oral Nutritional Supplementation on Health-Related Outcomes and Nutritional Biomarkers in Children and Adolescents with Undernutrition: A Systematic Review and Meta-Analysis.

This systematic review aims to synthesize scientific evidence on the effects of oral nutritional supplementation (ONS) on health-related outcomes and nutritional biomarkers among children and adolescents with undernutrition. The review protocol was reported following the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) guidelines. A comprehensive keyword and reference search was conducted in seven electronic bibliographic databases: PubMed, Academic Search Complete, Academic Search Premier, CINAHL, Global Health, Web of Science, and Scopus.

Phospholipid Phosphatase 3 () Induces Oxidative Stress to Accelerate Ovarian Aging in Pigs.

Ovarian aging results in reproductive disorders and infertility in mammals. Previous studies have reported that the ferroptosis and autophagy caused by oxidative stress may lead to ovarian aging, but the mechanisms remain unclear. In this study, we compared the morphological characteristics between the aged and young ovaries of pigs and found that the aged ovaries were larger in size and showed more corpora lutea.

Highly Selective Hydrogenation of Unsaturated Aldehydes in Aqueous Phase.

Chemoselective hydrogenation of carbonyl in unsaturated aldehydes is a significant process in the chemical industry, in which the development of aqueous-phase reaction systems as a substitution to organic ones is challenging. Herein, we report Ir atomic cluster catalysts anchored onto WO nanorods a reduction treatment at various temperatures (denoted as Ir/WO-T, = 200, 300, 400, and 500 °C), which accelerates the chemoselective hydrogenation of carbonyl groups in aqueous solutions. The optimal catalyst Ir/WO-300 exhibits exceptional activity (TOF value: 1313.

Targeting JMJD1C to selectively disrupt tumor T cell fitness enhances antitumor immunity.

Regulatory T (T) cells are critical for immune tolerance but also form a barrier to antitumor immunity. As therapeutic strategies involving T cell depletion are limited by concurrent autoimmune disorders, identification of intratumoral T cell-specific regulatory mechanisms is needed for selective targeting. Epigenetic modulators can be targeted with small compounds, but intratumoral T cell-specific epigenetic regulators have been unexplored.

Integrated transmission electron microscopy and proteomic analyses reveal the cytoarchitectural response to cucumber mosaic virus infection in tobacco.

Cucumber mosaic virus (CMV) causes huge economic losses to agriculture every year; thus, understanding the mechanism of plant resistance to CMV is imperative. In this study, an integrated analysis of transmission electron microscopy (TEM) observations and proteomic results was used to identify cytoarchitectural differences in Nicotiana tabacum cv. NC82 (susceptible) and cv.

Defining the Clinicoradiologic Syndrome of SARS-CoV-2 Acute Necrotizing Encephalopathy: A Systematic Review and 3 New Pediatric Cases.

Background And Objectives: We characterize clinical and neuroimaging features of SARS-CoV-2-related acute necrotizing encephalopathy (ANE).

Methods: Systematic review of English language publications in PubMed and reference lists between January 1, 2020, and June 30, 2023, in accordance with PRISMA guidelines. Patients with SARS-CoV-2 infection who fulfilled diagnostic criteria for sporadic and genetic ANE were included.

RIPK1 plays a crucial role in maintaining regulatory T-Cell homeostasis by inhibiting both RIPK3- and FADD-mediated cell death.

Regulatory T (T) cells play an essential role in maintaining immune balance across various physiological and pathological conditions. However, the mechanisms underlying T homeostasis remain incompletely understood. Here, we report that RIPK1 is crucial for T cell survival and homeostasis.

Dissecting embryonic and extraembryonic lineage crosstalk with stem cell co-culture.

Embryogenesis necessitates harmonious coordination between embryonic and extraembryonic tissues. Although stem cells of both embryonic and extraembryonic origins have been generated, they are grown in different culture conditions. In this study, utilizing a unified culture condition that activates the FGF, TGF-β, and WNT pathways, we have successfully derived embryonic stem cells (FTW-ESCs), extraembryonic endoderm stem cells (FTW-XENs), and trophoblast stem cells (FTW-TSCs) from the three foundational tissues of mouse and cynomolgus monkey (Macaca fascicularis) blastocysts.

Factors Associated With Family Surrogate Decisional-Regret Trajectories.

Context/objectives: The scarce research on factors associated with surrogate decisional regret overlooks longitudinal, heterogenous decisional-regret experiences and fractionally examines factors from the three decision-process framework stages: decision antecedents, decision-making process, and decision outcomes. This study aimed to fill these knowledge gaps by focusing on factors modifiable by high-quality end-of-life (EOL) care.

Methods: This observational study used a prior cohort of 377 family surrogates of terminal-cancer patients to examine factors associated with their membership in the four preidentified distinct decisional-regret trajectories: resilient, delayed-recovery, late-emerging, and increasing-prolonged trajectories from EOL-care decision making through the first two bereavement years by multinomial logistic regression modeling using the resilient trajectory as reference.

Biologic and clinical features of childhood gamma delta T-ALL: identification of STAG2/LMO2 γδ T-ALL as an extremely high risk leukemia in the very young.

Purpose: Gamma delta T-cell receptor-positive acute lymphoblastic leukemia (γδ T-ALL) is a high-risk but poorly characterized disease.

Methods: We studied clinical features of 200 pediatric γδ T-ALL, and compared the prognosis of 93 cases to 1,067 protocol-matched non-γδ T-ALL. Genomic features were defined by transcriptome and genome sequencing.

A Unified Analysis of AdaGrad With Weighted Aggregation and Momentum Acceleration.

Integrating adaptive learning rate and momentum techniques into stochastic gradient descent (SGD) leads to a large class of efficiently accelerated adaptive stochastic algorithms, such as AdaGrad, RMSProp, Adam, AccAdaGrad, and so on. In spite of their effectiveness in practice, there is still a large gap in their theories of convergences, especially in the difficult nonconvex stochastic setting. To fill this gap, we propose weighted AdaGrad with unified momentum and dubbed AdaUSM, which has the main characteristics that: 1) it incorporates a unified momentum scheme that covers both the heavy ball (HB) momentum and the Nesterov accelerated gradient (NAG) momentum and 2) it adopts a novel weighted adaptive learning rate that can unify the learning rates of AdaGrad, AccAdaGrad, Adam, and RMSProp.

CD38 as a pan-hematologic target for chimeric antigen receptor TÂ cells.

Many hematologic malignancies are not curable with chemotherapy and require novel therapeutic approaches. Chimeric antigen receptor (CAR) T-cell therapy is 1 such approach that involves the transfer of T cells engineered to express CARs for a specific cell-surface antigen. CD38 is a validated tumor antigen in multiple myeloma (MM) and T-cell acute lymphoblastic leukemia (T-ALL) and is also overexpressed in acute myeloid leukemia (AML).

BIN1, Myotubularin, and Dynamin-2 Coordinate T-Tubule Growth in Cardiomyocytes.

Background: Transverse tubules (t-tubules) form gradually in the developing heart, critically enabling maturation of cardiomyocyte Ca homeostasis. The membrane bending and scaffolding protein BIN1 (bridging integrator 1) has been implicated in this process. However, it is unclear which of the various reported BIN1 isoforms are involved, and whether BIN1 function is regulated by its putative binding partners MTM1 (myotubularin), a phosphoinositide 3'-phosphatase, and DNM2 (dynamin-2), a GTPase believed to mediate membrane fission.

Noncontact Acoustic Micro-Tapping Optical Coherence Elastography for Quantification of Corneal Anisotropic Elasticity: In Vivo Rabbit Study.

Purpose: The purpose of this study was to demonstrate accurate measurement of corneal elastic moduli in vivo with noncontact and noninvasive optical coherence elastography.

Methods: Elastic properties (in-plane Young's modulus, E, and both in-plane, μ, and out-of-plane, G, shear moduli) of rabbit cornea were quantified in vivo using noncontact dynamic acoustic micro-tapping optical coherence elastography (AµT-OCE). The intraocular pressure (IOP)-dependence of measured mechanical properties was explored in extracted whole globes following in vivo measurement.

Decisional-Regret Trajectories From End-of-Life Decision Making Through Bereavement.

Context: Regret plays a central role in surrogate decision making. Research on decisional regret in family surrogates is scarce and lacks longitudinal studies to illustrate the heterogenous, dynamic evolution of decisional regret.

Objectives: To identify distinct decisional-regret trajectories from end-of-life (EOL) decision making through the first two bereavement years among surrogates of cancer patients.

Disruption of Phosphodiesterase 3A Binding to SERCA2 Increases SERCA2 Activity and Reduces Mortality in Mice With Chronic Heart Failure.

Background: Increasing SERCA2 (sarco[endo]-plasmic reticulum Ca ATPase 2) activity is suggested to be beneficial in chronic heart failure, but no selective SERCA2-activating drugs are available. PDE3A (phosphodiesterase 3A) is proposed to be present in the SERCA2 interactome and limit SERCA2 activity. Disruption of PDE3A from SERCA2 might thus be a strategy to develop SERCA2 activators.