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.

Blended Phenotype of and Variants With Accelerated Large and Small Artery Crosstalk: A Case Report and Literature Review.

Objectives: Recent advancements in genome research have revealed not only the importance of variants associated with cerebrovascular diseases but also a notably high frequency of carriers harboring multiple variants, presenting with an elusive blended phenotype. In this study, we report the case of a 66-year-old man who experienced 3 stroke episodes over a 4-year period, starting at the age of 62 years. The patient presented with isolated infarcts in the left temporal pole with progressive stenosis in the ipsilateral middle cerebral artery based on large and small artery crosstalk.

Aggregation-Induced Emission-Active Photosensitizer-Mediated Photodynamic Therapy for Anti-Psoriasis.

Hyperproliferative keratinocytes and subcutaneous inflammation contribute to the characteristic symptoms of psoriasis, including erythema, scales, or scaly plaques on the skin. These symptoms significantly affect patients' quality of life and cause severe physical and psychological distress. However, current treatment strategies have limited therapeutic effect and may lead to adverse side effects.

Association between Gene Polymorphisms and SNP-SNP Interactions of the Matrix Metalloproteinase 2 Signaling Pathway and the Risk of Vascular Senescence.

Objective: This study aimed to explore the association of single nucleotide polymorphisms (SNP) in the matrix metalloproteinase 2 (MMP-2) signaling pathway and the risk of vascular senescence (VS).

Methods: In this cross-sectional study, between May and November 2022, peripheral venous blood of 151 VS patients (case group) and 233 volunteers (control group) were collected. Fourteen SNPs were identified in five genes encoding the components of the MMP-2 signaling pathway, assessed through carotid-femoral pulse wave velocity (cfPWV), and analyzed using multivariate logistic regression.

Two regulatory T cell populations in the visceral adipose tissue shape systemic metabolism.

Visceral adipose tissue (VAT) is an energy store and endocrine organ critical for metabolic homeostasis. Regulatory T (T) cells restrain inflammation to preserve VAT homeostasis and glucose tolerance. Here, we show that the VAT harbors two distinct T cell populations: prototypical serum stimulation 2-positive (ST2) T cells that are enriched in males and a previously uncharacterized population of C-X-C motif chemokine receptor 3-positive (CXCR3) T cells that are enriched in females.

Adoptive T therapy with metabolic intervention via perforated microneedles ameliorates psoriasis syndrome.

Regulatory T (T) cells underlie multiple autoimmune disorders and potentialize an anti-inflammation treatment with adoptive cell therapy. However, systemic delivery of cellular therapeutics often lacks tissue targeting and accumulation for localized autoimmune diseases. Besides, the instability and plasticity of T cells also induce phenotype transition and functional loss, impeding clinical translation.

Evaluation of the possible association of PDCD-1 and LAG3 gene polymorphisms with hepatocellular carcinoma risk.

Purpose: Programmed death-1 (PDCD-1) and lymphocyte activating 3 (LAG3), two important immunosuppressive molecules, play crucial roles in immune escape of tumor cells. This study evaluated the effects of PDCD-1 (rs10204525 and rs36084323), and LAG3 (rs870849 and rs1882545) gene polymorphisms on hepatocellular carcinoma (HCC) risk.

Methods: 341 patients with HCC and 350 cancer-free controls in the South Chinese population were included in a population-based case-control study.

The role of indoleamine 2,3-dioxygenase 1 in early-onset post-stroke depression.

Background: The immune-inflammatory response has been widely considered to be involved in the pathogenesis of post-stroke depression (PSD), but there is ambiguity about the mechanism underlying such association.

Methods: According to Diagnostic and Statistical Manual of Mental Disorders (5th edition), depressive symptoms were assessed at 2 weeks after stroke onset. 15 single nucleotide polymorphisms (SNPs) in genes of indoleamine 2,3-dioxygenase (IDO, including IDO1 and IDO2) and its inducers (including pro-inflammatory cytokines interferon [IFN]-γ, tumor necrosis factor [TNF]-α, interleukin [IL]-1β, IL-2 and IL-6) were genotyped using SNPscan™ technology, and serum IDO1 levels were detected by double-antibody sandwich enzyme-linked immune-sorbent assay.

IOP Injection, A Novel Superparamagnetic Iron Oxide Particle MRI Contrast Agent for the Detection of Hepatocellular Carcinoma: A Phase II Clinical Trial.

Background: MRI is crucial in diagnosing hepatocellular carcinoma (HCC). Superparamagnetic iron oxide particles (SPIO) are liver-specific contrast agents which enhance lesions in T -weighted images. Iron oxide nano-particle m-PEG-silane (IOP) Injection, a newly developed SPIO, showed promising imaging effects and good safety profile in preclinical studies and in phase I clinical trial.

Prosthetic Replacement of the Ocular Surface Ecosystem for Limbal Stem Cell Deficiency: A Case Series.

Objectives: To assess outcomes of limbal stem cell deficiency (LSCD) in patients treated with Prosthetic Replacement of the Ocular Surface Ecosystem (PROSE).

Methods: Retrospective case series. Patients with LSCD who received PROSE treatment were included.

Prosthetic Replacement of the Ocular Surface Ecosystem for Terrien Marginal Degeneration: A Case Series.

Objectives: To assess outcomes of the Prosthetic Replacement of the Ocular Surface Ecosystem (PROSE) treatment in patients with advanced Terrien marginal degeneration (TMD).

Methods: This is a retrospective case series of patients with advanced TMD who were assessed and fit with customized PROSE lenses. Data were collected on PROSE fitting details including visual acuity (VA) before and after PROSE, slit-lamp findings, and corneal tomography scans.

Sensitivity enhancement in magnetic sensor using CoFeB/YFeO resonator.

Magnonics, an emerging research field that uses the quanta of spin waves as data carriers, has a potential to dominate the post-CMOS era owing to its intrinsic property of ultra-low power operation. Spin waves can be manipulated by a wide range of parameters; thus, they are suitable for sensing applications in a wide range of physical fields. In this study, we designed a highly sensitive, simple structure, and ultra-low power magnetic sensor using a simple CoFeB/YFeO bilayer structure.

Unusual free oligosaccharides in human bovine and caprine milk.

Free oligosaccharides are abundant macronutrients in milk and involved in prebiotic functions and antiadhesive binding of viruses and pathogenic bacteria to colonocytes. Despite the importance of these oligosaccharides, structural determination of oligosaccharides is challenging, and milk oligosaccharide biosynthetic pathways remain unclear. Oligosaccharide structures are conventionally determined using a combination of chemical reactions, exoglycosidase digestion, nuclear magnetic resonance spectroscopy, and mass spectrometry.

Poincaré Plot Is Useful for Distinguishing Vasovagal Syncope From Postural Tachycardia Syndrome in Children.

Objectives: To explore the role of the Poincaré plot derived from a 24-hour Holter recording in distinguishing vasovagal syncope (VVS) from postural tachycardia syndrome (POTS) in pediatric patients.

Materials And Methods: Pediatric patients with VVS or POTS, hospitalized in Peking University First Hospital between January 2012 and December 2018, were included in a derivation study. The transverse axis (T), longitudinal axis (L), T/L ratio, product T × L, distance between the origin and the proximal end of the longitudinal axis (pro-D), and distance between the origin and distal end of the longitudinal axis (dis-D) of the Poincaré plot were compared between the VVS and POTS groups, and the differential diagnostic performance of the above-mentioned graphic parameters was evaluated using receiver operating characteristic curve analysis.

Aorta Regulatory T Cells with a Tissue-Specific Phenotype and Function Promote Tissue Repair through Tff1 in Abdominal Aortic Aneurysms.

In addition to maintaining immune tolerance, Foxp3 regulatory T cells (Tregs) perform specialized functions in tissue homeostasis and remodeling. However, whether Tregs in aortic aneurysms have a tissue-specific phenotype and function is unclear. Here, a special group of Tregs that potentially inhibit abdominal aortic aneurysm (AAA) progression are identified and functionally characterized.

Deep Learning Assisted Diagnosis of Musculoskeletal Tumors Based on Contrast-Enhanced Magnetic Resonance Imaging.

Background: Misdiagnosis of malignant musculoskeletal tumors may lead to the delay of intervention, resulting in amputation or death.

Purpose: To improve the diagnostic efficacy of musculoskeletal tumors by developing deep learning (DL) models based on contrast-enhanced magnetic resonance imaging and to quantify the improvement in diagnostic performance obtained by using these models.

Study Type: Retrospective.

CALCB rs3829222 T/T Genotype and Low Expression of CALCB Are High-Risk Factors for Adenoid Cystic Carcinoma of Salivary Gland.

Objectives: To investigate the relationship between polymorphisms of calcitonin-related peptide gene II (beta-calcitonin gene-related peptide (CGRP), CALCB) and serum CGRP levels in salivary adenoid cystic carcinoma.

Materials And Methods: Using the polymerase chain reaction (PCR) technique, the full-length amplification and genotype analysis of CALCB genes were performed in 39 patients with adenoid cystic carcinoma of salivary gland and 158 normal controls. The gene frequencies of major genotype of CALCB in adenoid cystic carcinoma of salivary gland and normal control group were analyzed.

Diagnoses and Outcomes of Prosthetic Replacement of the Ocular Surface Ecosystem Treatment-A Canadian Experience.

Objectives: To investigate underlying diagnoses and outcomes of patients undergoing Prosthetic Replacement of the Ocular Surface Ecosystem (PROSE) treatment at the first Canadian PROSE center.

Methods: A retrospective chart review was conducted on patients referred for PROSE treatment and fitted with PROSE devices from 2018 to 2020. Data were collected on diagnoses, presenting symptoms, previous lens modalities attempted, best-corrected visual acuities (BCVAs) pre-PROSE and post-PROSE, daily wear time, and failure rates.

A Unique Population of Regulatory T Cells in Heart Potentiates Cardiac Protection From Myocardial Infarction.

Background: Regulatory T cells (Tregs), traditionally recognized as potent suppressors of immune response, are increasingly attracting attention because of a second major function: residing in parenchymal tissues and maintaining local homeostasis. However, the existence, unique phenotype, and function of so-called tissue Tregs in the heart remain unclear.

Methods: In mouse models of myocardial infarction (MI), myocardial ischemia/reperfusion injury, or cardiac cryoinjury, the dynamic accumulation of Tregs in the injured myocardium was monitored.

A review of the genus Strophidon (Anguilliformes: Muraenidae), with description of a new species.

Strophidon McClelland is a muraenid genus with characteristic appearance of a very elongated body, a large mouth cleft and anteriorly placed eyes. The nomenclature and taxonomic history of species within Strophidon are contentious and its members are easily misidentified. In the present study, species of the genus Strophidon are revised based on morphological and molecular data, and five species are considered valid, including S.

Macular Thickness in Intermediate Age-Related Macular Degeneration Is Influenced by Disease Severity and Subretinal Drusenoid Deposit Presence.

Purpose: To investigate how macular thickness varies with intermediate age-related macular degeneration (iAMD) severity and the presence of subretinal drusenoid deposits (SDDs).

Methods: A longitudinal prospective study of 143 participants >50 years of age with no to intermediate AMD who were followed with multimodal imaging and functional testing. Participants were stratified by iAMD severity according to imaging features.

Validation and Disease Risk Assessment of Previously Reported Genome-Wide Genetic Variants Associated With Brugada Syndrome: SADS-TW BrS Registry.

Background: Brugada syndrome (BrS) is an oligogenic arrhythmic disease with increased risk of sudden cardiac arrest. Several BrS or ECG traits-related single-nucleotide polymorphisms (SNPs) were identified through previous genome-wide association studies in white patients. We aimed to validate these SNPs in BrS patients in the Taiwanese population, assessing the cumulative effect of risk alleles and the BrS-polygenic risk score in predicting cardiac events.

Sex-specific adipose tissue imprinting of regulatory T cells.

Adipose tissue is an energy store and a dynamic endocrine organ. In particular, visceral adipose tissue (VAT) is critical for the regulation of systemic metabolism. Impaired VAT function-for example, in obesity-is associated with insulin resistance and type 2 diabetes.

Effects of Pregnancy on the Pharmacokinetics of Metformin.

This study's primary objective was to fully characterize the pharmacokinetics of metformin in pregnant women with gestational diabetes mellitus (GDM) versus nonpregnant controls. Steady-state oral metformin pharmacokinetics in pregnant women with GDM receiving either metformin monotherapy ( = 24) or a combination with glyburide ( = 30) as well as in nonpregnant women with type 2 diabetes mellitus (T2DM) ( = 24) were determined utilizing noncompartmental techniques. Maternal and umbilical cord blood samples were collected at delivery from 38 women.