TLR7/8/9 agonists and low-dose cisplatin synergistically promotes tertiary lymphatic structure formation and antitumor immunity.

In situ vaccination (ISV) triggers antitumor immune responses using the patient's own cancer antigens, yet limited neoantigen release hampers its efficacy. Our novel combination therapy involves low-dose local cisplatin followed by ISV with a TLR7/8/9 agonist formulation (CR108), in which CR108 boosts and sustains the antitumor responses induced by the cisplatin-released neoantigens. In mouse models, the cisplatin+CR108 combination significantly outperformed cisplatin or CR108 alone in abrogating established 4T1 and B16 tumors.

Validation Status of Electronic Sphygmomanometers in China: A National Survey.

Background: Although the information on the validation status of electronic sphygmomanometer (ES) devices in use in health care institutions and households is much more clinically relevant than that of ES models available on the market, it remains insufficient.

Methods: A national survey was conducted across all administrative regions of mainland China to assess the validation status of ESs. Fifty-eight cities were selected with stratification by municipality, provincial capital, and other cities, and health care institutions and households in each city were chosen by convenience to identify ES devices in use according to the study protocol.

An antibody cocktail targeting two different CD73 epitopes enhances enzyme inhibition and tumor control.

CD73, an ectoenzyme responsible for adenosine production, is often elevated in immuno-suppressive tumor environments. Inhibition of CD73 activity holds great promise as a therapeutic strategy for CD73-expressing cancers. In this study, we have developed a therapeutic anti-human CD73 antibody cocktail, HB0045.

YTHDF2 promotes ATP synthesis and immune evasion in B cell malignancies.

Long-term durable remission in patients with B cell malignancies following chimeric antigen receptor (CAR)-T cell immunotherapy remains unsatisfactory, often due to antigen escape. Malignant B cell transformation and oncogenic growth relies on efficient ATP synthesis, although the underlying mechanisms remain unclear. Here, we report that YTHDF2 facilitates energy supply and antigen escape in B cell malignancies, and its overexpression alone is sufficient to cause B cell transformation and tumorigenesis.

Association of Glymphatic Function With Clinical Characteristics in Patients With Clinical and Asymptomatic Creutzfeldt-Jakob Disease.

Background And Objectives: Abnormal glymphatic system-related proteins have been identified in a small-scale pathologic study of patients with Creutzfeldt-Jakob disease (CJD). However, it remains unclear whether glymphatic dysfunction occurs in vivo in patients with CJD and whether this decline begins during the preclinical stage. This study aimed to investigate the relationship between glymphatic dysfunction and clinical characteristics in patients with CJD, as well as potential glymphatic impairment in preclinical CJD.

Individually addressed entangling gates in a two-dimensional ion crystal.

Two-dimensional (2D) ion crystals may represent a promising path to scale up qubit numbers for ion trap quantum information processing. However, to realize universal quantum computing in this system, individually addressed high-fidelity two-qubit entangling gates still remain challenging due to the inevitable micromotion of ions in a 2D crystal as well as the technical difficulty in 2D addressing. Here we demonstrate two-qubit entangling gates between any ion pairs in a 2D crystal of four ions.

Trem2/Tyrobp Signaling Protects Against Aortic Dissection and Rupture by Inhibiting Macrophage Activation in Mice.

Background: The development of aortic dissection (AD) is closely associated with inflammation. The Trem2 (triggering receptor expressed on myeloid cells 2)/Tyrobp (TYRO protein tyrosine kinase-binding protein) signaling pathway critically regulates innate immunity and has emerged as an important target in cardiovascular diseases; however, its role in AD remains unclear.

Methods: Transcriptome data from human and mouse ADs were used to perform differentially expressed gene-based protein-protein interaction network analyses.

Integrated Deep Learning Model for the Detection, Segmentation, and Morphologic Analysis of Intracranial Aneurysms Using CT Angiography.

Purpose To develop a deep learning model for the morphologic measurement of unruptured intracranial aneurysms (UIAs) based on CT angiography (CTA) data and validate its performance using a multicenter dataset. Materials and Methods In this retrospective study, patients with CTA examinations, including those with and without UIAs, in a tertiary referral hospital from February 2018 to February 2021 were included as the training dataset. Patients with UIAs who underwent CTA at multiple centers between April 2021 and December 2022 were included as the multicenter external testing set.

Spatial proteomics of single cells and organelles on tissue slides using filter-aided expansion proteomics.

Hydrogel-based tissue expansion combined with mass spectrometry (MS) offers an emerging spatial proteomics approach. Here, we present a filter-aided expansion proteomics (FAXP) strategy for spatial proteomics analysis of archived formalin-fixed paraffin-embedded (FFPE) specimens. Compared to our previous ProteomEx method, FAXP employed a customized tip device to enhance both the stability and throughput of sample preparation, thus guaranteeing the reproducibility and robustness of the workflow.

Single cell spatial profiling of FFPE splenic tissue from a humanized mouse model of HIV infection.

Background: Latency remains a major obstacle to finding a cure for HIV despite the availability of antiretroviral therapy. Due to virus dormancy, limited biomarkers are available to identify latent HIV-infected cells. Profiling of individual HIV-infected cells is needed to explore potential latency biomarkers and to study the mechanisms of persistence that maintain the HIV reservoir.

Ziresovir in Hospitalized Infants with Respiratory Syncytial Virus Infection.

Background: Respiratory syncytial virus (RSV) is a leading cause of severe illness in infants, with no effective treatment. Results of a phase 2 trial suggested that ziresovir may have efficacy in the treatment of infants hospitalized with RSV infection.

Methods: In a phase 3, multicenter, double-blind, randomized, placebo-controlled trial conducted in China, we enrolled participants 1 to 24 months of age who were hospitalized with RSV infection.

Variability in Lipid Profiles During Young Adulthood and the Risk of Coronary Artery Calcium Incidence in Midlife: Insights From the CARDIA Study.

Background: Intraindividual variability in lipid profiles is recognized as a potential predictor of cardiovascular events. However, the influence of early adulthood lipid profile variability along with mean lipid levels on future coronary artery calcium (CAC) incidence remains unclear.

Methods: A total of 2395 participants (41.

CCL19-producing fibroblasts promote tertiary lymphoid structure formation enhancing anti-tumor IgG response in colorectal cancer liver metastasis.

Tertiary lymphoid structures (TLSs) are associated with enhanced immunity in tumors. However, their formation and functions in colorectal cancer liver metastasis (CRLM) remain unclear. Here, we reveal that intra- and peri-tumor mature TLSs (TLS+) are associated with improved clinical outcomes than TLS- tumors.

Identification of Noncoding Functional Regulatory Variants of Gene in Idiopathic Pulmonary Arterial Hypertension.

Background: STIM1 (stromal interaction molecule 1) regulates store-operated calcium entry and is involved in pulmonary artery vasoconstriction and pulmonary artery smooth muscle cell proliferation, leading to pulmonary arterial hypertension (PAH).

Methods: Bioinformatics analysis and a 2-stage matched case-control study were conducted to screen for noncoding variants that may potentially affect transcriptional regulation in 242 patients with idiopathic PAH and 414 healthy controls. Luciferase reporter assay, real-time quantitative polymerase chain reaction, western blot, 5-ethynyl-2'-deoxyuridine (EdU) assay, and intracellular Ca measurement were performed to study the mechanistic roles of those noncoding variants in PAH.

Bispecific CAR-T cells targeting FAP and GPC3 have the potential to treat hepatocellular carcinoma.

Chimeric antigen receptor (CAR) T cell therapy has demonstrated robust efficacy against hematological malignancies, but there are still some challenges regarding treating solid tumors, including tumor heterogeneity, antigen escape, and an immunosuppressive microenvironment. Here, we found that SNU398, a hepatocellular carcinoma (HCC) cell line, exhibited high expression levels of fibroblast activation protein (FAP) and Glypican 3 (GPC3), which were negatively correlated with patient prognosis. The HepG2 HCC cell line highly expressed GPC3, while the SNU387 cell line exhibited high expression of FAP.

The Art of Finding the Right Drug Target: Emerging Methods and Strategies.

Drug targets are specific molecules in biological tissues and body fluids that interact with drugs. Drug target discovery is a key component of drug discovery and is essential for the development of new drugs in areas such as cancer therapy and precision medicine. Traditional in vitro or in vivo target discovery methods are time-consuming and labor-intensive, limiting the pace of drug discovery.

Positive Associations of Perfluoroalkyl and Polyfluoroalkyl Substances With Hypertension May Be Attenuated by Endogenous Sex Hormones: A Nationally Representative Cross-Sectional Study.

Background: Perfluoroalkyl and polyfluoroalkyl substance (PFAS) has endocrine-disrupting properties and may affect blood pressure. Endogenous hormones also play a crucial role in the progression of hypertension. However, their interaction with hypertension remains to be explored.

Hsc70 promotes anti-tumor immunity by targeting PD-L1 for lysosomal degradation.

Immune checkpoint inhibition targeting the PD-1/PD-L1 pathway has become a powerful clinical strategy for treating cancer, but its efficacy is complicated by various resistance mechanisms. One of the reasons for the resistance is the internalization and recycling of PD-L1 itself upon antibody binding. The inhibition of lysosome-mediated degradation of PD-L1 is critical for preserving the amount of PD-L1 recycling back to the cell membrane.

Spiral time-of-flight magnetic resonance angiography for intracranial vascular imaging: performance compared to conventional Cartesian angiogram.

Background: Computed tomography angiography (CTA) and digital subtraction angiography (DSA) usually raise the risk of potential malignancies with cumulative radiation doses. Current time-of-flight magnetic resonance angiography (TOF-MRA) (dubbed as cTOF), which is based on Cartesian sampling mode, may show limited diagnostic conspicuity at sinuous or branching regions. It is also prone to relatively high false positive diagnoses and undesirable display of distal intracranial vessels.