High spin-orbit torque efficiency induced by engineering spin absorption for fully electric-driven magnetization switching.

Realizing spin-orbit torque (SOT)-driven magnetization switching offers promising opportunities for the advancement of next-generation spintronics. However, the relatively low charge-spin conversion efficiency accompanied by an ultrahigh critical switching current density () remains a significant obstacle to the further development of SOT-based storage elements. Herein, spin absorption engineering at the ferromagnet/nonmagnet interface is firstly proposed to achieve high SOT efficiency in Pt/Co/Ir trilayers.

Nomogram for Predicting 90-day Outcomes in Patients with Acute Vertebrobasilar Artery Occlusion Undergoing Endovascular Treatment: A Multicenter Cohort Study.

Background And Purpose: In this study, we aimed to develop and validate a novel nomogram model for predicting 90-day non-favorable clinical outcomes in patients with acute vertebrobasilar artery occlusion after endovascular treatment by integrating clinical and MRI features.

Materials And Methods: This multicenter retrospective study analyzed data from 181 patients with vertebrobasilar artery occlusion eligible for endovascular treatment from two Chinese stroke centers. We developed a predictive model for non-favorable clinical outcomes (modified Rankin Scale score >3) using the data of 125 patients from Stroke Center A (2019-2023).

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.

Radiomics of Periprostatic Fat and Tumor Lesion Based on MRI Predicts the Pathological Upgrading of Prostate Cancer from Biopsy to Radical Prostatectomy.

Rationale And Objectives: To assess the predictive value of MRI-based radiomics of periprostatic fat (PPF) and tumor lesions for predicting Gleason score (GS) upgrading from biopsy to radical prostatectomy (RP) in prostate cancer (PCa).

Methods: A total of 314 patients with pathologically confirmed prostate cancer (PCa) after radical prostatectomy (RP) were included in the study. The patients were randomly assigned to the training cohort (n = 157) and the validating cohort (n = 157) in a 1:1 ratio.

Cardiovascular-Liver-Metabolic Health: Recommendations in Screening, Diagnosis, and Management of Metabolic Dysfunction-Associated Steatotic Liver Disease in Cardiovascular Disease via Modified Delphi Approach.

There is a new awareness of the widespread nature of metabolic dysfunction-associated steatotic liver disease (MASLD) and its connection to cardiovascular disease (CVD). This has catalyzed collaboration between cardiologists, hepatologists, endocrinologists, and the wider multidisciplinary team to address the need for earlier identification of those with MASLD who are at increased risk for CVD. The overlap in the pathophysiologic processes and parallel prevalence of CVD, metabolic syndrome, and MASLD highlight the multisystem consequences of poor cardiovascular-liver-metabolic health.

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.

A prognostic molecular signature of hepatic steatosis is spatially heterogeneous and dynamic in human liver.

Hepatic steatosis is a central phenotype in multi-system metabolic dysfunction and is increasing in parallel with the obesity pandemic. We use a translational approach integrating clinical phenotyping and outcomes, circulating proteomics, and tissue transcriptomics to identify dynamic, functional biomarkers of hepatic steatosis. Using multi-modality imaging and broad proteomic profiling, we identify proteins implicated in the progression of hepatic steatosis that are largely encoded by genes enriched at the transcriptional level in the human liver.

Insights into biofilm architecture and maturation enable improved clinical strategies for exopolysaccharide-targeting therapeutics.

Polysaccharide intercellular adhesin (PIA), an exopolysaccharide composed of poly-N-acetyl glucosamine (PNAG), is an essential component in many pathogenic biofilms. Partial deacetylation of PNAG is required for biofilm formation, but limited structural knowledge hinders therapeutic development. Employing a new monoclonal antibody (TG10) that selectively binds highly deacetylated PNAG and an antibody (F598) in clinical trials that binds highly acetylated PNAG, we demonstrate that PIA within the biofilm contains distinct regions of highly acetylated and deacetylated exopolysaccharide, contrary to the previous model invoking stochastic deacetylation throughout the biofilm.

Peli1 Deficiency in Macrophages Attenuates Pulmonary Hypertension by Enhancing Foxp1-Mediated Transcriptional Inhibition of IL-6.

Background: The infiltration of macrophages into the lungs is a common characteristic of perivascular inflammation, contributing to vascular remodeling in pulmonary hypertension (PH). Peli1 (pellino E3 ubiquitin-protein ligase 1) plays a critical role in regulating the production of proinflammatory cytokines and the polarization of macrophages in various diseases. However, the role of Peli1 in PH remains to be investigated.

The ClinGen Syndromic Disorders Gene Curation Expert Panel: Assessing the Clinical Validity of 111 Gene-Disease Relationships.

Purpose: The Clinical Genome Resource (ClinGen) Gene Curation Expert Panels (GCEPs) have historically focused on specific organ systems or phenotypes; thus, the ClinGen Syndromic Disorders GCEP (SD-GCEP) was formed to address an unmet need.

Methods: The SD-GCEP applied ClinGen's framework to evaluate the clinical validity of genes associated with rare syndromic disorders. 111 Gene-Disease Relationships (GDRs) associated with 100 genes spanning the clinical spectrum of syndromic disorders were curated.

Development of a streamlined NGS-based TCGA classification scheme for gastric cancer and its implications for personalized therapy.

Background: The Cancer Genome Atlas (TCGA) has identified four distinct molecular subtypes of gastric cancer (GC) with prognostic significance: Epstein-Barr virus (EBV)-positive, microsatellite instability (MSI)-high, genomically stable (GS), and chromosomal instability (CIN). Unfortunately, the complex analysis required for TCGA classification limits its practical use in clinical settings. Our study sought to devise a next-generation sequencing (NGS)-based method to classify GC more efficiently, serving as a promising biomarker for prognosis and immunotherapy efficacy.

Releasing a sugar brake generates sweeter tomato without yield penalty.

In tomato, sugar content is highly correlated with consumer preferences, with most consumers preferring sweeter fruit. However, the sugar content of commercial varieties is generally low, as it is inversely correlated with fruit size, and growers prioritize yield over flavour quality. Here we identified two genes, tomato (Solanum lycopersicum) calcium-dependent protein kinase 27 (SlCDPK27; also known as SlCPK27) and its paralogue SlCDPK26, that control fruit sugar content.

Spatial transcriptomic landscape unveils immunoglobin-associated senescence as a hallmark of aging.

To systematically characterize the loss of tissue integrity and organ dysfunction resulting from aging, we produced an in-depth spatial transcriptomic profile of nine tissues in male mice during aging. We showed that senescence-sensitive spots (SSSs) colocalized with elevated entropy in organizational structure and that the aggregation of immunoglobulin-expressing cells is a characteristic feature of the microenvironment surrounding SSSs. Immunoglobulin G (IgG) accumulated across the aged tissues in both male and female mice, and a similar phenomenon was observed in human tissues, suggesting the potential of the abnormal elevation of immunoglobulins as an evolutionarily conserved feature in aging.

Fully Automated Approach for Diagnosis of Supraspinatus Tendon Tear on Shoulder MRI by Using Deep Learning.

Rationale And Objectives: To explore the feasibility of applying deep learning (DL) approach to detect supraspinatus tendon (ST) tear on shoulder MRI by using arthroscopy as the reference standard.

Materials And Methods: In this retrospective study, a total of 431 participants from two different manufacturers and two centers was used to build and validate a DL-based ST tear detection system. The proposed system was developed by using U-Net networks to segment and isolate ST followed by a swin transformer architecture to determine the presence or absence of a ST tear.

Optimal restoration of spermatogenesis after testosterone therapy using human chorionic gonadotropin and follicle-stimulating hormone.

Objective: To study improvements in spermatogenesis in men with a history of testosterone therapy using a novel fertility treatment regimen.

Design: A single-center retrospective cohort analysis.

Setting: Clinic.

Tumor immune microenvironment analysis of non-small cell lung cancer development through multiplex immunofluorescence.

Background: Emerging evidence has underscored the crucial role of infiltrating immune cells in the tumor immune microenvironment (TIME) of non-small cell lung cancer (NSCLC) development and progression. With the implementation of screening programs, the incidence of early-stage NSCLC is rising. However, the high risk of recurrence and poor survival rates associated with this disease necessitate a deeper understanding of the TIME and its relationship with driver alterations.

Circulating Tumor DNA in Conjunctival Melanoma: Landscape and Surveillance Value.

Purpose: To evaluate the surveillance value of circulating tumor DNA (ctDNA) for detecting distant metastasis and indicating systemic therapeutic efficacy in conjunctival melanoma (CoM).

Design: Retrospective, observational case series.

Methods: From July 2021 to June 2023, 30 CoM patients in our center underwent plasma ctDNA assessment, out of which 12 individuals presented with distant metastases.

Observation of the decay.

Using proton-proton collision data corresponding to an integrated luminosity of collected by the CMS experiment at , the decay is observed for the first time, with a statistical significance exceeding 5 standard deviations. The relative branching fraction, with respect to the decay, is measured to be , where the first uncertainty is statistical, the second is systematic, and the third is related to the uncertainties in and .

A positive ReceptivaDx result for BCL6 does not correlate with abnormal ERA results or decreased expression of receptivity-associated markers: two sides of the endometrial receptivity coin in fertility evaluation and treatment.

Objective: To investigate if a positive result on ReceptivaDx for evaluation of B-cell lymphoma 6 (BCL6), a proposed marker of progesterone resistance associated with impaired uterine receptivity, correlates with a suboptimal profile of receptivity-associated markers in the window of implantation using the endometrial receptivity array and single-nucleus transcriptomic analysis.

Design: Retrospective clinical cohort study; pilot study of single-nucleus RNA sequencing of prospectively collected window of implantation endometrium undergoing ReceptivaDx BCL6 evaluation.

Setting: Academic center.

Development of an orally bioavailable CDK12/13 degrader and induction of synthetic lethality with AKT pathway inhibition.

Cyclin-dependent kinases 12/13 play pivotal roles in orchestrating transcription elongation, DNA damage response, and maintenance of genomic stability. Biallelic CDK12 loss has been documented in various malignancies. Here, we develop a selective CDK12/13 PROTAC degrader, YJ9069, which effectively inhibits proliferation in subsets of prostate cancer cells preferentially over benign immortalized cells.

Colocalization of Cancer-Associated Biomarkers on Single Extracellular Vesicles for Early Detection of Cancer.

Detection of cancer early, when it is most treatable, remains a significant challenge because of the lack of diagnostic methods sufficiently sensitive to detect nascent tumors. Early-stage tumors are small relative to their tissue of origin, heterogeneous, and infrequently manifest in clinical symptoms. The detection of early-stage tumors is challenging given the lack of tumor-specific indicators (ie, protein biomarkers, circulating tumor DNA) to enable detection using a noninvasive diagnostic assay.